Thoracic Aortic Injuries Following Intra-Aortic Balloon Pump Placement: A Retrospective Case Series.

Thoracic aortic injuries from intra-aortic balloon pump (IABP) are rare, and no publications exist in the context of patients awaiting heart transplantation. We present a single-institution case series involving five patients out of 107 who sustained thoracic aortic injuries following IABP placement awaiting heart transplantation. The goal of this study is to describe the characteristics of patients, presenting symptoms, treatment and the impact of these injuries on their suitability for transplantation. DESIGN: Retrospective, single-institution study through chart review of five patients with known thoracic aortic injuries following IABP placement awaiting heart transplant. SETTING: Tertiary care academic teaching hospital with all patients requiring cardiac ICU admission. PATIENTS: All five patients were diagnosed with advanced heart failure awaiting heart transplantation. INTERVENTIONS: Each patient had an IABP placed while awaiting transplant. MEASUREMENTS AND MAIN RESULTS: Five patients (4.6%) out of a total of 107 supported with IABP awaiting heart transplantation were identified with thoracic aortic injury. Three underwent transplantation and subsequently received thoracic endovascular aortic repair, and they are doing well with a mean follow-up of 6 months. One patient died acutely and the other did not require intervention. CONCLUSIONS: IABP-related aortic injuries may be more common in patients awaiting transplantation and that endovascular therapy is a suitable treatment modality with no immediate impact on transplantation outcomes. Pooled data from multiple centers may help identify patients risk profile to potentially design an algorithm that can more quickly identify these injuries.

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction.

Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. We divided the cohort in two groups base6d on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 (182-391) minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with time from PCI to treatment <271 minutes (222.6 [103.9-325.2] vs. 78.4 [44.3-131.2], P < 0.001) and those with time from PCI to treatment ≥271 minute (235.2 [131.4-603.4] vs. 75.5 [38.9-171.9], P < 0.001) (P > 0.05 for interaction). Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 minutes (5 [11%] vs. 9n[36%], log-rank χ 2 5.985, P = 0.014) as well as in patients with time from PCI to drug ≥271 minutes (2n[5%] vs. 7 [23%], log-rank χ 2 3.995, P = 0.046) (P > 0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. SIGNIFICANCE STATEMENT: In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, interleukin-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of interleukin-1 activity, and prevents heart failure events independent of time-to-treatment.

Interleukin-1 Blockade Inhibits the Acute Inflammatory Response in Patients With ST-Segment-Elevation Myocardial Infarction.

Background ST-segment-elevation myocardial infarction is associated with an intense acute inflammatory response and risk of heart failure. We tested whether interleukin-1 blockade with anakinra significantly reduced the area under the curve for hsCRP (high sensitivity C-reactive protein) levels during the first 14 days in patients with ST-segment-elevation myocardial infarction (VCUART3 [Virginia Commonwealth University Anakinra Remodeling Trial 3]). Methods and Results We conducted a randomized, placebo-controlled, double-blind, clinical trial in 99 patients with ST-segment-elevation myocardial infarction in which patients were assigned to 2 weeks treatment with anakinra once daily (N=33), anakinra twice daily (N=31), or placebo (N=35). hsCRP area under the curve was significantly lower in patients receiving anakinra versus placebo (median, 67 [interquartile range, 39-120] versus 214 [interquartile range, 131-394] mg·day/L; P<0.001), without significant differences between the anakinra arms. No significant differences were found between anakinra and placebo groups in the interval changes in left ventricular end-systolic volume (median, 1.4 [interquartile range, -9.8 to 9.8] versus -3.9 [interquartile range, -15.4 to 1.4] mL; P=0.21) or left ventricular ejection fraction (median, 3.9% [interquartile range, -1.6% to 10.2%] versus 2.7% [interquartile range, -1.8% to 9.3%]; P=0.61) at 12 months. The incidence of death or new-onset heart failure or of death and hospitalization for heart failure was significantly lower with anakinra versus placebo (9.4% versus 25.7% [P=0.046] and 0% versus 11.4% [P=0.011], respectively), without difference between the anakinra arms. The incidence of serious infection was not different between anakinra and placebo groups (14% versus 14%; P=0.98). Injection site reactions occurred more frequently in patients receiving anakinra (22%) versus placebo (3%; P=0.016). Conclusions In patients presenting with ST-segment-elevation myocardial infarction, interleukin-1 blockade with anakinra significantly reduces the systemic inflammatory response compared with placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01950299.

Rationale and design of the Virginia Commonwealth University-Anakinra Remodeling Trial-3 (VCU-ART3): A randomized, placebo-controlled, double-blinded, multicenter study.

There is clear association between the intensity of the acute inflammatory response during acute myocardial infarction (AMI) and adverse prognosis after AMI. Interleukin-1 (IL-1) is a pro-inflammatory cytokine released during AMI and involved in adverse remodeling and heart failure (HF). We describe a study to evaluate the safety and efficacy of IL-1 blockade using an IL-1 receptor antagonist (anakinra) during the acute phase of ST-segment elevation myocardial infarction (STEMI). The Virginia Commonwealth University-Anakinra Remodeling Trial-3 (VCU-ART3; http://www.ClinicalTrials.gov NCT01950299) is a phase 2, multicenter, double-blinded, randomized, placebo-controlled clinical trial comparing anakinra 100 mg once or twice daily vs matching placebo (1:1:1) for 14 days in 99 patients with STEMI. Patients who present to the hospital with STEMI within 12 hours of symptom onset will be eligible for enrollment. Patients will be excluded for a history of HF (functional class III-IV), severe valvular disease, severe kidney disease (stage 4-5), active infection, recent use of immunosuppressive drugs, active malignancy, or chronic autoimmune/auto-inflammatory diseases. We will measure the difference in the area under the curve for C-reactive protein between admission and day 14, separately comparing each of the anakinra groups with the placebo group. The P value will be considered significant if <0.025 to adjust for multiple comparisons. Patients will also be followed for up to 12 months from enrollment to evaluate cardiac remodeling (echocardiography), cardiac function (echocardiography), and major adverse cardiovascular outcomes (cardiovascular death, MI, revascularization, and new onset of HF).

Life-saving systemic thrombolysis in a patient with massive pulmonary embolism and a recent hemorrhagic cerebrovascular accident.

Massive pulmonary embolism is associated with mortality rates exceeding 50%. Current practice guidelines include the immediate administration of thrombolytic therapy in the absence of contraindications. However, thrombolysis for pulmonary embolism is said to be absolutely contraindicated in the presence of recent hemorrhagic stroke and other conditions. The current contraindications to thrombolytic therapy have been extrapolated from data on acute coronary syndrome and are not specific for venous thromboembolic disease. Some investigators have proposed that the current contraindications be viewed as relative, rather than absolute, in cases of high-risk pulmonary embolism. We present the case of a 60-year-old woman in whom massive pulmonary embolism led to cardiac arrest with pulseless electrical activity. Eight weeks earlier, she had sustained a hemorrhagic cerebrovascular accident-a classic absolute contraindication to thrombolytic therapy. Despite this practice guideline, we administered tissue plasminogen activator systemically in order to save the patient's life. This therapy did not evoke intracranial bleeding, and the patient was eventually discharged from the hospital. Until guidelines specific to venous thromboembolic disease are developed, we think that the current contraindications to thrombolysis should be considered on an individual basis in patients who are at high risk of death from massive pulmonary embolism.

Prevalence of troponin elevations in patients with cardiac arrest and implications for assessing quality of care in hypothermia centers.

The prevalence of troponin elevations in patients with cardiac arrest (CA) using newer generation troponin assays when the ninety-ninth percentile is used has not been well described. We studied patients admitted with CA without ST elevation myocardial infarction (MI). Treatment included a multidisciplinary protocol that included routine use of hypothermia for appropriate patients. Serial assessment of cardiac biomarkers, including troponin I was obtained over the initial 24 to 36 hours. Patients were classified into 1 of 5 groups on the basis of multiples of the ninety-ninth percentile (upper reference limit [URL]), using the peak troponin I value: <1×, 1 to 3×, 3 to 5×, 5 to 10×, and >10×. Serial changes between the initial and second troponin I values were also assessed. A total of 165 patients with CA (mean age 58 ± 16, 67% men) were included. Troponin I was detectable in all but 2 patients (99%); all others had peak troponin I values that were greater than or equal to the URL. Most patients had peak troponin I values >10× URL, including patients with ventricular fibrillation or ventricular tachycardia (85%), asystole (50%), and pulseless electrical activity (59%). Serial changes in troponin I were present in almost all patients: ≥20% change in 162 (98%), ≥30% change in 159 (96%), and an absolute increase of ≥0.02 ng/ml in 85% of patients. In conclusion, almost all patients with CA who survived to admission had detectable troponin I, most of whom met biomarker guideline criteria for MI. Given the high mortality of these patients, these data have important implications for MI mortality reporting at CA treatment centers.

Outcomes in patients with chronicity of left bundle-branch block with possible acute myocardial infarction.

INTRODUCTION: Guidelines derived from patients in clinical trials indicate that emergency department patients with likely myocardial infarction (MI) who have new left bundle-branch block (LBBB) should undergo rapid reperfusion therapy. Whether this pertains to lower risk emergency department patients with LBBB is unclear. METHODS: A total of 401 consecutive patients with LBBB undergoing an MI rule-out protocol were included. Left bundle-branch blocks were classified as chronic; new; or, if no prior electrocardiogram (ECG) was available, as presumably new. Left bundle-branch blocks were considered concordant if there was ≥1 mm concordant ST elevation or depression. Rates of MI, peak MB values in MI patients, and 30-day mortality were compared across groups. RESULTS: A majority of patients (64%) had new (37%) or presumably new LBBB (27%). A total of 116 patients (29%) had MI, with no significant difference in prevalence or size of MI among the 3 ECG groups. Myocardial infarction was diagnosed in 86% of patients with concordant ECG changes versus 27% of patients without concordant ECG changes (P < .01). Peak MB was >5× normal in 50% who had concordant ST changes compared to none of those who did not. Concordant ST changes were the most important predictor of MI (odds ratio 17, 95% CI 3.4-81, P < .001) and an independent predictor of mortality (odds ratio 4.3, 95% CI 1.3-15, P < .001); new or presumably new LBBB was neither. CONCLUSIONS: Most patients with possible MI with new or presumably new LBBB do not have MI. Concordant ECG changes were an important predictor of MI and death. Current guidelines regarding early reperfusion therapy for patients with LBBB should be reconsidered.

Emergency physician-initiated cath lab activation reduces door to balloon times in ST-segment elevation myocardial infarction patients.

OBJECTIVES: We evaluated the impact of emergency physician (EP)-initiated primary percutaneous coronary intervention (PCI) via a single-group page on door to balloon (D2B) interval times in patients with ST-segment elevation myocardial infarction. METHODS: Consecutive ST-segment elevation myocardial infarction patients presenting to the emergency department between February 2004 and September 2008 were divided into 4 groups: group 1, PCI performed on an ad hoc basis after cardiology consultation; group 2, primary PCI activated via a single-group page only on-call cardiology consultation; group 3, primary PCI with EP cardiac catheterization laboratory (CCL) activation via the same page strategy; group 4, prehospital CCL activation based on prehospital diagnostic electrocardiogram. Composite D2B and relevant time intervals were measured for each time group. RESULTS: A total of 295 consecutive patients undergoing emergent angiography were included. Times decreased for most time intervals from groups 1 to 4. Although there was no significant change in composite D2B or any measured interval time with the introduction of PCI after emergent cardiology consultation, each decreased significantly after implementing an EP-initiated PCI strategy except CCL2B (D2B 95 to 77 minutes, D2E 14 to 10 minutes, D2CCL 71 to 50 minutes). Further significant reductions in D2B time were achieved among all patients after the institution of emergency medicine services activation of the CCL (D2B 77 to 64 minutes, D2CCL 50 to 38 minutes, CCL2B 28 to 22 minutes). CONCLUSIONS: A systematic process of initiating D2B recommendations, including EP-initiated CCL activation via a single-group page, significantly reduces D2CCL and D2B times.

The impact of prehospital activation of the cardiac catheterization team on time to treatment for patients presenting with ST-segment-elevation myocardial infarction.

OBJECTIVE: We sought to evaluate the accuracy of emergency medical services (EMS) activation of the cardiac catheterization laboratory (CCL) for patients with ST-elevation myocardial infarction (STEMI) and its impact on treatment intervals from dispatch to reperfusion. METHODS: We conducted a before-and-after cohort study of patients presenting via EMS with prehospital electrocardiogram findings consistent with STEMI. Before August 20, 2007, percutaneous coronary intervention was initiated after patient arrival. Afterward, EMS providers could activate the CCL if the prehospital electrocardiogram automated interpretation indicated STEMI. All interval times from EMS dispatch to percutaneous coronary intervention were measured via synchronized timepieces. RESULTS: A total of 53 patients, 14 before and 39 after prehospital activation, were included. Emergency medical services CCL activation was 79.6% sensitive (95% confidence interval [CI], 65.2%-89.3%) and 99.7% specific (95% CI, 99.1%-99.9%). Mean door-to-hospital electrocardiogram and mean CCL-to-reperfusion times were unaffected by the intervention. Prehospital activation of the CCL significantly improved mean door-to-balloon (D2B) time by 18.2 minutes (95% CI, 7.69-28.71 minutes; P = .0029) and door-to-CCL by 14.8 minutes (95% CI, 6.20-23.39 minutes; P = .0024). Improvements in D2B were independent of presentation during peak hours (F ratio = 17.02, P < .0001). There were significant time savings reflected in all EMS intervals: 20.7 minutes (95% CI, 9.1-32.3 minutes; P = .0015) in mean dispatch-to-reperfusion time, 22.2 minutes (95% CI, 11.45-32.95 minutes; P = .0003) in mean first medical contact-to-reperfusion time, and 20 minutes (95% CI, 10.95-29.05 minutes; P = .0001) in recognition-to-reperfusion time. CONCLUSIONS: Emergency medical service providers can appropriately activate the CCL for patients with STEMI before emergency department arrival, significantly reducing mean D2B time. Significant reduction is demonstrated throughout EMS intervals.

Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study).

Acute myocardial infarction (AMI) initiates an intense inflammatory response in which interleukin-1 (IL-1) plays a central role. The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m(2) median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a -3.2 ml/m(2) median decrease (interquartile range -4.5, -1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m(2). On echocardiography, the median difference in the LVESVi change was 13.4 ml/m(2) (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m(2), p = 0.033) and echocardiography (9.4 ml/m(2), p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R = +0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI.

An evaluation of the accuracy of emergency physician activation of the cardiac catheterization laboratory for patients with suspected ST-segment elevation myocardial infarction.

STUDY OBJECTIVE: Current recommendations indicate that emergency physicians should activate cardiac catheterization laboratory personnel by a single page for ST-segment elevation myocardial infarction (STEMI) patients. We assessed the accuracy of emergency physician cardiac catheterization laboratory activations, angiographic findings, outcomes, and treatment times among patients with and without STEMI. METHODS: We classified the appropriateness and outcomes of consecutive emergency physician STEMI pages between June 2006 and September 2008. Emergency physician activations of the cardiac catheterization laboratory were classified according to the findings of the initial ECG compared with cardiology interpretation for the presence of STEMI and presence of coronary disease. RESULTS: During a 27-month period, emergency physician activation of the cardiac catheterization laboratory occurred 249 times. There were 188 (76%) patients with a true STEMI, of whom 13 did not receive emergency angiography. Of the 37 (15%) patients who had ECG findings meeting STEMI criteria and who ultimately did not have myocardial necrosis and underwent emergency angiography, 12 had significant disease and 5 had revascularization performed. Eleven patients had ECGs concerning for but not meeting STEMI criteria; all had emergency angiography (n=11) or received a diagnosis of non-STEMI (n=6). Only 13 patients were considered as having received unnecessary cardiac catheterization laboratory activations (5.2%) in which emergency angiography was not performed and myocardial infarction was excluded. CONCLUSION: A significant number of emergency physician STEMI cardiac catheterization laboratory activations are for patients who did not meet standard STEMI criteria. However, most had ECG findings and symptoms that lead to emergency angiography, had significant disease, or were diagnosed with non-STEMI. Only a small percentage of patients received unnecessary cardiac catheterization laboratory activations. Our findings support current recommendations for emergency physician cardiac catheterization laboratory activation for potential STEMI patients.

Mortality based on the presenting electrocardiogram in patients with myocardial infarction in the troponin era.

BACKGROUND: Studies reporting short-term mortality in patients with myocardial infarction (MI) based on the initial electrocardiogram (ECG) are often limited by requiring an ischemic ECG for inclusion. Because few patients with normal or nonspecific findings were included, outcomes in these patients are less clear, especially in the troponin era. METHODS: Consecutive patients diagnosed as having MI using troponin I (TnI) over a 6-year period were included and classified into 8 mutually exclusive groups based on the initial ECG using standard criteria. Patients were included in only 1 group. The MI size was estimated using multiples of peak creatine kinase-MB (CK-MB), and 30-day mortality rate was assessed. RESULTS: Among 1641 patients with MI, patients with ST elevation represented only 22% of all MIs. Patients with ST elevation had the largest MI size, with 2 of 3 having a peak CK-MB greater than 10 times normal. In contrast, most of the patients representing all the other ECG groups had a peak CK-MB less than 5 times normal, with approximately 1 of 3 having no CK-MB elevation and were diagnosed by TnI elevation alone. Patients could be separated into a high-risk group (ST elevation, ischemia, other, or left bundle-branch block), in which mortality rate exceeded 9% (mean, 14%), and a lower-risk group (prior MI, left ventricular hypertrophy, nonspecific changes, and normal), in which the 30-day mortality rate averaged 6% (P < .001; range, 5.23%-7.1%). CONCLUSIONS: Specific ECG findings other than ischemia portend poor outcomes in patients with MI. Once MI is diagnosed, patients are no longer low risk.

Ability of myoglobin to predict mortality in patients admitted for exclusion of myocardial infarction.

BACKGROUND: Myoglobin can be used as an early marker to diagnose myocardial infarction (MI); and although nonspecific for myocardial necrosis, it seems to be a strong mortality predictor. Because myoglobin elevations are often present in patients with renal insufficiency, it is possible that the predictive value of myoglobin is secondary to identifying patients with renal insufficiency. METHODS: Consecutive patients admitted for MI exclusion without ST elevation on the initial electrocardiogram underwent serial assessment of cardiac markers (creatine kinase [CK], CK-myocardial band [MB], and troponin I [TnI]). Myoglobin was assessed at the time of admission and/or 3 hours later. Renal insufficiency was defined as a creatinine clearance <60 mL/min. Multivariate analysis was performed to identify predictors of 30-day and 1-year all-cause mortality. RESULTS: A total of 3461 patients were included in the analysis. Overall 30-day and 1-year mortality was 2.4% and 9.7%. Myoglobin was elevated in 675 (20%), CK-MB in 421 (12%), and TnI in 517 (15%). Among the 993 patients with renal insufficiency, myoglobin was elevated in 43%, CK-MB in 17%, and TnI in 21%. Independent predictors of 30-day and 1-year mortality were similar and included age > or =65 years, prior MI, and an ischemic electrocardiogram, whereas myoglobin was the strongest multivariate predictor (odds ratio [OR] 2.8, 95% confidence interval [CI] 2.1-3.7), including those with renal insufficiency (OR 2.3, 95% CI 1.6-3.4). Troponin I had borderline predictive value (P = .08, OR 1.4, 95% CI 0.96-2.0), whereas CK-MB was not predictive in either group. CONCLUSIONS: Despite the absence of cardiac specificity, an elevated myoglobin strongly predicts mortality, even in patients with renal insufficiency.

Implication of the new low-density lipoprotein goals in dyslipidemia management of patients with acute coronary syndrome.

OBJECTIVE: To assess the ability of patients with an acute coronary syndrome (ACS) to meet the recommended low-density lipoprotein cholesterol (LDL-C) goal of 100 mg/dL and optional aggressive lowering to 70 mg/dL. PATIENTS AND METHODS: Patients diagnosed as having ACS who had lipid levels measured within 24 hours of admission from January 1, 1998, through December 31, 2002, were assessed for the ability to meet the 2 target LDL-C levels. Patients were considered to have ACS if they were diagnosed as having myocardial infarction, had significant disease on angiography, or had a history of coronary artery disease. Patients were classified into 1 of 4 groups on the basis of the degree of LDL-C lowering required to meet the 2 different goals: less than 33%, 33% to 39%, 40% to 49%, and 50% or more. Patients with myocardial infarction who had lipid sampling performed more than 24 hours after admission were excluded. RESULTS: The mean plus-or-minus SD LDL-C level was 111 plus-or-minus 43 mg/dL in the 1322 patients who met criteria for ACS and had LDL-C levels assessed. On the basis of a target LDL-C value of less than 100 mg/dL, 43% of patients were at goal and did not require treatment, and only 2.5% had an LDL-C level that required a 50% or greater reduction to meet goal. In contrast, using the newer LDL-C target of 70 mg/dL, 85% patients required treatment, and 23% of patients required a 50% or greater decrease in LDL-C level and therefore were likely to require more than 1 lipid-lowering agent. CONCLUSION: Decreasing the LDL-C target to less than 70 mg/dL substantially increases the number of patients with ACS who would require treatment. A significant proportion of patients will require a reduction in LDL-C level of 50% or more, which is not easily achievable with current lipid-lowering monotherapy.