Mortality of patients with ST-segment-elevation myocardial infarction without standard modifiable risk factors among patients without known coronary artery disease: Age-stratified and sex-related analysis from nationwide readmissions database 2010-2014.

Objective: The proportion of ST-segment elevation myocardial infarction (STEMI) patients without standard modifiable risk factors (SMuRFs: hypertension, diabetes, hypercholesterolemia and smoking) has increased over time. The absence of SMuRFs is known to be associated with worse outcomes, but its association with age and sex is uncertain. We sought to evaluate the association between age and sex with the outcomes of post-STEMI patients without SMuRFs among patients without preexisting coronary artery disease. Methods: Patients who underwent primary PCI for STEMI were identified from the Nationwide Readmission Database of the United States. Clinical characteristics, in-hospital, and 30-day outcomes in patients with or without SMuRFs were compared in men versus women and stratified into five age groups. Results: Between January 2010 and November 2014, of 474,234 patients who underwent primary PCI for STEMI, 52,242 (11.0%) patients did not have SMuRFs. Patients without SMuRFs had higher in-hospital mortality rates than those with SMuRFs. Among those without SMuRFs, the in-hospital mortality rate was significantly higher in women than men (10.6% vs 7.3%, p<0.001), particularly in older age groups. The absence of SMuRFs was associated with higher 30-day readmission-related mortality rates (0.5% vs 0.3% with SMuRFs, p<0.001). Among patients without SMuRFs, women had a higher 30-day readmission-related mortality rates than men (0.6% vs 0.4%, p<0.001). After multivariable adjustment, the increased rates of in-hospital (odds ratio 1.89 (95% CI 1.72 to 2.07) and 30-day readmission-related mortality (hazard ratio 1.30 (95% CI 1.01 to 1.67)) in patients without SMuRFs remained significant. Conclusions: STEMI patients without SMuRFs have a significantly higher risk of in-hospital and 30-day mortality than those with SMuRFs. Women and older patients without SMuRFs experienced significantly higher in-hospital and 30-day readmission-related mortality.

Thirty-Day Readmission Rates after Takotsubo Syndrome with or without Malignancy: A Nationwide Readmissions Database Analysis.

The association between malignancy and readmission after Takotsubo syndrome (TTS) hospitalization has not been fully described. We sought to examine the rates, cause, and cost of 30-day readmissions of TTS, with or without malignancy, by utilizing Nationwide Readmissions Databases from 2010 to 2014. We identified 61,588 index hospitalizations for TTS. TTS patients with malignancy tended to be older (70.6 ± 0.2 vs. 66.1 ± 0.1, p < 0.001), and the overall burden of comorbidities was higher than in those without malignancy. TTS patients with malignancy had significantly higher 30-day readmission rates than those without malignancy (15.9% vs. 11.0%; odds ratio (OR), 1.35; 95% confidence interval (CI), 1.18-1.56). Non-cardiac causes were the most common causes of readmission for TTS patients with malignancy versus without malignancy (75.5% vs. 68.1%, p < 0.001). The 30-day readmission rate due to recurrent TTS was very low in both groups (0.4% and 0.5%; p = 0.47). The total costs were higher by 25% (p < 0.001) in TTS patients with vs. without malignancy. In summary, among patients hospitalized with TTS, the presence of malignancy was associated with increased risk of 30-day readmission and increased costs. These findings highlight the importance of optimized management for TTS patients with malignancy.

Unveiling outcomes in coexisting severe aortic stenosis and transthyretin cardiac amyloidosis.

AIMS: Advances in diagnostic imaging have increased the recognition of coexisting transthyretin cardiac amyloidosis (ATTR-CA) and severe aortic stenosis (AS), with a reported prevalence between 8-16%. In this prospective study, we aimed to evaluate the implications of ATTR-CA on outcomes after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: At two academic centres, we screened patients with severe AS undergoing TAVR for ATTR-CA. Using Kaplan-Meier analysis, we compared survival free from death and a combined endpoint of death and first heart failure hospitalization between patients with and without ATTR-CA. Cox proportional-hazards models were used to determine the association of ATTR-CA with these endpoints. The rate of heart failure hospitalization was compared amongst those with and without ATTR-CA. Overall, 204 patients (83 years, 65% male, Society of Thoracic Surgeons score 6.6%, 72% New York Heart Association class III/IV) were included, 27 (13%) with ATTR-CA. Over a median follow-up of 2.04 years, there was no difference in mortality (log rank, P = 0.99) or the combined endpoint (log rank, P = 0.79) between patients with and without ATTR-CA. In Cox proportional-hazards models, the presence of ATTR-CA was not associated with death. However, patients with ATTR-CA had increased rates of heart failure hospitalization at 1 year (0.372 vs. 0.114 events/person-year, P < 0.004) and 3 years (0.199 vs. 0.111 events/person-year, P = 0.087) following TAVR. CONCLUSION: In moderate-risk patients with severe AS undergoing TAVR, there was a 13% prevalence of ATTR-CA, which did not affect mortality. The observed increase in heart failure hospitalization following TAVR in those with ATTR-CA suggests the consequences of the underlying infiltrative myopathy.

Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) has been reported in patients with aortic stenosis (AS) but its prevalence and phenotype are not known. We examine elderly patients with severe symptomatic AS undergoing transcatheter aortic valve replacement (TAVR) and determine the prevalence and phenotype of ATTR-CA non-invasively. METHODS AND RESULTS: We performed technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy prospectively on patients who underwent TAVR, to screen for ATTR-CA. Transthoracic echocardiography and speckle-strain imaging were performed. We assessed the association of several parameters with ATTR-CA using multivariable logistic regression and constructed receiver operating curves to evaluate the best predictors of ATTR-CA. Among 151 patients (mean age 84 ± 6 years, 68% men), 16% (n = 24) screened positive for ATTR-CA with 99mTc-PYP scintigraphy. Compared with patients without ATTR-CA, ATTR-CA patients had a thicker interventricular septum (1.3 vs. 1.1 cm, P = 0.007), higher left ventricular (LV) mass index (130 vs. 98 g/m2, P = 0.002), and lower stroke volume index (30 vs. 36 mL/m2, P = 0.009). ATTR-CA patients had advanced diastolic dysfunction with higher E/A ratio (2.3 vs. 0.9, P = 0.001) and lower deceleration time (176 vs. 257 ms, P < 0.0001); impairment in systolic function with lower ejection fraction (48% vs. 56%, P = 0.011), myocardial contraction fraction (26 vs. 41, P < 0.0001), and average of lateral and septal mitral annular tissue Doppler S' (4.0 vs. 6.6 cm/s, P < 0.0001). While ATTR-CA patients had more impaired global longitudinal strain (-12 vs. -16%, P = 0.007), relative apical longitudinal strain was the same regardless of ATTR-CA diagnosis (0.98 vs. 0.98, P = 0.991). Average S' best predicted ATTR-CA in multivariable logistic regression (odds ratio 16.67 per 1 cm/s decrease with AUC 0.96, 95% confidence interval 0.90-0.99, P = 0.002) with a value ≤6 conferring 100% sensitivity for predicting a positive 99mTc-PYP amyloid scan. CONCLUSIONS: Transthyretin cardiac amyloidosis is prevalent in 16% of patients with severe calcific AS undergoing TAVR and is associated with a severe AS phenotype of low-flow low-gradient with mildly reduced ejection fraction. Average tissue Doppler mitral annular S' of < 6 cm/s may be a sensitive measure that should prompt a confirmatory 99mTc-PYP scan and subsequent testing for ATTR-CA. Prospective assessment of outcomes after TAVR is needed in patients with and without ATTR-CA.

Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging: Predicting Survival for Patients With ATTR Cardiac Amyloidosis.

Importance: Transthyretin cardiac amyloidosis (also known as ATTR cardiac amyloidosis) is an increasingly recognized cause of heart failure with preserved ejection fraction. In single-center studies, technetium 99m pyrophosphate (Tc 99m PYP) cardiac imaging noninvasively detects ATTR cardiac amyloidosis, but the accuracy of this technique in a multicenter study and the association of Tc 99m PYP myocardial uptake with survival are unknown. Objective: To assess Tc 99m PYP cardiac imaging as a diagnostic tool for ATTR cardiac amyloidosis and its association with survival in a multicenter study. Design, Setting, and Participants: Retrospective cohort study performed at 3 academic specialty centers for cardiac amyloidosis in the United States in which 229 participants were evaluated for cardiac amyloidosis and also underwent Tc 99m PYP cardiac imaging. The date of analysis and final confirmation from the statistician was May 4, 2016. Exposure: Tc 99m PYP cardiac imaging for detection of ATTR cardiac amyloidosis. Main Outcomes and Measures: Retention of Tc 99m PYP in the heart was assessed using both a semiquantitative visual score (range, 0 [no uptake] to 3 [uptake greater than bone]) and a quantitative heart to contralateral (H/CL) ratio. The H/CL ratio was calculated as total counts in a region of interest over the heart divided by background counts in an identical size region of interest over the contralateral chest. The outcome measured was time to death after Tc 99m PYP imaging. Results: Tc 99m PYP imaging of 171 participants (121 with ATTR cardiac amyloidosis and 50 with non-ATTR cardiac amyloidosis [34 with AL amyloidosis and 16 with nonamyloid heart failure with preserved ejection fraction]; 86% male; median [IQR] age, 73 years [65-79 years]) demonstrated 91% sensitivity and 92% specificity for detecting ATTR cardiac amyloidosis with an area under the curve of 0.960 (95% CI, 0.930-0.981). Univariable and multivariable Cox proportional hazards regression analyses among participants with ATTR cardiac amyloidosis showed that an H/CL ratio of 1.6 or greater predicted worse survival (hazard ratio, 3.911 [95% CI, 1.155-13.247]; P = .03 for univariable analysis and 7.913 [95% CI, 1.679-37.296]; P = .01 for multivariable analysis). In Kaplan-Meier analysis over a 5-year follow-up period, survival was significantly worse if the H/CL ratio was 1.6 or greater rather than less than 1.6 (log-rank P = .02). Conclusions and Relevance: In this multicenter study, Tc 99m PYP cardiac imaging conferred a high level of sensitivity and specificity for differentiation of patients with ATTR cardiac amyloidosis (irrespective of genotype) from patients with AL cardiac amyloidosis and patients with nonamyloid heart failure with preserved ejection fraction. An H/CL ratio of 1.6 or greater was associated with worse survival among patients with ATTR cardiac amyloidosis. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, Tc 99m PYP may be of diagnostic and prognostic importance.

Wild-Type Transthyretin Cardiac Amyloidosis: Novel Insights From Advanced Imaging.

Amyloidosis is caused by extracellular deposition of abnormal protein fibrils, resulting in destruction of tissue architecture and impairment of organ function. The most common forms of systemic amyloidosis are light-chain and transthyretin-related (ATTR). ATTR can result from an autosomal dominant hereditary transmission of mutated genes in the transthyretin or from a wild-type form of disease (ATTRwt), previously known as senile cardiac amyloidosis. With the aging of the worldwide population, ATTRwt will emerge as the most common type of cardiac amyloidosis that clinicians encounter. Diagnosis of systemic amyloidosis is often delayed, either because of the false assumption that it is a rare disease, or because of misdiagnosis as a result of mistaking it with other conditions. Clinicians must integrate clinical clues from history, physical examination, and common diagnostic tests to raise suspicion for ATTRwt. The historical gold standard for diagnosis of cardiac amyloid is endomyocardial biopsy analysis with pathological distinction of precursor protein type, but this method often results in delayed diagnosis because of the limited availability of expertise to perform and interpret the endomyocardial biopsy specimen. Emerging noninvasive imaging modalities provide easier, accurate screening for ATTRwt. These modalities include advanced echocardiography, using strain imaging and the myocardial contraction fraction; nuclear scintigraphy, which can differentiate between ATTR and light-chain cardiac amyloid; and cardiac magnetic resonance imaging, using extracellular volume measurement, late gadolinium enhancement, and distinct T1 mapping. These novel approaches reveal insights into the prevalence, clinical course, morphological effects, and prognosis of ATTRwt.

The prevalence of long QT interval in post-operative intensive care unit patients.

The severity of patient illnesses and medication complexity in post-operative critically ill patients increase the risk for a prolonged QT interval. We determined the prevalence of prolonged QTc in surgical intensive care unit (SICU) patients. We performed a prospective cross-sectional study over a 15-month period at a major academic center. SICU pre-admission and admission EKGs, patient demographics, and laboratory values were analyzed. QTc was evaluated as both a continuous and dichotomous outcome (prolonged QTc > 440 ms). 281 patients were included in the study: 92 % (n = 257) post-operative and 8 % (n = 24) non-operative. On pre-admission EKGs, 32 % of the post-operative group and 42 % of the non-operative group had prolonged QTc (p = 0.25); on post-admission EKGs, 67 % of the post-operative group but only 33 % of the non-operative group had prolonged QTc (p < 0.01). The average change in QTc in the post-operative group was +30.7 ms, as compared to +2 ms in the non-operative group (p < 0.01). On multivariable adjustment for long QTc as a dichotomous outcome, pre-admission prolonged QTc (OR 3.93, CI 1.93-8.00) and having had an operative procedure (OR 4.04, CI 1.67-9.83) were associated with developing prolonged QTc. For QTc as a continuous outcome, intra-operative beta-blocker use was associated with a statistically-significant decrease in QTc duration. None of the patients developed a lethal arrhythmia in the ICU. Prolonged QTc is common among post-operative SICU patients (67 %), however lethal arrhythmias are uncommon. The operative experience increases the risk for long QTc.

Short-term and longer-term survival after veno-arterial extracorporeal membrane oxygenation in an adult patient population: does older age matter?

BACKGROUND: Veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) is increasingly being used for patients with refractory cardiopulmonary failure. This study evaluates the short-term (to discharge) and longer-term (1 year) survival among older (⩾65 years) versus younger (<65 years) adults, adjusted for comorbidities, in a diverse cohort of V-A ECMO patients. METHODS: This was a retrospective cohort analysis of 131 adult patients (28% ⩾65 years old) who received V-A ECMO at an academic medical center from 2004-2013. Demographics, comorbidities and surgical characteristics were abstracted from the medical records and verified. Mortality status at discharge and at one year post-ECMO were determined by the hospital clinical information system, updated monthly with Social Security Death Index data. Cox proportional hazard analyses were conducted to evaluate associations between age strata and mortality at discharge and at one year post ECMO initiation, adjusted for covariates. RESULTS: The survival rate following V-A ECMO was 48% (n=68/131) to discharge and 44% (n=58/131) to one year. Age ⩾65 versus <65 was significantly associated with increased mortality during hospitalization (HR:2.03; 95%CI=1.23-3.33) and at one year (HR:1.81; 95% CI=1.12-2.93); these associations were attenuated and did not retain statistical significance after adjustment for comorbidities (HR:1.61; 95%CI=0.90-2.88 and HR:1.42; 95% CI=0.81-2.50, respectively). Statistically significant predictors of mortality at discharge and one year included history of coronary artery bypass graft, peripheral vascular disease and renal failure/dialysis (p<0.05). CONCLUSIONS: Older age was not independently associated with short-term or longer-term survival among V-A ECMO patients, but may reflect greater comorbidity, suggesting that age alone may not disqualify patients from V-A ECMO therapy.

Duration of conventional cardiopulmonary resuscitation prior to extracorporeal cardiopulmonary resuscitation and survival among adult cardiac arrest patients.

PURPOSE: The purpose of this study was to evaluate the association between survival and the duration of conventional cardiopulmonary resuscitation (CCPR) prior to extracorporeal cardiopulmonary resuscitation (ECPR) and possible confounding factors. METHODS: This was a retrospective analysis of 31 adults who received ECPR at an academic medical center between 2004 and 2013. Odds of 30-day survival and Kaplan Meier survival curves were compared among patients who received CCPR ⩾ 45 min (n=8, 26%) vs. <45 min (n=23, 74%). RESULTS: There was a trend for greater survival up to 14 days in patients who received CCPR <45 vs. ⩾ 45 minutes (57% vs. 50%) with no significant difference at 30 days (OR 1.09, 95% CI 0.22-5.45) and survival did not differ by demographic factors. CONCLUSION: More than half of all patients who received ECPR survived to 30 days. Longer duration CCPR was associated with reduced survival within 2 weeks, but not at 30 days.

Survival Following Veno-Venous Extracorporeal Membrane Oxygenation and Mortality in a Diverse Patient Population.

Racial and ethnic disparities in cardiovascular disease are well established; however, there is limited information about survival differences following veno-venous extracorporeal membrane oxygenation (VV-ECMO) in contemporary adult populations. The purpose of this study was to assess survival at discharge, 30 days, and at 1 year following institution of VV-ECMO in an ethnically diverse population, and to examine potential risk factors for mortality. This was a single-center study of 41 patients (49% female, 27% minorities, 7% > 65 years) who received VV-ECMO between the years 2004 and 2013 at an academic medical center. Kaplan-Meier estimates were calculated to assess survival up to 1 year, and cox proportional hazard models were used to evaluate the association between risk factors, mortality, and confounders. Overall, 76% (n = 31) of VV-ECMO patients survived to discharge and 30 days and 71% (n = 29) survived to 1 year. Whites (n = 30) had a higher survival at 1 year compared to minorities (n = 11) (83% vs. 36%, respectively, p = .01). Minorities had a significantly increased risk of mortality at 30 days (hazard ratio [HR] = 5.07, 95% confidence interval [CI] = 1.42-18.09) and at 1 year (HR = 5.19, 95% CI = 1.63-16.55). Race/ethnicity remained a significant independent predictor of survival at 30 days except when history of shock or lung transplantation was included in adjusted regression models. VV-ECMO was associated with an excellent overall survival up to 1 year. Racial/ethnic minorities had a 5-fold increased risk for 30-day mortality, which was largely explained by a lower likelihood of lung transplantation and increased risk of shock.

25-Hydroxyvitamin D and ankle-brachial blood pressure index in adults without peripheral artery disease.

BACKGROUND: Inverse association between lower level of 25-hydroxyvitamin D [25(OH)D] and higher prevalence of peripheral arterial disease (PAD) among individuals with cardiovascular diseases (CVD) is known. Less is known about the relationship between 25(OH)D and ankle-brachial blood pressure index (ABPI) in asymptomatic adults. We hypothesized a nonlinear relationship between 25(OH)D and ABPI in asymptomatic adults without PAD. METHODS: Data from the continuous NHANES (2001-2004) was used. Minimum of the two reported ABPI value was chosen for each individual (>18 years). Linear regression models with spline adjusted for demographic and traditional risk factors for CVD were used to examine nonlinear relationship between 25(OH)D and ABPI. Mean changes in ABPI per 10 ng/mL change in 25(OH)D were reported. RESULTS: Mean (SD) age and 25(OH)D levels of 4979 participants (48% females) were 60.4 (13.22) years and 22.1 (8.68) ng/mL, respectively, while mean (SD) ABPI was 1.07 (0.15). We observed positive association between 25(OH)D and ABPI both in the univariable and multivariable regression models (all p < 0.05). In univariable regression with spline, a significant increase in ABPI (ß = 0.03, 95% CI: 0.02-0.04) was observed until 25(OH)D reached but not above 27 ng/mL. Similarly, in multivariable spline models, 25(OH)D was positively associated with ABPI (ß = 0.02, 95% CI: 0.01-0.03) only up to 27 ng/mL. CONCLUSIONS: In asymptomatic adults without PAD, rising serum 25(OH)D concentration but not above 27 ng/mL was associated with statistically significant increase in ABPI.

Mortality among marathon runners in the United States, 2000-2009.

BACKGROUND: As participation in marathon running has increased, there has also been concern regarding its safety. PURPOSE: To determine if the increase in marathon participation from 2000 to 2009 has affected mortality and overall performance. STUDY DESIGN: Descriptive epidemiology study. METHODS: We used publicly available racing and news databases to analyze the number of marathon races, finishing race times, and deaths from 2000 to 2009 in marathons in the United States. RESULTS: The total number of marathon finishers has increased over this decade from 299,018 in 2000 to 473,354 in 2009. The average overall marathon finishing time has remained unchanged from 2000 to 2009 (4:34:47 vs 4:35:28; P = .85). Of 3,718,336 total marathon participants over the 10-year study period, we identified 28 people (6 women and 22 men) who died during the marathon race and up to 24 hours after finishing. The overall, male, and female death rates for the 10-year period were 0.75 (95% confidence interval [CI], 0.38-1.13), 0.98 (95% CI, 0.48-1.36), and 0.41 (95% CI, 0.21-0.79) deaths per 100,000 finishers, respectively. There was no change in the death rate during this time period for overall, male, or female groups (P = .860, .533, and .238, respectively). The median age among deaths was 41.5 years (interquartile range, 25.5 years). Fifty percent (14/28) of deaths occurred in participants less than 45 years old. Myocardial infarction/atherosclerotic heart disease caused 93% (13/14) of deaths in those 45 years and older. A variety of conditions caused death in younger racers, the most common being cardiac arrest not otherwise specified (21%, n = 3). CONCLUSION: Participation in marathons has increased without any change in mortality or average overall performance from 2000 to 2009.