In hospital, the detection of cardiac standstill with ultrasound predicts a fatal outcome from cardiac arrest with a high degree of accuracy. A similar finding has been made in the prehospital setting. Interestingly, it was a better predictor than other commonly recognised factors associated with outcome: the presence of asystole, down time, bystander CPR, or end-tidal CO2 levels.
Introduction. The prognostic value of emergency echocardiography (EE) in the management of cardiac arrest patients has previously been studied in an in-hospital setting. These studies mainly included patients who underwent cardiopulmonary resuscitation (CPR) by emergency medicine technicians at the scene and who arrived at the emergency department (ED) still in a state of cardiac arrest. In most European countries, cardiac arrest patients are normally treated by physician-staffed emergency medical services (EMS) teams on scene. Transportation to the ED while undergoing CPR is uncommon. Objective. To evaluate the ability of EE to predict outcome in cardiac arrest patients when it is performed by ultrasound-inexperienced emergency physicians on scene.
Methods. We performed a prospective, observational study of nonconsecutive, nontrauma, adult cardiac arrest patients who were treated by physician-staffed urban EMS teams on scene. Participating emergency physicians (EPs) received a two-hour course in EE during CPR. After initial procedures were accomplished, EE was performed during a rhythm and pulse check. A single subxiphoid, four-chamber view was required for study enrollment. We defined sonographic evidence of cardiac kinetic activity as any detected motion of the myocardium, ranging from visible ventricular fibrillation to coordinated ventricular contractions. The CPR had to be continued for at least 15 minutes after the initial echocardiography. No clinical decisions were made based on the results of EE.
Results. Forty-two patients were enrolled in the study. The heart could be visualized successfully in all patients. Five (11.9%) patients survived to hospital admission. Of the 32 patients who had cardiac standstill on initial EE, only one (3.1%) survived to hospital admission, whereas four out of 10 (40%) patients with cardiac movement on initial EE survived to hospital admission (p = 0.008). Neither asystole on initial electrocardiogram nor peak capnography value, age, bystander CPR, or downtime was a significant predictor of survival. Only cardiac movement was associated with survival, and cardiac standstill at any time during CPR resulted in a positive predictive value of 97.1% for death at the scene.
Conclusion. Our results support the idea of focused echocardiography as an additional criterion in the evaluation of outcome in CPR patients and demonstrate its feasibility in the prehospital setting.
Two cases of failed cardioversion of SVT after tibial intraosseous administration of adenosine in infants are described in this month’s Pediatric Emergency Care. Both cases were subsequently cardioverted by intravenous adenosine. The maximum intraosseous dose given was 0.25 mg/kg. The successful IV doses were not higher than the IO doses.
It has been noted before that infants may require relatively higher doses of adenosine than children and that 0.2 mg/kg might even be considered a starting dose in infancy. I wonder if a bigger IO dose would have been effective, or whether a proximal humeral insertion site would make a difference. IO adenosine has been successfully used in infants and piglets.
This interesting case series provides a helpful caution in the management of paediatric SVT.
ABSTRACT: Supraventricular tachycardia (SVT) is a common tachyarrhythmia in the pediatric population that can necessitate immediate treatment. Adenosine has been well studied as a mainstay treatment, but the methods of adenosine administration have not been very well delineated. The intraosseous technique has presented itself as a possible method of administration. We describe 2 cases in which adenosine was administered through bone marrow infusion to convert SVT without success. The cases we describe show that intraosseous is not a reliable method of administering adenosine to stop SVT. Both patients presented with SVT refractory to vagal maneuvers and difficult intravenous placement. Intraosseous access was achieved, but administration of adenosine at increasing doses was unable to successfully convert the arrhythmia.
An editorial1 reviewing options for circulatory support in patients with cardiogenic shock argues that traditional inotrope therapy may be replaced by newer alternatives that have a less detrimental effect on myocardial oxygen demand.
Newer inotropic agents include levosimendan, istaroxime, and omecamtiv mecarbil. Mechanical therapies include intra-aortic balloon pumps (IABP), ventricular assist devices (VAD), and extracorporeal membrane oxygenation (ECMO).
Levosimendan is an inodilator, with the following characteristics:
stabilises the myocardial calcium-troponin C complex
activates adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle and cardiac mitochondria,
acts as a traditional phosphodiesterase inhibitor at higher doses
improved cardiac output and a reduction in filling pressures compared with dobutamine
may also improve diastolic function by increasing relaxation rate
modulates the neuroendocrine response to heart failure by reducing brain natriuretic peptide levels
has anti-apoptotic and anti-inflammatory effects
renal function may also improve
is associated with a similar risk of ventricular arrhythmias to dobutamine
increases risk of new onset atrial fibrillation
has conflicting literature surrounding mortality
has shown a lack of consistent outcome benefits in studies
may be useful in postmyocardial infarction cardiac dysfunction and septic shock through increasing coronary flow and attenuating inflammatory activation, respectively2.
Istaroxime, a novel inotrope with positive lusitropic (cardiac relaxant) effects3:
is an inhibitor of the sodium-potassium-ATPase (resulting, like digoxin, in elevated intracellular calcium) with additional stimulatory effects on the sarcoplasmic reticulum calcium pump (SERCA)
provides a dose-dependant increase in cardiac output without significant change in heart rate or arrhythmia
in one study reducesd pulmonary capillary wedge pressure, increased systolic blood pressure, and reduced heart rate and left ventricular end-diastolic volume
requires further clinical evaluation.
Omecamtiv mecarbil is a cardiac myosin activator. This new drug:
improves myocardial contraction by increasing the hydrolysis of ATP by myosin ATPase
this produces the power stroke between actin and myosin and subsequent shortening of sarcomere length
in phase-2a studies in patients with systolic heart failure it demonstrated improved stroke volume without an increase in heart rate, although cardiac ischaemia emerged at high plasma concentrations4,5.
PURPOSE OF REVIEW: ICU patients frequently develop low output syndromes due to cardiac dysfunction, myocardial injury, and inflammatory activation. Conventional inotropic agents seem to be useful in restoring hemodynamic parameters and improving peripheral organ perfusion, but can increase short-term and long-term mortality in these patients. Novel inotropes may be promising in the management of ICU patients, having no serious adverse effects. This review summarizes all the current knowledge about the use of conventional and new inotropic agents in various clinical entities of critically ill patients.
RECENT FINDINGS: In recent European Society of Cardiology guidelines, inotropic agents are administered in patients with low output syndrome due to impaired cardiac contractility, and signs and symptoms of congestion. The most recommended inotropes in this condition are levosimendan and dobutamine (both class of recommendation: IIa, level of evidence: B). Recent data indicate that levosimendan may be useful in postmyocardial infarction cardiac dysfunction and septic shock through increasing coronary flow and attenuating inflammatory activation, respectively. Furthermore, calcium sensitizing by levosimendan can be effectively used for weaning of mechanical ventilation in postcardiac surgery patients and has also cardioprotective effect as expressed by the absence of troponin release in this patient population. Finally, new agents, such as istaroxime and cardiac myosin activators may be safe and improve central hemodynamics in experimental models of heart failure and heart failure patients in phase II clinical trials; however, large-scale randomized clinical trials are required.
SUMMARY: In an acute cardiac care setting, short-term use of inotropic agents is crucial for the restoration of arterial blood pressure and peripheral tissue perfusion, as well as weaning of cardiosurgery. New promising agents should be tested in randomized clinical trials.
Heart failure (HF) patients are a medically complex and heterogeneous population with multiple cardiac and non-cardiac comorbidities. Although there are a multitude of etiologic substrates and initiating and amplifying mechanisms contributing to disease progression, these pathophysiologic processes ultimately all lead to impaired myocardial function. The myocardium must both pump oxygenated, nutrient-rich blood throughout the body (systolic function) and receive deoxygenated, nutrient-poor blood returning from the periphery (diastolic function). At the molecular level, it is well-established that Ca2+ plays a central role in excitation-contracting coupling with action potentials stimulating the opening of L-type Ca2+ in the plasma membrane and ryanodine receptor 2 (RyR2) in the sarcoplasmic reticulum (SR) membrane during systole and the Na-Ca2+ exchanger and SERCA2a returning Ca2+ to the extracellular space and SR, respectively, during diastole. However, there is increasing recognition that impaired Ca2+ cycling may contribute to myocardial dysfunction. Preclinical studies and clinical trials indicate that combining SERCA2a activation and Na-K ATPase inhibition may increase contractility (inotropy) and facilitate active relaxation (lusitropy), improving both systolic and diastolic functions. Istaroxime, a novel luso-inotrope that activates SERCA2a and inhibits the Na-K ATPase, is currently in phase II clinical development and has been shown to improve systolic and diastolic functions and central hemodynamics, increase systolic but not diastolic blood pressure, and decrease substantially heart rate. Irrespective of its clinical utility, the development of istaroxime has evolved our understanding of the clinical importance of inhibiting the Na-K ATPase in order to obtain a clinically significant effect from SERCA2a activation in the setting of myocardial failure.
4. Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study Lancet. 2011 Aug 20;378(9792):667-75
BACKGROUND: Decreased systolic function is central to the pathogenesis of heart failure in millions of patients worldwide, but mechanism-related adverse effects restrict existing inotropic treatments. This study tested the hypothesis that omecamtiv mecarbil, a selective cardiac myosin activator, will augment cardiac function in human beings.
METHODS: In this dose-escalating, crossover study, 34 healthy men received a 6-h double-blind intravenous infusion of omecamtiv mecarbil or placebo once a week for 4 weeks. Each sequence consisted of three ascending omecamtiv mecarbil doses (ranging from 0·005 to 1·0 mg/kg per h) with a placebo infusion randomised into the sequence. Vital signs, blood samples, electrocardiographs (ECGs), and echocardiograms were obtained before, during, and after each infusion. The primary aim was to establish maximum tolerated dose (the highest infusion rate tolerated by at least eight participants) and plasma concentrations of omecamtiv mecarbil; secondary aims were evaluation of pharmacodynamic and pharmacokinetic characteristics, safety, and tolerability. This study is registered at ClinicalTrials.gov, number NCT01380223.
FINDINGS: The maximum tolerated dose of omecamtiv mecarbil was 0·5 mg/kg per h. Omecamtiv mecarbil infusion resulted in dose-related and concentration-related increases in systolic ejection time (mean increase from baseline at maximum tolerated dose, 85 [SD 5] ms), the most sensitive indicator of drug effect (r(2)=0·99 by dose), associated with increases in stroke volume (15  mL), fractional shortening (8% ), and ejection fraction (7% ; all p<0·0001). Omecamtiv mecarbil increased atrial contractile function, and there were no clinically relevant changes in diastolic function. There were no clinically significant dose-related adverse effects on vital signs, serum chemistries, ECGs, or adverse events up to a dose of 0·625 mg/kg per h. The dose-limiting toxic effect was myocardial ischaemia due to excessive prolongation of systolic ejection time.
INTERPRETATION: These first-in-man data show highly dose-dependent augmentation of left ventricular systolic function in response to omecamtiv mecarbil and support potential clinical use of the drug in patients with heart failure.
FUNDING: Cytokinetics Inc.
5. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial Lancet. 2011 Aug 20;378(9792):676-83
BACKGROUND: Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are characteristic of systolic heart failure and might be improved by a new therapeutic class, cardiac myosin activators. We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure.
METHODS: We undertook a double-blind, placebo-controlled, crossover, dose-ranging, phase 2 trial investigating the effects of omecamtiv mecarbil (formerly CK-1827452), given intravenously for 2, 24, or 72 h to patients with stable heart failure and left ventricular systolic dysfunction receiving guideline-indicated treatment. Clinical assessment (including vital signs, echocardiograms, and electrocardiographs) and testing of plasma drug concentrations took place during and after completion of each infusion. The primary aim was to assess safety and tolerability of omecamtiv mecarbil. This study is registered at ClinicalTrials.gov, NCT00624442.
FINDINGS: T45 patients received 151 infusions of active drug or placebo. Placebo-corrected, concentration-dependent increases in left ventricular ejection time (up to an 80 ms increase from baseline) and stroke volume (up to 9·7 mL) were recorded, associated with a small reduction in heart rate (up to 2·7 beats per min; p<0·0001 for all three measures). Higher plasma concentrations were also associated with reductions in end-systolic (decrease of 15 mL at >500 ng/mL, p=0·0026) and end-diastolic volumes (16 mL, p=0·0096) that might have been more pronounced with increased duration of infusion. Cardiac ischaemia emerged at high plasma concentrations (two patients, plasma concentrations roughly 1750 ng/mL and 1350 ng/mL). For patients tolerant of all study drug infusions, no consistent pattern of adverse events with either dose or duration emerged.
INTERPRETATION: Omecamtiv mecarbil improved cardiac function in patients with heart failure caused by left ventricular dysfunction and could be the first in class of a new therapeutic agent.
Trauma specialists from Arizona and California describe patients with penetrating cardiac wounds, a quarter of whom survive to discharge. Survival post discharge is good, with a range of complications at follow up but no operative intervention was required for the complications.
A significant rate of postdischarge complications is associated with penetrating cardiac injuries.
DESIGN: Retrospective trauma registry review.
SETTING: Level I trauma center.
PATIENTS: All patients sustaining penetrating cardiac injuries between January 2000 and June 2010. Patient demographics, clinical data, operative findings, outpatient follow-up, echocardiogram results, and outcomes were extracted.
MAIN OUTCOME MEASURES: Cardiac-related complications and mortality.
RESULTS: During the 10.5-year study period, 406 of 40,706 trauma admissions (1.0%) sustained penetrating cardiac injury. One hundred nine (26.9%) survived to hospital discharge. The survivors were predominantly male (94.4%), with a mean (SD) age of 30.8 (11.7) years, and 74.3% sustained a stab wound. Signs of life were present on admission in 92.6%. Cardiac chambers involved were the right ventricle (45.9%), left ventricle (40.3%), right atrium (10.1%), left atrium (0.9%), and combined (2.8%). In-hospital follow-up was available for a mean (SD) of 11.0 (9.8) days (median, 8 days; range, 3-65 days) and outpatient follow-up was available in 46 patients (42.2%) for a mean (SD) of 1.9 (4.1) months (median, 0.9 months; range, 0.2-12 months). Abnormal echocardiograms demonstrated pericardial effusions (9), abnormal wall motion (8), decreased ejection fraction (<45%) (8), intramural thrombus (4), valve injury (4), cardiac enlargement (2), conduction abnormality (2), pseudoaneurysm (1), aneurysm (1), and septal defect (1). No operative intervention was required for the complications. The 1-year and 9-year survival rates were 97% and 88%, respectively.
CONCLUSIONS: Penetrating cardiac injuries remain highly lethal. A significant rate of cardiac complications can be expected and follow-up echocardiographic evaluation is warranted prior to discharge. The majority of these, however, can be managed without the need for surgical intervention.
Atrial fibrillation can occur in the setting of severe sepsis, and often presents a therapeutic conundrum for critical care physicians, in that it can be relatively resistant to treatment until the sepsis has resolved, and its prognostic significance is unclear. A new study on a massive dataset shows atrial fibrillation in the setting of severe sepsis is associated with an increased risk of stroke and increased hospital mortality. Patients with severe sepsis who developed new-onset AF had a greater risk of in-hospital stroke than patients with preexisting AF and individuals without a history of AF.
Context New-onset atrial fibrillation (AF) has been reported in 6% to 20% of patients with severe sepsis. Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in the setting of severe sepsis is uncertain.
Objective To determine the in-hospital stroke and in-hospital mortality risks associated with new-onset AF in patients with severe sepsis.
Design and Setting Retrospective population-based cohort of California State Inpatient Database administrative claims data from nonfederal acute care hospitals for January 1 through December 31, 2007.
Patients Data were available for 3 144 787 hospitalized adults. Severe sepsis (n = 49 082 [1.56%]) was defined by validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 995.92. New-onset AF was defined as AF that occurred during the hospital stay, after excluding AF cases present at admission.
Main Outcome Measures A priori outcome measures were in-hospital ischemic stroke (ICD-9-CM codes 433, 434, or 436) and mortality.
Results Patients with severe sepsis were a mean age of 69 (SD, 16) years and 48% were women. New-onset AF occurred in 5.9% of patients with severe sepsis vs 0.65% of patients without severe sepsis (multivariable-adjusted odds ratio [OR], 6.82; 95% CI, 6.54-7.11; P < .001). Severe sepsis was present in 14% of all new-onset AF in hospitalized adults. Compared with severe sepsis patients without new-onset AF, patients with new-onset AF during severe sepsis had greater risks of in-hospital stroke (75/2896 [2.6%] vs 306/46 186 [0.6%] strokes; adjusted OR, 2.70; 95% CI, 2.05-3.57; P < .001) and in-hospital mortality (1629 [56%] vs 18 027 [39%] deaths; adjusted relative risk, 1.07; 95% CI, 1.04-1.11; P < .001). Findings were robust across 2 definitions of severe sepsis, multiple methods of addressing confounding, and multiple sensitivity analyses.
Conclusion Among patients with severe sepsis, patients with new-onset AF were at increased risk of in-hospital stroke and death compared with patients with no AF and patients with preexisting AF.
An interesting finding: in patients with myocardial infarction, hospital mortality increased consistently as the number of risk factors declined. There was also an inverse relationship between age and the number of coronary heart disease risk factors.
The authors discuss the possibility that the some of the zero risk factor group may have had risk factors unknown to the patient or not reported in the history, or may have had other factors that influence the disease, for example insulin resistance, abdominal obesity, psychosocial factors, poor nutrition, or physical inactivity.
Context Few studies have examined the association between the number of coronary heart disease risk factors and outcomes of acute myocardial infarction in community practice.
Objective To determine the association between the number of coronary heart disease risk factors in patients with first myocardial infarction and hospital mortality.
Design Observational study from the National Registry of Myocardial Infarction, 1994-2006.
Patients We examined the presence and absence of 5 major traditional coronary heart disease risk factors (hypertension, smoking, dyslipidemia, diabetes, and family history of coronary heart disease) and hospital mortality among 542 008 patients with first myocardial infarction and without prior cardiovascular disease.
Main Outcome Measure All-cause in-hospital mortality.
Results A majority (85.6%) of patients who presented with initial myocardial infarction had at least 1 of the 5 coronary heart disease risk factors, and 14.4% had none of the 5 risk factors. Age varied inversely with the number of coronary heart disease risk factors, from a mean age of 71.5 years with 0 risk factors to 56.7 years with 5 risk factors (P for trend < .001). The total number of in-hospital deaths for all causes was 50 788. Unadjusted in-hospital mortality rates were 14.9%, 10.9%, 7.9%, 5.3%, 4.2%, and 3.6% for patients with 0, 1, 2, 3, 4, and 5 risk factors, respectively. After adjusting for age and other clinical factors, there was an inverse association between the number of coronary heart disease risk factors and hospital mortality adjusted odds ratio (1.54; 95% CI, 1.23-1.94) among individuals with 0 vs 5 risk factors. This association was consistent among several age strata and important patient subgroups.
Conclusion Among patients with incident acute myocardial infarction without prior cardiovascular disease, in-hospital mortality was inversely related to the number of coronary heart disease risk factors.
The physician-staffed mobile intensive care units of SAMU (Service d’Aide Médicale Urgente) in France provided the location for this randomised controlled trial of CPAP for acute cardiogenic pulmonary oedema.
STUDY OBJECTIVE: The purpose of this randomized controlled trial was to determine the immediate and delayed effects of noninvasive ventilation for patients in acute cardiogenic pulmonary edema (ACPE) in addition to aggressive usual care in a medical prehospital setting.
METHODS: Out-of-hospital patients in severe ACPE were eligible for the study. Patients were randomized to receive either usual care, including conventional optimal treatment with furosemide, oxygen, and high-dose boluses of isosorbide dinitrate plus oxygen, or conventional medications plus out-of-hospital continuous positive airway pressure (CPAP). The primary outcome was the treatment success defined as all of respiratory rate less than 25 breaths per minute and oxygen saturation of greater than 90% at the end of 1-hour study. Secondary end points included death during 30 days after inclusion. Lengths of intensive care unit and hospital stays were also recorded.
RESULTS: In total, 124 patients were enrolled into the study. The 2 groups had similar baseline characteristics. For the primary outcome analysis, 22 (35.5%) of 62 patients were considered as experiencing a treatment success in the usual care group vs 19 (31.7%) of 60 in the CPAP group (P = .65). Seven patients died within 30 days in the usual care group vs 6 in the CPAP group (P = .52). There were no statistically significant differences between the treatment groups for length of stay either in hospital or in the intensive care unit.
CONCLUSION: In the prehospital setting, in spite of its potential advantages for patients in ACPE, CPAP may not be preferred to a strict optimal intravenous treatment.
A case report describes a patient with right ventricular cardiogenic shock due to a dissected right coronary artery1. There was deterioration despite fluid, inotropic and intraaortic balloon pump therapy, followed by improvement with the introduction of inhaled nitric oxide (iNO) at 12 to 15 ppm (a selective pulmonary vasodilator), to the point where vasoactive medication was withdrawn. The cessation of iNO was associated with deterioration which resolved with its reintroduction. It was more gradually withdrawn and the patient made a good recovery.
The rationale for the use of iNO in patients with acute RV heart failure due to MI is afterload reduction without systemic hypotension.
It has been shown to improve haemodynamics in RV MI patients with cardiogenic shock in a previous case series2 (abstract below) in which its effects on pulmonary vasodilation are thought be beneficial. In RV MI with shock increased pulmonary vascular tone is postulated to result from the following mechanisms:
A low cardiac output results in a decreased mixed venous blood oxygen content, which enhances pulmonary artery vasoconstriction.
The intravenous infusion of alpha-adrenergic vasoconstrictors can contribute to pulmonary vasoconstriction.
Mechanical ventilation with positive end-expiratory pressure can increase the pulmonary vascular resistance through compression of the pulmonary vasculature.
Interstitial pulmonary edema, which may occur in some patients with coexisting LV dysfunction, can also cause pulmonary constriction
OBJECTIVES: We sought to determine whether or not inhaled nitric oxide (NO) could improve hemodynamic function in patients with right ventricular myocardial infarction (RVMI) and cardiogenic shock (CS).
BACKGROUND: Inhaled NO is a selective pulmonary vasodilator that can decrease right ventricular afterload.
METHODS: Thirteen patients (7 males and 6 females, age 65 +/- 3 years) presenting with electrocardiographic, echocardiographic, and hemodynamic evidence of acute inferior myocardial infarction associated with RVMI and CS were studied. After administration of supplemental oxygen (inspired oxygen fraction [F(i)O(2)] = 1.0), hemodynamic measurements were recorded before, during inhalation of NO (80 ppm at F(i)O(2) = 0.90) for 10 min, and 10 min after NO inhalation was discontinued (F(i)O(2) = 1.0).
RESULTS: Breathing NO decreased the mean right atrial pressure by 12 +/- 3%, mean pulmonary arterial pressure by 13 +/- 2%, and pulmonary vascular resistance by 36 +/- 8% (all p < 0.05). Nitric oxide inhalation increased the cardiac index by 24 +/- 11% and the stroke volume index by 23 +/- 12% (p < 0.05). The NO administration did not change systemic arterial or pulmonary capillary wedge pressures. Contrast echocardiography identified three patients with a patent foramen ovale and right-to-left shunt flow while breathing at F(i)O(2) = 1.0. Breathing NO decreased shunt flow by 56 +/- 5% (p < 0.05) and was associated with markedly improved systemic oxygen saturation.
CONCLUSIONS: Nitric oxide inhalation results in acute hemodynamic improvement when administered to patients with RVMI and CS.
Newer high-sensitivity troponin tests can be positive in patients who would have negative tests with the ‘traditional’ assay, which can result in confusion about what to do with the patient, particularly those patients without an obvious cardiac presentation. A recent study1 shows that the majority of patients that fall into this group had non-cardiac discharge diagnoses.
Background: High sensitivity troponin T (hsTnT) detects lower levels of troponin T with greater precision than the 4th generation (cTnT) assay. However, the clinical implications of this are uncertain.
Objectives: Primary: Describe the proportion of patients who test ‘positive’ with hsTnT but negative with cTnT. Secondary: Determine proportion in each group with an adverse event (representation, AMI or died) within 90 days of the index test.
Method: 161 patients samples were tested with cTnT and hsTNT assays. McNemar’s test was used to compare paired samples. Electronic medical records were reviewed, with discharge diagnosis and 90 day outcomes determined blind to hsTnT results. Patients were then classified as ‘TnT negative’ (hsTnT was <0.014 mcg/mL), 'new positive' (hsTnT was ≥0.014 mcg/mL and cTnT <0.03 mcg/mL) and 'TnT positive' (cTNT was ≥0.03 mcg/mL)
Results: Positive results more than doubled with the hsTnT assay (50% vs 22%, P < 0.001). 81 patients were ‘TnT negative’, 44 were ‘new positive’ and 36 ‘cTnT positive’. The discharge diagnosis for ‘new positives’ was AMI in 4 (9%), other cardiac in 13 (30%) and non-cardiac in 27 (61%). At 90 days adverse events occurred in 30%, 54% and 50% of the groups respectively. There were no late cases of AMI or cardiovascular death in ‘new positive’ patients.
Conclusion: Many patients with diagnoses other than AMI will have hsTNT above the reference level. Indiscriminate testing with hsTnT might lead to more patients requiring serial troponin testing and/or invasive further tests, which will have process and resource implications for EDs and health services.
An accompanying editorial2 highlights that:
Elevations are seen in pathological conditions, including structural heart disease, renal impairment and pulmonary embolism, but might also be seen in extreme exertion, such as marathon runners. It is now clear that when using a highly sensitive assay, circulating levels of troponin will be detected in many normal people.
The editorial makes the interesting observation that the duration of rise may help elucidate the cause; ischaemic elevation of troponin falls rapidly, since the rise might be due to the release of small amounts of troponin that exist free within the cytoplasm, in contrast to the more persistent elevation seen with myocardial necrosis. The editorialist provides the following caution:
Overall, our practice for ordering troponin will need to be urgently reviewed. Single troponin values will continue to be of little to no use in defining disease states in the ED. Identifying a chronic versus an acute elevation will only be revealed by serial troponin testing. The time interval between testing is currently contentious.
High sensitivity troponins are referred to in the newly published 2011 Addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the Management of Acute Coronary Syndromes (full text link below)3:
RECOMMENDED PROTOCOL FOR TROPONIN TESTING USING HIGH SENSITIVITY ASSAYS IN “RULING-OUT” ACS
All patients with a suspected ACS should undergo troponin testing on arrival at ED to ‘rule in’ ACS within the differential diagnosis
For a patient with a positive troponin result or a change in troponin levels over time, neither ACS nor other significant pathology (e.g. pulmonary embolus, aortic dissection, and sepsis) can be excluded. These patients are at higher risk of subsequent events. A positive result should be considered within the entire clinical context (history, examination, ECG findings and other investigations). Further investigations directed at all plausible clinical diagnoses should be considered and, if ACS is thought to be the likely cause, these patients may require cardiology assessment.
All patients with a negative result should undergo repeat testing 3–4 hours later.
The testing interval to ‘rule out’ MI may be reduced to 3 hours, provided that one sample is taken at least 6 hours after symptom onset:
Patients with a negative result at 3 hours after presentation and at least 6 hours after the onset of pain should be considered for early assessment by non-invasive anatomic or functional testing, as determined by local availability.
For patients presenting more than 6 hours after pain onset, a single high sensitivity troponin assay is sufficient to rule out myocardial infarction in the absence of ongoing chest pain.
High sensitivity troponin assays have an increased sensitivity for the detection of “myonecrosis”, but a reduced specificity for the diagnosis of “MI”. A positive result (≥99th centile for reference population OR where there is a change of ≥50% above an initial baseline level) should be interpreted in the context of the entire clinical presentation and does not necessarily represent an indication for coronary angiography. The management MI secondary to other conditions (e.g. anaemia, thyrotoxicosis, and sepsis) should be primarily directed at those conditions.
The finding of troponin concentrations that remain stable over time suggests that the presence of troponin is due to chronic disease. Acute exacerbations of chronic disease that result in elevated troponin levels can mimic an MI release pattern.
Most people reach for the adenosine once vagotonic manouevres have failed in SVT, but some patients find the side effects – albeit short-lived – pretty unpleasant. For this reason I’ve heard Jerry Hoffman espouse the relative benefits of verapamil in patients without contra-indications. A recent meta-analysis suggests both verapamil and adenosine have about a 90% success rate. The study did not look at recurrence rates of SVT, which one might expect to be higher with the shorter-acting adenosine.
The authors conclude: The choice between the agents should be made on a case by case basis with awareness of the respective adverse effect profiles, and should involve informed discussion with the patient where appropriate.
OBJECTIVE: Verapamil and adenosine are the most common agents used to treat paroxysmal supraventricular tachycardia (PSVT). We performed a systematic review and meta-analysis to determine the relative effectiveness of these drugs and to examine their respective adverse effect profiles. METHODS: We searched MEDLINE, EMBASE, CINAHL, the Cochrane database, and international clinical trial registers for randomized controlled trials comparing adenosine (or adenosine compounds) with verapamil for the treatment of PSVT in stable adult patients. The primary outcome was rate of reversion to sinus rhythm. Secondary outcome was occurrence of pooled adverse events. Odds ratios and 95% confidence intervals (CIs) were calculated using a random effects model (RevMan v5). RESULTS: Eight trials were appropriate and had the available data. The reversion rate for adenosine was 90.8% (95% CI: 87.3-93.4%) compared with 89.9% for verapamil (95% CI: 86.0-92.9%). The pooled odds ratio for successful reversion was 1.27 (95% CI: 0.63-2.57) favouring adenosine. This was not statistically significant. There was a higher rate of minor adverse effects described with adenosine (16.7-76%) compared with verapamil (0-9.9%). The rate of hypotension was lower with adenosine [0.6% (95% CI: 0.1-2.4%)] compared with verapamil [3.7% (95% CI: 1.9-6.9%)]. CONCLUSION: Adenosine and verapamil have similar efficacy in treating PSVT. Adenosine has a higher rate of minor adverse effects, and of overall adverse effects, whereas verapamil has a higher rate of causing hypotension. A decision between the two agents should be made on a case-by-case basis and ideally involve informed discussion with the patient where appropriate.