The effect of tablet computer-based telemonitoring added to an established telephone disease management program on heart failure hospitalizations: The Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) III Randomized Controlled Trial.

BACKGROUND: Mobile health applications are becoming increasingly common. Prior work has demonstrated reduced heart failure (HF) hospitalizations with HF disease management programs; however, few of these programs have used tablet computer-based technology. METHODS: Participants with a diagnosis of HF and at least 1 high risk feature for hospitalization were randomized to either an established telephone-based disease management program or the same disease management program with the addition of remote monitoring of weight, blood pressure, heart rate and symptoms via a tablet computer for 90 days. The primary endpoint was the number of days hospitalized for HF assessed at 90 days. RESULTS: From August 2014 to April 2019, 212 participants from 3 hospitals in Massachusetts were randomized 3:1 to telemonitoring-based HF disease management (n = 159) or telephone-based HF disease management (n = 53) with 98% of individuals in both study groups completing the 90 days of follow-up. There was no significant difference in the number of days hospitalized for HF between the telemonitoring disease management group (0.88 ± 3.28 days per patient-90 days) and the telephone-based disease management group (1.00 ± 2.97 days per patient-90 days); incidence rate ratio 0.82 (95% confidence interval, 0.43-1.58; P = .442). CONCLUSIONS: The addition of tablet-based telemonitoring to an established HF telephone-based disease management program did not reduce HF hospitalizations; however, study power was limited.

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

Exploring the Relationship Between Medication Adherence and Diabetes Disparities among Hispanic Patients in a Large Health System.

BACKGROUND: Sub-optimal HbA1c control is a driver of disparities in diabetes outcomes among Hispanic patients. Differences in medication adherence may underlie racial/ethnic differences in HbA1c level. OBJECTIVE: To examine the relationship between medication adherence and disparities in HbA1c level among Hispanic patients, relative to other racial/ethnic groups, obtaining care in the University of California Health System (UC Health). DESIGN: This study used clinical, administrative, and prescription dispensing data (January-December 2021) derived from the electronic health records of 5 Academic Medical Centers in UC Health, and linear regression models (LRMs) to conduct a cross-sectional analysis of the association between medication adherence, race/ethnicity, and HbA1c level. Adjusted LRMs were run with and without the measure of medication adherence to assess this relationship. PARTICIPANTS: Patients with a UC Health primary care physician (PCP), with ≥ 1 PCP visit within the last 3 years, ages 18-75, reporting Asian, Hispanic, or White race/ethnicity, and who had ≥ 2 encounters with an ICD diagnosis of diabetes or had a prescription for a diabetes medication within the last 2 years, as of 12/31/21 (N = 27, 542; Asian = 6253, Hispanic = 7216, White = 14,073). MAIN MEASURES: Our measure of medication adherence was the proportion of days covered (PDC) for diabetes medications in 2021. Our outcome was the most recent HbA1c value. KEY RESULTS: In the LRM excluding the PDC, Hispanic ethnicity was positively associated with HbA1c level (ß = 0.31, p = < 0.001). In the LRM model including PDC, PDC was negatively associated with HbA1c level (ß = - 0.18, p = < 0.001). However, the positive relationship between Hispanic ethnicity and HbA1c level did not change (ß = 0.31, p = < 0.001). CONCLUSIONS: The findings of this study suggest that the relationship between Hispanic ethnicity, HbA1c level, and factors outside of medication adherence should be explored among primary care patients receiving care in Academic Medical Centers.

Novel computational methods on electronic health record yields new estimates of transfusion-associated circulatory overload in populations enriched with high-risk patients.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is a severe adverse reaction (AR) contributing to the leading cause of mortality associated with transfusions. As strategies to mitigate TACO have been increasingly adopted, an update of prevalence rates and risk factors associated with TACO using the growing sources of electronic health record (EHR) data can help understand transfusion safety. STUDY DESIGN AND METHODS: This retrospective study aimed to provide a timely and reproducible assessment of prevalence rates and risk factors associated with TACO. Novel natural language processing methods, now made publicly available on GitHub, were developed to extract ARs from 3178 transfusion reaction reports. Other patient-level data were extracted computationally from UCSF EHR between 2012 and 2022. The odds ratio estimates of risk factors were calculated using a multivariate logistic regression analysis with case-to-control matched on sex and age at a ratio of 1:5. RESULTS: A total of 56,208 patients received transfusions (total 573,533 units) at UCSF during the study period and 102 patients developed TACO. The prevalence of TACO was estimated to be 0.2% per patient (102/total 56,208). Patients with a history of coagulopathy (OR, 1.36; 95% CI, 1.04-1.79) and transplant (OR, 1.99; 95% CI, 1.48-2.68) were associated with increased odds of TACO. DISCUSSION: While TACO is a serious AR, events remained rare, even in populations enriched with high-risk patients. Novel computational methods can be used to find and continually surveil for transfusion ARs. Results suggest that patients with history or presence of coagulopathy and organ transplant should be carefully monitored to mitigate potential risks of TACO.

Emerging Therapies for Transthyretin Amyloidosis.

PURPOSE OF REVIEW: This review provides an overview of the available therapies for treating neuropathic and/or cardiac manifestations of transthyretin amyloidosis (ATTR), as well as investigational therapeutic agents in ongoing clinical trials. We discuss additional emergent approaches towards thwarting this life-threatening disease that until recently was considered virtually untreatable. RECENT FINDINGS: Advances in noninvasive diagnostic methods for detecting ATTR have facilitated easier diagnosis and detection at an earlier stage of disease when therapeutic interventions are likely to be more effective. There are now several ATTR-directed treatments that are clinically available, as well as investigational agents that are being studied in clinical trials. Therapeutic strategies include tetramer stabilization, gene silencing, and fibril disruption. ATTR has been historically underdiagnosed. With advances in diagnostic methods and the advent of disease-modifying treatments, early diagnosis and initiation of treatment is revolutionizing management of this disease.

Disseminated mucormycosis masquerading as rejection early after orthotopic heart transplantation.

Mucorales organisms are an uncommon cause of invasive fungal infections after solid organ transplantation but are associated with great morbidity and mortality. We report a fatal case of disseminated Cunninghamella infection early after heart transplantation. The patient developed graft dysfunction and elevated markers of myocyte injury and autopsy revealed fulminant fungal myocarditis. This case highlights the need for a high index of suspicion in immunocompromised patients who are not improving with standard antimicrobial therapy.

Acute Hemodynamic Effects of Intra-aortic Balloon Counterpulsation Pumps in Advanced Heart Failure.

BACKGROUND: The utility of intra-aortic balloon counterpulsation pumps (IABPs) in low cardiac output states is unknown and no studies have explored the impact of IABP therapy on ventricular workload in patients with advanced heart failure (HF). For these reasons, we explored the acute hemodynamic effects of IABP therapy in patients with advanced HF. METHODS: We prospectively studied 10 consecutive patients with stage D HF referred for IABP placement before left ventricular assist device (LVAD) surgery and compared with 5 control patients with preserved left ventricular (LV) ejection fraction (EF) who did not receive IABP therapy. Hemodynamics were recorded using LV conductance and pulmonary artery catheters. Cardiac index (CI)-responder and CI-nonresponder status was assigned a priori as being "equal to or above" or below the median of the IABP effect on CI, respectively, within 24 hours after IABP activation. RESULTS: Compared with controls, patients with advanced HF had lower LVEF, lower LV end-systolic pressure, lower LV stroke work, and higher LV end-diastolic pressures and volumes before IABP activation. IABP activation reduced LV stroke work primarily by reducing end-systolic pressure. IABP therapy increased CI by a median of 20% as well as increased diastolic pressure time index and the myocardial oxygen supply:demand ratio. Compared with CI-nonresponders, CI-responders had higher systemic vascular resistance, lower right heart filling pressures, and a trend toward lower left heart filling pressures with improved indices of right heart function. Compared with CI-nonresponders, the diastolic pressure time index was increased among CI-responders. CONCLUSIONS: IABP therapy may be effective at reducing LV stroke work, increasing CI, and favorably altering the myocardial oxygen supply:demand ratio in patients with advanced HF, especially among patients with low right heart filling pressures and high systemic vascular resistance.

Preoperative three-dimensional echocardiography to assess risk of right ventricular failure after left ventricular assist device surgery.

BACKGROUND: Right ventricular failure (RVF) is associated with significant morbidity after left ventricular assist device (LVAD) surgery. Hemodynamic, clinical, and 2-dimensional echocardiographic variables poorly discriminate patients at risk of RVF. We examined the utility of 3-dimensional echocardiography (3DE) right ventricular (RV) volumetric assessment to identify patients at risk for RVF. METHODS AND RESULTS: RVF was defined as the need for inotropic infusion for >14 days after LVAD surgery or the need for biventricular assist device support. Preoperative RV volumes and ejection fraction (EF) were measured, blinded to clinical data, from transthoracic 3DE full volume data sets in 26 patients. Baseline variables and 3DE RV indices were compared between patients with and without RVF. Twenty-four patients received continuous-flow LVADs, and 2 required biventricular support devices. Ten patients required prolonged inotropes after LVAD placement. Baseline characteristics associated with RVF included higher right atrial pressure, higher right atrial pressure to pulmonary capillary wedge pressure ratio, and lower cardiac index and RV stroke work index (RVSWI). Echocardiographic indices associated with RVF included 3DE indexed RV end-diastolic and end-systolic volumes (RVEDVI and RVESVI) and RV ejection fraction (RVEF). The relationship between 3DE quantification of RV volumes and the development of RVF was independent from RVSWI: RVEDVI: odds ratio (OR) 1.16, 95% confidence interval (CI) 1.00-1.33 (P = .04); RVESVI: OR 1.14, 95% CI 1.01-1.28 (P = .03). CONCLUSIONS: Quantitative 3DE is a promising method for pre-LVAD RV assessment. RV volumes assessed by 3DE are predictive of RVF in LVAD recipients independently from hemodynamic correlates of RV function.

Left Ventricular Ejection Time Derived From the Common Carotid Artery Doppler Waveform: Association With Left Ventricular Ejection Fraction and Prediction of Heart Failure.

OBJECTIVES: Left ventricular ejection time (LVET) is measured from blood pressure tracings as the interval from end diastole to the dicrotic notch and shows associations with left ventricular ejection fraction (LVEF) and heart failure. LVET can be measured on common carotid artery Doppler waveforms. We therefore studied the possible associations of common carotid artery LVET with LVEF measured by echocardiography and heart failure. METHODS: We performed a retrospective study of 110 patients who had transthoracic echocardiography and carotid Doppler evaluations within 1 day of each other. LVEF was determined by the biplane modified Simpson method. LVET was measured from left common carotid artery Doppler tracings. Linear regression was used to evaluate associations between LVET and LVEF. We also used logistic regression with LVEF of less than 40% as a cut point for heart failure to generate a receiver operating characteristic curve, estimate the area under the curve, and calculate sensitivity and specificity. RESULTS: LVET was associated with LVEF (P < .0001). The area under the curve of LVET for heart failure was 0.81 (95% confidence interval [CI], 0.72-0.87), and the sensitivity and specificity were 76.9% (95% CI, 65.4%-88.4%) and 65.5% (95% CI, 53.4%-77.8%), respectively, for LVET of 321 milliseconds. CONCLUSIONS: LVET measured on common carotid artery Doppler tracings decreases with LVEF and is strongly associated with prevalent heart failure. Based on what is known of blood pressure-measured LVET, common carotid artery Doppler waveform-derived LVET could be used to serially monitor cardiac function.

Association of common carotid artery Doppler-determined dicrotic notch velocity with the left ventricular ejection fraction.

OBJECTIVES: The appearance of the dicrotic notch on blood pressure tracings is associated with impaired cardiac function. Common carotid artery waveforms have similar fiduciary markers, yet they have not been related to cardiac function. We studied associations of common carotid artery dicrotic notch velocities with the left ventricular ejection fraction (LVEF) determined by echocardiography. METHODS: We conducted a retrospective study of 37 patients who had cardiac echocardiography and carotid Doppler evaluations within 1 day of each other. The LVEF was determined by the biplane modified Simpson rule. Doppler parameters were measured from tracings of the left common carotid artery 4 cm from the flow divider. Linear regression and stepwise multivariable linear regression models were used to evaluate any association between the LVEF and the following variables: age, sex, peak systolic velocity (PSV), end-diastolic velocity (EDV), dicrotic notch velocity, rise time (EDV to PSV), resistive index, and cardiac cycle length. RESULTS: The dicrotic notch velocity was the only variable associated with the LVEF (P = .028) in a bivariate analyses. A backward selection stepwise multivariable equation predicting the LVEF had the dicrotic notch (P = .001) and resistive index (P = .01) as significant predictors, whereas the cardiac cycle length (P = .08) and PSV (P = .08) were borderline not significant. Model goodness of fit was R(2) = 0.37 (P = .004). CONCLUSIONS: Dicrotic notch velocities measured from common carotid artery Doppler waveforms are associated with the LVEF and might offer some clinical value in selected cases.

The syndrome of degenerative calcific aortic stenosis: prevalence of multiple pathophysiologic disorders in association with valvular stenosis and their implications.

BACKGROUND: We hypothesized that degenerative calcific aortic stenosis (DCAS) is a syndrome influenced by factors beyond aortic valve stenosis (AS). The aim of this study was to assess how frequently DCAS is complicated by increased vascular load, systolic and/or diastolic left ventricular (LV) dysfunction, and comorbid disorders. METHODS: In 215 consecutive patients > 60 years of age with severe and moderate AS, we analyzed systemic arterial compliance, global hemodynamic load, LV ejection fraction (EF), the presence of diastolic dysfunction, and other valvular or systemic disorders. RESULTS: A total of 164 patients had severe AS and 51 had moderate AS. In patients with severe AS, the prevalence of increased vascular load was 42%; LV systolic and diastolic dysfunction was present in 27% and 42%; other valve diseases in 23%; and comorbid disorders in 82%. In the moderate AS group, abnormal vascular load was found in 52%; LV systolic and diastolic dysfunction was prevalent in 26% and 31%; other valve diseases in 17%; and comorbid disorders in 78% patients. More than half the patients in both groups had symptoms. In both severe and moderate AS groups, the prevalence of increased vascular load and systolic dysfunction was higher in the symptomatic group. CONCLUSION: Considerable number of patients with DCAS have abnormal vascular load, abnormal LV function, and significant coexisting disorders. These could influence the total pathophysiologic burden on the heart and symptom expression. Thus, DCAS should not be considered just as valvular stenosis, but a syndrome of DCAS because of the diagnostic, prognostic, and therapeutic implications of various factors associated with it.

Blood pressure changes during routine transthoracic echocardiography.

Background: Increased afterload affects many of the flow dependent metrics assessed during transthoracic echocardiography (TTE) especially in the evaluation valvular disease. A single timepoint blood pressure (BP) may not accurately reflect the afterload present at the time of flow-dependent imaging and quantification. We assessed the magnitude of change in BP at discrete timepoints during routine TTE. Method: We conducted a prospective study where participants underwent automated BP measurement while undergoing a clinically indicated TTE. The first reading was obtained right after the patient lay supine and subsequent readings were taken at 10-min intervals during image acquisition. Result: We included 50 participants (66% were male, with a mean age of 64 years). After 10 min, 40 (80%) participants had a drop in systolic BP of >10 mmHg. Compared to the baseline, there was a significant drop in systolic BP (mean decrease 20.0 ± 12.8 mmHg; P < 0.05), and diastolic BP (mean decrease 15.7 ± 13.2 mmHg; P < 0.05) at 10 min. The systolic BP remained different from the baseline value throughout the duration of the study (average decrease from baseline to study end was 12.4 ± 16.0 mmHg, p < 0.05). Conclusion: BP recorded just prior to TTE does not accurately reflect the afterload present during most of the study. This finding has important implications for valvular heart disease imaging protocols that incorporate flow dependent metrics, where the presence or absence of hypertension may lead to under- or over-estimation of disease severity.

Second-Line Pharmaceutical Treatments for Patients with Type 2 Diabetes.

Importance: Assessing the relative effectiveness and safety of additional treatments when metformin monotherapy is insufficient remains a limiting factor in improving treatment choices in type 2 diabetes. Objective: To determine whether data from electronic health records across the University of California Health system could be used to assess the comparative effectiveness and safety associated with 4 treatments in diabetes when added to metformin monotherapy. Design, Setting, and Participants: This multicenter, new user, multidimensional propensity score-matched retrospective cohort study with leave-one-medical-center-out (LOMCO) sensitivity analysis used principles of emulating target trial. Participants included patients with diabetes receiving metformin who were then additionally prescribed either a sulfonylurea, dipeptidyl peptidase-4 inhibitor (DPP4I), sodium-glucose cotransporter-2 inhibitor (SGLT2I), or glucagon-like peptide-1 receptor agonist (GLP1RA) for the first time and followed-up over a 5-year monitoring period. Data were analyzed between January 2022 and April 2023. Exposure: Treatment with sulfonylurea, DPP4I, SGLT2I, or GLP1RA added to metformin monotherapy. Main Outcomes and Measures: The main effectiveness outcome was the ability of patients to maintain glycemic control, represented as time to metabolic failure (hemoglobin A1c [HbA1c] ≥7.0%). A secondary effectiveness outcome was assessed by monitoring time to new incidence of any of 28 adverse outcomes, including diabetes-related complications while treated with the assigned drug. Sensitivity analysis included LOMCO. Results: This cohort study included 31 852 patients (16 635 [52.2%] male; mean [SD] age, 61.4 [12.6] years) who were new users of diabetes treatments added on to metformin monotherapy. Compared with sulfonylurea in random-effect meta-analysis, treatment with SGLT2I (summary hazard ratio [sHR], 0.75 [95% CI, 0.69-0.83]; I2 = 37.5%), DPP4I (sHR, 0.79 [95% CI, 0.75-0.84]; I2 = 0%), GLP1RA (sHR, 0.62 [95% CI, 0.57-0.68]; I2 = 23.6%) were effective in glycemic control; findings from LOMCO sensitivity analysis were similar. Treatment with SGLT2I showed no significant difference in effectiveness compared with GLP1RA (sHR, 1.26 [95% CI, 1.12-1.42]; I2 = 47.3%; no LOMCO) or DPP4I (sHR, 0.97 [95% CI, 0.90-1.04]; I2 = 0%). Patients treated with DPP4I and SGLT2I had fewer cardiovascular events compared with those treated with sulfonylurea (DPP4I: sHR, 0.84 [95% CI, 0.74-0.96]; I2 = 0%; SGLT2I: sHR, 0.78 [95% CI, 0.62-0.98]; I2 = 0%). Patients treated with a GLP1RA or SGLT2I were less likely to develop chronic kidney disease (GLP1RA: sHR, 0.75 [95% CI 0.6-0.94]; I2 = 0%; SGLT2I: sHR, 0.77 [95% CI, 0.61-0.97]; I2 = 0%), kidney failure (GLP1RA: sHR, 0.69 [95% CI, 0.56-0.86]; I2 = 9.1%; SGLT2I: sHR, 0.72 [95% CI, 0.59-0.88]; I2 = 0%), or hypertension (GLP1RA: sHR, 0.82 [95% CI, 0.68-0.97]; I2 = 0%; SGLT2I: sHR, 0.73 [95% CI, 0.58-0.92]; I2 = 38.5%) compared with those treated with a sulfonylurea. Patients treated with an SGLT2I, vs a DPP4I, GLP1RA, or sulfonylurea, were less likely to develop indicators of chronic hepatic dysfunction (sHR vs DPP4I, 0.68 [95% CI, 0.49-0.95]; I2 = 0%; sHR vs GLP1RA, 0.66 [95% CI, 0.48-0.91]; I2 = 0%; sHR vs sulfonylurea, 0.60 [95% CI, 0.44-0.81]; I2 = 0%), and those treated with a DPP4I were less likely to develop new incidence of hypoglycemia (sHR, 0.48 [95% CI, 0.36-0.65]; I2 = 22.7%) compared with those treated with a sulfonylurea. Conclusions and Relevance: These findings highlight familiar medication patterns, including those mirroring randomized clinical trials, as well as providing new insights underscoring the value of robust clinical data analytics in swiftly generating evidence to help guide treatment choices in diabetes.

Left ventricular stroke volume index following transcatheter aortic valve replacement is an early predictor of 1-year survival.

BACKGROUND: Adverse cardiac events are common following transcatheter aortic valve replacement (TAVR). Our aim was to investigate the low left ventricular stroke volume index (LVSVI) 30 days after TAVR as an early echocardiographic marker of survival. HYPOTHESIS: Steady-state (30-day) LVSVI after TAVR is associated with 1-year mortality. METHODS: A single-center retrospective analysis of all patients undergoing TAVR from 2017 to 2019. Baseline and 30-day post-TAVR echocardiographic LVSVI were calculated. Patients were stratified by pre-TAVR transaortic gradient, surgical risk, and change in transvalvular flow following TAVR. RESULTS: This analysis focuses on 238 patients treated with TAVR. The 1-year mortality rate was 9% and 124 (52%) patients had normal flow post-TAVR. Of those with pre-TAVR low flow, 67% of patients did not normalize LVSVI at 30 days. The 30-day normal flow was associated with lower 1-year mortality when compared to low flow (4% vs. 14%, p = .007). This association remained significant after adjusting for known predictors of risk (adjusted odds ratio [OR] of 3.45, 95% confidence interval: 1.02-11.63 [per 1 ml/m2 decrease], p = .046). Normalized transvalvular flow following TAVR was associated with reduced mortality (8%) when compared to those with persistent (15%) or new-onset low flow (12%) (p = .01). CONCLUSIONS: LVSVI at 30 days following TAVR is an early echocardiographic predictor of 1-year mortality and identifies patients with worse intermediate outcomes. More work is needed to understand if this short-term imaging marker might represent a novel therapeutic target.

Automated Detection of Aortic Stenosis Using Machine Learning.

BACKGROUND: Aortic stenosis (AS) is a degenerative valve condition that is underdiagnosed and undertreated. Detection of AS using limited two-dimensional echocardiography could enable screening and improve appropriate referral and treatment of this condition. The aim of this study was to develop methods for automated detection of AS from limited imaging data sets. METHODS: Convolutional neural networks were trained, validated, and tested using limited two-dimensional transthoracic echocardiographic data sets. Networks were developed to accomplish two sequential tasks: (1) view identification and (2) study-level grade of AS. Balanced accuracy and area under the receiver operator curve (AUROC) were the performance metrics used. RESULTS: Annotated images from 577 patients were included. Neural networks were trained on data from 338 patients (average n = 10,253 labeled images), validated on 119 patients (average n = 3,505 labeled images), and performance was assessed on a test set of 120 patients (average n = 3,511 labeled images). Fully automated screening for AS was achieved with an AUROC of 0.96. Networks can distinguish no significant (no, mild, mild to moderate) AS from significant (moderate or severe) AS with an AUROC of 0.86 and between early (mild or mild to moderate AS) and significant (moderate or severe) AS with an AUROC of 0.75. External validation of these networks in a cohort of 8,502 outpatient transthoracic echocardiograms showed that screening for AS can be achieved using parasternal long-axis imaging only with an AUROC of 0.91. CONCLUSION: Fully automated detection of AS using limited two-dimensional data sets is achievable using modern neural networks. These methods lay the groundwork for a novel method for screening for AS.

The Emerging Significance of Amyloid Deposits in the Ligamentum Flavum of Spinal Stenosis Patients: A Review.

Spinal stenosis is one of the most common neurosurgical diseases and a leading cause of pain and disability. Wild-type transthyretin amyloid (ATTRwt) has been found in the ligamentum flavum (LF) of a significant subset of patients with spinal stenosis who undergo decompression surgery. Histologic and biochemical analyses of LF specimens from spinal stenosis patients, normally discarded as waste, have the potential to help elucidate the underlying pathophysiology of spinal stenosis and possibly allow for medical treatment of stenosis and screening for other systemic diseases. In the present review, we discuss the utility of analyzing LF specimens after spinal stenosis surgery for ATTRwt deposits. Screening for ATTRwt amyloidosis cardiomyopathy through LF specimens has led to the early diagnosis and treatment of cardiac amyloidosis in several patients, with more expected to benefit from this process. Emerging evidence in the literature also point to ATTRwt as a contributor to a previously unrecognized subtype of spinal stenosis in patients who might, in the future, benefit from medical therapy. In the present report, we review the current literature regarding the early detection of ATTRwt cardiomyopathy via LF screening and the possible contribution of ATTRwt deposits in the LF to spinal stenosis development.

Real-world performance of SARS-Cov-2 serology tests in the United States, 2020.

BACKGROUND: Real-world performance of COVID-19 diagnostic tests under Emergency Use Authorization (EUA) must be assessed. We describe overall trends in the performance of serology tests in the context of real-world implementation. METHODS: Six health systems estimated the odds of seropositivity and positive percent agreement (PPA) of serology test among people with confirmed SARS-CoV-2 infection by molecular test. In each dataset, we present the odds ratio and PPA, overall and by key clinical, demographic, and practice parameters. RESULTS: A total of 15,615 people were observed to have at least one serology test 14-90 days after a positive molecular test for SARS-CoV-2. We observed higher PPA in Hispanic (PPA range: 79-96%) compared to non-Hispanic (60-89%) patients; in those presenting with at least one COVID-19 related symptom (69-93%) as compared to no such symptoms (63-91%); and in inpatient (70-97%) and emergency department (93-99%) compared to outpatient (63-92%) settings across datasets. PPA was highest in those with diabetes (75-94%) and kidney disease (83-95%); and lowest in those with auto-immune conditions or who are immunocompromised (56-93%). The odds ratios (OR) for seropositivity were higher in Hispanics compared to non-Hispanics (OR range: 2.59-3.86), patients with diabetes (1.49-1.56), and obesity (1.63-2.23); and lower in those with immunocompromised or autoimmune conditions (0.25-0.70), as compared to those without those comorbidities. In a subset of three datasets with robust information on serology test name, seven tests were used, two of which were used in multiple settings and met the EUA requirement of PPA ≥87%. Tests performed similarly across datasets. CONCLUSION: Although the EUA requirement was not consistently met, more investigation is needed to understand how serology and molecular tests are used, including indication and protocol fidelity. Improved data interoperability of test and clinical/demographic data are needed to enable rapid assessment of the real-world performance of in vitro diagnostic tests.

Real-world utilization of SARS-CoV-2 serological testing in RNA positive patients across the United States.

BACKGROUND: As diagnostic tests for COVID-19 were broadly deployed under Emergency Use Authorization, there emerged a need to understand the real-world utilization and performance of serological testing across the United States. METHODS: Six health systems contributed electronic health records and/or claims data, jointly developed a master protocol, and used it to execute the analysis in parallel. We used descriptive statistics to examine demographic, clinical, and geographic characteristics of serology testing among patients with RNA positive for SARS-CoV-2. RESULTS: Across datasets, we observed 930,669 individuals with positive RNA for SARS-CoV-2. Of these, 35,806 (4%) were serotested within 90 days; 15% of which occurred <14 days from the RNA positive test. The proportion of people with a history of cardiovascular disease, obesity, chronic lung, or kidney disease; or presenting with shortness of breath or pneumonia appeared higher among those serotested compared to those who were not. Even in a population of people with active infection, race/ethnicity data were largely missing (>30%) in some datasets-limiting our ability to examine differences in serological testing by race. In datasets where race/ethnicity information was available, we observed a greater distribution of White individuals among those serotested; however, the time between RNA and serology tests appeared shorter in Black compared to White individuals. Test manufacturer data was available in half of the datasets contributing to the analysis. CONCLUSION: Our results inform the underlying context of serotesting during the first year of the COVID-19 pandemic and differences observed between claims and EHR data sources-a critical first step to understanding the real-world accuracy of serological tests. Incomplete reporting of race/ethnicity data and a limited ability to link test manufacturer data, lab results, and clinical data challenge the ability to assess the real-world performance of SARS-CoV-2 tests in different contexts and the overall U.S. response to current and future disease pandemics.

Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis Cardiac Study (TRACS).

BACKGROUND: TRACS sought to describe the clinical outcomes and disease progression of transthyretin (TTR) cardiac amyloidosis (ATTR) in an observational study. Clinical course is largely determined by disease type with ATTR categorized as wild-type (ATTRwt) or genetic-variant protein (ATTRm). Prospective data are lacking in the most common TTR mutation, V122I, present in approximately 3.5% of African Americans. METHODS: Patients with ATTRwt (n = 18) and V122I ATTRm (n = 11) were longitudinally assessed every 6 months for up to 2 years by functional class assessments, biochemical markers, and echocardiography. RESULTS: At baseline, no differences in clinical characteristics, biomarkers, or echocardiographic parameters were noted between patients with ATTRwt and patients with ATTRm. After 15.5 ± 8 months, there were 11 deaths and 1 cardiac transplant, with higher mortality (73% vs 22%, P = .03) and cardiovascular hospitalization (64% vs 28%, P = .02) among patients with ATTRm. The median survival from diagnosis was 25.6 months for ATTRm vs 43.0 months for ATTRwt (P = .04). Univariate predictors of mortality included disease duration, heart rate ≥ 70 beats/min, baseline stroke volume, left ventricular ejection fraction <50%, and ATTRm status. For each 6-month increment, the mean 6-minute walk distance declined by 25.8 m, N-terminal pro b-type natriuretic peptide increased by 1,816 pg/mL, and left ventricular ejection fraction fell by 3.2%, for the entire cohort. CONCLUSIONS: In this prospective study, disease progression, morbidity, and mortality were observed in ATTR cardiomyopathy, particularly due to V122I, over a short duration. Given the prevalence of this mutation, further study of V122I in at-risk African American patients is warranted.

The pulmonary artery pulsatility index identifies severe right ventricular dysfunction in acute inferior myocardial infarction.

BACKGROUND: Right ventricular dysfunction (RVD) is a major cause of morbidity and mortality in the setting of acute inferior wall myocardial infarction (IWMI), and early detection may improve clinical outcomes. We defined a novel hemodynamic index, the pulmonary artery pulsatility index (PAPi), and explored whether the PAPi correlates with severe RVD in acute IWMI. METHODS: From 2008 to 2010, we identified 20 patients presenting with angiographically confirmed proximal right coronary artery occlusion and suspected RVD (sRVD) as defined by hemodynamic instability, profound bradycardia, or ST-elevation in lead V4R. Two controls groups were studied (1) 50 patients with nonobstructive coronary artery disease (Non-CAD) and (2) 14 patients presenting with acute coronary syndrome requiring left coronary stenting (ACS). Hemodynamic indices analyzed at the time of catheterization included: (1) the right atrial to pulmonary capillary wedge pressure ratio (RA:PCWP), (2) right ventricular stroke work (RVSW), and (3) the PAPi. Qualitative echocardiographic scores of RV systolic function were determined by two blinded investigators within 24 hr of catheterization. RESULTS: Among subjects with sRVD, 7 (35%) received a percutaneous RV support device (pRVSD) for medically refractory RV failure and 4 (20%) died prior to hospital discharge. Compared to Non-CAD and ACS controls, subjects with sRVD had a significantly lower PAPi (4.32 ± 3.04 vs. 5.52 ± 4.40 vs. 1.11 ± 0.57, respectively, P < 0.01) and a higher RA:PCWP ratio (0.48 ± 0.24 vs. 0.51 ± 0.26 vs. 0.81 ± 0.30, respectively, P < 0.05). Both the PAPi and RA:PCWP ratios correlated significantly with RVSW and qualitative echocardiographic grading. The PAPi demonstrated the highest sensitivity (88.9%) and specificity (98.3%) for predicting in-hospital mortality and/or requirement of a pRVSD. Using ROC curve derived cut-points, a PAPi ≤ 0.9 provided 100.0% sensitivity and 98.3% specificity (C-statistic: 0.998) for predicting these outcomes, exceeding the predictive value of the RA:PCWP ratio or RVSW. CONCLUSIONS: The PAPi is a simple, invasive hemodynamic measure that may help identify high-risk patients with acute IWMI with severe RVD. Earlier identification of this high-risk population may improve clinical outcomes.