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.

Sex-Specific Thresholds for Cardiac Biomarkers-We Need to Move Forward.

Cardiovascular biomarkers play a major diagnostic role for cardiologists. Different biomarkers provide different insights into a variety of cardiovascular conditions and in doing so they improve diagnosis and management. Often, these biomarkers are deployed without carefully evaluating the use of sex-specific cut off values. It is now becoming apparent that the use of such cut off values can improve prognostication and discrimination in some clinical situations. This review paper will focus on the data indicating that there is benefit to the use of sex-specific thresholds. It should be clear that these thresholds will vary depending on the analyte being measured and the specific clinical indication for which the patients are being evaluated; and sex-specific cut off values may be important in some situations but not others. Nonetheless, it is now clear that when evaluating sex-specific cut off values, one often finds benefit. We will highlight these situations using specific cardiac biomarkers as examples.

Diuresis-Related Weight Loss Reflects Interstitial Compartment Decongestion with Minimal Impact on Intravascular Volume Expansion or Outcomes in Post-Acute Heart Failure: Metrics of Decongestion and Volume Status.

BACKGROUND: Findings from heart failure (HF) studies linking diuresis-related weight loss to clinical decongestion and outcomes are mixed. Differential responses of interstitial and intravascular volume compartments to diuretic therapy and heterogeneity in volume profiles may confound the clinical interpretation of weight loss in patients with HF. METHODS AND RESULTS: Data were prospectively collected in hospitalized patients requiring diuresis. Plasma volume (PV) was measured using I-131-labelled albumin indicator-dilution methodology. The cohort was stratified by tertiles of weight loss and analyzed for interstitial fluid loss relative to changes in PV and HF-related morality or first rehospitalization. Among 92 patients, the admission PV was expanded +42% (4.7 ± 1.2 L) above normal with significant variability (14% normal PV, 18% mild-moderate expansion, and 68% with large PV expansion [>+25% above normal]). With diuresis there were proportional decreases in interstitial volume (-6.5 ± 4.4%) and PV (-7.5 ± 11%); however, absolute decreases in the PV (-254 mL, interquartile range -11 to -583 mL) were less than 10% of interstitial volume loss (-5040 mL, interquartile range -2800 to -7989 mL); greater interstitial fluid loss did not translate into better outcomes (log-rank P = .430). CONCLUSIONS: Diuresis-related decreases in weight reflect fluid loss from the interstitial compartment with only minor changes in the PV and without an impact on outcomes. Further, the degree of PV expansion at hospital admission does not drive the magnitude of the diuresis response, even with a wide spectrum of body weights; interstitial fluid overload is preferentially targeted and PV relatively preserved. Therefore, greater interstitial fluid loss reflects clinical decongestion, but not better outcomes, and a limited association with intravascular volume profiles potentially confounding weight loss as a prognostic metric in HF.

Acute coronary occlusion and percutaneous coronary intervention after out-of-hospital cardiac arrest.

OBJECTIVES: Early coronary angiography (CAG) has been recommended in selected patients following out-of-hospital-cardiac-arrest (OHCA). We aimed to identify clinical features associated with acute coronary occlusion (ACO) and evaluate the associations between ACO, successful percutaneous coronary intervention (PCI) and outcomes in this population. METHODS: We included comatose OHCA patients treated with targeted temperature management (TTM) between December 2005 and September 2016 who underwent early CAG within 24 hours. The co-primary outcomes were all-cause 30-day mortality and good neurological outcome (modified Rankin Score [mRS] ≤2) at hospital discharge. RESULTS: Among 155 patients (93% shockable arrest rhythm, 55% with ST elevation), 133 (86%) had coronary artery stenosis ≥50% and 65 (42%) had ACO. ST elevation (sensitivity 74%, specificity 59%, OR 4.0, 95% CI 2.0-8.1) and elevated first troponin (sensitivity 88%, specificity 26%, OR 2.5, 95% CI 1.1-6.1) had limited sensitivity and specificity for ACO. Unadjusted 30-day mortality did not differ significantly by coronary disease severity or ACO. Successful PCI was associated with a lower risk of 30-day mortality (adjusted HR 0.5, 95% CI 0.2-0.9, P=.03), especially among patients with ACO (adjusted HR 0.4, 95% CI 0.1-0.9, P=0.03). After adjustment, ACO and PCI were not associated with the probability of good neurological outcome. CONCLUSIONS: In this select cohort of resuscitated OHCA patients undergoing CAG, unstable coronary disease is highly prevalent and successful PCI was associated with a higher probability of 30-day survival, especially among those with ACO. Neither ACO nor successful PCI were independently associated with good neurological outcome.

Serial high sensitivity troponin sampling in patients with SARS-CoV-2 infection.

INTRODUCTION: Multiple studies have investigated the role of cardiac troponin (cTn) in the risk stratification of patients with COVID-19. Most of these investigations are based on cTn values at presentation and do not consider the prognostic significance of cTn changes over time. This study aimed to investigate the prognostic role of serial cTn measurements in patients hospitalized with COVID-19 with samples that were not obtained for clinical indications. METHODS: Patients hospitalized between April 2020 and March 2021 with PCR-confirmed SARS-CoV-2 infection were evaluated. Blood samples collected for any reason were stored for subsequent analysis. If clinical high sensitivity hs-cTnT (Roche) was not measured, samples were tested separately in batches. Hs-cTnI (Abbott) was also evaluated. RESULTS: There were 228 unique patients. There were 21 (9.2 %) deaths. No patient with a low hs-cTnT (<6 ng/L) died and 1 patient with low hs-cTnI (<5 ng/L) died. Myocardial injury was associated with higher odds of death, when defined by hs-cTnT (OR: 7.88, 95 % CI: 2.04-30.40, p = 0.003) or hs-cTnI (OR: 7.46, 95 % CI: 2.68-20.77, p < 0.001). This association remained after propensity weighting. An increasing pattern was associated with higher odds of death compared to a stable pattern for hs-cTnT (OR: 5.45, 95 % CI: 1.81-16.40, p = 0.003) and hs-cTnI (OR: 4.49, 95 % CI: 1.02-19.81, p = 0.048). Among patients with myocardial injury defined by hs-cTnT, an increasing pattern was associated with higher odds of death compared to a decreasing pattern (OR: 4.80, 95 % CI: 1.16-19.97, p = 0.031). CONCLUSIONS: Patients hospitalized with COVID-19 with myocardial injury have higher odds of death. Serial hs-cTn testing provides additional risk stratification in these patients.

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

AIMS: 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 AND RESULTS: Observational US cohort study of emergency department 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 h hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). 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, positive predictive values (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 h 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 h hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.

Measuring copeptin, a surrogate for vasopressin in patients with hypertension - Can it identify those who are volume Responsive?

BACKGROUND: Among hypertensive patients, plasma renin activity is lower and the response to diuretic monotherapy greater in volume responsive hypertensive patients. We hypothesized that hormones influencing extracellular volume such as vasopressin / antidiuretic hormone (ADH) might permit the development of a simple test to identify those with volume-related hypertension. Such a test might be of particular benefit to the Black population which is purported to have a higher incidence of volume-related and responsive hypertension. Thus, using copeptin, a surrogate marker for ADH, we studied if there were differences in this hormone between those with and without volume responsive hypertension. METHODS: Serum copeptin was measured in biobanked blood samples from the Genetic Epidemiology of Responses to Antihypertensives (GERA) I study and analyzed with other variables from the study dataset. RESULTS: There was no relationship between PRA and copeptin values nor could the response in blood pressure be predicted by the copeptin values. However, baseline copeptin levels were higher in Black than in White subjects (7.5 pmol/L vs 5.4 pmol/L, P < 0.001) while plasma sodium and calculated plasma osmolality were slightly lower in keeping with the concept that Black subjects have more volume-related hypertension. In addition, after hydrochlorothiazide (HCTZ), copeptin was significantly lower in Black (6.2 pmol/L, P = 0.004) but unchanged in White subjects (5.2 pmol/L, P = 0.901) and there were also changes in sodium. CONCLUSION: The current study suggests differences in ADH physiology between hypertensive Black and White patients. However, the use of copeptin to identify volume responsive patients could not be confirmed.

Absence of significant myocardial injury following elective direct current cardioversion for atrial fibrillation.

Background: Direct current (DC) cardioversion is used to terminate cardiac arrhythmias. Current guidelines list cardioversion as a cause of myocardial injury. Objective: This study determined whether external DC cardioversion results in myocardial injury measured by serial changes in high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI). Methods: This was a prospective study of patients undergoing elective external DC cardioversion for atrial fibrillation. hs-cTnT and hs-cTnI were measured precardioversion and at least 6 hours postcardioversion. Myocardial injury was present when there were significant changes in both hs-cTnT and hs-cTnI. Results: Ninety-eight subjects were analyzed. Median cumulative energy delivered was 121.9 (interquartile range [IQR] 102.2-302.7) J. Multiple cases 23 (23.5%) required 300 J or more. Maximum cumulative energy delivered was 2455.1 J. There were small significant changes in both hs-cTnT (median precardioversion 12 [IQR 7-19) ng/L], median postcardioversion 13 [IQR 8-21] ng/L; P < .001) and hs-cTnI (median precardioversion 5 [IQR 3-10) ng/L], median postcardioversion 7 [IQR 3.6-11) ng/L; P < .001). Results were similar in patients with high-energy shocks and did not vary based on precardioversion values. Only 2 (2%) cases met criteria for myocardial injury. Conclusion: DC cardioversion resulted in a small but statistically significant changes in hs-cTnT and hs-cTnI in 2% of patients studied irrespective of shock energy. Patients with marked troponin elevations after elective cardioversion should be assessed for other causes of myocardial injury. It should not be assumed the myocardial injury was from the cardioversion.

Use of the HEAR Score for 30-Day Risk-Stratification in Emergency Department Patients.

BACKGROUND: The 2021 American College of Cardiology/American Heart Association chest pain guidelines recommend risk scores such as HEAR (History, Electrocardiogram, Age, Risk factors) for short-term risk stratification, yet limited data exist integrating them with high-sensitivity cardiac troponin T (hs-cTnT). METHODS: Retrospective, multicenter (n = 2), observational, US cohort study of consecutive emergency department patients without ST-elevation myocardial infarction who had at least one hs-cTnT (limit of quantitation [LoQ] <6 ng/L, and sex-specific 99th percentiles of 10 ng/L for women and 15 ng/L for men) measurement on clinical indications in whom HEAR scores (0-8) were calculated. The composite major adverse cardiovascular event (MACE) outcome was 30-day prognosis. RESULTS: Among 1979 emergency department patients undergoing hs-cTnT measurement, 1045 (53%) were low risk (0-3), 914 (46%) intermediate risk (4-6), and 20 (1%) high risk (7-8) based on HEAR scores. HEAR scores were not associated with increased risk of 30-day MACE in adjusted analyses. Patients with quantifiable hs-cTnT (LoQ-99th) had an increased risk for 30-day MACE (3.4%) irrespective of HEAR scores. Those with serial hs-cTnT <99th percentile remained at low risk (range 0%-1.2%) across all HEAR score strata. Higher scores were not associated with long-term (2-year) events. CONCLUSIONS: HEAR scores are of limited value in those with baseline hs-cTnT 99th percentile to define short-term prognosis. In those with baseline quantifiable hs-cTnT within the reference range (<99th percentile), a higher risk (>1%) for 30-day MACE exists even in those with low HEAR scores. With serial hs-cTnT measurements, HEAR scores overestimate risk when hs-cTnT remains <99th percentile.

Structural Cardiac Abnormalities in Patients with Atrial Fibrillation/Flutter and Myocardial Injury.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTnT) is often increased in patients with atrial fibrillation/flutter, portending a poor prognosis. The etiologies for these increases have not been systematically investigated. Our aim was to define prevalence/significance of structural cardiac abnormalities in patients with atrial fibrillation/flutter and high-sensitivity cardiac troponin T (hs-cTnT) increases. METHODS: This is a retrospective observational cohort study of patients with atrial fibrillation/flutter diagnosis with hs-cTnT measurements, echocardiograms, and coronary angiograms. Myocardial injury was defined as hs-cTnT >10 ng/L for women and >15 ng/L for men. Cases with myocardial injury were adjudicated according to the Fourth Universal Definition of Myocardial Infarction. RESULTS: Patients with definite causes for increased hs-cTnT (n = 875) were tabulated but not evaluated further; common diagnoses were type 1 myocardial infarction, critical illness, and known heart failure. Of the remaining 401, increased hs-cTnT was present in 336 (84%) patients. Of those, 78% had nonischemic myocardial injury, the remaining (n = 75, 22%) had type 2 myocardial infarction. Patients with elevated hs-cTnT had greater left ventricular mass index, left ventricular filling pressures, and right ventricular systolic pressure. They more frequently had significant coronary artery disease (47% vs 31%, P = .016), especially in type 2 myocardial infarction. With logistic regression, age, sex (F), diabetes, left ventricular mass index, e' medial velocity, and right ventricular systolic pressure were independent determinants of myocardial injury. One-year mortality was higher in patients with myocardial injury. CONCLUSIONS: Structural heart abnormalities are common in patients with atrial fibrillation/flutter and increased hs-cTnT. Causes of myocardial injury should be elucidated in each patient to craft appropriate therapies.

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.

Using high sensitivity cardiac troponin values in patients with SARS-CoV-2 infection (COVID-19): The Padova experience.

BACKGROUND: The spectrum of Coronavirus Disease 2019 (COVID-19) is broad and thus early appropriate risk stratification can be helpful. Our objectives were to define the frequency of myocardial injury using high-sensitivity cardiac troponin I (hs-cTnI) and to understand how to use its prognostic abilities. METHODS: Retrospective study of patients with COVID-19 presenting to an Emergency Department (ED) in Italy in 2020. Hs-cTnI was sampled based on clinical judgment. Myocardial injury was defined as values above the sex-specific 99th percentile upper reference limits (URLs). Most data is from the initial hospital value. RESULTS: 426 unique patients were included. Hs-cTnI was measured in 313 (73.5%) patients; 85 (27.2%) had myocardial injury at baseline. Patients with myocardial injury had higher mortality during hospitalization (hazard ratio = 9 [95% confidence interval (CI) 4.55-17.79], p < 0.0001). Multivariable analysis including clinical and laboratory variables demonstrated an AUC of 0.942 with modest additional value of hs-cTnI. Myocardial injury was associated with mortality in patients with low APACHE II scores (<13) [OR (95% CI): 4.15 (1.40, 14.22), p = 0.014] but not in those with scores > 13 [OR (95% CI): 0.48 (0.08, 2.65), p = 0.40]. Initial hs-cTnI < 5 ng/L identified 33% of patients that were at low risk with 97.8% sensitivity (95% CI 88.7, 99.6) and 99.2% negative predictive value. Type 1 myocardial infarction (MI) and type 2 MI were infrequent. CONCLUSIONS: hs-cTnI at baseline is a significant predictor of mortality in COVID-19 patients. A value < 5 ng/L identified patients at low risk.

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.

Bolus 5-fluorouracil (5-FU) In Combination With Oxaliplatin Is Safe and Well Tolerated in Patients Who Experienced Coronary Vasospasm With Infusional 5-FU or Capecitabine.

INTRODUCTION: Coronary vasospasm associated with fluoropyrimidine (FP)-based chemotherapy is a potentially serious complication and reported to occur more often with infusional 5-fluorouracil (5-FU) or capecitabine than with bolus 5-FU. Given the additional benefit of oxaliplatin over FP alone in the management of colorectal cancer, retaining oxaliplatin in the treatment regimen is desirable, but the safety of combining bolus 5-FU with oxaliplatin in patients with FP-induced vasospasm is not well established. We performed a retrospective review to explore the safety of substituting FLOX (bolus 5-FU, oxaliplatin, leucovorin) for FOLFOX (infusional 5-FU, oxaliplatin, leucovorin) and CAPOX (capecitabine, oxaliplatin) in patients who had FP-induced coronary vasospasm. PATIENTS AND METHODS: The pharmacy database of Mayo Clinic was queried to identify patients who developed coronary vasospasm associated with FOLFOX or CAPOX between January 2011 and January 2018 and were subsequently treated with FLOX. Detailed information was obtained on these patients by retrospective electronic chart review. RESULTS: A total of 10 patients (median age, 56.5 years; range, 36-77 years) were identified, 9 with FOLFOX and 1 with CAPOX. Among the patients treated with FOLFOX, 8 patients had chest pain as the presenting complaint that had started within 48 hours of beginning of the 5-FU infusion. In 9 of 10 patients, coronary vasospasm occurred with the first cycle of therapy. All patients made full recovery after discontinuation of infusional 5-FU or capecitabine. All patients subsequently received FLOX with 7 median bolus 5-FU doses (range, 2-22 doses) and 7 median oxaliplatin doses (range, 2-12 doses) at 7 days to 18 months after the event, with 7 patients treated within 4 weeks of the event. FLOX did not cause any cardiovascular adverse events in any of the 10 patients. CONCLUSION: Bolus 5-FU in combination with oxaliplatin is safe in patients who have experienced coronary vasospasm with infusional 5-FU or capecitabine.

5-fluorouracil and cardiotoxicity: a review.

Fluoropyrimidines such as 5-fluorouracil (5-FU) form the foundation of a wide variety of chemotherapy regimens. 5-FU is in fact the third most commonly used chemotherapeutic agent in the treatment of solid malignancies across the world. As with all chemotherapy, balancing the potential benefits of therapy against the risks of drug-related toxicity is crucial when clinicians and patients make shared decisions about treatment. 5-FU is the second most common chemotherapeutic drug associated with cardiotoxicity after anthracyclines, which can manifest as chest pain, acute coronary syndrome/myocardial infarction or death. Nevertheless a widespread appreciation of 5-FU-related cardiotoxicity and its implications is lacking amongst clinicians. In this review, we outline the incidence, possible risk factors, and likely pathophysiological mechanisms that may account for 5-FU-related cardiotoxicity and also highlight potential management strategies for this poorly understood clinical entity.

Significance of High-Sensitivity Troponin T After Elective External Direct Current Cardioversion for Atrial Fibrillation or Atrial Flutter.

External transthoracic direct current (DC) cardioversion is a commonly used method of terminating cardiac arrhythmias. Previous research has shown that DC cardioversion resulted in myocardial injury as evidenced by increased levels of cardiac troponin, even though only minimally. Many of these studies were based on the outdated monophasic defibrillators and older, less sensitive troponin assays. This study aimed to assess the effect of external transthoracic DC cardioversion on myocardial injury as measured by the change in the new high-sensitivity cardiac troponin T (hs-cTnT) using the more modern biphasic defibrillators. Patients who were admitted for elective DC cardioversion for atrial fibrillation or atrial flutter were recruited. Hs-cTnT levels were taken before cardioversion and at 6 hours after cardioversion. A total of 120 cardioversions were performed. Median (twenty-fifth to seventy-fifth interquartile range) cumulative energy was 161 J (155 to 532 J). A total of 49 (41%) patients received a cumulative energy of 300 J or higher. The median hs-cTnT level before cardioversion was 7 ng/L (4 to 11 ng/L) and that after cardioversion was 7 ng/L (4 to 10 ng/L). A Wilcoxon signed-rank test showed no significant difference between pre- and post-cardioversion hs-cTnT levels (Z = -0.940, p = 0.347). In conclusion, external DC cardioversion did not result in myocardial injury within the first 6 hours as measured by high-sensitivity troponin T. Patients who are cardioverted and are found to have a significant increase in cardiac troponin after cardioversion should be assessed for causes of myocardial injury and not assumed to have myocardial injury due to the cardioversion itself.

The use of conscious sedation in elective external direct current cardioversion: a single centre experience.

External direct current (DC) cardioversion is a commonly used method of terminating atrial arrhythmias. The chance of procedural success is inversely related to the duration of the arrhythmia. In many hospitals, the procedure is carried out under general anaesthesia, necessitating the presence of anaesthetic as well as medical staff. Frequently, it may be difficult to coordinate the availability of the two teams, causing delays to each patient, waste of staff time, an inefficient service and increased costs. The primary aim of the study was to determine the safety and tolerability of conscious sedation using intravenous midazolam in elective external DC cardioversion of patients with atrial flutter or atrial fibrillation attending University Hospital Limerick, Ireland. Patients who were electively admitted for DC cardioversion for atrial fibrillation or atrial flutter were recruited. A pre-defined sedation protocol using intravenous midazolam was used. The midazolam was given by the cardiology registrar without the presence of an anaesthetist. DC cardioversion was then performed according to the hospital protocol. Any complications arising during the procedure were noted. Prior to discharge, patients were given a questionnaire to determine their awareness of the procedure and if they would have the procedure done again in the future if needed. A total of 100 patients were recruited. The median number of shocks was one (highest number of shocks being four). The median dose of midazolam was 7.5 mg, with the highest dose being 20 mg. All of patients surveyed were not aware of the shock that was administered to them. All of the patients surveyed were happy with the service and would be happy to return for a repeat cardioversion in the future if required. The use of conscious sedation for DC cardioversion of patients with atrial fibrillation / atrial flutter was found to be safe and tolerable.

A commentary on the disparate perspectives of clinical microbiologists and surgeons: ad hoc antimicrobial use.

Prosthetic joints and other orthopedic implants have improved quality of life for patients world-wide and the use of such devices is increasing. However, while infection rates subsequent to associated surgery are relatively low (<3%), the consequences of incidence are considerable, encompassing morbidity (including amputation) and mortality in addition to significant social and economic costs. Emphasis, therefore, has been placed on mitigating microbial risk, with clinical microbiologists and surgeons utilizing rapidly evolving molecular laboratory techniques in detection and diagnosis of infection, which still occurs despite sophisticated patient management. Multidisciplinary approaches are regularly adopted to achieve this. In this commentary, we describe an unusual case of Actinomyces infection in total hip arthroplasty and, in that context, describe the perspectives of the clinical microbiology and surgical teams and how they contrasted. More specifically, this case demonstrates an ad hoc approach to structured eradication of biofilms and intracellular bacteria related to biomaterials, as reflected in early usage of linezolid. This is a complex topic and, as described in this case, such accelerated treatment can be effective. This commentary focuses on the merits of such inadvisable use of potent antimicrobials amid the risk of diminishing valuable antimicrobial efficacy, albeit resulting in desirable patient outcomes.