Acute Cardiac Care, June 2014; 16(2): 63–66 Copyright © 2014 Informa UK, Ltd ISSN 1748-2941 print/ISSN 1748-295X online DOI: 10.3109/17482941.2014.881503
ORIGINAL ARTICLE
A clinical audit of thrombolytic therapy in patients with normotensive pulmonary embolism and intermediate risk Carla Nobre1, Dinis Mesquita2, Boban Thomas2, Teresinha Ponte1, Luis Santos2 & João Tavares2 Medicine Service, Centro Hospitalar Barreiro-Montijo, EPE, Lisbon, Portugal, 2Cardiology Service, Centro Hospitalar Barreiro-Montijo, EPE, Lisbon, Portugal Acute Card Care Downloaded from informahealthcare.com by Nyu Medical Center on 06/09/15 For personal use only.
1Internal
Introduction: There is considerable debate regarding the use of thrombolytic therapy in patients with pulmonary embolism, normal blood pressure and intermediate clinical risk, as defined by right ventricular dysfunction on transthoracic echocardiography or elevated serum markers of cardiac necrosis. Aims and objectives: A clinical audit of normotensive patients diagnosed with acute pulmonary embolism using multidetector computerized tomography pulmonary angiography (MDCTPA) and intermediate risk, was conducted to determine clinical outcomes at 30 days. The specific role played by imaging findings and clinical severity, on the decision to thrombolyse, was assessed. Methods: The two cohorts who did (n ⴝ 15) and did not receive thrombolysis (n ⴝ 20) were compared for age, heart rate, blood pressure and oxyhemoglobin saturation at presentation, and the simplified PESI score was calculated in each patient. MDCTPA findings suggestive of adverse clinical outcome including central PE and an increased RV/LV diameter were determined for each patient. RV dysfunction on echocardiography was compared to clinical scoring, and findings on MDCTPA. Results: The patients who received thrombolytic therapy were younger (48.6 ⴞ 19.11 years versus 64.2 ⴞ 13.83 years) (P ⬍ 0.01) and had a higher heart rate (107.6 ⴞ 17.1/min versus 91.7 ⴞ 17.8/min) (P ⬍ 0.05). More patients with a higher clinical severity, as determined by the simplified PESI score (12/20) and a higher shock index (0.94 ⴞ 0.23), were thrombolysed as compared to the proportion with a lower score (3/15) (P ⬍ 0.05) or index (0.70 ⴞ 0.20) (P ⬍ 0.005). In-hospital mortality and hemorrhagic complications at 30 days were zero in both groups. RV dysfunction by echocardiography was not a strong determinant for choosing thrombolytic therapy while central PE on MDCTPA tilted the decision towards thrombolysis. Conclusion: Our clinical audit revealed a predilection to use thrombolysis in younger patients with clinical severity and imaging findings on MDCTPA being the key drivers.
A perception of a fragile hemodynamic status, as implied by a higher heart rate and shock index, despite a normal BP probably inclined us to thrombolyse. Pulmonary embolism, thrombolytic therapy, normotensive
Keywords:
Introduction Pulmonary embolism (PE) is a potentially fatal disease if not diagnosed and treated promptly. Although there are guidelines, based on evidence derived from clinical trials (1,2), clinical decisions are individualized. Risk stratification of PE is based on clinical or imaging findings. Clinical risk stratification has evolved through the development and subsequent validation of scores such as the PESI score and the simplified PESI score (sPESI) (3). Imaging modalities used to stratify patients include echocardiographic features suggestive of RV dysfunction in the absence of hemodynamic compromise, and findings on multi-detector CT pulmonary angiography (MDCTPA) (4–6). There is currently no clear consensus on the use of thrombolytic therapy in intermediate risk patients, defined as those without shock or hypotension, but with predictors of an adverse event as RV dysfunction by TTE or elevated serum markers. With the recent disclosure of the partial results of the Pulmonary Embolism Thrombolysis (PEITHO) trial (8), there seems to be more evidence suggesting some potential benefit of thrombolytic therapy, in younger patients albeit at the expense of increased bleeding complications. Owing to these uncertainties, we performed a clinical audit of patients admitted to the cardiology service through the emergency room after MDCTPA diagnosed PE to determine outcomes and the primary drivers for the decision to administer thrombolytic therapy. Clinical audits, an important component of clinical governance in the National Health Service, in the UK (8), provide a snapshot of what is actually
Correspondence: Boban Thomas, Centro Hospitalar Barreiro-Montijo, EPE, Av. Movimento das Forças Armadas 2830–094 Barreiro, Lisbon, Portugal. E-mail: [email protected] (Received 21 September 2013; accepted 27 December 2013)
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happening in the trenches of clinical practice. To the best of our knowledge, there exists no clinical audit on the use of thrombolytic therapy in patients with PE who are normotensive, with an intermediate risk.
Acute Card Care Downloaded from informahealthcare.com by Nyu Medical Center on 06/09/15 For personal use only.
Methods A retrospective analysis of 41 patients admitted to the coronary care unit after MDCTPA performed in the emergency room was diagnostic for PE. Each patient was classified as having a central PE (CPE) or non-central PE (NCPE) based on MDCTPA findings. CPE was described as PE that was detected in the main pulmonary artery (MPA) or its principal branches. NCPE was either lobar or segmental PE (Figure 1). All CT scans were read by the radiologist on-call, but they were all reclassified for this study and read by one of the authors who has extensive experience in MDCTPA and cardiac magnetic resonance angiography of the pulmonary vasculature. Five physicians treated all these patients and only one had training in MDCTPA interpretation. All physicians had extensive experience in TTE and transesophageal echocardiography (TEE). The decision to administer thrombolytic therapy was left to the discretion of the physician who admitted the patient. The agents used were either alteplase in the recommended dose of 100 mg over two hours intravenously, or tenecteplase with dosage determined by weight as used for acute myocardial infarction. Normotension was described for the purposes of this study as a systolic pressure greater than 90 mmHg without any inotropic support. Among the 41 patients, 6 patients were hypotensive and 4 received thrombolysis. They are excluded from the audit leaving 35 patients in the final analysis with the clinical characteristics of the patients described in Table I. The simplified PESI (sPESI) score, which includes the variables of age, neoplasia, chronic cardiopulmonary disease, heart rate, systolic blood pressure (BP) and oxyhemoglobin saturation levels, was calculated for each patient retrospectively and, therefore, was not used in deciding to administer thrombolytic therapy. The shock index, which is the heart rate divided by the systolic BP, was also calculated retrospectively. As the sPESI score and the shock index are clinical markers of elevated risk, we used these to determine the
Figure 1. A patient with a dilated RV with low-risk clinical score.
quality of clinical triaging without formal calculation of these indices in the decision to use thrombolysis. All continuous variables were compared using the students’ t-test and for comparing non-categorical data including proportions, the Fisher exact test was used instead of the Chi-squared test as some of the cells had fewer than five subjects. A P ⬍ 0.05 was considered significant. The two MDCTPA findings with prognostic importance, namely the RV/LV diameter ratio ⬎ 1.00 and the presence of CPE versus NCPE were compared to the echocardiographic findings suggestive of RV dysfunction (defined as one of the following— RV dilatation, McConnell sign, RV systolic dysfunction as determined by tricuspid annular plane systolic excursion (TAPSE), or interventricular septal paradoxical movement). Each of these prognostic imaging findings were then compared with the simplified PESI (sPESI) score to determine if imaging findings correlated with clinical severity.
Results 15 out of the 35 patients underwent thrombolytic therapy with alteplase the selected agent in 12 patients. At 30 days the mortality was zero in both cohorts with no bleeding complications. Thrombolysis was interrupted in 1 patient due to a cutaneous eruption 60 min after starting the intravenous infusion. 1 patient developed shock and was intubated and ventilated due to uncompensated metabolic acidosis. Thrombolysis was used more frequently in those with a higher sPESI (1–5) (P ⫽ 0.03). Only 3 low-risk patients (sPESI ⫽ 0) received thrombolysis compared to 12 with a higher score. For the whole cohort, thrombolysed patients were younger (48.6 ⫾ 19.11 years) compared to those who were not (64.2 ⫾ 13.83 years) (P ⬍ 0.01). The heart rate of the thrombolysed group was higher (107.6 ⫾ 17.1/min) compared to those who were not (91.7 ⫾ 17.8/min) (P ⬍ 0.05). The systolic, the diastolic BP and the arterial oxygen saturation were similar between both groups. The shock index was significantly different between those who received thrombolysis and those did not (0.94 ⫾ 0.23 versus 0.70 ⫾ 0.20; P ⬍ 0.005). However, in all patients with a higher risk (sPESI 1–5), those thrombolysed (n ⫽ 12) were younger and had a lower BP (for age—70 ⫾ 12 years for those not thrombolysed versus 48 ⫾ 20 years in the thrombolysed group, P ⫽ 0.007; BP for those not thrombolysed 138 ⫾ 20 mmHg versus 117 ⫾ 16 mmHg for those thrombolysed, P ⫽ 0.04). The presence of CPE on MDCTPA, seemed to tilt the decision towards thrombolysis as 93% of those thrombolysed had CPE compared to 60% who did not (P ⬍ 0.05). Elevated troponin levels, was not determinant in the decision to thrombolyse, and neither was RV dysfunction detected by echocardiography. Patients with CPE tended to have a higher sPESI score (P ⫽ 0.06). Echocardiographic parameters of RV dysfunction (any one present) were significantly correlated with both the presence of CPE (P ⬍ 0.01) and RV/LV ⬎ 1.00 on MDCTPA (P ⬍ 0.0001). Acute Cardiac Care
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Table I. Baseline features among the two groups of patients in our cohort.
Acute Card Care Downloaded from informahealthcare.com by Nyu Medical Center on 06/09/15 For personal use only.
Parameter Age (years) Heart rate (bpm) Systolic BP (mmHg) Diastolic BP (mmHg) SaO2 (%) Shock índex Central PE (MDCTPA) RV/LV ⬎ 1.00 (MDCTPA) sPESI 1–5 Echo RV dysfunction Abnormal ECG Symptoms Syncope/presyncope Dyspnea Palpitations Chest pain Risk factors Neoplastic disorder Prolonged immobility Age ⬎ 75 years Recent surgery Pregnancy Hormone therapy Previous DVT/PE Smoking Obesity Thrombophilia
Thrombolysis (n ⫽ 15)
Not thrombolysed (n ⫽ 20)
48.6 ⫾ 19.1 107.6 ⫾ 17.1 127 ⫾ 20 78.5 ⫾ 10.6 90.7 ⫾ 6.7 0.94 ⫾ 0.23 93% 87% 80% 93% 93%
64.2 ⫾ 13.8 91.7 ⫾ 17.8 131.8 ⫾ 22.5 77.5 ⫾ 10.4 91.1 ⫾ 8.2 0.70 ⫾ 0.20 60% 55% 40% 80% 65%
6 8 1 0
6 13 0 5
1 3 2 2 0 6 1 3 4 3
1 3 5 1 0 2 2 2 1 1
Significance (P-value) ⬍ 0.01 ⬍ 0.05 NS NS NS ⬍ 0.005 ⬍ 0.05 P ⫽ 0.06 ⬍ 0.05 NS ⬍ 0.05
NS, not significant.
Discussion Clinical audits performed in patients with PE have addressed mainly diagnostic efficiency and resource utilization (9–10). Once PE is diagnosed, risk stratification is sometimes hindered by varying criteria as in the case of echocardiography for evaluating RV dysfunction. Although guidelines exist, it is well established that experienced clinicians may use a heuristic approach to diagnosis and treatment especially in situations where, despite guidelines, nebulous areas exist (1–2). An example is the use of thrombolytic therapy in normotensive patients, which carries an almost equivalent risk– benefit ratio, unlike those with hypotension, where the benefits clearly outweigh the risks of thrombolytic therapy and are clearly endorsed in current guidelines. However, normotensive patients with PE may deteriorate rapidly and echocardiographic parameters may be useful to predict deterioration based on the assessment of RV dysfunction. As the sPESI score was not used for clinical decision making, and was calculated retrospectively, this clinical audit also attempts to examine the process of decision making by the clinicians. As outcomes were the same with or without thrombolysis, the clinical severity in the two groups was ascertained. The sPESI score is very good at identifying lowrisk patients (score ⫽ 0) from those with higher scores (1–5), although graded severity is not reflected by increasing scores. The fact that a larger proportion of thrombolysed patients had a higher sPESI score indicates that although it was not calculated prospectively, the clinical decision made, probably © 2014 Informa UK, Ltd.
heuristically, was correct in our cohort. Implicitly, a majority of patients with a low sPESI score, with lower risk, was not thrombolysed. The patients in the thrombolysed cohort were younger. This could imply that physicians were less concerned about hemorrhagic complications in this cohort as they were younger. Our decision to do this is confirmed by the findings from the PEITHO trial which suggested the largest benefit with fewer bleeding complications for patients less than 75 years of age. The heart rate was also higher in those who were thrombolysed, when comparing the two groups as a whole, irrespective of PESI score. This could imply that this group was hemodynamically more fragile. This premise of ours is confirmed by the significantly different shock index values between the two groups—a higher value indicates a greater hemodynamic instability. The higher shock index in the thrombolysed group confirms that those patients were probably more unstable, as the index is a composite picture of the hemodynamic status of the patient. A more aggressive therapeutic approach, with thrombolysis, catheter fragmentation or surgical embolectomy, is recommended for patients with a shock index ⬎ 1.00 (11). Interestingly, the phase that precedes septic shock, designated as the systemic inflammatory response syndrome (SIRS) is characterized by tachycardia without hypotension. A similar possibility might exist with PE prior to the development of overt cardiogenic shock. We also decided to evaluate the role that the perceived severity of the PE as communicated by the MDCTPA images
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may have had in the use of thrombolysis. There was a clear correlation between the two imaging findings on MDCTPA, indicative of severity, namely the presence of CPE and RV/ LV ⬎ 1.00, and the use of thrombolysis. The influence on the presence of central PE was much stronger than the presence of severe RV dilatation as indicated by RV/LV ⬎ 1.00 on MDCTPA. Interestingly, in our cohort, RV dysfunction detected by TTE did not seem to be a determinant in the use of thrombolysis, although all of the treating physicians had extensive experience in TTE and only 1 had experience in both modalities. RV dysfunction detected on echo, correlated significantly with the presence of CPE on MDCTPA. It is unclear if the sPESI score is better than imaging findings in the stratification of risk in normotensive patients. In a comparison, neither approach (sPESI versus imaging/ biomarker risk stratification) was clearly superior to the other, but the sPESI was better at identifying the lower risk patients while the imaging findings maintained its prognostic ability at the subgroup classified as high risk by sPESI (12). Despite these nuances, clinical and hemodynamic status should take preference over an algorithmic approach based on imaging indices and markers as exemplified by the patient with dilated cardiomyopathy, who had a dilated LV and a saddle embolus with minimal RV dilatation but entered into cardiogenic shock resulting in severe metabolic acidosis (Figure 2). Serum markers and imaging indices may not convey the whole clinical picture. A cursory view of the use of thrombolytic therapy in our cohort reveals that 43% of normotensive patients received thrombolysis, which may seem high comparing that the usual reported rates vary from 10–15%. However, if we were to strictly use the criteria suggested in the ESC guidelines, namely the presence of either serum markers of myocardial injury or RV dysfunction by echo, then 94% would be eligible. Our study has certain limitations. This was a retrospective analysis and all patients did not have levels of D-dimer, BNP, TnI estimated at the same timeframe in all patients, thereby precluding a comparison, between the two cohorts. The RV/LV ratio was calculated from the axial images and
Figure 2. The patient had cardiogenic shock when she had the PE as she also had dilated cardiomyopathy with poor LV function as evident from the CT images. Owing to the dilated LV, the patient had a RV/ LV ratio ⬍ 1.00.
some studies have shown that reconstructed views of the four-chamber RV/LV images are probably better.
Conclusions In our center, without using pre-specified clinical or imaging criteria, intermediate-risk patients with PE who received thrombolysis were younger and had a fragile hemodynamic status, as reflected in a higher shock index despite being normotensive with the presence of central PE on MDCTPA, tilting the decision towards thrombolysis. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Guyatt G. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141:7S–47S. 2. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, et al. Guidelines on the Diagnosis and management of Acute Pulmonary Embolism (ESC). Eur Heart J. 2008;29: 2276–315. 3. Jiménez D, Aujesky D, Moores L, Gómez V, Lobo JL, Uresandi F, et al. Simplification of the Pulmonary Embolism Severity Index for prognostication in Patients with Acute Symptomatic Pulmonary Embolism. Arch Intern Med. 2010;170:1383–9. 4. Vedovati MC, Becattini C, Agnelli G, Kamphuisen PW, Masotti L, Pruszczyk P. et al. Multidetector CT Scan for Acute Pulmonary Embolism – Embolic Burden and Clinical Outcome. Chest 2012;142:1417–24. 5. Kang DK, Thilo C, Schoepf UJ, Barraza JM Jr, Nance JW Jr, Bastarrika G. et al. CT Signs of Right ventricular Dysfunction. Prognostic role in acute Pulmonary Embolism. J Am Coll Cardiol Img. 2011;4:841–9. 6. Becattini C, Agnelli G, Vedovati MC, Pruszczyk P, Casazza F, Grifoni S, et al. Multidetector Computed Tomography for Acute Pulmonary Embolism: Diagnosis and Risk Stratification in a Single Test. Eur Heart J. 2011;32:1657–63. 7. Konstantinides SV, Meyer G, Lang I, Verschuren F, Meneveau N, Charbonnier B, et al. Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury: rationale and design of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Am Heart J. 2012;163:33–8. 8. Benjamin A. Audit: How to do it in practice. Br Med J. 2008;336:1241–5. 9. Saro G, Campo JF, Hernández MJ, Anta M, Olmos JM, GonzálezMacías J. Diagnostic Approach to Patients with Suspected Pulmonary Embolism: a report from the real world. Postgrad Med J. 1999;75:285–9. 10. Man EMW, Luk SY, Cheng CS. Audit of computed tomographic angiograms for pulmonary embolism in a regional hospital in Hong Kong. J Hong Kong Col Radiol. 2010;13:68–72. 11. Kucher N, Luder CM, Dornhofer T. Windecker S, Meieir B, Hess OM. Novel management strategy for patients with suspected pulmonary embolism. Eur Heart J. 2003;24:366–76. 12. Lankeit M, Gómez V, Wagner C, Aujesky D, Recio M, Briongos S. et al. A Strategy Combining Imaging and Laboratory Biomarkers in comparisation with a Simplified Clinical score Risk Stratification of Patients with Acute Pulmonary Embolism. Chest 2012;141:916–22. Acute Cardiac Care
ORIGINAL ARTICLE
A clinical audit of thrombolytic therapy in patients with normotensive pulmonary embolism and intermediate risk Carla Nobre1, Dinis Mesquita2, Boban Thomas2, Teresinha Ponte1, Luis Santos2 & João Tavares2 Medicine Service, Centro Hospitalar Barreiro-Montijo, EPE, Lisbon, Portugal, 2Cardiology Service, Centro Hospitalar Barreiro-Montijo, EPE, Lisbon, Portugal Acute Card Care Downloaded from informahealthcare.com by Nyu Medical Center on 06/09/15 For personal use only.
1Internal
Introduction: There is considerable debate regarding the use of thrombolytic therapy in patients with pulmonary embolism, normal blood pressure and intermediate clinical risk, as defined by right ventricular dysfunction on transthoracic echocardiography or elevated serum markers of cardiac necrosis. Aims and objectives: A clinical audit of normotensive patients diagnosed with acute pulmonary embolism using multidetector computerized tomography pulmonary angiography (MDCTPA) and intermediate risk, was conducted to determine clinical outcomes at 30 days. The specific role played by imaging findings and clinical severity, on the decision to thrombolyse, was assessed. Methods: The two cohorts who did (n ⴝ 15) and did not receive thrombolysis (n ⴝ 20) were compared for age, heart rate, blood pressure and oxyhemoglobin saturation at presentation, and the simplified PESI score was calculated in each patient. MDCTPA findings suggestive of adverse clinical outcome including central PE and an increased RV/LV diameter were determined for each patient. RV dysfunction on echocardiography was compared to clinical scoring, and findings on MDCTPA. Results: The patients who received thrombolytic therapy were younger (48.6 ⴞ 19.11 years versus 64.2 ⴞ 13.83 years) (P ⬍ 0.01) and had a higher heart rate (107.6 ⴞ 17.1/min versus 91.7 ⴞ 17.8/min) (P ⬍ 0.05). More patients with a higher clinical severity, as determined by the simplified PESI score (12/20) and a higher shock index (0.94 ⴞ 0.23), were thrombolysed as compared to the proportion with a lower score (3/15) (P ⬍ 0.05) or index (0.70 ⴞ 0.20) (P ⬍ 0.005). In-hospital mortality and hemorrhagic complications at 30 days were zero in both groups. RV dysfunction by echocardiography was not a strong determinant for choosing thrombolytic therapy while central PE on MDCTPA tilted the decision towards thrombolysis. Conclusion: Our clinical audit revealed a predilection to use thrombolysis in younger patients with clinical severity and imaging findings on MDCTPA being the key drivers.
A perception of a fragile hemodynamic status, as implied by a higher heart rate and shock index, despite a normal BP probably inclined us to thrombolyse. Pulmonary embolism, thrombolytic therapy, normotensive
Keywords:
Introduction Pulmonary embolism (PE) is a potentially fatal disease if not diagnosed and treated promptly. Although there are guidelines, based on evidence derived from clinical trials (1,2), clinical decisions are individualized. Risk stratification of PE is based on clinical or imaging findings. Clinical risk stratification has evolved through the development and subsequent validation of scores such as the PESI score and the simplified PESI score (sPESI) (3). Imaging modalities used to stratify patients include echocardiographic features suggestive of RV dysfunction in the absence of hemodynamic compromise, and findings on multi-detector CT pulmonary angiography (MDCTPA) (4–6). There is currently no clear consensus on the use of thrombolytic therapy in intermediate risk patients, defined as those without shock or hypotension, but with predictors of an adverse event as RV dysfunction by TTE or elevated serum markers. With the recent disclosure of the partial results of the Pulmonary Embolism Thrombolysis (PEITHO) trial (8), there seems to be more evidence suggesting some potential benefit of thrombolytic therapy, in younger patients albeit at the expense of increased bleeding complications. Owing to these uncertainties, we performed a clinical audit of patients admitted to the cardiology service through the emergency room after MDCTPA diagnosed PE to determine outcomes and the primary drivers for the decision to administer thrombolytic therapy. Clinical audits, an important component of clinical governance in the National Health Service, in the UK (8), provide a snapshot of what is actually
Correspondence: Boban Thomas, Centro Hospitalar Barreiro-Montijo, EPE, Av. Movimento das Forças Armadas 2830–094 Barreiro, Lisbon, Portugal. E-mail: [email protected] (Received 21 September 2013; accepted 27 December 2013)
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happening in the trenches of clinical practice. To the best of our knowledge, there exists no clinical audit on the use of thrombolytic therapy in patients with PE who are normotensive, with an intermediate risk.
Acute Card Care Downloaded from informahealthcare.com by Nyu Medical Center on 06/09/15 For personal use only.
Methods A retrospective analysis of 41 patients admitted to the coronary care unit after MDCTPA performed in the emergency room was diagnostic for PE. Each patient was classified as having a central PE (CPE) or non-central PE (NCPE) based on MDCTPA findings. CPE was described as PE that was detected in the main pulmonary artery (MPA) or its principal branches. NCPE was either lobar or segmental PE (Figure 1). All CT scans were read by the radiologist on-call, but they were all reclassified for this study and read by one of the authors who has extensive experience in MDCTPA and cardiac magnetic resonance angiography of the pulmonary vasculature. Five physicians treated all these patients and only one had training in MDCTPA interpretation. All physicians had extensive experience in TTE and transesophageal echocardiography (TEE). The decision to administer thrombolytic therapy was left to the discretion of the physician who admitted the patient. The agents used were either alteplase in the recommended dose of 100 mg over two hours intravenously, or tenecteplase with dosage determined by weight as used for acute myocardial infarction. Normotension was described for the purposes of this study as a systolic pressure greater than 90 mmHg without any inotropic support. Among the 41 patients, 6 patients were hypotensive and 4 received thrombolysis. They are excluded from the audit leaving 35 patients in the final analysis with the clinical characteristics of the patients described in Table I. The simplified PESI (sPESI) score, which includes the variables of age, neoplasia, chronic cardiopulmonary disease, heart rate, systolic blood pressure (BP) and oxyhemoglobin saturation levels, was calculated for each patient retrospectively and, therefore, was not used in deciding to administer thrombolytic therapy. The shock index, which is the heart rate divided by the systolic BP, was also calculated retrospectively. As the sPESI score and the shock index are clinical markers of elevated risk, we used these to determine the
Figure 1. A patient with a dilated RV with low-risk clinical score.
quality of clinical triaging without formal calculation of these indices in the decision to use thrombolysis. All continuous variables were compared using the students’ t-test and for comparing non-categorical data including proportions, the Fisher exact test was used instead of the Chi-squared test as some of the cells had fewer than five subjects. A P ⬍ 0.05 was considered significant. The two MDCTPA findings with prognostic importance, namely the RV/LV diameter ratio ⬎ 1.00 and the presence of CPE versus NCPE were compared to the echocardiographic findings suggestive of RV dysfunction (defined as one of the following— RV dilatation, McConnell sign, RV systolic dysfunction as determined by tricuspid annular plane systolic excursion (TAPSE), or interventricular septal paradoxical movement). Each of these prognostic imaging findings were then compared with the simplified PESI (sPESI) score to determine if imaging findings correlated with clinical severity.
Results 15 out of the 35 patients underwent thrombolytic therapy with alteplase the selected agent in 12 patients. At 30 days the mortality was zero in both cohorts with no bleeding complications. Thrombolysis was interrupted in 1 patient due to a cutaneous eruption 60 min after starting the intravenous infusion. 1 patient developed shock and was intubated and ventilated due to uncompensated metabolic acidosis. Thrombolysis was used more frequently in those with a higher sPESI (1–5) (P ⫽ 0.03). Only 3 low-risk patients (sPESI ⫽ 0) received thrombolysis compared to 12 with a higher score. For the whole cohort, thrombolysed patients were younger (48.6 ⫾ 19.11 years) compared to those who were not (64.2 ⫾ 13.83 years) (P ⬍ 0.01). The heart rate of the thrombolysed group was higher (107.6 ⫾ 17.1/min) compared to those who were not (91.7 ⫾ 17.8/min) (P ⬍ 0.05). The systolic, the diastolic BP and the arterial oxygen saturation were similar between both groups. The shock index was significantly different between those who received thrombolysis and those did not (0.94 ⫾ 0.23 versus 0.70 ⫾ 0.20; P ⬍ 0.005). However, in all patients with a higher risk (sPESI 1–5), those thrombolysed (n ⫽ 12) were younger and had a lower BP (for age—70 ⫾ 12 years for those not thrombolysed versus 48 ⫾ 20 years in the thrombolysed group, P ⫽ 0.007; BP for those not thrombolysed 138 ⫾ 20 mmHg versus 117 ⫾ 16 mmHg for those thrombolysed, P ⫽ 0.04). The presence of CPE on MDCTPA, seemed to tilt the decision towards thrombolysis as 93% of those thrombolysed had CPE compared to 60% who did not (P ⬍ 0.05). Elevated troponin levels, was not determinant in the decision to thrombolyse, and neither was RV dysfunction detected by echocardiography. Patients with CPE tended to have a higher sPESI score (P ⫽ 0.06). Echocardiographic parameters of RV dysfunction (any one present) were significantly correlated with both the presence of CPE (P ⬍ 0.01) and RV/LV ⬎ 1.00 on MDCTPA (P ⬍ 0.0001). Acute Cardiac Care
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65
Table I. Baseline features among the two groups of patients in our cohort.
Acute Card Care Downloaded from informahealthcare.com by Nyu Medical Center on 06/09/15 For personal use only.
Parameter Age (years) Heart rate (bpm) Systolic BP (mmHg) Diastolic BP (mmHg) SaO2 (%) Shock índex Central PE (MDCTPA) RV/LV ⬎ 1.00 (MDCTPA) sPESI 1–5 Echo RV dysfunction Abnormal ECG Symptoms Syncope/presyncope Dyspnea Palpitations Chest pain Risk factors Neoplastic disorder Prolonged immobility Age ⬎ 75 years Recent surgery Pregnancy Hormone therapy Previous DVT/PE Smoking Obesity Thrombophilia
Thrombolysis (n ⫽ 15)
Not thrombolysed (n ⫽ 20)
48.6 ⫾ 19.1 107.6 ⫾ 17.1 127 ⫾ 20 78.5 ⫾ 10.6 90.7 ⫾ 6.7 0.94 ⫾ 0.23 93% 87% 80% 93% 93%
64.2 ⫾ 13.8 91.7 ⫾ 17.8 131.8 ⫾ 22.5 77.5 ⫾ 10.4 91.1 ⫾ 8.2 0.70 ⫾ 0.20 60% 55% 40% 80% 65%
6 8 1 0
6 13 0 5
1 3 2 2 0 6 1 3 4 3
1 3 5 1 0 2 2 2 1 1
Significance (P-value) ⬍ 0.01 ⬍ 0.05 NS NS NS ⬍ 0.005 ⬍ 0.05 P ⫽ 0.06 ⬍ 0.05 NS ⬍ 0.05
NS, not significant.
Discussion Clinical audits performed in patients with PE have addressed mainly diagnostic efficiency and resource utilization (9–10). Once PE is diagnosed, risk stratification is sometimes hindered by varying criteria as in the case of echocardiography for evaluating RV dysfunction. Although guidelines exist, it is well established that experienced clinicians may use a heuristic approach to diagnosis and treatment especially in situations where, despite guidelines, nebulous areas exist (1–2). An example is the use of thrombolytic therapy in normotensive patients, which carries an almost equivalent risk– benefit ratio, unlike those with hypotension, where the benefits clearly outweigh the risks of thrombolytic therapy and are clearly endorsed in current guidelines. However, normotensive patients with PE may deteriorate rapidly and echocardiographic parameters may be useful to predict deterioration based on the assessment of RV dysfunction. As the sPESI score was not used for clinical decision making, and was calculated retrospectively, this clinical audit also attempts to examine the process of decision making by the clinicians. As outcomes were the same with or without thrombolysis, the clinical severity in the two groups was ascertained. The sPESI score is very good at identifying lowrisk patients (score ⫽ 0) from those with higher scores (1–5), although graded severity is not reflected by increasing scores. The fact that a larger proportion of thrombolysed patients had a higher sPESI score indicates that although it was not calculated prospectively, the clinical decision made, probably © 2014 Informa UK, Ltd.
heuristically, was correct in our cohort. Implicitly, a majority of patients with a low sPESI score, with lower risk, was not thrombolysed. The patients in the thrombolysed cohort were younger. This could imply that physicians were less concerned about hemorrhagic complications in this cohort as they were younger. Our decision to do this is confirmed by the findings from the PEITHO trial which suggested the largest benefit with fewer bleeding complications for patients less than 75 years of age. The heart rate was also higher in those who were thrombolysed, when comparing the two groups as a whole, irrespective of PESI score. This could imply that this group was hemodynamically more fragile. This premise of ours is confirmed by the significantly different shock index values between the two groups—a higher value indicates a greater hemodynamic instability. The higher shock index in the thrombolysed group confirms that those patients were probably more unstable, as the index is a composite picture of the hemodynamic status of the patient. A more aggressive therapeutic approach, with thrombolysis, catheter fragmentation or surgical embolectomy, is recommended for patients with a shock index ⬎ 1.00 (11). Interestingly, the phase that precedes septic shock, designated as the systemic inflammatory response syndrome (SIRS) is characterized by tachycardia without hypotension. A similar possibility might exist with PE prior to the development of overt cardiogenic shock. We also decided to evaluate the role that the perceived severity of the PE as communicated by the MDCTPA images
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may have had in the use of thrombolysis. There was a clear correlation between the two imaging findings on MDCTPA, indicative of severity, namely the presence of CPE and RV/ LV ⬎ 1.00, and the use of thrombolysis. The influence on the presence of central PE was much stronger than the presence of severe RV dilatation as indicated by RV/LV ⬎ 1.00 on MDCTPA. Interestingly, in our cohort, RV dysfunction detected by TTE did not seem to be a determinant in the use of thrombolysis, although all of the treating physicians had extensive experience in TTE and only 1 had experience in both modalities. RV dysfunction detected on echo, correlated significantly with the presence of CPE on MDCTPA. It is unclear if the sPESI score is better than imaging findings in the stratification of risk in normotensive patients. In a comparison, neither approach (sPESI versus imaging/ biomarker risk stratification) was clearly superior to the other, but the sPESI was better at identifying the lower risk patients while the imaging findings maintained its prognostic ability at the subgroup classified as high risk by sPESI (12). Despite these nuances, clinical and hemodynamic status should take preference over an algorithmic approach based on imaging indices and markers as exemplified by the patient with dilated cardiomyopathy, who had a dilated LV and a saddle embolus with minimal RV dilatation but entered into cardiogenic shock resulting in severe metabolic acidosis (Figure 2). Serum markers and imaging indices may not convey the whole clinical picture. A cursory view of the use of thrombolytic therapy in our cohort reveals that 43% of normotensive patients received thrombolysis, which may seem high comparing that the usual reported rates vary from 10–15%. However, if we were to strictly use the criteria suggested in the ESC guidelines, namely the presence of either serum markers of myocardial injury or RV dysfunction by echo, then 94% would be eligible. Our study has certain limitations. This was a retrospective analysis and all patients did not have levels of D-dimer, BNP, TnI estimated at the same timeframe in all patients, thereby precluding a comparison, between the two cohorts. The RV/LV ratio was calculated from the axial images and
Figure 2. The patient had cardiogenic shock when she had the PE as she also had dilated cardiomyopathy with poor LV function as evident from the CT images. Owing to the dilated LV, the patient had a RV/ LV ratio ⬍ 1.00.
some studies have shown that reconstructed views of the four-chamber RV/LV images are probably better.
Conclusions In our center, without using pre-specified clinical or imaging criteria, intermediate-risk patients with PE who received thrombolysis were younger and had a fragile hemodynamic status, as reflected in a higher shock index despite being normotensive with the presence of central PE on MDCTPA, tilting the decision towards thrombolysis. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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