Roberto Piero Dabizzi

Increase of myocardial salvage and left ventricular function recovery with intracoronary abciximab downstream of the coronary occlusion in patients with acute myocardial infarction treated with primary coronary intervention

In this prospective randomized trial on patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI), we hypothesized that abciximab administered intracoronarily, downstream of the coronary occlusion, leads to a greater degree of myocardial salvage and better left ventricular function recovery compared with the usual abciximab administration. Forty‐five consecutive patients with first AMI and infarct‐related artery TIMI flow 0–1 undergoing primary PCI were enrolled. Twenty‐two patients were randomly assigned to the intracoronary treatment and 23 to the usual treatment. The initial perfusion defect, final infarct size, myocardial salvage, salvage index, and left ventricular function recovery were assessed by serial scintigraphic scans performed at admission and 7 days and 1 month after PCI. Angiographic myocardial blush grade, corrected TIMI frame count, and electrocardiographic ST segment elevation reduction were also assessed as markers of myocardial reperfusion. Final infarct size was significantly smaller (P = 0.043) and salvage index significantly higher (P = 0.003) in the intracoronary treatment group as a result of a greater degree of myocardial salvage (P = 0.0001). The increase of left ventricular ejection fraction at 1 month was significantly higher in the intracoronary treatment patients (P = 0.013). The markers of myocardial reperfusion were also significantly better in the intracoronary treatment group. In patients with AMI and occluded infarct‐related artery treated with primary PCI, intracoronary abciximab given just before PCI downstream of the occlusion is associated to a greater degree of myocardial salvage than the usual abciximab protocol. This benefit is mainly related to a substantial reduction in final infarct size, which leads to an improvement in left ventricular ejection fraction. Catheter Cardiovasc Interv 2004;62:186–192.

Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation

This study was performed to evaluate, using a randomized double-blind, placebo-controlled protocol, the long-term efficacy and safety of propafenone and sotalol in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation (AF). The maintenance of sinus rhythm in patients with recurrent AF has several potential benefits, the most important being a reduced risk of thromboembolic events. Three hundred patients with recurrent AF (> or = 4 episodes in the last year) and AF at enrollment lasting < 48 hours were randomized to receive either propafenone (mean daily dose 13 +/- 1.5 mg/kg; 102 patients), sotalol (mean daily dose 3 +/- 0.4 mg/kg; 106 patients), or placebo (92 patients). After 1-year follow-up, Kaplan-Meier estimates of the proportion of patients remaining in sinus rhythm were comparable between propafenone (63%) and sotalol (73%) and superior to placebo (35%; p = 0.001 vs both drugs). Symptomatic recurrences occurred later with propafenone and sotalol than with placebo. Nine patients (9%) in the propafenone group, 11 (10%) in the sotalol group, and 3 (3%) in the placebo group discontinued therapy due to adverse effects. Malignant nonfatal arrhythmias due to proarrhythmic effects were documented with sotalol only, and occurred < 72 hours from the beginning of therapy in 4 patients (4%). During recurrences, the ventricular rate was significantly reduced in patients taking propafenone and sotalol (p = 0.001 for both drugs vs placebo). The likelihood of remaining in sinus rhythm during follow-up was higher in younger patients with smaller left atrial size and without concomitant heart disease. In patients with recurrent symptomatic AF, propafenone and sotalol are not significantly different from each other and are superior to placebo in maintaining sinus rhythm at 1 year. Recurrences occur later and tend to be less symptomatic with propafenone and sotalol compared with placebo.

Coronary artery anatomy in corrected transposition of the great arteries

Congenitally corrected transposition of the great arteries is an unusual cardiac malformation with discordant atrioventricular and ventriculoarterial alignments. Because knowledge of the coronary artery anatomy is a prerequisite for successful repair of this cardiac anomaly, selective coronary arteriography was performed in 13 children (4 male and 9 female; age range 18 months to 16 years) and 1 adult (aged 59 years) with congenitally corrected transposition of the great arteries and associated intracardiac defects. The typical coronary distribution of corrected transposition (that is, coronary artery-ventricular concordance) was found in 11 patients. In one patient, a single coronary ostium was observed; the right sinus of Valsalva gave rise to a short common branch that divided into three arteries: a left circumflex artery going to the right, a well developed left anterior descending artery running into the anterior interventricular groove and a third vessel that continued on the normal course of the right coronary artery directed posteriorly. In one patient, the left circumflex artery was particularly small. In another patient, with severe hypoplasia of the left anterior descending coronary artery, the anterior ventricular wall of the heart was supplied by three small branches that ended a short distance from their origins. The adult patient had a large anterior ventricular branch arising from the morphologic left coronary ventricular as well as a large acute marginal branch, with a wide distribution, from the morphologic right coronary artery. Presurgical coronary angiographic documentation is helpful because, in congenitally corrected transposition as well as in complex congenital heart disease, coronary anomalies (in origin, course and distribution) are occasionally present and knowledge of their presence can help determine the most appropriate surgical approach.

Usefulness of Dobutamine Tc-99m Sestamibi-Gated Single-Photon Emission Computed Tomography for Prediction of Left Ventricular Ejection Fraction Outcome After Coronary Revascularization for Ischemic Cardiomyopathy

Gated single-photon emission computed tomography (SPECT) imaging allows analysis of myocardial perfusion and assessment of baseline global and regional left ventricular (LV) function and their changes during low-dose dobutamine infusion. The study examined whether the changes in LV ejection fraction induced by dobutamine and evaluated using technetium-99m sestamibi- gated SPECT predict the evolution of ejection fraction after revascularization in patients with ischemic cardiomyopathy. Thirty-seven patients underwent resting and dobutamine nitrate-enhanced sestamibi-gated SPECT before revascularization and baseline-resting sestamibi gated SPECT after intervention to assess global functional changes. A postrevascularization improvement in ejection fraction > or =5 U was defined as significant. At follow-up, ejection fraction increased significantly in 19 patients. According to receiver-operating characteristic curve analysis, an increase in ejection fraction > or =5 U during dobutamine was the optimal cutoff value for predicting a significant postrevascularization improvement, with 79% sensitivity, 78% specificity, and 78% accuracy. A significant correlation was found between dobutamine and postrevascularization ejection fraction (r = 0.85; p <0.0001). The increase in ejection fraction during dobutamine is a good predictor of an improvement in ejection fraction after revascularization. This represents another important diagnostic contribution obtained using gated SPECT imaging for the assessment of myocardial viability in patients with ischemic cardiomyopathy.

Prediction of functional recovery in patients with chronic coronary artery disease and left ventricular dysfunction combining the evaluation of myocardial perfusion and of contractile reserve using nitrate-enhanced technetium-99m sestamibi gated single-photon emission computed tomography and Dobutamine stress

This study aimed to assess whether contractile reserve evaluation using dobutamine gated single-photon emission computed tomography (SPECT) improves the capability of quantitative perfusion analysis to predict functional recovery of viable hibernating myocardium. Resting and dobutamine nitrate-enhanced technetium-99m sestamibi (sestamibi) gated SPECT studies were performed in patients with coronary artery disease who had left ventricular dysfunction. Tracer activity was quantified, and wall motion and thickening visually scored. Reversible dysfunction was identified with gated SPECT repeated after coronary revascularization. Using the best activity threshold, perfusion quantification achieved 85% sensitivity and 55% specificity. Contractile reserve detection was significantly less sensitive (64%, p <0.0005), but more specific (88%, p <0.00001) than perfusion quantification. However, in the subgroup of hypokinetic segments, the sensitivity of contractile reserve assessment was just slightly lower than perfusion quantification (72% vs 91%, p = NS), whereas specificity was significantly higher (94% vs 23%, p <0.00001). Conversely, in the adyskinetic segments, perfusion quantification was significantly more sensitive than contractile reserve (82% vs 59%, p <0.005), but similarly specific (76% vs 85%, p = NS). Therefore, the identification of reversible dysfunction based on perfusion quantification in adyskinetic segments and on contractile reserve detection in hypokinetic segments was significantly more specific (83% vs 55%, p <0.00001) than standard quantitative perfusion SPECT, without major loss in sensitivity (78% vs 85%, p = NS). In conclusion, contractile reserve evaluation using dobutamine gated SPECT enhances the reliability of nitrate-enhanced sestamibi SPECT when used to predict reversible dysfunction in hypokinetic segments, whereas perfusion quantification remains superior in adyskinetic segments.

Technetium-99m sestamibi imaging to predict left ventricular ejection fraction outcome after revascularisation in patients with chronic coronary artery disease and left ventricular dysfunction: comparison between baseline and nitrate-enhanced imaging

Abstract. Acceptance of technetium-99m sestamibi as a tracer of myocardial viability is growing, particularly when nitrate-enhanced imaging is used. However, few data are available on the ability of 99mTc-sestamibi to predict the evolution of global left ventricular ejection fraction (EF). The aim of this study was to examine the ability of resting and nitrate 99mTc-sestamibi single-photon emission tomography (SPET) to predict EF changes after revascularisation in patients who have chronic coronary artery disease with left ventricular dysfunction. Using baseline resting and nitrate 99mTc-sestamibi SPET, we studied 61 patients scheduled for revascularisation because of left ventricular dysfunction. EF was estimated using two-dimensional echocardiography before and after the intervention. A post-revascularisation improvement of ≥5 EF units was defined as significant. Using a 13-segment model, 99mTc-sestamibi activity was quantified and the nitrate-induced activity changes calculated. Three different criteria for detecting viability (defined as post-revascularisation reversible dysfunction) in asynergic segments were compared: (1) resting 99mTc-sestamibi activity ≥60%; (2) nitrate 99mTc-sestamibi activity ≥65%; and (3) nitrate-induced increase >+10% or nitrate-induced increase ≤+10% and nitrate activity ≥65%. EF increased significantly in 32 patients. The number of viable asynergic segments was significantly higher in these patients than in the remaining 29 subjects, and the difference was greater (P<0.0002) using definition (3) than using either baseline (P<0.002) or nitrate activity (P<0.0005). There was a significant relationship between EF changes and number of viable asynergic segments: Spearman R=0.38, P<0.005 using baseline; Spearman R=0.39, P<0.002 using nitrate activity; and Spearman R=0.55, P<0.000005 using definition (3). According to receiver operating characteristic (ROC) curve analysis, this last criterion achieved the best results (81% sensitivity, 69% specificity and 75% accuracy), with an area under the ROC curve of 0.838; this area was significantly larger than when using either baseline (0.744, P<0.02) or nitrate activity (0.747, P<0.005). 99mTc-sestamibi SPET appears able to predict the evolution of global left ventricular EF after revascularisation, thereby confirming the value of 99mTc-sestamibi as a tracer of myocardial viability. The combination of baseline resting and nitrate imaging seems to significantly improve the diagnostic accuracy of 99mTc-sestamibi SPET for this particular purpose.

Abnormal cardiocoronary thromboxane A2 production in patients with unstable angina

Thromboxane B2 (TXB2), the stable metabolite of thromboxane A2 (TXA2), was measured in the coronary sinus and in aortic blood before and after cold pressor test (CPT) in 21 patients suffering from ischemic heart disease (7 affected by stable effort angina and 14 by unstable angina) and in 12 patients not suffering from myocardial ischemia (control group) during coronary angiography. Aspirin (10 mg/kg intravenously) was administered before catheterization in order to prevent platelet and leukocyte TXA2 formation. Control subjects and patients with effort angina had TXB2 resting levels lower than unstable angina patients without a transcardiac gradient which, on the contrary, was found in unstable angina patients. Only in these patients CPT resulted in a significant TXB2 increase more marked in the coronary sinus (from 50.0 +/- 18.9 pg/ml to 73.0 +/- 35.1 pg/ml, p less than 0.001) than in the aorta (from 33.4 +/- 17.1 pg/ml to 42.6 +/- 24.0 pg/ml, p less than 0.05), so that the transcardiac TXB2 gradient significantly increased. In all but two unstable angina patients, TXB2 elevation was not associated with a fall of cardiac lactate extraction. The resting and CPT-induced TXB2 gradients were unrelated to the presence and severity of coronary angiographic lesions. These results indicate that unstable angina patients show an abnormal cardiocoronary capacity to synthesize TXA2, which seems not to be elicited by the occurrence of myocardial ischemia.

Intravenous propafenone: Efficacy and safety in the conversion to sinus rhythm of recent onset atrial fibrillation—A single-blind placebo-controlled study

SummaryThe effectiveness of intravenous propafenone for conversion to sinus rhythm (SR) of paroxysmal atrial fibrillation (AF), lasting less than 7 days, was evaluated with a single-blind, randomized, placebo-controlled study, given the possible spontaneous conversion of this arrhythmia. Group 1 (98 patients) received intravenous propafenone (2 mg/kg iv over 10 minutes followed by 0.007 mg/kg/min); and group 2 (84 patients) received intravenous placebo (0.9% saline solution). The infusion was continued until restoration of SR but no longer than 24 hours. Eight-nine patients (90.8%) received propafenone and 27 patients (32%) receiving placebo were converted to SR (p<0.005). The mean conversion time was 2.46±2.59 hours in group 1 and 17.15±5.78 hours in group 2 (p<0.005). In patients treated with propafenone, conversion of SR mostly occurred in the first 4 hours (86.5%), considered to be the optimal infusion time in our experience. In both groups, the left atrial size was significantly larger in nonconverted than in converted patients. Similarly, the duration of the arrhythmia was significantly longer in nonconverted patients. In nonconverted patients, the mean ventricular rate decreased from 143±beats/min to 101±18 beats/min after propafenone and from 135±19 beats/min to 199 ±16 beats/min after placebo (group 1 vs. group 2: p<0.005). Two episodes of sinus standstill (3.4 and 3.8, seconds, respectively) occurred at SR restoration obtained with propafenone. Intravenous propafenone is an effective, safe, and usually rapid drug for AF treatment. Moreover, it produces a real and significant reduction in the mean ventricular rate in nonconverted patients.

Propafenone and sotalol in the prevention of paroysmal atrial fibrillation: long-term safety and efficacy study

Abstract The efficacy and tolerability of propafenone and sotalol in the prevention of paroysmal atrial fibrillation (AF) were assessed in a doubleblind placebo-controlled study over 1 year. Participants included 300 patients (168 men and 132 women) with an average age of 52.3 years. Patients were randomly divided into three groups: group A (n = 102) received propafenone (13 mg/kg per day); group B (n = 106) received sotalol (3 mg/kg per day); and group C (n = 92) received placebo. Therapy was administered orally three times daily. All patients had suffered, on at least four occasions during the preceding 12 months, from symptomatic paroxysmal AF. In the follow-up period, the occurence of artrial tachyarrhythmias, the recurrence of AF, or the appearance of atrial flutter or supraventricular tachycardia were evaluated. In 3 patients (3.0%) in group A and 5 patients (4.7%) in group B, treatment was discontinued because of side effects. In 11 patients (37%), follow-up was not completed. In the remaining 281 patients, atrial tachyarrhythmias were observed in 43 patients (46.2%) in group A, 28 (29.5%) in group B, and 67 (74.4%) in group C. The rate of occurrence was significantly less ( P P P

Impaired cardiac PGI2 and PGE2 biosynthesis in patients with angina pectoris

Thirty-four patients with unstable angina and 14 patients with stable effort angina were investigated for cardiac prostacyclin and prostaglandin E2 (PGE2) biosynthesis, under resting conditions and after cold pressor testing. Twenty-seven patients undergoing cardiac catheterization and coronary angiography for congenital or acquired heart diseases other than coronary artery disease were studied as a control group. Prostacyclin (as 6-keto-PGF1 alpha) and PGE2 were measured by specific radioimmunoassay of blood from the coronary sinus and aorta. During resting conditions no significant differences in plasma 6-keto-PGF1 alpha and PGE2 concentrations were found between coronary sinus and aortic blood, and no transcardiac gradient existed either in control subjects or in patients with stable and unstable angina, respectively. In control subjects cold pressor testing induced a significant increase in 6-keto-PGF1 alpha and PGE2 levels in blood from the different sampling sites, and a significant transcardiac gradient occurred (+11.2 +/- 6.4 pg/ml for 6-keto-PGF1 alpha and +5.1 +/- 3.4 pg/ml for PGE2). However, in angina patients no significant increase in 6-keto-PGF1 alpha and PGE2 plasma levels was found and no transcardiac gradient was formed after cold pressor testing. These results indicate impaired cardiac prostacyclin and PGE2 biosynthesis both in patients with stable and unstable effort angina.