Abstract Background Wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly recognized as an important cause of heart failure. Objectives The purpose of this study was to determine the ...natural history of ATTRwt and the predictors of survival. Methods We retrospectively reviewed patients diagnosed with ATTRwt at the Mayo Clinic through 2013 and recorded clinical data and survival data. Factors affecting overall survival (OS) were identified, and a prognostic staging system was developed. Results The median age of the 360 patients diagnosed before death was 75 years (range: 47 to 94 years), and 91% were male. Presenting signs and symptoms included dyspnea or heart failure in 67% and atrial arrhythmias in 62%. Median OS from diagnosis was 3.6 years and did not change over time. Multivariate predictors of mortality included age, ejection fraction, pericardial effusion, N-terminal pro–B-type natriuretic peptide, and troponin T. A staging system was developed that used thresholds of troponin T (0.05 ng/ml) and N-terminal pro–B-type natriuretic peptide (3,000 pg/ml). The respective 4-year OS estimates were 57%, 42%, and 18% for stage I (both values below cutoff), stage II (one above), and stage III (both above), respectively. Stage III patients were at an increased risk of mortality after adjustment for age and sex compared with stage I patients (hazard ratio: 3.6; p < 0.001). Conclusions The natural history of ATTRwt is poor. We report a novel cardiac biomarker staging system that enables risk stratification in an era of emerging treatment strategies.
Abstract Background Papillary fibroelastomas (PFE) are benign neoplasms with little available outcome data. Objectives This study sought to describe the frequency and clinical course of patients with ...surgically removed PFE and echocardiographically suspected, but unoperated, PFE. Methods Mayo Clinic pathology and echocardiography databases (January 1, 1995, to December 31, 2010) were queried, resulting in 511 patients: group 1 (n = 185), including patients with surgically removed, histopathologically confirmed PFE; group 1a (n = 94; 51%) with PFE removed at primary surgery; and group 1b (n = 91; 49%) with PFE removal at time of another cardiac surgery. Group 2 (n = 326) patients had echocardiographic evidence of PFE but no cardiac surgery to remove PFE. Results Group 1 had mean age of 63 ± 14 years (116 women 63%). During the study period, we identified 112 cardiac myxomas in the pathology database and 142 in the echocardiographic database. Mean age in group 2 was 67 ± 14 years (162 women 50%). PFE occurred most commonly on cardiac valves (n = 400 78%). In group 1, transient ischemic attack or stroke was the presenting symptom in 58 patients (32%). With surgical removal of valvular PFE, the valve was preserved in 92 (98%). Recurrence was documented in 3 patients (1.6%). Follow-up stroke risk in groups 1, 1a, and 1b at 1 year was 2%, 0%, and 4%; at 5 years, 8%, 5%, and 11%, respectively. Cerebrovascular accident risk in group 2 at 1 and 5 years was 6% and 13%. Conclusions In patients with echocardiographically suspected PFE who do not undergo surgical removal, rates of cerebrovascular accident and mortality are increased.
Abstract Objective Lower extremity peripheral arterial disease (PAD) is highly prevalent and affects millions of individuals worldwide. We developed a natural language processing (NLP) system for ...automated ascertainment of PAD cases from clinical narrative notes and compared the performance of the NLP algorithm with billing code algorithms, using ankle-brachial index test results as the gold standard. Methods We compared the performance of the NLP algorithm to (1) results of gold standard ankle-brachial index; (2) previously validated algorithms based on relevant International Classification of Diseases, Ninth Revision diagnostic codes (simple model); and (3) a combination of International Classification of Diseases, Ninth Revision codes with procedural codes (full model). A dataset of 1569 patients with PAD and controls was randomly divided into training (n = 935) and testing (n = 634) subsets. Results We iteratively refined the NLP algorithm in the training set including narrative note sections, note types, and service types, to maximize its accuracy. In the testing dataset, when compared with both simple and full models, the NLP algorithm had better accuracy (NLP, 91.8%; full model, 81.8%; simple model, 83%; P < .001), positive predictive value (NLP, 92.9%; full model, 74.3%; simple model, 79.9%; P < .001), and specificity (NLP, 92.5%; full model, 64.2%; simple model, 75.9%; P < .001). Conclusions A knowledge-driven NLP algorithm for automatic ascertainment of PAD cases from clinical notes had greater accuracy than billing code algorithms. Our findings highlight the potential of NLP tools for rapid and efficient ascertainment of PAD cases from electronic health records to facilitate clinical investigation and eventually improve care by clinical decision support.
Transthyretin (ATTR) cardiac amyloidosis may be because of mutant transthyretin causing familial amyloid cardiomyopathy (FAC) or wild-type transthyretin causing systemic senile amyloidosis (SSA). ...Histologic confirmation is often challenging and may require endomyocardial biopsy (EMB). The purpose of this study was to determine the frequency of amyloid protein deposition in positive noncardiac organ biopsy or fat aspiration in patients with ATTR cardiac amyloidosis. The medical records of 286 patients (mean age 66 ± 11, 85% men) with a diagnosis of ATTR cardiac amyloidosis at our institution who underwent noncardiac biopsy or subcutaneous fat aspiration were reviewed, including 186 patients (65%) with FAC and 100 patients (35%) with SSA. One hundred and thirty-one patients (46%) had EMB, all of which were positive. There were 210 patients (73%) with positive noncardiac tissue sampling, including 175 patients (94%) with FAC and 35 patients (35%) with SSA (p <0.001). There were 141 patients (76%) with FAC and 84 patients (84%) with SSA who underwent fat aspiration, and 67% and 14% were positive, respectively, whereas 100 (54%) and 64 (64%) underwent bone marrow biopsy, and 41% and 30% were positive, respectively. Rectal and sural nerve biopsies were performed in 52 (28%) and 54 (29%) patients with FAC and were positive in 81% and 83%, respectively. Biopsy of other noncardiac sites was performed with relatively lower frequency. In conclusion, although EMB is more commonly required to establish the diagnosis of SSA than FAC, noncardiac biopsy or fat aspiration could be considered as initial testing in patients evaluated for ATTR cardiac amyloidosis with characteristic echocardiography findings.
Objectives This study sought to investigate plasma levels of circulating cardiac natriuretic peptides, atrial natriuretic peptide (ANP) and B-type or brain natriuretic peptide (BNP), in the general ...community, focusing on their relative differences in worsening human hypertension. Background Although ANP and BNP are well-characterized regulators of blood pressure in humans, little is known at the population level about their relationship with hypertension. The authors hypothesized that hypertension is associated with a lack of activation of these hormones or their molecular precursors. Methods The study cohort (N = 2,082, age >45 years) was derived from a random sample from Rochester, Minnesota, and each subject had a medical history, clinical examination, and assessment of different plasma forms of ANP and BNP. Patients were stratified by blood pressure. Multivariable linear regression was used to assess differences in natriuretic peptide levels in worsening hypertension. Results Compared to normotensive, BNP1–32 and N-terminal proBNP1–76 (NT-proBNP1–76 ) were significantly decreased in pre-hypertension (p < 0.05), with BNP1–32 significantly decreased in stage 1 as well (p < 0.05). Although proBNP1–108 remained unchanged, the processed form was significantly increased only in stage 2 hypertension (p < 0.05). ANP1–28 remained unchanged, while NT-ANP1–98 was reduced in pre-hypertension (p < 0.05). Conclusions The authors demonstrated the existence of an impaired production and/or release of proBNP1–108 along with a concomitant reduction of BNP1–32 and NT-proBNP1–76 in the early stages of hypertension, with a significant elevation only in stage 2 hypertension. Importantly, they simultaneously demonstrated a lack of compensatory ANP elevation in advanced hypertension.
Several studies have demonstrated evidence for preclinical left ventricular (LV) diastolic dysfunction in patients with diabetes mellitus (DM) independent of coronary disease or hypertension. The ...objectives of our study were to determine if LV diastolic dysfunction determined by tissue Doppler indexes worsens with duration of DM and to quantify severity of dysfunction as a function of DM duration. From 1996 to 2007, all Olmsted County, Minnesota, residents with DM free of heart failure who had a subsequent measurement of diastolic function using tissue Doppler echocardiography were identified. We identified a validated group of 486 patients with incident DM with a subsequent tissue Doppler echocardiographic assessment of diastolic function. There was a significant association between the ratio of early mitral velocity (E) to medial mitral annulus velocity (e′) and time from diabetes diagnosis to echocardiogram using simple linear regression; for every 1 year after the onset of diabetes, E/e′ increased by 0.23 (95% confidence interval CI 0.16 to 0.30, p = 0.007) after adjustment for age, gender, body mass index, previous coronary disease, previous hypertension, and ejection fraction. A duration of diabetes ≥4 years was independently associated with LV diastolic dysfunction (E/e′ >15) in multivariable logistic regression modeling after adjustment for age, gender, body mass index, previous coronary disease, previous hypertension, and ejection fraction (odds ratio 1.91, 95% CI 1.19 to 3.07, p = 0.007). There were 48 deaths in the validated cohort (6 cardiac deaths). In multivariable proportional hazard modeling, E/e′ ratio was predictive of all-cause mortality after adjustment for age, gender, coronary disease, hypertension, ejection fraction, left atrial volume, and time from DM to echocardiogram (risk ratio 1.11, 95% CI 1.03 to 1.20, p = 0.005). In conclusion, duration of DM of ≥4 years is correlated with significant LV diastolic dysfunction. LV diastolic dysfunction is predictive of all-cause mortality in patients with DM independent of hypertension and coronary disease.
Abstract Background Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for ...structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. Objectives This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. Methods We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). Results Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio HR: 1.48; confidence interval CI: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). Conclusions SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality.
Abstract Objective We have previously used a 12-lead, signal-processed ECG to calculate blood potassium levels. We now assess the feasibility of doing so with a smartphone-enabled single lead, to ...permit remote monitoring. Patients and methods Twenty-one hemodialysis patients held a smartphone equipped with inexpensive FDA-approved electrodes for three 2 min intervals during hemodialysis. Individualized potassium estimation models were generated for each patient. ECG-calculated potassium values were compared to blood potassium results at subsequent visits to evaluate the accuracy of the potassium estimation models. Results The mean absolute error between the estimated potassium and blood potassium 0.38 ± 0.32 mEq/L (9% of average potassium level) decreasing to 0.6 mEq/L using predictors of poor signal. Conclusions A single-lead ECG acquired using electrodes attached to a smartphone device can be processed to calculate the serum potassium with an error of 9% in patients undergoing hemodialysis. Summary A single-lead ECG acquired using electrodes attached to a smartphone can be processed to calculate the serum potassium in patients undergoing hemodialysis remotely.
To analyze the effectiveness of a certified child life specialist (CCLS) in reducing the frequency of daily anesthesia at our institution, and to quantify the potential health care payer cost savings ...of CCLS utilization in the United States.
From 2006 to 2014, 738 children (aged ≤21 years) were treated with radiation therapy at our institution. We retrospectively analyzed the frequency of daily anesthesia before and after hiring a CCLS in 2011 after excluding patients aged 0 to 2 and >12 years. In the analyzed cohort of 425 patients the median age was 7.6 years (range, 3-12.9 years). For the pre-CCLS period the overall median age was 7.5 years; for the post-CCLS period the median age was 7.7 years. An average 6-week course of pediatric anesthesia for radiation therapy costs $50,000 in charges to the payer. The average annual cost to employ one CCLS is approximately $50,000.
Before employing a CCLS, 69 of 121 children (57%) aged 3 to 12 years required daily anesthesia, including 33 of 53 children (62.3%) aged 5 to 8 years. After employing a CCLS, 124 of 304 children (40.8%) aged 3 to 12 years required daily anesthesia, including only 34 of 118 children (28.8%) aged 5 to 8 years (P<.0001). With a >16% absolute reduction in anesthesia use after employment of a CCLS, the health care payer cost savings was approaching $50,000 per 6 children aged 3 to 12 years treated annually with radiation therapy in our institution. This reduction resulted in a total of only 6 children aged 3 to 12 years required anesthesia to be treated per year at our center to achieve nearly break-even cost savings to the health care payer if the payer were to subsidize the employment expense of a CCLS. Overall, the CCLS intervention can provide an average annualized health care payer cost savings of "$(anesthesia cost to payer during radiation therapy course/6) - (CCLS expense to payer/N)" per child (N) treated with radiation therapy, where N equals the number of children aged 3 to 12 years treated in 1 year. This formula assumes that the payer subsidizes the cost for the employment of a CCLS, although our institution absorbed this expense for this data cohort. The predicted annualized health care system cost savings from reducing the frequency of anesthesia with radiation therapy when treating 100 children aged 3 to 12 years per year could exceed $775,000.
These data suggest that a CCLS significantly reduces the frequency of daily anesthesia for children treated with radiation therapy. Health care system payers may achieve significant cost savings by financially supporting the employment of a CCLS in high-volume pediatric radiation therapy centers.
Frailty is prevalent in patients with cardiovascular disease, but few studies have evaluated relations between frailty and echocardiographically determined cardiac indexes. To assess the prevalence ...of frailty and its association with echocardiographic characteristics, we prospectively measured frailty in 257 patients ≥65 years who underwent echocardiography (transthoracic echocardiography TTE) from June 2012 to February 2013. Deficits of weight loss, exhaustion, physical activity, gait speed, and handgrip strength were used to categorize patients as frail (≥3 features), intermediately frail (1 or 2 features), or nonfrail (0 features). Pearson correlation was used to examine bivariate associations between TTE variables and frailty. Kaplan-Meier methods were used to estimate overall survival based on frailty status. A multivariable model was used to examine TTE indexes associated with frailty while accounting for age and baseline cardiac co-morbidities. Of the 257 patients studied, 40 (15.6%) were nonfrail, 167 (65.0%) intermediately frail, and 50 (19.4%) frail. Left atrial volume ( r = 0.14; p = 0.03), stroke volume ( r = −0.19; p <0.01), E/A ratio ( r = 0.26; p <0.001), and pulmonary artery systolic pressure ( r = 0.33; p <0.001) correlated with fraility. After age and baseline cardiac comorbidities were accounted for, larger left atrial volumes, lower stroke volumes, and higher pulmonary artery systolic pressures remained independently associated with frailty. Frail patients had worse survival compared with nonfrail and intermediately frail patients (p = 0.016 by log-rank). In conclusion, 1/5 of older patients who underwent clinically indicated TTE were frail, with worse survival and a unique fingerprint of TTE findings distinguishing them from nonfrail patients.
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