Antonella Lombardo

Inflammation as a Possible Link Between Coronary and Carotid Plaque Instability

Background— Multiple complex stenoses, plaque fissures, and widespread coronary inflammation are common in acute coronary syndromes. A systemic cause of atherosclerotic plaque instability is also suggested by studies of ischemic cerebrovascular disease. We investigated the association between coronary and carotid plaque instability and the potential common causal role of inflammation. Methods and Results— The ultrasound characteristics of carotid plaques were evaluated retrospectively in patients scheduled for coronary bypass surgery, 181 with unstable and 92 with stable angina, and prospectively in a similar group of patients, 67 with unstable and 25 with stable angina, in whom serum C-reactive protein levels were also measured. The prevalence of carotid plaques was similar in the retrospective and prospective studies and >64% in both unstable and stable coronary patients. The prevalence of complex, presumably unstable carotid plaques was 23.2% in unstable versus 3.2% in stable patients (P <0.001) in the retrospective study and 41.8% versus 8.0% (P =0.002) in the prospective study. C-reactive protein levels were higher in patients with complex (7.55 mg/L) than in those with simple (3.94 mg/L; P <0.05) plaques or without plaques (2.45 mg/L; P <0.05). On multivariate analysis, unstable angina and C-reactive protein levels >3 mg/L were independently associated with complex carotid plaques (OR, 6.09; 95% CI, 1.01 to 33.72; P =0.039, and OR, 5.80; 95% CI, 1.55 to 21.69; P =0.009, respectively). Conclusions— In unstable angina, plaque instability may not be confined to coronary arteries, and inflammation may be the common link with carotid plaque instability. These observations may have relevant implications for understanding the mechanisms of acute widespread atherothrombotic plaque inflammation.

Temporal evolution and functional outcome of no reflow: sustained and spontaneously reversible patterns following successful coronary recanalisation.

Objective: To identify in humans the temporal patterns of no reflow and their functional implications. Methods: 24 patients with first acute myocardial infarction and successful coronary recanalisation by recombinant tissue-type plasminogen activator (n = 15) or primary percutaneous transluminal coronary angioplasty (n = 9) were studied by myocardial contrast echocardiography within 24 hours of recanalisation and at one month’s follow up. Myocardial contrast echocardiography was performed by intermittent harmonic power Doppler and intravenous Levovist. The regional contrast score index (CSI) was calculated within dysfunctioning myocardium. Videointensity was measured (dB) within risk and control areas and their ratio was calculated. Results: In 8 patients reflow was observed at 24 hours and persisted at one month. Conversely in 16 patients areas of no reflow were detectable at 24 hours. At one month, no reflow was spontaneously reversible in 9 patients (mean (SD) CSI and videointensity ratio improved from 2.5 (0.5) to 1.4 (0.6) and from 0.6 (0.1) to 0.7 (0.1), respectively; p < 0.05) and was sustained in the remaining 7 patients (CSI and videointensity ratio remained unchanged from 2.6 (0.6) to 2.6 (0.5) and from 0.5 (0.2) to 0.5 (0.2), respectively; NS). Left ventricular function improved significantly in patients with reflow and reversible no reflow. Volumes were enlarged only in patients with sustained no reflow. Conclusions: No reflow detected at 24 hours may be sustained or spontaneously reversible at one month. Such reversibility of the phenomenon is associated with preserved left ventricular volumes and function. Clarification of the mechanisms of delayed reversibility may lead to tailored treatment of no reflow even in the subacute phase of myocardial infarction.

Significance of transient ST-T segment changes during dobutamine testing in Q wave myocardial infarction

OBJECTIVES We evaluated dobutamine stress electrocardiography for detecting potentially reversible contractile dysfunction or residual ischemia in the infarct-related area. BACKGROUND ST-T segment changes in pathologic Q wave leads during stress testing may reflect contractile reserve, inducible ischemia or passive mechanical stretching. Dobutamine echocardiography allows detection of contractile reserve at low doses and inducible ischemia at high doses. METHODS We used low (5 to 10 microg/kg body weight per min) and high doses (20 to 40 microg/kg per min) of dobutamine in 49 patients with a previous Q wave myocardial infarction and analyzed the relation between ST-T segment changes in pathologic Q wave leads and regional contraction. RESULTS At low dose dobutamine, regional contraction improved in the infarct-related area in 23 patients. New or further ST segment elevation and pseudonormalization of negative T waves developed at low doses more frequently in patients with than without contractile reserve (both p < 0.001), giving a sensitivity of 43.5% and 60.9% and a specificity of 100% and 96.2%, respectively. At high dose dobutamine (43 patients), new or further ST segment elevation and pseudonormalization of negative T waves, occurring beyond those observed at low doses, had a low predictive accuracy for contractile reserve (sensitivity of 9.5% and 14.3% and specificity of 68.2% and 81.8%, respectively). Pseudonormalization of negative T waves at high dose dobutamine was 100% specific (but only 25% sensitive) for homozonal ischemia. CONCLUSIONS ST segment elevation or pseudonormalization of negative T waves, or both, is indicative of contractile reserve in the infarct-related area when either develops at low dose dobutamine, but may be associated with worsening or no change in contractile function at high doses.

Contractile reserve of dysfunctional myocardium after revascularization: a dobutamine stress echocardiography study.

OBJECTIVES We sought to investigate the effects of revascularization on the contractile reserve of dysfunctional myocardium. BACKGROUND The improvement in dysfunctional but viable myocardium after revascularization is frequently less than expected from the amount of contractile reserve detected on dobutamine stress echocardiography. The fate of the contractile reserve, when it does not result in an adequate contractile recovery, is unknown. METHODS Basal contraction and contractile reserve of infarct zones were assessed by dobutamine stress echocardiography in 21 postinfarction male patients before and > 3 months after revascularization (30 infarct zones; mean +/- SD left ventricular ejection fraction 35 +/- 8%). An infarct zone wall motion score index (WMSI) was calculated. RESULTS Before revascularization, contractile reserve was present in 14 infarct zones (12 patients) and absent in 16 (9 patients). After revascularization, ejection fraction increased by 5 +/- 4% (p < 0.01) in patients classified as positive for contractile reserve and remained unchanged in those classified as negative. New York Heart Association classification improved in 58.3% and 22.2% of patients, respectively. Basal contraction improved in eight zones with previous contractile reserve (57.1%) and in one zone without (6.3%) (p < 0.01). Contractile reserve was still evident in 13 zones with previous contractile reserve (93%; 8 with contractile recovery), and it developed in 6 zones without (38%; none with contractile recovery). WMSI values after revascularization were decreased from values before revascularization during low dose dobutamine in zones with and without previous contractile reserve (p < 0.01 and < 0.05, respectively). CONCLUSIONS After revascularization, contractile reserve is maintained or even increases in viable infarct zones that do not recover as expected. It may also develop in some infarct zones judged not to be viable before revascularization. This increased contractile reserve may play a role in the functional improvement of patients after revascularization.

Risk stratification of patients undergoing peripheral vascular revascularization by combined resting and dipyridamole echocardiography

Patients with advanced peripheral vascular disease have an increased cardiac morbidity and mortality. The aim of this study was to assess the predictive value of rest and stress echocardiography for perioperative and late cardiac events in 110 patients undergoing limb revascularization. All patients underwent preoperative clinical and echocardiographic evaluation at rest and by dipyridamole stress testing to assess cardiac risk. Patients with > or =3 clinical Eagle markers, low left ventricular ejection fraction at rest, or positive dipyridamole stress test results were considered at high cardiac risk. To record adverse cardiac events, all patients were monitored during and after surgery, and followed for at least 1 year after hospital discharge. Cardiac complications occurred in 10 patients (9.7%) perioperatively (2 fatal myocardial infarctions), and in 13 (13%) at 1-year follow-up (7 fatal myocardial infarctions). Echocardiographic evaluation was the best predictor of early (p <0.00003) and late (p <0.0003) cardiac complications. No patient with a negative dipyridamole stress test result and good left ventricular ejection fraction had cardiac complications, either postoperatively or during follow-up. Clinical evaluation does not appear sufficiently sensitive for predicting perioperative cardiac events, but was valuable in predicting late cardiac complications (p <0.0002). Our data show that echocardiographic evaluation of resting dysfunction and of the ischemic response to dipyridamole is a good predictor of perioperative cardiac risk, and is superior to generally available clinical data. Echocardiographic evaluation is useful in defining a low-risk group of patients who can safely undergo limb revascularization, whichever surgical procedure is proposed.

Regional wall motion analysis by dobutamine stress echocardiography to distinguish between ischemic and nonischemic dilated cardiomyopathy

To distinguish between ischemic and nonischemic dilated cardiomyopathy (DCM), we studied 43 patients with left ventricular dysfunction (15 ischemic and 28 nonischemic detected by coronary angiography) by dobutamine stress echocardiography. At rest, there were more normal segments (p<0.001) and a trend toward more akinetic segments (p, not significant) per ischemic than per nonischemic DCM patient. However, either at rest or with low-dose dobutamine, individual data largely overlapped. At peak dose, in ischemic DCM, regional contraction worsened in many normal or dys-synergic regions at rest (in the latter case after improvement with low-dose dobutamine); in contrast, in nonischemic DCM, further mild improvement was observed in a variable number of left ventricular areas. Thus with peak-dose dobutamine, more akinetic and less normal segments were present per ischemic than per nonischemic DCM patient (both, p<0.001). A value of six or more akinetic segments was 80% sensitive and 96% specific for ischemic DCM. Our data show that analysis of regional contraction by dobutamine stress echocardiography can distinguish between ischemic and nonischemic DCM.

Reversible microvascular dysfunction coupled with persistent myocardial dysfunction: implications for post‐infarct left ventricular remodelling

Background: Recent studies have shown that microvascular dysfunction after myocardial infarction is a dynamic phenomenon. Aims: To evaluate the implications of dynamic changes in microvascular dysfunction on contractile recovery and left ventricular remodelling, and to identify the ideal timing of assessment of such microvascular dysfunction. Methods and results: In 39 patients with a first myocardial infarction who underwent successful percutaneous coronary intervention, microvascular dysfunction was studied by myocardial contrast echocardiography (MCE) at 24 h, 1 week and 3 months after the procedure. Real-time MCE was performed by contrast pulse sequencing and intravenous Sonovue. 14 patients exhibited left ventricular remodelling at 3 months (>20% increase in left ventricular end-diastolic volume, group B), whereas 25 did not (group A). Microvascular dysfunction was similar in the two groups at 24 h and improved in group A only, being significantly better than that of group B at 1 week (p<0.05) and 3 months (p<0.005). Improvement in microvascular dysfunction was not associated with improvement in wall motion in the same segments. With multivariate analysis including all echocardiographic variables, microvascular dysfunction at 1 week was found to be the only independent predictor of left ventricular remodelling (p<0.01). With a cut-off value of 1.4, 1-week microvascular dysfunction predicts left ventricular remodelling with sensitivity and specificity of 73%. Conclusions: Improvement in microvascular dysfunction occurs early after myocardial infarction, although it is not associated with a parallel improvement in wall motion but is beneficial in preventing left ventricular remodelling. Accordingly, 1-week microvascular dysfunction is a powerful and independent predictor of left ventricular remodelling.

Assessment of resting perfusion defects in patients with acute myocardial infarction: comparison of myocardial contrast echocardiography, combined first-pass/delayed contrast-enhanced magnetic resonance imaging and 99mTC-sestamibi SPECT.

BackgroundInformation on the accuracy of both magnetic resonance imaging (MRI) and myocardial contrast echocardiography (MCE) for the identification of perfusion defects in patients with acute myocardial infarction is limited. We evaluated the accuracy of MRI and MCE, using Single Photon Emission Computed Tomography (SPECT) imaging as reference technique.MethodsFourteen consecutive patients underwent MCE, MRI and 99mTc-MIBI SPECT after acute myocardial infarction to assess myocardial perfusion. MCE was performed by Harmonic Power Angio Mode, with end-systolic triggering 1:4, using i.v. injection of Levovist®. First-pass and delayed enhancement MRI was obtained after i.v administration of Gadolinium-DTPA. At MCE, homogeneous perfusion was considered as normal and absent or “patchy” perfusion as abnormal. At MRI, homogenous contrast enhancement was defined as normal whereas hypoenhancement at first-pass followed by hyperenhancement or persisting hypoenhancement in delayed images was defined as abnormal.ResultsAt MCE 153 (68%) of segments were suitable for analysis compared to 220 (98%) segments at MRI (p<0.001). Sensitivity, specificity and accuracy of MCE for segmental perfusion defects in these 153 segments were 83, 73 and 77%, respectively. Sensitivity, specificity and accuracy of MRI were 63, 82, and 77%, respectively. MCE and MRI showed a moderate agreement with SPECT (k: 0.52 and 0.46, respectively). The agreement between MCE and MRI was better (k: 0.67) that the one of each technique with SPECT.ConclusionMCE and MRI may be clinically useful in the assessment of perfusion defects in patients with acute myocardial infarction, even thought MCE imaging may be difficult to obtain in a considerable proportion of segments when the Intermittent Harmonic Angio Mode is used.

Predictors of impaired heart rate variability and clinical outcome in patients with acute myocardial infarction treated by primary angioplasty.

Objective To investigate the determinants and prognostic value of heart rate variability (HRV) in acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention (PCI). Methods We studied 64 patients with AMI (58.4 ± 10 years, 56 men), treated by PCI within 12 h of symptom onset. Patients underwent 24-h electrocardiographic Holter recording before discharge. HRV was measured in the time- and frequency-domain. Cardiac events were assessed at 6 months. Results At univariate analysis, Thrombolysis in Myocardial Infarction (TIMI) flow grade < 3 was significantly predictive of reduced frequency-domain variables. On multivariate analysis, diabetes and pre-PCI time > 6 h were the strongest predictors of depressed HRV, with peak creatine kinase myocardial-type and lower left ventricular ejection fraction being also variably correlated with impaired HRV. At 6-month follow-up, seven patients (10.1%) had cardiac events (one AMI, six revascularization procedures). A low standard deviation of RR intervals was a significant predictor of events (P = 0.009), although only age was associated with the endpoint (P = 0.05) on multivariate analysis. Conclusions Our study shows that, in AMI patients treated by primary PCI, a delay in coronary revascularization and AMI extension are key factors for determining depressed HRV.

Low incidence of serotonin-induced occlusive coronary artery spasm in patients with recent myocardial infarction

Intracoronary infusion of serotonin has been reported to induce varying degrees of coronary vasoconstriction in different coronary syndromes, but it has never been studied in patients after myocardial infarction. In patients with recent myocardial infarction, we found a low incidence (11%) of serotonin-induced occlusive spasm only in the infarct-related artery (IRA), and a significantly higher vasoconstriction in the distal segment of the IRA than in the same segment of the non-IRA.