Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T.

BACKGROUND: Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations. METHODS: Observational U.S. cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with >1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2-hour hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (eGFR <60 ml/min/1.73m2). RESULTS: The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of >52, >100, >200 or >300 ng/L, PPVs for MI were 36% (95% CI 28-45), 53% (95% CI 39-67), 73% (95% CI 50-89) and 80% (95% CI 44-98), and in those without CKD, 61% (95% CI 47-73), 69% (95% CI 49-85), 59% (95% CI 33-82) and 54% (95% CI 25-81). In CKD patients with a 2-hour hs-cTnT delta of >10, >20 or >30 ng/L, PPVs were 66% (95% CI 51-79), 86% (95% CI 68-96) and 88% (95% CI 68-97), and in those without CKD, 64% (95% CI 50-76), 73% (95% CI 57-86) and 75% (95% CI 58-88). CONCLUSION: Diagnostic performance of standard baseline and serial 2-hour hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.

Deformation of Transcatheter Aortic Valve Prostheses: Implications for Hypoattenuating Leaflet Thickening and Clinical Outcomes.

BACKGROUND: Although transcatheter aortic valve replacement (TAVR) therapy continues to grow, there have been concerns about the occurrence of hypoattenuating leaflet thickening (HALT), which may affect prosthesis function or durability. This study aimed to examine prosthesis frame factors and correlate their extent to the frequency of HALT and clinical outcomes. METHODS: We prospectively examined 565 patients with cardiac computed tomography screening for HALT at 30 days after balloon-expandable SAPIEN3 and self-expanding EVOLUT TAVR. Deformation of the TAVR prostheses, asymmetric prosthesis leaflet expansion, prosthesis sinus volumes, and commissural alignment were analyzed on the postprocedural computed tomography. For descriptive purposes, an index of prosthesis deformation was calculated, with values >1.00 representing relative midsegment underexpansion. A time-to-event model was performed to evaluate the association of HALT with the clinical outcome. RESULTS: Overall, HALT was present in 21% of SAPIEN3 patients and in 16% of EVOLUT patients at 30 days after TAVR. The occurrence of HALT was directly associated with greater prosthesis frame deformation (P<0.001), worse asymmetry of the leaflets (P<0.001), and smaller TAVR neosinus volumes (P<0.001). These relations were present in both prosthetic types and in all of their size ranges (all P<0.05). In multivariable analyses that include clinical variables previously associated with HALT (eg, anticoagulant therapy), variables of TAVR prosthesis deformation remained predictive of HALT. Although HALT was not associated with changes in prosthetic hemodynamics, its presence was associated with the risk of mortality at 1 year, with respect to greater incidences of all-cause mortality (hazard ratio, 2.98 [95% CI, 1.57-5.63]; P=0.001), cardiac death (hazard ratio, 4.58 [95% CI, 1.81-11.6]; P=0.001), and a composite outcome of all-cause mortality and heart failure hospitalization (hazard ratio, 1.94 [95% CI, 1.14-3.30]; P=0.02) with adjustment for age, sex, and comorbidities. CONCLUSIONS: Nonuniform expansion of TAVR prostheses resulting in frame deformation, asymmetric leaflet, and smaller neosinus volume is related to occurrence of HALT in patients who undergo TAVR. These data may have implications for both prosthesis valve design and deployment techniques to improve clinical outcomes for these patients.

Major adverse cardiovascular events after diagnosis of myocardial injury and types 1 and 2 myocardial infarction.

AIMS: Limited US outcome data exist among patients with myocardial injury and types 1 and 2 myocardial infarction (MI) evaluated with high-sensitivity cardiac troponin (hs-cTn). METHODS AND RESULTS: This is an observational US cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Post-discharge major adverse cardiovascular events (MACE) included death, MI, heart failure (HF) hospitalization, stroke or transient ischaemic attack, and new-onset atrial fibrillation or flutter during 2 years follow-up. Among 2002 patients, 857 (43%) had ≥1 hs-cTnT >99th percentile. Among these, 702 (81.9%) had myocardial injury, 64 (7.5%) had type 1 MI, and 91 (10.6%) had type 2 MI. Compared with patients without myocardial injury, type 2 MI [8.4 vs. 50%; adjusted hazard ratio (HR) 2.31, 95% confidence interval (CI) 1.49-3.58] and myocardial injury (8.4 vs. 47%; adjusted HR 3.13, 95% CI 2.39-4.09) had a higher risk of MACE, in large part because of death and HF hospitalizations. Compared with patients with type 1 MI, type 2 MI (23 vs. 50%; adjusted HR 2.24; 95% CI 1.23-4.10) and myocardial injury (23 vs. 47%; adjusted HR 2.02; 95% CI 1.20-3.40) also have a higher risk of MACE. CONCLUSION: Among unselected US ED patients undergoing hs-cTnT measurement, most increases are due to myocardial injury, and type 2 MI is more frequent than type 1 MI. Patients with myocardial injury and type 2 MI have morbid outcomes, in large part due to death and HF.

Rapid Exclusion of Acute Myocardial Injury and Infarction With a Single High-Sensitivity Cardiac Troponin T in the Emergency Department: A Multicenter United States Evaluation.

BACKGROUND: There are good data to support using a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of detection of 5 ng/L to exclude acute myocardial infarction. Per the US Food and Drug Administration, hs-cTnT can only report to the limit of quantitation of 6 ng/L, a threshold for which there are limited data. Our goal was to determine whether a single hs-cTnT below the limit of quantitation of 6 ng/L is a safe strategy to identify patients at low risk for acute myocardial injury and infarction. METHODS: The efficacy (proportion identified as low risk based on baseline hs-cTnT<6 ng/L) of identifying low-risk patients was examined in a multicenter (n=22 sites) US cohort study of emergency department patients undergoing at least 1 hs-cTnT (CV Data Mart Biomarker cohort). We then determined the performance of a single hs-cTnT<6 ng/L (biomarker alone) to exclude acute myocardial injury (subsequent hs-cTnT >99th percentile in those with an initial hs-cTnT<6 ng/L). The clinically intended rule-out strategy combining a nonischemic ECG with a baseline hs-cTnT<6 ng/L was subsequently tested in an adjudicated cohort in which the diagnostic performance for ruling out acute myocardial infarction and safety (myocardial infarction or death at 30 days) were evaluated. RESULTS: A total of 85 610 patients were evaluated in the CV Data Mart Biomarker cohort, among which 24 646 (29%) had a baseline hs-cTnT<6 ng/L. Women were more likely than men to have hs-cTnT<6 ng/L (38% versus 20%, P<0.0001). Among 11 962 patients with baseline hs-cTnT<6 ng/L and serial measurements, only 1.2% developed acute myocardial injury, resulting in a negative predictive value of 98.8% (95% CI, 98.6-99.0) and sensitivity of 99.6% (95% CI, 99.5-99.6). In the adjudicated cohort, a nonischemic ECG with hs-cTnT<6 ng/L identified 33% of patients (610/1849) as low risk and resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for myocardial infarction or death. CONCLUSIONS: A single hs-cTnT below the limit of quantitation of 6 ng/L is a safe and rapid method to identify a substantial number of patients at very low risk for acute myocardial injury and infarction.

Clinical Impact of Hypoattenuating Leaflet Thickening After Transcatheter Aortic Valve Replacement.

BACKGROUND: Hypoattenuated leaflet thickening (HALT), identified on functional cardiac computed tomography (CTA), can affect valve function and clinical outcomes. The objective of this study was to assess the impact of HALT on clinical outcomes in patients treated with transcatheter aortic valve replacement (TAVR). METHODS: In July 2015, Minneapolis Heart Institute implemented prospective screening of HALT at 30-day post-TAVR with CTA. Patients with evidence of HALT were recommended to initiate anticoagulation for 3 to 6 months with warfarin. Echocardiographic, ischemic, and bleeding outcomes were compared between HALT+ and HALT- patients. Survival rates were compared between HALT+ and HALT- patients using log-rank test, with Cox regression analysis used to identify variables independently associated with long-term death landmarked at time of CTA. This analysis included patients treated from July 1, 2015 to October 31, 2019. RESULTS: Of 856 patients undergoing TAVR during the study period, 638 (75%) underwent CTA post-TAVR (median time 31 [30-37] days). HALT+ was evident in 79 (12.3%). HALT+ patients were more likely prescribed warfarin at 1, 3, and 12 months (all P<0.001) and had similar gradients compared with HALT- patients. After a median follow-up of 2.2 years (1.5-3.2), HALT+ patients had increased mortality (30% versus 20%; P=0.001). In Cox regression analysis, presence of HALT (hazard ratio, 1.83 [95% CI, 1.13-2.97]; P=0.014) remained independently associated with long-term mortality. CONCLUSIONS: In a large, real-world cohort of patients receiving TAVR followed by systematic screening with CTA 30-days post-procedure, HALT was found in 12% of patients and independently associated with long-term mortality. Findings of this nonrandomized, observational cohort study require independent validation.

Diabetic Patients Who Present With ST-Elevation Myocardial Infarction.

BACKGROUND: The long-term outcomes of diabetic patients presenting with ST-segment elevation myocardial infarction (STEMI) in contemporary practice have received limited study. METHODS: We evaluated the clinical characteristics and outcomes of STEMI patients with and without diabetes in a large regional STEMI program designed to facilitate timely primary percutaneous coronary intervention (PCI) (Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, MN). The primary and secondary outcome measures were in-hospital mortality, 1-year major adverse cardiovascular events (MACE) (stroke, myocardial infarction, unplanned PCI or coronary artery bypass graft [CABG] surgery, and all-cause mortality), and 5-year mortality. RESULTS: Of the 6292 patients included, 1158 (18.4%) had Diabetes Mellitus (DM) (95.3% Type II, 4.7% Type I). Patients with DM were older (mean age 66 vs. 62.8 years, p < 0.01), had more co-morbidities and were more likely to receive medical therapy without reperfusion (13% vs. 10%, p = 0.003). Patients with DM had higher in-hospital (8% vs. 5%, p = 0.001), 1-year (8% vs. 4%, p < 0.001) and 5-year mortality (16% vs. 9%, p < 0.001) compared to non-diabetics. On Cox proportional hazards analysis, DM was independently associated with worse mortality (hazard ratio: 1.70, 95% confidence interval (CI): 1.32-2.19, p < 0.001) and MACE [HR: 1.63 (95% (CI)): 1.28-2.08, p < 0.001]. CONCLUSIONS: Despite advancements in medical therapy and revascularization strategies for STEMI, DM remains independently associated with higher short- and long-term morbidity and mortality in contemporary practice.

Frequency, Etiology, and Impact of Unplanned Repeat Coronary Angiography After ST-Elevation Myocardial Infarction.

Unplanned repeat coronary angiography (CAG) after balloon angioplasty for ST-elevation myocardial infarction (STEMI) was common before the advent of coronary stenting. Limited data are available regarding the role of unplanned repeat CAG in contemporary percutaneous coronary intervention (PCI) for STEMI. Therefore, we analyzed a large, 2-center prospective STEMI registry (January 2011 to June 2020) stratified by the presence or absence of unplanned repeat CAG during index hospitalization. Patients with planned CAG for staged PCI or experimental drug administration were excluded. Among 3,637 patients with STEMI, 130 underwent unplanned repeat CAG (3.6%) during index hospitalization. These patients were more likely to have cardiogenic shock (16% vs 9.8%, p = 0.021), left anterior descending culprit (44% vs 31%, p <0.001), lower left ventricular ejection fraction (45% vs 52%, p <0.001), and higher peak troponin levels (22 vs 8 ng/ml, p <0.001) than those without repeat CAG. At repeat CAG, 80 patients had a patent stent (62%) including 65 requiring no further intervention (50%) and 15 who underwent intervention on a nonculprit lesion (12%). Only 32 patients had stent thrombosis (25%). Repeat CAG was associated with a higher incidence of recurrent MI (19% vs 0%, p <0.001) and major bleeding (12% vs 4.5%, p <0.001), yet similar in-hospital mortality (7% vs 6.4%, p = 0.93) than those without repeat CAG. In conclusion, in the era of contemporary PCI for STEMI, unplanned repeat CAG during index hospitalization was infrequent and more commonly observed in patients with left anterior descending culprit in the presence of significant left ventricular dysfunction or shock and was associated with higher in-hospital recurrent myocardial infarction and major bleeding complications.

Incidence and Long-Term Outcomes of Stroke in Patients Presenting With ST-Segment Elevation-Myocardial Infarction: Insights From the Midwest STEMI Consortium.

Background Contemporary real-world data on stroke in patients presenting with ST-segment-elevation myocardial infarction (STEMI) are scarce. Methods and Results We evaluated the incidence, trends, cause, and predictors of stroke from 2003 to 2019 in 4 large regional STEMI programs in the upper Midwest that use similar transfer and treatment protocols. We also evaluated the long-term impact of stroke on 5-year mortality. Multivariate logistic and Cox regression analysis was used to identify variables independently associated with stroke in patients presenting with STEMI and identify variables associated with 5-year mortality. A total of 12 868 patients presented with STEMI during the study period. Stroke occurred in 98 patients (0.76%). The incidence of stroke remained stable over time (0.5% in 2003, 1.2% in 2019; P-trend=0.22). Most (75%) of strokes were ischemic, with a median time to stroke symptoms of 14 hours after primary percutaneous coronary intervention (interquartile range, 4-72 hours), which led to a small minority (3%) receiving endovascular treatment and high in-hospital mortality (18%). On multivariate regression analysis, age (increment of 10 years) (odds ratio [OR], 1.32; 95% CI, 1.10-1.58; P-value=0.003) and preintervention cardiogenic shock (OR, 2.03; (95% CI, 1.03-3.78; P=0.032)) were associated with a higher risk of in-hospital stroke. In-hospital stroke was independently associated with increased risk of 5-year mortality (hazard ratio, 2.01; 95% CI, 1.13-3.57; P=0.02). Conclusions In patients presenting with STEMI, the risk of stroke is low (0.76%). A stroke in patients presenting with STEMI is associated with significantly higher in-hospital (18%) and long-term mortality (35% at 5 years). Stroke was associated with double the risk of 5-year death.

Clinical Impact of High-Sensitivity Cardiac Troponin T Implementation in the Community.

BACKGROUND: Limited U.S. data exist regarding high-sensitivity cardiac troponin (cTn) implementation. OBJECTIVES: This study sought to evaluate the impact of high-sensitivity cardiac troponin T (cTnT) implementation. METHODS: Observational U.S. cohort study of emergency department (ED) patients undergoing measurement of cTnT during the transition from 4th (pre-implementation March 12, 2018, to September 11, 2018) to 5th generation (Gen) cTnT (post-implementation September 12, 2018, to March 11, 2019). Diagnoses were adjudicated following the Fourth Universal Definition of Myocardial Infarction (MI). Resources evaluated included length of stay, hospitalizations, and cardiac testing. RESULTS: In this study, 3,536 unique patients were evaluated, including 2,069 and 2,491 ED encounters pre- and post-implementation. Compared with 4th Gen cTnT, encounters with ≥1 cTnT >99th percentile increased using 5th Gen cTnT (15% vs. 47%; p < 0.0001). Acute MI (3.3% vs. 8.1%; p < 0.0001) and myocardial injury (11% vs. 38%; p < 0.0001) increased. Although type 1 MIs increased (1.7% vs. 2.9%; p = 0.0097), the overall MI increase was largely due to more type 2 MIs (1.6% vs. 5.2%; p < 0.0001). Women were less likely than men to have MI using 4th Gen cTnT (2.3% vs. 4.4%; p = 0.008) but not 5th Gen cTnT (7.7% vs. 8.5%; p = 0.46). Overall length of stay and stress testing were reduced, and angiography was increased (all p < 0.05). Among those without cTnT increases, there were more ED discharges and a reduction in length of stay, echocardiography, and stress tests (all p < 0.05). CONCLUSIONS: High-sensitivity cTnT implementation resulted in a marked increase in myocardial injury and MI, particularly in women and patients with type 2 MI. Despite this, except for angiography, overall resource use did not increase. Among those without cTnT increases, there were more ED discharges and fewer cardiac tests.

High-Sensitivity Cardiac Troponin T for the Detection of Myocardial Injury and Risk Stratification in COVID-19.

BACKGROUND: Limited data exist on high-sensitivity cardiac troponin (hs-cTn) for risk-stratification in COVID-19. METHODS: We conducted a multicenter, retrospective, observational, US-based study of COVID-19 patients undergoing hs-cTnT. Outcomes included short-term mortality (in-hospital and 30-days post-discharge) and a composite of major adverse events, including respiratory failure requiring mechanical ventilation, cardiac arrest, and shock within the index presentation and/or mortality during the index hospitalization or within 30-days post-discharge. RESULTS: Among 367 COVID-19 patients undergoing hs-cTnT, myocardial injury was identified in 46%. They had a higher risk for mortality (20% vs 12%, P < 0.0001; unadjusted HR 4.44, 95% CI 2.13-9.25, P < 0.001) and major adverse events (35% vs. 11%, P < 0.0001; unadjusted OR 4.29, 95% CI 2.50-7.40, P < 0.0001). Myocardial injury was associated with major adverse events (adjusted OR 3.84, 95% CI 2.00-7.36, P < 0.0001) but not mortality. Baseline (adjusted OR 1.003, 95% CI 1.00-1.007, P = 0.047) and maximum (adjusted OR 1.005, 95% CI 1.001-1.009, P = 0.0012) hs-cTnT were independent predictors of major adverse events. Most (95%) increases were due to myocardial injury, with 5% (n = 8) classified as type 1 or 2 myocardial infarction. A single hs-cTnT <6 ng/L identified 26% of patients without mortality, with a 94.9% (95% CI 87.5-98.6) negative predictive value and 93.1% sensitivity (95% CI 83.3-98.1) for major adverse events in those presenting to the ED. CONCLUSIONS: Myocardial injury is frequent and prognostic in COVID-19. While most hs-cTnT increases are modest and due to myocardial injury, they have important prognostic implications. A single hs-cTnT <6 ng/L at presentation may facilitate the identification of patients with a favorable prognosis.

Fluorescent angiography used as a tool to guide angiosome-directed endovascular therapy for diabetic foot ulcers.

Angiosome-directed endovascular therapy for the treatment of chronic limb-threatening ischemia (CLTI) remains controversial owing to the overlap of wound angiosomes. Angiographic grading of success has limitations and translesional pressure assessments are seldom performed in the infrapopliteal vessels. Objective criteria to determine revascularization success in tibiopedal vessels have not been well described. Quantifying perfusion to a wound bed after establishing direct or indirect (via collateral) flow after revascularization is an important component for treating CLTI patients yet is seldom performed. We report the use of fluorescent angiography to quantitatively examine perfusion of a diabetic foot ulcer before and after angiosome-directed endovascular therapy.

Measurement of Ejection Fraction by Cardiac Magnetic Resonance Imaging and Echocardiography to Monitor Doxorubicin-Induced Cardiotoxicity.

Doxorubicin is a standard treatment option for breast cancer, lymphoma, and leukemia, but its benefits are limited by its potential for cardiotoxicity. The primary objective of this study was to compare cardiac magnetic resonance imaging (CMRI) versus echocardiography (ECHO) to detect a reduction in left ventricular ejection function, suggestive of doxorubicin cardiotoxicity. We studied eligible patients who were 18 years or older, who had breast cancer or lymphoma, and who were offered treatment with doxorubicin with curative intent dosing of 240 to 300 mg/m 2 body surface area between March 1, 2009 and October 31, 2013. Patients underwent baseline CMRI and ECHO. Both imaging studies were repeated after four cycles of treatment. Ejection fraction (EF) calculated by both methods was compared and analyzed with the inferential statistical Student's t test. Twenty-eight eligible patients were enrolled. Two patients stopped participating in the study before undergoing baseline CMRI; 26 patients underwent baseline ECHO and CMRI. Eight of those 26 patients declined posttreatment studies, so the final study population was 18 patients. There was a significant difference in EF pre- and posttreatment in the CMRI group ( p = 0.009) versus the ECHO group that showed no significant differences in EF ( p = NS). It appears that CMRI is superior to ECHO for detecting doxorubicin-induced reductions in cardiac systolic function. However, ECHO is less expensive and more convenient for patients because of its noninvasive character and bedside practicality. A larger study is needed to confirm these findings.

Acute infection of Viabahn stent graft in the popliteal artery.

Peripheral stents are increasingly used for treatment of peripheral arterial disease, yet all implanted devices are potentially at risk for infection. We describe a 51-year-old man who underwent stenting in the femoropopliteal artery and presented 3 days later with leg pain, fever, and evidence of peripheral stigmata of embolization. Blood cultures grew methicillin-resistant Staphylococcus aureus and remained persistently positive despite antibiotic therapy. At surgical exploration, the popliteal artery had essentially been disintegrated by the infection, with only visible stent graft maintaining arterial continuity. Acute stent graft infections are rare and must be managed promptly to reduce morbidity.