Hanoch Hod

Mortality and morbidity rates of patients older and younger than 75 years with acute myocardial infarction treated with intravenous streptokinase

The influence of patient age on mortality risk and on the incidence of serious hemorrhagic complications after treatment of acute myocardial infarction (AMI) with intravenous streptokinase (SK) and heparin was examined in 120 consecutive patients. No upper age limit was set for patient inclusion. The mortality rate increased abruptly in patients aged 75 years or older such that the 24 patients in that age group had a 10-fold higher in-hospital mortality rate (33% vs 3%) and 1-year mortality rate (42% vs 4%) than the 96 patients younger than 75 years. This increased mortality rate in the elderly patients was related to a 2-fold higher incidence of major hemorrhagic complications (24% vs 11%) and an increased incidence of anterior AMI, healed prior AMI, multiple-vessel coronary artery disease and extensive myocardial necrosis estimated by peak creatine kinase-MB. Hemorrhagic complications were more frequent in women than in men and in patients with diabetes mellitus or systemic hypertension; all of these conditions were more prevalent in patients aged 75 years and older than in those younger than 75 years. In contrast, the incidence of hemorrhagic complications in nondiabetic elderly men (1 of 12) was similar to the incidence of bleeding in the patients younger than 75 years. Based on our data and those from other studies reporting no reduction in mortality in elderly patients with AMI who are treated with intravenous SK, it is recommended that patients aged 75 years or older should not be routinely treated with intravenous SK.(ABSTRACT TRUNCATED AT 250 WORDS)

Shoulo thrombolytic therapy be administered in the mobile intensive care unit in patients with evolving myocardial infarction? A pilot study

The growing recognition of the importance of early thrombolysis in evolving myocardial infarction was the basis for the present study, which evaluated the effectiveness, feasibility and safety of prehospital thrombolytic therapy. In a relatively small study, 118 patients were allocated to receive either prehospital treatment with recombinant tissue-type plasminogen activator (rt-PA) in the mobile intensive care unit (group A, 74 patients) or hospital treatment (group B, 44 patients). A total of 120 mg of rt-PA was infused over a period of 6 h. All patients were fully heparinized and underwent radionuclide left ventriculography and coronary angiography during hospitalization. Although group A was treated significantly earlier than group B after onset of symptoms (94 +/- 36 versus 137 +/- 45 min, respectively; p less than 0.001), no significant differences were observed between the groups in 1) extent of myocardial necrosis, 2) global left ventricular ejection fraction at discharge, 3) patency of infarct-related artery, 4) length of hospital stay, and 5) mortality at 60 days. However, a trend to a lower incidence of congestive heart failure at hospital discharge was observed in the prehospital-treated compared with the hospital-treated group (7% versus 16%, respectively; p = NS). No major complications occurred during transportation. It is concluded that myocardial infarction can be accurately diagnosed and thrombolytic therapy initiated relatively safely during the prehospital phase by the mobile intensive care team, thus instituting a beneficial clinical trend in favor of prehospital thrombolysis.

Usefulness of a rapid initial increase in plasma creatine kinase activity as a marker of reperfusion during thrombolytic therapy for acute myocardial infarction

This study evaluates a new nonangiographic marker of reperfusion--a rapid initial increase in plasma creatine kinase (CK) and CK-MB activity--in 50 patients receiving intracoronary streptokinase. Blood for CK and CK-MB activity was sampled at 30-minute intervals and angiography performed at 15-minute intervals or earlier if there were clinical signs suggestive of reperfusion. An absolute first-hour increase in CK activity of 480 +/- 345 IU/liter (range 54 to 1,440 IU/liter), or a relative first-hour increase of 34 +/- 18% (range 13 to 67% of the peak rise), or an absolute first-hour increase in CK-MB activity of 48 +/- 36 IU/liter (range 10 to 144 IU/liter) or a relative first-hour increase of 27 +/- 13% (range 13 to 57%) was found in patients immediately after reperfusion with Thrombolysis In Myocardial Infarction (TIMI) grade 3 perfusion of the artery of infarction. The onset of rapid increase in CK and CK-MB activity closely reflected the time of angiographic documentation of reperfusion. In contrast, in the absence of reperfusion, the absolute rate of increase in CK activity measured in the last hour of the 2 1/2-hour period beginning with the start of treatment was only 15 +/- 9 IU/liter on the average (range 2 to 30 IU/liter) and the relative rate of rise was 3 +/- 2% on the average (range 1 to 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Improved posterobasal segment function after thrombolysis is associated with decreased incidence of significant mitral regurgitation in a first inferior myocardial infarction

OBJECTIVESnThis study was designed to investigate the association between wall motion abnormalities and the occurrence of ischemic mitral regurgitation in patients with a first inferior or posterior myocardial infarction and to reassess the role of thrombolytic treatment in these patients.nnnBACKGROUNDnWe previously demonstrated that thrombolytic therapy reduces the incidence of significant mitral regurgitation in patients with a first inferior myocardial infarction, but the mechanisms responsible for this decrease were not clear.nnnMETHODSnWall motion score on two-dimensional echocardiography (16 segments) and mitral regurgitation grade (0 to 3) on Doppler color flow imaging were assessed in 95 patients (in 47 after thrombolysis) at 24 h, 7 to 10 days and 1 month after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3).nnnRESULTSnMultivariate analysis revealed that the presence of an advanced wall motion abnormality of the posterobasal segment of the left ventricle was the most significant independent variable associated with significant mitral regurgitation: odds ratio (OR) 15.0, 90% confidence interval (CI) 1.4 to 165.6 at 24 h; OR 2.8, CI 0.9 to 9.3 at 7 to 10 days; OR 4.2, CI 1.2 to 11.4 at 1 month. Thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment at 24 h (55% vs. 75%, OR 0.5, CI 0.2 to 0.99), 7 to 10 days (44% vs. 73%, OR 0.3, CI 0.1 to 0.7) and 1 month (36% vs. 56%, OR 0.4, CI 0.2 to 0.9).nnnCONCLUSIONSnThere is a strong association between advanced wall motion abnormalities in the posterobasal segment and significant mitral regurgitation. In this study group, thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment and thereby reduced the incidence of significant mitral regurgitation.

Inferior ST segment changes during acute anterior myocardial infarction: A marker of the presence or absence of concomitant inferior wall ischemia

The significance of inferior ST segment changes during acute anterior myocardial infarction was studied in 60 patients with acute anterior infarction who had angiographic visualization of the entire distribution of the left anterior descending artery after thrombolytic therapy with streptokinase. In 34 patients (Group 1) this artery supplied the anterior wall of the left ventricle up to or including the apex but did not reach the inferior wall; in 16 patients (Group 2) it continued beyond the apex onto the inferior wall of the left ventricle; and in 10 patients with prior inferior infarction (Group 3) it partially supplied the inferior wall of the left ventricle through collateral channels to an occluded right or dominant circumflex coronary artery. Consistent with this anatomy, evidence of inferior wall ischemia was significantly more frequent in Groups 2 and 3 than in Group 1 by thallium-201 scintigraphy (91 versus 7%) and by contrast left ventriculography (91 versus 13%). There was no difference in the magnitude of precordial ST segment elevation among the three groups but the inferior ST segment depression was significantly smaller in Groups 2 and 3 with concomitant inferior wall ischemia than in Group 1 (aVF: -0.5 +/- 0.7; -0.5 +/- 1.0; -1.8 +/- 0.8 mm, respectively; p less than 0.001) with 10 of the 26 patients in Groups 2 and 3 having an elevated or isoelectric ST segment in aVF compared with none of the 34 patients in Group 1 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Myocarditis: Noninvasive Evaluation with Cardiac MRI and Transthoracic Echocardiography

OBJECTIVEnThe diagnosis of acute myocarditis is challenging. Nonspecific clinical presentation and an overlap with the diagnosis of acute myocardial infarction present a diagnostic dilemma. The purpose of this article is to describe the role of cardiac MRI and transthoracic echocardiography (TTE) in the diagnosis of acute myocarditis.nnnMATERIALS AND METHODSnThirty-two sequential patients (all male; average age, 33 years) with clinically suspected myocarditis were included. All patients underwent cardiac MRI with sequences dedicated for the evaluation of myocardial delayed enhancement and TTE for the evaluation of wall motion abnormalities (WMAs). Nine patients were excluded because of diagnosis of acute myocardial infarction (n=2) or inadequate cardiac MRI technique (n=7). Retrospective analysis of the images of the remaining 23 patients was performed.nnnRESULTSnAn epicardial pattern of abnormal patchy myocardial delayed enhancement was seen on cardiac MRI in 21 of 23 (91%) patients. WMAs were seen on TTE in eight of 23 (35%) patients. Regional rather than global involvement was seen mainly in the inferolateral segments, with a predominance in the midventricular portion.nnnCONCLUSIONnCardiac MRI might have a greater impact than TTE in confirming the presence of acute myocarditis and evaluating the extent of myocardial involvement. Cardiac MRI provides noninvasive imaging that may obviate invasive procedures such as coronary catheter angiography or endomyocardial biopsy.

Repeat infusions of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction and early recurrent myocardial ischemia

When conventional treatment of patients with early clinical reinfarction after thrombolytic therapy fails, mechanical revascularization may be attempted. An alternative strategy, repeat thrombolytic infusions, is reported. Fifty-two patients with acute myocardial infarction were treated with one or two additional thrombolytic infusions of recombinant tissue-type plasminogen activator (rt-PA) because of nonsustained ischemia after initial treatment with rt-PA or streptokinase. Thirty-five patients received the second infusion within 1 h of the first; 13 patients received the second infusion 1 to 72 h after the first and 4 patients received it later during their hospitalization. Bleeding complications occurred in 10 patients (19%); however, most of these were minor (no intracranial bleeding) and only 2 patients required blood transfusion. In 14 patients in whom the decrease in fibrinogen and plasminogen levels was measured after the first and second infusions, this decrease was only 25% and 63%, respectively--only slightly higher than the 22% and 53% decreases measured in 63 patients who had only one rt-PA infusion. In 44 patients (85%), the acute ischemia resolved completely within 1 h after initiation of the second infusion. In 23 patients (44%), pain and ST segment elevation did not recur and invasive coronary intervention was avoided. Thus, repeat rt-PA infusions can stabilize a substantial number of patients with acute reinfarction and, even when relief is temporary, repeat rt-PA infusions can minimize myocardial damage while patients await mechanical revascularization.

Increased mean platelet volume is associated with non-responsiveness to clopidogrel

Prior studies have demonstrated significant individual variability of platelet response to clopidogrel, which affects clinical outcome. In patients with stable coronary artery disease (CAD) smoking, diabetes mellitus, elevated body mass index and renal insufficiency, significantly impact response to clopidogrel. The determinants of platelet response to clopidogrel in patients with acute coronary syndrome are unknown. Adenosine diphosphate (ADP)-induced platelet aggregation (PA), hs C-reactive protein, platelet count and mean platelet volume (MPV) were determined 72 hours post clopidogrel loading in 276 consecutive acute myocardial infarction (AMI) patients. Patients with ADP-platelet aggregation ≥ 70% were considered to be clopidogrel non-responders. Eighty-four patients (30%) were clopidogrel non-responders and 192 (70%) were responders (ADP-induced PA: 81 ± 17% vs 49 ± 17%, respectively, p<0.001). Both study groups were comparable with respect to age, gender, prior cardiovascular history, prior aspirin use and risk factors for CAD, including smoking (42% for both groups) and diabetes mellitus (26% vs 22%, respectively, p=0.4). Responders and non-responders had similar angiographic characteristics, indices of infarct size, and similar hs-CRP (29 ± 34 vs 28 ± 34 mg/l, p=0.7) and creatinine (1.08 ± 0.4 mg% vs 1.07 ± 0.4, p=0.9) levels. On the contrary non-responders had significantly larger mean MPV (9 ± 1.2 fl vs 8 ± 1 fl, respectively, p=0.0018), and when patients were stratified into quartiles based on MPV, ADP-induced PA increased gradually and significantly across the quartiles of MPV (p<0.001). In conclusion, increased MPV associated with platelet activation, predicts non-responsiveness to clopidogrel among patients with acute coronary syndrome.

Statins have an early antiplatelet effect in patients with acute myocardial infarction

Statins confer an antiplatelet effect in hypercholesterolemic subjects and in stable coronary artery disease patients. We explored the antiplatelet effects of statins in ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. Of 120 STEMI patients, 80 (67%) received statins while 40 (33%) did not. Ex vivo platelet reactivity was studied on admission and 72 hours later by conventional aggregometry and under flow conditions (Impact R). Measures of platelet reactivity under flow conditions included aggregate size and surface coverage, signifying platelet aggregation and adhesion respectively. The effect of statins on platelet function under flow conditions and platelet aggregation was studied in vitro in platelets from 10 STEMI patients. Platelets from each patient were incubated in vitro with lovastatin or PBS as a control. The effect of lovastatin in the presence of a nitric oxide synthase inhibitor (L-NMMA) was also studied. Patients treated with statins were compared with those who did not have significantly lower ADP-induced platelet aggregation on the 4th day (56u2009±u200918% vs. 64u2009±u200917%, pu2009=u20090.02). Platelet deposition under flow conditions as measured by surface coverage was reduced from admission to 72 hours later among statin-treated patients (19u2009±u200928% reduction, pu2009<u20090.01), but was unchanged in non-treated patients (for comparison pu2009<u20090.01). The extent of platelet inhibition was unrelated to patient characteristics, including lipid profile and type of statin administered (lipophylic vs. hydrophilic). In the in vitro study platelet incubation with statin compared with PBS resulted in a lower aggregate-size (29u2009±u20099u2009µm2 vs. 39u2009±u200915u2009µm2, pu2009<u20090.01), and lower surface coverage (8.5u2009±u20094% vs. 12u2009±u20094%, pu2009<u20090.01). The effect of the statin on both parameters was significantly blunted by L-NMMA. Incubation with statin also resulted in a reduction in collagen-induced platelet aggregation (31u2009±u200920% vs. 54u2009±u200925%, pu2009<u20090.01). We concluded that in acute myocardial infarction patients, statins have an early antiplatelet effect, in addition to that afforded by standard antiplatelet therapy.

The outcome of patients with a first non-Q wave acute myocardial infarction presenting with ST segment depression, ST segment elevation, or no ST deviations on the admission electrocardiogram

UNLABELLEDnWe evaluated the prognosis of patients with a first non-Q wave myocardial infarction according to their admission electrocardiogram. Hospital and 1-year mortality rates in patients with ST elevation (15%, and 21% respectively) and ST depression (17%, and 27% respectively) were similar and significantly higher than in patients with no ST changes (3%, and 10% respectively). Likewise, the adjusted hospital and 1-year mortality risks of patients with ST elevation or depression were comparable but higher than the corresponding mortality risk of patients with no ST deviations. The cumulative 5-year mortality rate was highest among patients with ST segment depression (51%) compared to patients with ST elevation (34%) or no ST deviation (21%), (p<0.001 for both comparisons). The adjusted 5-year mortality risk of patients with ST depression was higher (HR: 1.83, 95% C.I., 1.17-2.83) compared to patients with baseline ST elevation (HR-1.33, 95% C.I., 0.83-2.12) or patients with no ST changes (reference group). Patients with baseline ST segment elevation and coexistent ST segment depression in other electrocardiogram leads, had a higher in-hospital mortality rate (19%) compared to counterparts without concomitant ST depression (10%) and a tendency for higher in-hospital mortality risk but not for subsequent 1- and 5-year mortality risks.nnnCONCLUSIONSnPatients with a first non-Q wave MI with ST elevation or depression on admission have similar hospital and 1-year mortality risk, but the long-term mortality risk is higher among patients with ST segment depression. Patients with ST elevation and concomitant ST segment depression are at increased risk for mortality during the index hospitalization.