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Biomedical subjects

Shaul Atar

Publications and source records attributed to Shaul Atar.

At least 19 recordsLinked to original sources

Grade 3 ischemia on admission electrocardiogram and chest pain duration predict failure of ST-segment resolution after primary percutaneous coronary intervention for acute myocardial infarction.

OBJECTIVES: ST resolution (STR) is a surrogate marker of myocardial tissue reperfusion and a predictor of outcome after primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI). Terminal QRS distortion (grade 3 ischemia) has been shown to predict failure of STR after thrombolysis for STEMI, but the ability of grade 3 ischemia to predict STR with pPCI is unclear. METHODS: We retrospectively analyzed 155 patients who underwent pPCI and compared grade 2 ischemia (ST elevation without terminal QRS distortion; n = 89) to grade 3 ischemia (n = 66) on admission for baseline characteristics, in-hospital course, and STR immediately after pPCI and at 18 to 24 hours. RESULTS: Patients with grade 3 ischemia were older (60 +/- 12 vs 56 +/- 11 years; P = .018), had more anterior STEMI (42% vs 17%; P = .0004), and were less often smokers (41% vs 90%; P = .004). The grade 3 ischemic group had significantly less complete STR (35% vs 75% [P < .00001] immediately after pPCI and 33% vs 79% [P < .00001] 18-24 hours after pPCI), a longer hospital stay (6.4 +/- 4.1 vs 4.9 +/- 1.9 days; P = .008), and higher peak CKMB (292 +/- 231 vs 195 +/- 176 ng/mL; P = .0005). Duration of symptoms before pPCI (odds ratio [OR], 0.838; 95% confidence interval [CI], 0.724-0.969; P = .017) and grade 3 ischemia (OR, 0.181; 95% CI, 0.068-0.480; P < .001) were negative predictors of complete STR, whereas nonanterior STEMI (OR, 5.95; 95% CI, 2.154-16.436; P < .001) and initial sum of ST elevation (OR, 3.132; 95% CI, 1.140-8.605; P = .027) were positive predictors. CONCLUSION: Grade 3 ischemia on presentation of STEMI and duration of chest pain are strong independent predictors of failure to achieve complete STR after pPCI.

Angioplasty, Balloon, Coronary↗

Systematic overview and clinical applications of pacing atrial stress echocardiography.

Pacing atrial stress echocardiography (PASE) has been studied over the past 3 decades for the evaluation of myocardial ischemia. Published studies suggest that PASE may be used as an alternative to exercise or pharmacologic stress imaging. The recent introduction of improved pacing electrodes, together with use of accelerated and shortened pacing protocols and improvements in transthoracic echocardiographic imaging techniques, makes PASE an appealing stress imaging method. A critical analysis of the diagnostic accuracy of PASE shows equivalence with other imaging stress modalities. PASE has been found to be highly feasible and accurate technique that may expedite the diagnosis and risk stratification of patients with coronary artery disease. This review addresses the history, hemodynamics, protocols, accuracy, clinical utility, and cost-effectiveness of PASE as well as elucidating its place among other stress modalities.

Animals↗

Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions.

We assessed 1) whether pretreatment before ischemia with pioglitazone (Pio) limits infarct size (IS) and whether this protective effect is due to nitric oxide synthase (NOS) and/or prostaglandin production, as has been shown for atorvastatin (ATV); and 2) whether Pio and ATV have synergistic effects on myocardial protection. Sprague-Dawley rats received oral ATV (10 mg.kg-1.day-1), Pio (10 mg.kg-1.day-1), their combination (Pio+ATV), or water alone for 3 days. Additional rats received Pio (10 mg.kg-1.day-1) for 3 days and intravenous SC-58125 [a cyclooxygenase-2 (COX-2) inhibitor] or SC-560 (a COX-1 inhibitor) 15 min before ischemia. Rats underwent 30 min of myocardial ischemia and 4 h of reperfusion, or hearts were harvested for analysis. IS in the Pio and in the ATV groups was significantly smaller than in the sham-treated group. IS in the Pio+ATV group was smaller than in all other groups (P<0.001 vs. each group). The protective effect of Pio was abrogated by SC-58125 but not by SC-560. Pio, ATV, and Pio + ATV increased the expression and activity of cytosolic phospholipase A2 (cPLA2) and COX-2. ATV increased phosphorylated-Akt, phosphorylated-endothelial NOS (P-eNOS), inducible NOS, and COX-2 levels. In contrast, Pio caused an insignificant increase in myocardial levels of phosphorylated-Akt but did not change P-eNOS and iNOS expression. In conclusion, the IS-limiting effects of Pio and ATV involve COX-2. However, the upstream steps differ. ATV induced eNOS phosphorylation and iNOS, cPLA2, and COX-2 expression, whereas Pio induced mainly the expression and activity of cPLA2. The effects of Pio and ATV were additive.

Animals↗

Hypercalcemia-induced ST-segment elevation mimicking acute myocardial infarction.

We describe a patient who presented with abdominal pain radiating to the chest and ST elevation in the precordial leads, mimicking acute myocardial infarction. Urgent coronary angiography revealed normal coronary arteries and his serum troponin has not increased. Subsequently, he was found to have severe hypercalcemia. ST segment elevation resolved after correction of hypercalcemia. This phenomenon of ST elevation secondary to hypercalcemia has been described only two times in the English literature to date.

Adult↗

An unusual complication after aortic valve replacement.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa, though rare, can occur after aortic valve replacement. We report an asymptomatic patient who developed this unusual complication and describe the use of transesophageal and 3-dimensional echocardiography to help confirm the diagnosis.

Adult↗

Enhanced cardioprotection against ischemia-reperfusion injury with combining sildenafil with low-dose atorvastatin.

PURPOSE: Both ATV and SL reduce myocardial infarct size (IS) by enhancing expression and activity of NOS isoforms. We investigated whether atorvastatin (ATV) and sildenafil (SL) have synergistic effects on myocardial infarct size (IS) reduction and enhancing nitric oxide synthase (NOS) expression. METHOD: Rats were randomized to nine groups: ATV-1 (1 mg/kg/d); ATV-10 (10 mg/kg/d); SL-0.7 (0.7 mg/kg); SL-1 (1 mg/kg); ATV-1 + SL-0.7; water alone (controls); 1400W (iNOS inhibitor; 1 mg/kg); ATV-10 + 1400W; and ATV-1 + SL-0.7 + 1400W. ATV was administered orally for 3 days. SL was administered intraperitoneally 18 h before surgery and 1400W intravenously 15 min before surgery. Rats either underwent 30 min ischemia-4 h reperfusion or the hearts were explanted for immunoblotting and enzyme activity tests without being exposed to ischemia. RESULTS: IS (% risk area, mean +/- SEM) was smaller in the ATV-10 (13 +/- 1%), SL-1 (11 +/- 2%), SL-0.7 (18 +/- 2%) and ATV-1 + SL-0.7 (9 +/- 1%) groups as compared with controls (34 +/- 3%; P < 0.001), whereas ATV-1 had no effect (29 +/- 2%). ATV-1 + SL-0.7 (9 +/- 1%) reduced IS more than SL-0.7 alone (p = 0.012). 1400W abrogated the protective effect of ATV-10 (35 +/- 3%) and ATV-1 + SL-0.7 (34 +/- 1%). SL-0.7 and ATV-10 increased phosphorylated endothelial (P-eNOS; 210 +/- 2.5% and 220 +/- 8%) and inducible (iNOS; 151 +/- 1% and 154 +/- 1%) NOS expression, whereas ATV-1 did not. These changes were significantly enhanced by ATV-1 + SL-0.7 (P-eNOS, 256 +/- 2%, iNOS 195 +/- 1%). SL-1 increased P-eNOS (311 +/- 22%) and iNOS (185 +/- 1%) concentrations. CONCLUSIONS: Combining low-dose ATV with SL augments the IS limiting effects through enhanced P-eNOS and iNOS expression.

Amidines↗

Statins are associated with lower risk of gastrointestinal bleeding in patients with unstable coronary syndromes: analysis of the Orbofiban in Patients with Unstable coronary Syndromes-Thrombolysis In Myocardial Infarction 16 (OPUS-TIMI 16) trial.

BACKGROUND: It has recently been shown that statins increase the myocardial content of prostaglandin (PG) I2 (prostacyclin) and PGE2. A systemic increase of PG production may protect the gastric mucosa and prevent gastrointestinal (GI) bleeding. We hypothesized that statins would lower the risk of GI bleeding associated with antiplatelet therapy in patients with acute coronary syndromes (ACS). METHODS: We retrospectively analyzed data on 10288 patients with ACS included in the OPUS-TIMI 16 trial and received aspirin and either the oral IIb/IIIa inhibitor orbofiban or placebo. RESULTS: Inhospital GI bleeding rate was significantly lower in patients who were receiving lipid-lowering drugs before admission compared with those who were not (0.2% vs 0.6%, P = .031). Throughout 10 months of follow-up, GI bleeding occurred in 1.8% of non-statin users compared with 1.0% of statin users (P = .001). Statin use was associated with less overall bleeding in both the orbofiban (1.4% vs 2.4%, P = .006) and the placebo groups (0.2% vs 0.8%, P = .047). Severe and major bleeding occurred less frequently with statin use (0.8% vs 1.5%, P = .001) in both the orbofiban (1.1% vs 2.0%, P = .006) and the placebo groups (0.1% vs 0.5%, P = .119). Logistic regression analysis showed that age > 65 years, orbofiban treatment, Killip class > 1, history of cerebrovascular disease, and calcium-channel blocker use were associated with higher risk of GI bleeding, whereas statin therapy was associated with a lower risk (odds ratio 0.68, 95% CI 0.45-1.04, P = .079). CONCLUSIONS: Statins may exert protective effect against GI bleeding in patients with ACS. Additional studies are warranted to explore this additional potential benefit of statins.

Acute Disease↗

Electrocardiographic markers of reperfusion in ST-elevation myocardial infarction.

The outcome of patients who fail to reperfuse with thrombolytic therapy or percutaneous coronary intervention (PCI) for ST-elevation acute myocardial infarction (STEMI) may be improved with additional pharmacologic and mechanical interventions such as rescue PCI or intravenous glycoprotein IIb/IIIa infusion. The standard 12-lead ECG is the most commonly available and suitable tool for routine bedside evaluation of the success of reperfusion therapy for STEMI. This article reviews and discusses the current data on the four ECG markers for prediction of the perfusion status of the ischemic myocardium: ST-segment deviation, T-wave configuration, QRS changes, and reperfusion arrhythmias.

Arrhythmias, Cardiac↗

Electrocardiographic diagnosis of ST-elevation myocardial infarction.

The ECG is an essential part of the initial evaluation of patients who have chest pain, especially in the immediate decision-making process in patients who have ST-elevation myocardial infarction. This article reviews and summarizes the current information that can be obtained from the admission ECG in patients who have ST-elevation acute myocardial infarction, with an emphasis on: (1) prediction of final infarct size, (2) estimation of prognosis, and (3) the correlations between various ECG patterns and the localization of the infarct and the underlying coronary anatomy.

Electrocardiography↗

Stress echocardiography in octogenarians: transesophageal atrial pacing is accurate, safe, and well tolerated.

The feasibility and diagnostic accuracy of transesophageal pacing stress echocardiography for detection of inducible myocardial ischemia were evaluated in 161 patients 80 years of age or older (mean 84 +/- 3.9, range 80-97). The pacing time was 5.5 +/- 2.5 minutes with a total test time of 37 +/- 7 minutes. The mean achieved heart rate was 96 +/- 7% (83%-121%) of maximum predicted with an average rate pressure product of 21,560 +/- 5175 beats/min x mm Hg. There were minor adverse events in 8% of cases and no major complications occurred. Patient acceptance was high. When compared with myocardial single photon emission computed tomography, pacing stress echocardiography had a sensitivity of 89% and a specificity of 93% for the detection of myocardial ischemia, and 91% agreement (kappa = 0.80, P < .001). We demonstrate that pacing stress echocardiography is safe and accurate for detection of myocardial ischemia and, thus, a reliable substitute to exercise and pharmacologic stress testing in octogenarians.

Aged, 80 and over↗

Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2.

We determined the effects of cyclooxygenase-1 (COX-1; SC-560), COX-2 (SC-58125), and inducible nitric oxide synthase (iNOS; 1400W) inhibitors on atorvastatin (ATV)-induced myocardial protection and whether iNOS mediates the ATV-induced increases in COX-2. Sprague-Dawley rats received 10 mg ATV.kg(-1).day(-1) added to drinking water or water alone for 3 days and received intravenous SC-58125, SC-560, 1400W, or vehicle alone. Anesthesia was induced with ketamine and xylazine and maintained with isoflurane. Fifteen minutes after intravenous injection rats underwent 30-min myocardial ischemia followed by 4-h reperfusion [infarct size (IS) protocol], or the hearts were explanted for biochemical analysis and immunoblotting. Left ventricular weight and area at risk (AR) were comparable among groups. ATV reduced IS to 12.7% (SD 3.1) of AR, a reduction of 64% vs. 35.1% (SD 7.6) in the sham-treated group (P < 0.001). SC-58125 and 1400W attenuated the protective effect without affecting IS in the non-ATV-treated rats. ATV increased calcium-independent NOS (iNOS) [11.9 (SD 0.8) vs. 3.9 (SD 0.1) x 1,000 counts/min; P < 0.001] and COX-2 [46.7 (SD 1.1) vs. 6.5 (SD 1.4) pg/ml of 6-keto-PGF(1alpha); P < 0.001] activity. Both SC-58125 and 1400W attenuated this increase. SC-58125 did not affect iNOS activity, whereas 1400W blocked iNOS activity. COX-2 was S-nitrosylated in ATV-treated but not sham-treated rats or rats pretreated with 1400W. COX-2 immunoprecipitated with iNOS but not with endothelial nitric oxide synthase. We conclude that ATV reduced IS by increasing the activity of iNOS and COX-2, iNOS is upstream to COX-2, and iNOS activates COX-2 by S-nitrosylation. These results are consistent with the hypothesis that preconditioning effects are mediated via PG.

Animals↗

Benefits, unresolved questions, and technical issues of cardiac resynchronization therapy for heart failure.

This review aims to provide a synthesis of the published evidence regarding the rationale and clinical benefits of cardiac resynchronization therapy (CRT) with implantable atrial-synchronized biventricular pacing (BVP) devices in patients with moderate to advanced heart failure and intra- and interventricular conduction delays. In addition, it addresses clinical and technical issues that have yet to be resolved, such as the selection of the most suitable candidates for CRT; the usefulness of combining BVP with automatic defibrillation backup; the value of CRT in patients with atrial fibrillation; the importance of alternative sites of pacing, such as the atrial septum and the right ventricular (RV) outflow tract; the harmful effects of the long-standing practice of producing an iatrogenic left bundle branch block by conventional RV pacing in patients receiving standard permanent pacemakers; the question of precisely where on the left ventricle optimal pacing is achieved; and the potential applications of CRT in patients with pediatric or congenital heart disease. Considering how major advances have been achieved since the first clinical application of CRT in 1994, one can be optimistic about the future of the electrotherapeutic management of heart failure.

Cardiac Pacing, Artificial↗

Feasibility, safety, and morphologic predictors of outcome of repeat percutaneous balloon mitral commissurotomy.

Early and mid-term results of repeat percutaneous balloon mitral commissurotomy (PBMC) were analyzed in 35 patients with symptomatic valvular restenosis: 12 patients (34%) after first successful PBMC and 23 patients (66%) after successful surgical closed mitral commissurotomy. Twenty-one patients had bilateral fused commissures, and 14 patients had unilateral or bilateral split commissures. Mitral valve area gain was significantly greater in the group with fused commissures compared with the group with split commissures (0.6 +/- 0.2 vs 0.3 +/- 0.2 cm(2), respectively, p = 0.04).

Adult↗

Ischemia-induced ST-segment elevation: classification, prognosis, and therapy.

The standard 12-lead electrocardiogram (ECG) remains the most useful tool for the diagnosis, early risk stratification, triage, and guidance of therapy in patients with acute coronary syndromes. However, the initial and the terminal part of the QRS complex, the ST segments, and the T waves are influenced by anatomical and metabolic factors such as the "myocardium at risk" and "severity" and "duration" of ischemia. Moreover, there are complex interactions between all these factors. The ECG can identify potential candidates for reperfusion therapy as well as the completeness and success of reperfusion, whereas it can also identify those patients who will have no benefit from reperfusion because of either late arrival or nonischemic etiologies of ECG changes. These patients may have a "pseudo" ST-elevation acute myocardial infarction (STEAMI) or "pseudo-pseudo" STEAMI. The presence of Q waves and additional ST-segment depression and T-wave inversion on the admission ECG in patients with STEAMI may provide us information regarding the potential myocardial reserves, and various ECG scoring systems are in current use for that purpose. The pattern and timing of changes in Q waves, ST segment, and T waves may all be markers of the patency status of the infarct-related artery. We review and discuss each of the dynamic ECG variables during ischemia and reperfusion: the initial QRS (Q and R waves), the terminal QRS (Sclarovsky-Birnbaum score), the ST segment, and the T waves.

Electrocardiography↗