Maria Krzemińska-Pakuła

The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute ST-segment elevation myocardial infarction patients ineligible for reperfusion (TETAMI): a randomized trial.

OBJECTIVES The aims of the Safety and Efficacy of Subcutaneous Enoxaparin Versus Intravenous Unfractionated Heparin and Tirofiban Versus Placebo in the Treatment of Acute ST-Segment Elevation Myocardial Infarction Patients Ineligible for Reperfusion (TETAMI) study were to demonstrate that enoxaparin was superior to unfractionated heparin (UFH) and that tirofiban was better than placebo in patients with acute ST-segment elevation myocardial infarction (STEMI) who do not receive timely reperfusion. BACKGROUND An optimal treatment strategy has not been identified for the many STEMI patients ineligible for acute reperfusion. METHODS A total of 1224 patients were enrolled in 91 centers in 14 countries between July 1999 and July 2002. Patients with STEMI ineligible for reperfusion were randomized to enoxaparin, enoxaparin plus tirofiban, UFH, or UFH plus tirofiban. All patients received oral aspirin. The primary efficacy end point was the 30-day combined incidence of death, reinfarction, or recurrent angina; the primary analysis was the comparison of the pooled enoxaparin and UFH groups. RESULTS The incidence of the primary efficacy end point was 15.7% enoxaparin versus 17.3% for UFH (odds ratio 0.89 [95% confidence interval CI = 0.66 to 1.21]) and 16.6% for tirofiban versus 16.4% for placebo (odds ratio 1.02 [95% CI 0.75 to 1.38]). The Thrombolysis In Myocardial Infarction (TIMI) major hemorrhage rate was 1.5% for enoxaparin versus 1.3% for UFH (odds ratio 1.16 [95% CI 0.44 to 3.02]) and 1.8% versus 1% for tirofiban versus placebo (odds ratio 1.82 [95% CI 0.67 to 4.95]). CONCLUSIONS This study did not show that enoxaparin significantly reduced the 30-day incidence of death, reinfarction, and recurrent angina compared with UFH in non-reperfused STEMI patients. However, enoxaparin appears to have a similar safety and efficacy profile to UFH and may be an alternative treatment. Additional therapy with tirofiban did not appear beneficial.

Myocardial ischemia and autonomic activity in dippers and non-dippers with coronary artery disease: assessment of normotensive and hypertensive patients.

OBJECTIVES The aim of this study was to assess the relations between the circadian variations of blood pressure (BP) and the pattern of ischemia and autonomic activity in normotensive and hypertensive patients with coronary artery disease (CAD). PATIENTS AND METHODS On the basis of the results of ambulatory BP monitoring, 115 patients with stable CAD were divided into Group 1 (with arterial hypertension) and Group 2 (normotensives). Groups were subdivided into dippers and non-dippers. Holter monitoring was performed to assess the occurrence and circadian pattern of ischemic episodes. Time domain and frequency domain HRV analyses were performed to evaluate the autonomic activity. RESULTS The total number of ischemic episodes was similar in dippers and non-dippers. Non-dippers had a greater number of silent episodes and a different circadian pattern of ischemia with more night episodes. Among the time-domain HRV parameters, only SDNN was similar in dippers and non-dippers. Non-dippers had lower pNN50 and rMSSD-the parameters expressing parasympathetic activity. Differences between diurnal and nocturnal results of spectral HRV analysis were observed in dipper patients only. They presented an elevation of HF power and a decline of LF power at night. All differences between dippers and non-dippers were of similar significance in both hypertensives and normotensives. CONCLUSIONS A lack of a nocturnal fall in BP is present in normotensive and hypertensive patients with CAD. Non-dippers with CAD had silent and nighttime ischemia more often. They also had an abnormal pattern of autonomic activity with higher sympathetic and lower parasympathetic modulation.

Prospective Evaluation of Clinical Outcomes After Acute ST-Elevation Myocardial Infarction in Patients Who Are Ineligible for Reperfusion Therapy: Preliminary Results From the TETAMI Registry and Randomized Trial

Background—Treatment with lytics or primary percutaneous coronary interventions (PCI) reduces the mortality rate of patients with ST-elevation myocardial infarction (STEMI) presenting within 12 hours. Patients presenting >12 hours are generally considered to be ineligible for reperfusion therapy, and there are currently no specific treatment recommendations for this subgroup. Methods—All patients with STEMI <24 hours were included in the Treatment with Enoxaparin and Tirofiban in Acute Myocardial Infarction (TETAMI) randomized trial or registry. Those patients who were ineligible for acute reperfusion, had no cardiogenic shock, and were not planned for revascularization within 48 hours were randomized to 1 of 4 antithrombotic regimens involving enoxaparin or unfractionated heparin (UFH), in combination with tirofiban or placebo for 2 to 8 days. A concurrent registry tracked STEMI patients coming in within <12 hours, and who underwent reperfusion. This registry also tracked the remaining STEMI patients who neither received reperfusion nor were enrolled in the TETAMI randomized trial. The demographics and clinical outcomes of all three groups (received reperfusion therapy, too late for reperfusion and enrolled in the randomized trial, neither received reperfusion therapy nor were enrolled in the randomized trial) were prospectively tracked. Results and Conclusion—There were 2,737 patients who presented with STEMI or a new left branch bundle block (LBBB), of which 1,654 (60%) presented ≤12 hours. There were 1,196 (72%) of 1,654 patients who received reperfusion therapy. There were 458 (28%) of the 1,654 patients deemed “ineligible” for reperfusion, mostly because of a contraindication to lytics or for being “too old.” In contrast, 1,083 (40%) of 2,737 patients presented >12 hours. Apart from 34 of these patients who had a stuttering infarction and were referred for reperfusion, the remaining patients did not receive reperfusion therapy.Registry patients who received reperfusion therapy, compared with TETAMI randomized patients (all of whom received antithrombotic therapy) and registry patients who did not receive reperfusion, were younger (61 years versus 63 years and 67 years), were more likely to be male (78% versus 73% and 63%), and had persistent ST-segment elevation as opposed to LBBB or Q waves. Registry patients who received reperfusion therapy had better clinical outcomes, even after adjusting for admission Killip class, compared with TETAMI randomized patients and registry patients who did not receive reperfusion therapy. TETAMI randomized patients had better outcomes than registry patients who did not receive reperfusion therapy.The major obstacle to expanding the delivery of reperfusion therapy to patients with STEMI is the large fraction of patients who present too late for reperfusion therapy. Examination of prospectively gathered data on STEMI patients who are ineligible for reperfusion may help optimize their treatment.

Arterial dysfunction in syndrome X: results of arterial reactivity and pulse wave propagation tests

Objective: To assess arterial distensibility using pulse wave velocity (PWV) measurements and its relation with endothelium dependent vasodilatation (EDV) in patients with cardiological syndrome X. Methods: The study group consisted of 92 patients: 52 with syndrome X (34 women, 18 men, mean (SD) age 45 (3) years) and 40 healthy volunteer controls (27 women, 13 men, mean (SD) age 41 (2) years) without risk factors of atherosclerosis and with negative ECG exercise test and normal proximal coronaries on transoesophageal echocardiography. Patients with arterial hypertension, diabetes mellitus, valvar disease, or cardiomyopathy were excluded. PWV measured by a Complior Colson device was calculated for each patient. EDV was assessed from two dimensional Doppler measurement using an Acuson Sequoia with 8 MHz linear transducer at rest, during postischaemic reactive hyperaemia, and after an oral dose of 400 μg of glyceryl trinitrate. Results: PWV was significantly higher in patients with syndrome X than in healthy subjects (9.3 (0.7) m/s v 8.2 (0.9) m/s, respectively, p < 0.001). Baseline brachial artery diameter was similar in the syndrome X and control groups (4.0 (0.6) mm v 4.08 (0.64) mm, NS). EDV was impaired in patients with syndrome X compared with controls (6.6 (3.0)% v 11.1 (3.9)%, p < 0.001). Endothelium independent vasodilatation was similar in both groups. In patients with syndrome X there was a positive correlation between PWV and the degree of EDV (r = 0.864, p < 0.001). The cut off value for PWV was 8.5 m/s, with a sensitivity of 62% and a specificity of 91%. Conclusions: EDV but not glyceryl trinitrate induced vasodilatation is decreased in patients with syndrome X. There is a strong correlation between PWV and the degree of endothelial dysfunction of peripheral arteries in patients with syndrome X. PWV assessment may be useful to identify abnormal vascular physiology in these patients.

Accelerated Stress Real-Time Myocardial Contrast Echocardiography for the Detection of Coronary Artery Disease: Comparison with 99mTc Single Photon Emission Computed Tomography

OBJECTIVE The aims of this prospective study were to compare the diagnostic value of accelerated vasodilator stress real-time myocardial contrast echocardiography (MCE) and single photon emission computed tomography (SPECT) against coronary angiography and to evaluate whether the addition of MCE perfusion data improves the diagnostic accuracy of stress echocardiography. METHODS A total of 103 patients with suspected or known stable coronary artery disease (CAD) underwent SPECT and accelerated high-dose dipyridamole (0.84 mg/kg intravenously for 4 minutes) atropine (up to 1 mg intravenously) stress real-time qualitative MCE. The presence of CAD was detected by coronary angiography. RESULTS CAD defined as >or= 70% stenosis was detected in 77% of patients, whereas 86% of patients had CAD defined as >or= 50% stenosis. In a territory-by-territory analysis, the concordance between MCE and SPECT in detecting perfusion defects varied from 72.8% (kappa = 0.386) to 89.3% (kappa = 0.642). There were no significant differences between MCE and SPECT in sensitivity, specificity, and diagnostic accuracy for identifying patients with CAD. Combining MCE and wall motion abnormality analysis significantly improved the sensitivity of the test compared with wall motion abnormality analysis alone. CONCLUSIONS Accelerated vasodilator stress real-time MCE yields a good concordance with SPECT in detection of perfusion defects and a similar diagnostic value for the detection of CAD. The addition of MCE perfusion data improves the diagnostic value of stress echocardiography.

Prognostic value of platelet indices after acute myocardial infarction treated with primary percutaneous coronary intervention

BACKGROUND Mean platelet volume (MPV) is a strong predictor of impaired angiographic reperfusion and 6-month mortality in ST-elevation myocardial infarction (MI) treated with primary percutaneous coronary intervention (PCI). No data is available for other platelet volume indices: platelet distribution width (PDW) and platelet large cell ratio (P-LCR). The aim was to assess the impact of 3 platelet volume indices on long-term prognosis in patients treated with primary PCI in acute MI. METHODS This prospective study enrolled 538 patients who underwent primary PCI in acute MI. Admission blood samples were measured for MPV, PDW, and P-LCR. The patients were followed-up a mean period of 26 ± 11 months with regard to cardiac death, non-fatal reinfarction, re-PCI or coronary artery bypass grafting. RESULTS Kaplan-Meier survival analysis showed a significantly higher 26-month mortalityrate in patients with high MPV (≥ 11.7 fL) than in those with low MPV (< 11.7 fL) (14.6% vs. 5.5%, p = 0.0008). Similar findings were related to high P-LCR (≥ 38.1%) vs. low P-LCR (< 38.1%) - mortality 13.8% vs. 5.8%, p = 0.0025. Higher PDW values (≥ 16 fL) correlated with higher mortality rate as compared to PDW < 16 fL (17.4% vs. 6.3%, p = 0.0012). PDW was found to be an independent prognostic factor for cardiac mortality and composite endpoint. CONCLUSIONS Mean platelet volume, platelet distribution width and platelet large cell ratio measured on admission are strong, independent prognostic factors in PCI-treated acute MI.

Elevated resistin opposed to adiponectin or angiogenin plasma levels as a strong, independent predictive factor for the occurrence of major adverse cardiac and cerebrovascular events in patients with stable multivessel coronary artery disease over 1-year follow-up.

Summary Background Adipokines such as adiponectin and resistin, as well as angiogenin, may be associated with inflammation and atherosclerosis. The relationship between their levels and prognosis in high risk patients is, however, still unclear. The aim of this study was to evaluate the prognostic value of these adipokines in patients with stable multivessel coronary artery disease (MCAD). Material/Methods The study group comprised 107 MCAD patients (74% males, mean age 63±8 years). Adiponectin, resistin and angiogenin plasma levels were measured at admission and after 1-year follow-up. Primary end point (major adverse cardiac and cerebrovascular events – MACCE) was defined as cardiac death, nonfatal myocardial infarction, stroke, and hospitalization for angina or heart failure over a 1-year period. Results After 1-year follow-up, 9 (8%) patients died, all from cardiovascular causes. Primary end point was experienced by 32% of patients. Surgical treatment (CABG) was received by 51% of patients, while 49% were treated medically alone. Total cholesterol concentration levels ≥173 mg/dl were associated with a 7-fold increase (OR 7.3; 95% CI, 1.6–33.0); LDL ≥93.5 mg/dl with a 16-fold increase (OR 16.3; 95% CI, 2.8–93.8), and resistin ≥17.265 ng/ml with a 13-fold increase in MACCE risk (OR 13.5; 95% CI, 2.3–80.3). In multivariate analysis, a medical treatment strategy (p=0.001), a higher CCS class (p=0.004), resistin levels (p=0.003) and a higher Gensini score (p=0.03) were independent predictors of MACCE. Conclusions In stable patients with MCAD, elevated plasma resistin (as opposed to adiponectin or angiogenin) is a strong, independent predictive factor for the occurrence of MACCE over 1-year follow-up.

Melatonin for nondippers with coronary artery disease: assessment of blood pressure profile and heart rate variability.

The aim of this study was to assess the effects of 5 mg melatonin before sleep in patients with coronary artery disease (CAD) and with an abnormal circadian pattern of blood pressure (BP) on changes in circadian BP profile and heart rate variability (HRV). Sixty patients with CAD, nondippers aged 48–80 years (male 75%), were included. In addition to previous treatment, they were randomly allocated to melatonin or placebo. After 90 days, a second 24-h BP monitoring was carried out. Each patient had two sessions (before randomization and at the end of study) of 24-h ECG monitoring to assess the changes in HRV. Inclusion of melatonin led to BP pattern normalization in 35% of patients in the melatonin group and in 15% of controls (P=0.609). This effect was reached not only by a decrease in nighttime BP, but also by an increase in daytime BP (significant in the melatonin group). A nonoptimal effect for BP profile was observed in 12.5% of patients: extreme- or reverse dippers. In patients with conversion from nondippers to dippers (responders), an increase in standard deviation of normal-to-normal intervals between initial and final HRV analyses was observed. Nonresponders represented an increase in the mean circadian heart rate. To avoid nonoptimal effects, the inclusion of melatonin in pharmacotherapy of patients with CAD should be based on monitoring of circadian BP profile, before and during treatment. As melatonin caused not only a nocturnal decrease in BP but also a daytime increase, it should not be recommended in patients with ‘high normal’ values of BP because of the danger of induction of arterial hypertension.

Regression of left ventricular dilatation and hypertrophy after aortic valve replacement

The aim of the study was to assess the influence of aortic valve replacement on left ventricular size and muscle hypertrophy according to the type of preexisting valve disease (aortic stenosis, insufficiency or combined disease). The study group consisted of 143 consecutive patients (pts) after aortic valve replacement (109 men, 34 women, mean age 48.1 +/- 10.9 years). Reason for the operation was aortic stenosis in 35 pts, aortic insufficiency in 64 pts and combined disease in 44 pts. Echocardiography was performed before surgery, 1 month and 1 year after operation, and yearly during 5-year follow-up. Transvalvular aortic pressure gradients decreased significantly after valve replacement in all subsets without further changes during follow-up (Pmax (mmHg): from 54.2 +/- 20.7 to 17.9 +/- 9.6 in combined disease pts, from 72.3 +/- 19.9 to 21.6 +/- 14.6 in aortic stenosis and from 34.5 +/- 24.2 to 15.6 +/- 11.3 in aortic insufficiency pts, respectively, P < 0.0005). One year after surgery the diastolic dimension of the left ventricle decreased significantly in all subjects, whereas the systolic dimension only in aortic insufficiency and combined disease pts (from 44 +/- 11.8 to 31.6 +/- 5.4 mm, P < 0.001 and from 41.9 +/- 11.5 to 33 +/- 6.7 mm, P < 0.05, respectively). Further decrease of both diastolic and systolic dimensions was observed only in the aortic insufficiency group. Ejection fraction of left ventricle increased only in combined disease pts (from 51.6 +/- 10% to 56.8 +/- 8.2%, P < 0.05). Wall thickness of the left ventricle decreased 1 year after valve replacement only in the aortic stenosis group and in further follow-up in the aortic stenosis and combined disease group. Normalization of left ventricular size is observed in more than 90% of patients during 5-year follow-up as opposed to left ventricular muscle hypertrophy, regressed only in less than a half of the study population. In patients with aortic valve disease the greatest hemodynamic improvement is observed 1 year after valve replacement. This is expressed by marked reduction of the left ventricular dimensions and wall thickness, without significant improvement of the ejection fraction. Further regression of left ventricle dimensions occurs in patients operated on due to predominant valve insufficiency, whereas regression of left ventricular hypertrophy is observed in patients with preexisting valvular stenosis.

Enlarged Left Atrium Is a Simple and Strong Predictor of Poor Prognosis in Patients after Myocardial Infarction

Background and Aim: Patients after myocardial infarction (MI) differ according to the extend of myocardial damage and prognosis. Diastolic function impairment may have great impact on development of heart failure and outcomes. We evaluated the prognostic value of various echocardiographic measurements in 18‐month and 3‐year observation after MI. Methods: 60 patients after MI (44 male, mean age 60 ± 11) were examined by transthoracic echocardiography with the assessment of wide spectrum of parameters. Mortality and combined end points (cardiac deaths and heart failure exacerbation) were assessed after 18‐month and 3‐year observation and groups with and without end points were compared. Optimal cutoff values were estimated by receiver operating characteristic (ROC) analysis and resulting Kaplan–Meier curves were compared. Results and Conclusions: After 18 months, 11 deaths occurred and 20 subjects experienced hospitalization caused by heart failure exacerbation. Although the group with cardiac events showed a greater enlargement of the left ventricle and lower ejection fraction, the highest relative risk of poor outcome (RR = 5.0) was related to the left atrial enlargement above 44 mm. Although restrictive or pseudonormal inflows were connected with 2.1 relative risk of combined end point, all patients with E deceleration time ≤130 ms experienced heart failure exacerbation or death. Despite tissue Doppler and propagation parameters describing elevated end‐diastolic pressure differed between groups with various outcomes in multivariate analysis, only enlarged left atrium was an independent predictor for both combined end point and cardiac death. Further 3‐year follow‐up solely confirmed the role of above described predictors.