Leszek Bryniarski

Electrocardiography and prognosis of patients with acute pulmonary embolism

BACKGROUND To assess the influence of electrocardiographic (ECG) pattern on prognosis and complications of patients hospitalized with acute pulmonary embolism (APE). METHODS We performed a retrospective analysis of 292 patients who had confirmed APE. There were 183 females and 109 males, the age range was 17 to 89 years, and the mean age was 65.4 ± 15.5 years. RESULTS In our study group, there were 33 deaths (mortality rate, 11.3%), and 73 (25%) patients developed complications during hospitalization. Based on European Society of Cardiology risk stratification, we classified 75 (25.7%) patients as high risk, 163 (55.8%) patients as intermediate risk, and 54 (18.5%) patients as low risk. A comparison between patients with complicated APE and those with no complications during hospitalization indicated that the following ECG parameters were more common in patients who had complications: atrial fibrillation, S1Q3T3 sign, negative T waves in leads V2-V4, ST segment depression in leads V4-V6, ST segment elevation in leads III, V1 and aVR, qR in lead V1, complete right bundle branch block (RBBB), greater number of leads with negative T waves, and greater sum of the amplitude of negative T waves. In multivariate analysis, the sum of negative T waves (OR 0.88; p = 0.22), number of leads with negative T waves (OR 1.46; p = 0.001), RBBB (OR 2.87; p = 0.02) and ST segment elevation in leads V1 (OR 3.99; p = 0.00017) and aVR (OR 2.49; p = 0.011) were independent predictors of complications during hospitalization. In turn, in multivariate analysis, only the sum of negative T waves (OR 0.81; p = 0.0098), number of leads with negative T waves [OR 1.68; p = 0.00068] and ST segment elevation in lead V1 (OR 4.47; p = 0.0003) were independent predictors of death during hospitalization. CONCLUSIONS In our population of APE patients, the sum of negative T waves, the number of leads with negative T waves and the ST segment elevation in lead V1 were independent predictors of death during hospitalization. In turn, the sum of negative T waves, the number of leads with negative T waves, and RBBB and ST segment elevation in leads V1 and aVR were independent predictors of complications during hospitalization. We conclude that ECG analysis may be a useful noninvasive method for risk stratification of patients with APE.

Efficacy and Safety of Adding Fenofibrate 160 mg in High-Risk Patients With Mixed Hyperlipidemia Not Controlled by Pravastatin 40 mg monotherapy

Patients with mixed hyperlipidemia and at high risk of coronary heart disease may not achieve recommended low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol goals on statin monotherapy. This study was designed to evaluate the efficacy and safety of a fenofibrate 160 mg/pravastatin 40 mg fixed-dose combination therapy in high-risk patients not at their LDL cholesterol goal on pravastatin 40 mg. In this 12-week, multicenter, randomized, double-blind, double-dummy, parallel-group study, after a run-in on pravastatin 40 mg, 248 patients were randomly assigned to fenofibrate/pravastatin combination therapy or to pravastatin monotherapy. Combination therapy produced significantly greater complementary decreases in non-HDL cholesterol (primary end point) than pravastatin monotherapy (-14.1% vs -6.1%, p = 0.002). Significantly greater improvements were also observed in LDL cholesterol (-11.7% vs -5.9%, p = 0.019), HDL cholesterol (+6.5% vs +2.3%, p = 0.009), triglycerides (-22.6% vs -2.0%, p = 0.006), and apolipoprotein B (-12.6% vs -3.8%, p <0.0001). Significantly more patients receiving the fenofibrate/pravastatin combination therapy than pravastatin alone achieved the LDL cholesterol (<100 mg/dl) and non-HDL cholesterol (<130 mg/dl) goals (p <0.01). Combination therapy was generally well tolerated with incidences of clinical and laboratory adverse experiences similar between the 2 groups. In conclusion, the fenofibrate 160 mg/pravastatin 40 mg fixed-dose combination therapy significantly improved the global atherogenic lipid profile in high-risk patients with mixed hyperlipidemia not controlled by pravastatin 40 mg monotherapy.

Facilitated percutaneous coronary intervention in patients with acute myocardial infarction transferred from remote hospitals

P percutaneous coronary intervention (PCI) is the preferred therapy for myocardial infarction (MI) in centers that have access to immediate invasive treatment because it confers higher patency rates, lower mortality, and lower intracranial hemorrhage rates than fibrinolysis alone.1–3 Current guidelines suggest that primary PCI could be offered as an alternative to thrombolytic therapy if performed by experienced operators within 90 30 minutes after admission.4 Recent studies have suggested that PCI for MI is superior to thrombolysis even if treatment is delayed by 120 minutes by transferring the patient to an interventional center.5,6 However, delay in restoring myocardial blood flow is known to adversely impact long-term outcome.7 If safe and feasible, restoration of myocardial blood flow by thrombolytic therapy during transfer would make longer transfer times to primary PCI acceptable without compromising myocardial salvage. In the present study we tested a combined therapy of a reduced dose of fibrinolytic drug and glycoprotein IIb/IIIa inhibitor during transfer of patients with acute MI from remote community hospitals to a routine emergency angiographic center and possible invasive treatment of MI. • • • The study was approved by the institutional review board and patients gave informed consent. Patients were enrolled at the community hospitals if: (1) they presented with an acute MI (onset of chest pain 12 hours earlier and ST elevation 1 mm in 2 contiguous electrocardiographic leads) to the emergency department of a hospital without a catheterization laboratory; (2) they had no contraindications to thrombolytic therapy and were 75 years of age; and (3) if anticipated transfer time to an interventional center was 90 minutes. Two hundred eligible patients received an IV bolus of 60 U/kg heparin (maximum 5,000), 15 mg alteplase, and 0.25 mg/kg abciximab at the remote center and were transferred, in the presence of a physician, to a single tertiary referral center for diagnostic angiography and possible PCI. Demographic data and time intervals between different stages of patient care are listed in Table 1. Infusion of alteplase (35 mg/60 min) was continued during transfer. Infusion of abciximab From the Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. This study was financed entirely by the National Health Care Agency of Poland, Krakow Regional Division, as a part of the program to improve early detection and treatment of myocardial infarction in that region of Poland. Dr. Dudek’s address is: 2nd Department of Cardiology, Kopernika Str.17, 31-501 Krakow, Poland. E-mail: mcdudek@cyf-kr.edu.pl. Manuscript received July 8, 2002; revised manuscript received and accepted August 30, 2002. TABLE 1 Baseline Demographics, Risk Factors, Clinical Characteristics, and Time Intervals Between Different Stages of Patient Care

Electrocardiographic abnormalities in patients with acute pulmonary embolism complicated by cardiogenic shock

BACKGROUND Cardiogenic shock (CS) is a predictor of poor prognosis in patients with acute pulmonary embolism (APE). OBJECTIVES The aim of this study was to compare electrocardiography (ECG) parameters in patients with APE presenting with or without CS. METHODS A 12-lead ECG was recorded on admission at a paper speed of 25 mm/s and 10 mm/mV amplification. All ECGs were examined by a single cardiologist who was blinded to all other clinical data. All ECG measurements were made manually. RESULTS Electrocardiographic data from 500 patients with APE were analyzed, including 92 patients with CS. The following ECG parameters were associated with CS: S1Q3T3 sign, (odds ratio [OR]: 2.85, P<.001), qR or QR morphology of QRS in lead V1, (OR: 3.63, P<.001), right bundle branch block (RBBB) (OR: 2.46, P=.004), QRS fragmentation in lead V1 (OR: 2.94, P=.002), low QRS voltage (OR: 3.21, P<.001), negative T waves in leads V2 to V4 (OR: 1.81, P=.011), ST-segment depression in leads V4 to V6 (OR: 3.28, P<.001), ST-segment elevation in lead III (OR: 4.2, P<.001), ST-segment elevation in lead V1 (OR: 6.78, P<.01), and ST-segment elevation in lead aVR (OR: 4.35, P<.01). The multivariate analysis showed that low QRS voltage, RBBB, and ST-segment elevation in lead V1 remained statistically significant predictors of CS. CONCLUSIONS In patients with APE, low QRS voltage, RBBB, and ST-segment elevation in lead V1 were associated with CS.

Relation of atrial fibrillation and right-sided cardiac thrombus to outcomes in patients with acute pulmonary embolism.

Atrial fibrillation (AF) can induce a hypercoagulable state in both the left and right atria. Thrombus in the right side of the heart (RHT) may lead to acute pulmonary embolism (APE). The aim of the study was to determine the prevalence of RHT and AF and to assess their impact on outcomes in patients with APE. The retrospective cohort included 1,006 patients (598 female), with a mean age of 66 ± 15 years. The primary end point was all-cause mortality. The secondary end point was incidence of complications (death, cardiogenic shock, cardiac arrest, vasopressor/inotrope treatment, or ventilatory support). Atrial fibrillation was detected in 231 patients (24%). RHT was observed in 50 patients (5%). The combination of AF and RHT was observed in 16 patients (2%). The overall mortality rate was significantly higher in patients with RHT compared with those without (32% vs 14%, respectively, odds ratio [OR] 3.0, 95% confidence interval [CI] 1.6 to 5.6, p = 0.001). The rate of complications was significantly higher in patients with RHT in comparison to those without (40% vs 22%, respectively, OR 2.4, 95% CI 1.3 to 4.4, p = 0.004). The mortality rate in patients with both AF and RHT was significantly higher in comparison to those with AF but without RHT (50% vs 20%, respectively, OR 3.86, 95% CI 1.3 to 11.2, p = 0.01). In multivariate analysis, RHT (p = 0.03) was an independent predictor of death. In conclusion, AF is a frequent co-morbidity in patients with APE, and the presence of RHT is not uncommon. Among patients with APE, the presence of RHT increases the mortality approximately threefold regardless of the presence of known AF.

Effect of exercise rehabilitation on heart rate variability in hypertensives after myocardial infarction.

Objective The aim of the study was to find out whether the presence of hypertension affects heart rate variability in patients rehabilitated after myocardial infarction. Design Echocardiography, exercise testing and 24 h Holter monitoring were performed before and after 27 days of early postdischarge cardiac rehabilitation. Patients The study population consisted of 64 patients aged 34–65 years (mean ± SD 51.6 ± 6.6) discharged from hospital after a first myocardial infarction who were subdivided into two groups, group A comprising 34 patients with arterial hypertension which had lasted 4.8 ± 2.1 years and group B comprising 30 normotensives. Main outcome We expected exercise rehabilitation to affect heart rate variability, exercise tolerance and myocardial ischemia in patients after myocardial infarction with and without arterial hypertension. Results At baseline no intergroup differences were seen in the duration of exercise, workload and heart rate variability parameters. All parameters increased significantly after cardiac rehabilitation (P < 0.01): SD of all normal RR intervals 123.4 ± 30.0 versus 123.8 ± 30.0 ms; SD of the averages of normal RR intervals in all 5-min segments of the entire recording 115.1 ± 30.5 versus 116.3 ± 28.3 ms; mean of the SD of all normal RR intervals for all 5-min segments of the entire recording 49.0 ± 12.5 versus 48.3 ± 11.8 ms; square root of the mean of the sum of the squares of differences between adjacent RR intervals 29.7 ± 9.1 versus 28.0 ± 8.5 ms; percentage of differences between adjacent RR intervals > 50 ms 7.9 ± 6.0 versus 7.1 ± 6.1% (group A versus group B, respectively, NS). The duration of exercise and the workload were significantly increased (the rise was higher in normotensives). No differences were seen in the frequency and severity of silent myocardial ischemia. Conclusions Early stationary exercise rehabilitation after myocardial infarction improves heart rate variability parameters and exercise tolerance both in hypertensives and in normotensives.

T-wave inversion in patients with acute pulmonary embolism: Prognostic value

INTRODUCTION T-wave inversion (TWI) is a common ECG finding in patients with acute pulmonary embolism (APE). OBJECTIVES To determine the prevalence of TWI in patients with APE and to describe their relationship to outcomes. METHODS Retrospective study of 437 patients with APE. TWI patterns were described in two distributions: inferior (II, III, aVF) and precordial (V1-V6). RESULTS TWI was observed in 258 (59%) patients. The mortality rate was significantly higher in the group with TWI in the inferior AND precordial leads compared to the group without TWI (OR: 2.74; p = 0.024) and the group with TWI in the inferior OR precordial leads (OR: 2.43; p = 0.035). As compared those with TWI in <5 leads, patients with TWI in ≥5 leads experienced significantly higher rates of death (17.1% vs. 6.6%, OR: 2.92; p = 0.002) and complications. CONCLUSIONS TWI and the quantitative assessment thereof can be useful to risk stratify patients with APE.

Comparison of the ipsi-lateral versus contra-lateral retrograde approach of percutaneous coronary interventions in chronic total occlusions

Retrograde recanalization of coronary chronic total occlusions (CTO) via contralateral (CL) collateral connections (CCs) is successful in 60–70% of patients in whom conventional antegrade approach fails or is unpromising. This study describes our experience with retrograde CTO‐PCI via ipsi‐lateral (IL) CCs in patients with unfavorable CL CCs.

Safety of a fixed-dose combination of fenofibrate/pravastatin 160 mg/40 mg in patients with mixed hyperlipidaemia: A pooled analysis from a database of clinical trials

AbstractBackground: Fenofibrate can be prescribed concomitantly with an HMG-CoA reductase inhibitor (statin) to improve achievement of lipid goals in patients with atherogenic mixed hyperlipidaemia. However, some safety concerns, particularly an increased risk of myopathy, have been reported when these drugs are taken together. Objective: The aim of this analysis was to assess the general safety and tolerability of a fenofibrate/pravastatin (FF/PRA) 160 mg/40 mg fixed-dose combination (FDC) capsule based on a pooled database of phase III clinical trials in patients with mixed hyperlipidaemia. Methods: Safety data were pooled from five phase III studies (four double-blind with an uncontrolled extension and one open) of ≥12 to 64 weeks’ duration. Adverse event (AE) profiles of FF/PRA 160 mg/40 mg (n = 645 in the double-blind cohort) were evaluated relative to comparators (statins, n = 519 or fenofibrate, n = 122). Absolute incidence rates were calculated in both the double-blind cohort and the all-studies cohort (FF/PRA 160 mg/40 mg, n = 1566) for all AEs, drug-related AEs, serious AEs, discontinuations due to AEs, AEs of specific interest including abnormal laboratory data, and deaths. Results: The frequency and/or intensity of overall AEs, drug-related AEs, serious AEs and discontinuations due to AEs were not significantly increased for the FDC (36.0%, 12.3%, 1.7% and 5.1%, respectively) versus the statin (28.7%, 8.9%, 0.8% and 2.7%, respectively) and fenofibrate (59.0%, 21.3%, 0% and 4.9%, respectively) monotherapies. No deaths were reported during the course of treatment in clinical trials. Nevertheless, three deaths were reported more than 30 days after the patients completed the study; none of these deaths were assessed as being related to FF/PRA 160 mg/40 mg treatment. Among the AEs of special interest, no myopathy or rhabdomyolysis were reported; no patients were considered to have experienced a drug-induced liver injury; no case of pancreatitis occurred in the double-blind cohort and four patients reported pancreatitis in the all-studies cohort, two of them being study-treatment related; no case of pulmonary embolism was reported in the double-blind cohort and two patients presented with pulmonary embolism, unrelated to the study drug, in the all-studies cohort; there were more cases of decreased creatinine clearance in the FF/PRA 160 mg/40 mg group (1.7%) than in the statin group (0.6%). Conclusion: Within the limitations of this database (notably low percentage of very elderly patients, limited sample size of patients with mild renal insufficiency, and mode of selection in the clinical trials), no particular safety concern was raised with FF/PRA 160 mg/40 mg in the double-blind cohort as compared with statin and fenofibrate monotherapies. The acceptable long-term safety profile of FF/PRA 160 mg/40 mg was confirmed with a low frequency of AEs of interest, comparable to that observed in the 12-week double-blind cohort. Emergent effects possibly related to FF/PRA 160 mg/40 mg were mainly those attributable to fenofibrate (decrease in creatinine clearance and pancreatitis).

Impact of advanced age on the safety and effectiveness of paclitaxel-eluting stent implantation in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty: The HORIZONS-AMI trial.

To assess the impact of age on safety and efficacy of paclitaxel‐eluting stent (PES) implantation during primary percutaneous coronary intervention (PCI) in patients with ST‐segment elevation myocardial infarction (STEMI).