Carlo Iacoboni

Influence of residual perfusion within the infarct zone on the natural history of left ventricular dysfunction after acute myocardial infarction: A myocardial contrast echocardiographic study

OBJECTIVES This study used myocardial contrast echocardiography to investigate the extent of residual perfusion within the infarct zone in a select group of patients with recently reperfused myocardial infarction and evaluated its influence on the ultimate infarct size. BACKGROUND Limited information is available on the status of myocardial perfusion within postischemic dysfunctional segments at predischarge and on its influence on late regional and global functional recovery. METHODS Twenty patients with acute myocardial infarction were selected for the study. Patients met the following inclusion criteria: 1) single-vessel coronary artery disease; 2) patency of infarct-related artery with persistent postischemic dysfunctional segments at predischarge; 3) stable clinical condition up to 6 months after hospital discharge. All selected patients underwent coronary angiography and myocardial contrast echocardiography before hospital discharge and repeated the echocardiographic examination 6 months later. Patients were grouped according to the pattern of contrast enhancement in predischarge dysfunctional segments. RESULTS In nine patients (group I), the length of segments showing abnormal contraction coincided with that of the contrast defect segments. In the remaining 11 patients (group II), postischemic dysfunctional segments were partly or completely reperfused. There was no difference between the two groups in asynergic segment length at predischarge (7.3 +/- 2.5 vs. 7.2 +/- 4.3 cm, p = NS). At follow-up study, asynergic segment length was significantly reduced in group II patients, whereas no changes were observed in group I patients (from 7.2 +/- 4.3 to 4.7 +/- 3.7 cm, p < 0.005; and from 7.3 +/- 2.5 to 7.5 +/- 2.9 cm, p = NS, respectively). CONCLUSIONS Among patients with a predischarge patent infarct-related artery, further improvement in regional and global function may be expected during follow-up when residual perfusion in the infarct zone is present.

Global and regional longitudinal strain assessed by two-dimensional speckle tracking echocardiography identifies early myocardial dysfunction and transmural extent of myocardial scar in patients with acute ST elevation myocardial infarction and relatively preserved LV function.

AIMS Global and regional longitudinal strain (GLS-RLS) assessed by two-dimensional speckle tracking echocardiography (2D-STE) are considered reliable indexes of left-ventricular (LV) function and myocardial viability in chronic ischaemic patients when compared with delayed-enhanced cardiac magnetic resonance (DE-CMR). In the present study, we tested whether GLS and RLS could also identify early myocardial dysfunction and transmural extent of myocardial scar in patients with acute ST elevation myocardial infarction (STEMI) and relatively preserved LV function. METHODS AND RESULTS Twenty STEMI patients with LVEF ≥40%, treated with PPCI within 6 h from symptoms onset, underwent DE-CMR and 2D-echocardiography for 2D-STE analysis 6 ± 2 days after STEMI. Wall motion score index (WMSI) and LV ejection fraction (LVEF) were calculated by both methods. Infarct size and transmural extent of necrosis were assessed by CMR. GLS and RLS were obtained by 2D-STE. Mean GLS of the study population was -14 ± 3.3, showing a significant correlation with both LVEF and WMSI, by CMR (r = -0.86, P = 0.001, and r = 0.80, P = 0.001, respectively) and time-to-PCI (r = 0.66, P = 0.038). A weaker correlation was found between GLS and LVEF and WMSI assessed by 2D-echo (r = -0.65, P = 0.001, and r = 0.53, P = 0.013, respectively). RLS was significantly lower in DE-segments when compared with normal myocardium (P < 0.0001). A cut-off value of RLS of -12.3% by receiver-operating characteristic (ROC) curves identified DE-segments (sensitivity 82%, specificity 78%), whereas a cut-off value of -11.5% identified transmural extent of DE (sensitivity 75%, specificity 78%). CONCLUSION Our findings indicate that RLS and GLS evaluation provides an accurate assessment of global myocardial function and of the presence of segments with transmural extent of necrosis, with several potential clinical implications.

Prognostic factors in severe pulmonary hypertension patients who need parenteral prostanoid therapy: The impact of late referral

BACKGROUND Oral drugs have made the treatment of pulmonary hypertension (PH) feasible in non-expert centers, which could delay patient access to prostanoid therapy. METHODS Fifty-seven consecutive patients with precapillary PH received a prostanoid in our center. Data at prostanoid initiation included modality of center referral, medical history, New York Heart Association [NYHA] class, exercise capacity, echocardiographic parameters, and hemodynamics. RESULTS Overall survival at 1, 2, and 3 years was 85%, 69%, 55%, respectively. Non-survivors had worse NYHA class III/IV (17/12) than survivors (27/1; p < 0.01) and exercise capacity on 6-minute-walk distance (254 ± 114 vs 354 ± 91 meters; p < 0.01). Non-survivors were more frequently referred on oral therapy (83% vs 36%; p < 0.01) and had a higher rate of urgent prostanoid treatment (69% vs 17%; p < 0.0001). Multivariate analysis (hazard ratio [95% confidence interval]) found the independent prognostic factors were urgent prostanoid therapy (2.0 [1.1-3.9]) and NYHA class (3.5 [1.5-8.2]). Survivors had a significant response to prostanoid, improving NYHA class from 2.8 ± 0.4 to 2.3 ± 0.5 (p = 0.002), 6-minute walk distance from 354 ± 91 to 426 ± 82 meters (p = 0.0001), and pulmonary hemodynamics (pulmonary artery pressure from 56 ± 13 to 44 ± 18 mm Hg [p < 0.05]; cardiac index from 2.0 ± 1.2 to 3.1 ± 1.2 liters/min/m(2) [p = 0.002], and pulmonary vascular resistance from 17 ± 10 to 8 ± 6 WU [p = 0.001]). CONCLUSIONS Referral of patients on oral treatment to a tertiary PH center is delayed and significantly affects prognosis.

Quantitative analysis of intraventricular blood flow dynamics by echocardiographic particle image velocimetry in patients with acute myocardial infarction at different stages of left ventricular dysfunction

AIMS Left ventricular (LV) diastolic filling is characterized by the formation of a vortex that supports an efficient transit into systolic ejection. Aim of this study was to assess the intraventricular (IV) blood flow dynamics among patients with ST elevated myocardial infarction (STEMI) at different degrees of LV dysfunction, in the attempt to find novel indicators of LV pump efficiency. METHODS AND RESULTS Sixty-four subjects, 34 consecutive STEMI patients and 30 healthy controls, underwent before hospital discharge 2D speckle tracking echocardiography to assess global longitudinal strain (GLS), and echo-particle image velocimetry analysis to assess flow energetic parameters. Left ventricular volumes ejection fraction (LVEF) and global wall motion score index (GWMSI) were evaluated by 3D echocardiography. ST elevated myocardial infarction patients were subdivided into three groups according to LVEF. Energy dissipation, vorticity fluctuation, and kinetic energy fluctuation indexes, which characterize the degree of disturbance in the flow, exhibit a biphasic behaviour in STEMI patients when compared with controls, with the highest values in patients with still preserved LV function and progressive lower values with LV function worsening. Significant linear correlations were found between energy dissipation index and both LVEF and GLS (r = 0.57, P < 0.001 and r = -0.61, P = 0.001, respectively). Kinetic energy fluctuation index significantly correlates with both LVEF (r = 0.75, P < 0.001) and GLS (-0.58, P = 0.002). Finally, a significant correlation was observed between GWMSI and energy dissipation index (-0.56, P = 0.008). CONCLUSIONS The present study describes, for the first time, the progression of IV flow energetic properties in patients with acute myocardial infarction at different stages of LV dysfunction when compared with healthy controls. Further data are needed to assess the role of these parameters in the development and maintenance of LV dysfunction.

Right intraventricular dyssynchrony in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension: Clinical impact and reversibility

OBJECTIVES The aim of this study was to determine the prevalence of right intraventricular dyssynchrony, its determinants and prognostic impact in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension. BACKGROUND Right ventricular dyssynchrony has been described in pulmonary arterial hypertension, but no evidence is available on its prognostic impact and evolution after therapy. METHODS In 83 consecutive therapy-naïve patients, right ventricular dyssynchrony was evaluated by 2-dimensional speckle-tracking echocardiography calculating the standard deviation of the times to peak-systolic strain for the 4 mid-basal right ventricular segments (RV-SD4). After baseline (World Health Organization [WHO] class, pulmonary hemodynamics, 6-min walk test [6 MWT]), a second assessment was performed after 12 months or when clinical worsening occurred. RESULTS Patients with right ventricular dyssynchrony (RV-SD4 >18 ms) had advanced WHO class, worse 6 MWT, right ventricular remodeling, and hemodynamic profile compared with patients ≤ 18 ms. Determinants of dyssynchrony included pulmonary vascular resistance, QRS duration, and right ventricular end-diastolic area (r(2) = 0.38; p < 0.000001). At 12 months, 32.5% of patients presented clinical worsening (actuarial rates: 19% at 6 months, 31% at 1 year). Multivariable models for clinical worsening prediction showed that the addition of RV-SD4 to clinical and hemodynamic variables (WHO IV, 6 MWT, and cardiac index) significantly increased the prognostic power of the model (0.74 vs. 0.81; p = 0.005, 95% confidence interval [CI]: 0.02 to 0.11). Receiver operating characteristic analysis identified RV-SD4 ≥ 23 ms as the best cutoff value for clinical worsening prediction (95% negative predictive value). At 12 months, normalization of dyssynchrony was achieved in patients with a large reduction of pulmonary vascular resistance (-42 ± 4%). CONCLUSIONS Right ventricular dyssynchrony is frequent in pulmonary arterial hypertension, is an independent predictor of clinical worsening, and might regress during effective treatments.

The complex relation between myocardial viability and functional recovery in chronic left ventricular dysfunction

Preserved myocardial viability and recurrent symptomatic ischemia are the most widely accepted criteria indicating that coronary revascularization should take place in patients with postischemic left ventricular dysfunction. However, the presence of viable myocardium within the infarct zone does not necessarily imply recovery of function after coronary revascularization. The complex relation between the extent of transmural necrosis and the degree of residual perfusion within the infarct area plays an important role. However, independently of functional recovery, cell viability may have important clinical implications, since it may improve long-term prognosis by attenuating left ventricular remodeling processes. Several different methods are used to detect hibernating myocardium. Mounting evidence suggests that thallium-201 scintigraphy is most sensitive in identifying tissue viability, whereas dobutamine echocardiography is most specific in predicting functional recovery after revascularization. In between, myocardial contrast echocardiography is the only technique able to evaluate the microvascular integrity that is a condition sine qua non for both cell viability and later functional recovery. Combined information derived from these 3 different approaches might be considered as the best way to understand how the combination of contractile, viable but noncontractile, and dead tissue affect resultant function and prognosis.

Usefulness of the dipyridamole-Doppler test for diagnosis of coronary artery disease

Two-dimensional and Doppler echocardiographic studies and a hemodynamic investigation were performed during dipyridamole testing in 42 subjects (13 control subjects and 29 patients with coronary artery disease [CAD]), to evaluate the ability of dipyridamole Doppler echocardiography in identifying patients with ischemic left ventricular dysfunction. In the control group, after dipyridamole infusion, Doppler-derived parameters increased significantly from baseline (p less than 0.001). In patients with CAD, peak flow velocity, flow velocity integral and stroke volume failed to increase after dipyridamole infusion (0.89 +/- 0.21 to 0.85 +/- 0.18 m/s, difference not significant; 14 +/- 3 to 12 +/- 4 cm, difference not significant, and 56 +/- 13 to 50 +/- 14 ml/beat, p less than 0.05, respectively). Heart rate, rate pressure product, systemic vascular resistance and mean right atrial pressure had similar variations in the 2 groups. Changes in the 3 Doppler-derived parameters are closely related to the variations of peak positive dP/dt, stroke volume (thermodilution) and left ventricular end-diastolic pressure and are closely related to the coronary angiography jeopardy score and to the appearance of wall motion abnormalities. Thus, by combining Doppler and 2-dimensional echocardiography, dipyridamole-induced myocardial ischemia may be detected in a high percentage of CAD patients, providing a sensitive tool for identifying patients with high-risk coronary artery anatomy.

Dipyridamole myocardial contrast echocardiography in patients with single-vessel coronary artery disease: Perfusion, anatomic, and functional correlates

The aim of this study was to examine whether myocardial contrast echocardiography (MCE) may be used to study regional myocardial blood flow distribution during dipyridamole-induced hyperemia. MCE was performed before and after dipyridamole infusion in 11 patients with a proximal, significant left anterior descending (LAD) coronary artery stenosis. The relation between contrast-derived parameters and the degree of coronary narrowing and the occurrence of transient regional wall motion abnormalities was also investigated. In the territory supplied by left circumflex coronary artery, mean peak contrast intensity increased after dipyridamole from 50 +/- 18 to 76 +/- 27 IU (p < 0.001). In contrast, a significant reduction in mean peak intensity was observed after dipyridamole in the LAD territory (from 41 +/- 27 to 13 +/- 13 IU, p < 0.01). Similar results were obtained with the use of the area under the time-intensity curve. An increase in peak intensity > or = 10 IU after dipyridamole administration separated normal regions from those supplied by a significant coronary artery lesion with a sensitivity of 91% and a specificity of 91%. Perfusion abnormalities were always detected by contrast echocardiography when septal motion abnormalities developed and, in five patients they were detected in the absence of clinical, electrocardiographic, and echocardiographic signs of ischemia. A weak correlation was found between both peak intensity and area under the curve and percent coronary diameter stenosis and cross-sectional area. In conclusion, dipyridamole MCE can be used during routine coronary angiography to assess myocardial blood flow distribution in patients with coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Integrin β2-chain (CD18) over-expression on CD4+ T cells and monocytes after ischemia/reperfusion in patients undergoing primary percutaneous revascularization

β2-integrin subunit (CD18) plays an essential role in leukocyte recruitment and adhesion in sites of endothelial injury. We analyzed the surface expression of CD18 on T lymphocytes and monocytes in a series of patients presenting acute coronary syndrome (ACS) who underwent primary percutaneous intervention (PCI) for coronary artery revascularization. We found that basal CD18 expression on peripheral blood-derived CD4+ (but not CD8+) T lymphocytes was significantly increased in ACS patients as compared with age-matched healthy volunteers. During primary PCI, a significant increase in CD18 molecule density was detected immediately after balloon deflation (reperfusion) on both CD4+ T cells and monocytes obtained from the right atrium (RT) as compared with basal values. These data suggest that upregulation of CD18 molecules plays an important role in local recruitment of CD4+ T cells and monocytes to the site of endothelial damage after ischemia/reperfusion, therefore being responsible, at least in part, for the inflammatory-mediated complications associated with primary PCI.

Physiologic role of coronary PGl2 and PGE2 in modulating coronary vascular response to sympathetic stimulation

To investigate a physiologic role of coronary prostacyclin (PGI2) and prostaglandin E2 (PGE2) 30 patients who were not affected by coronary heart disease were evaluated for coronary hemodynamics and coronary PGI2 and PGE2 production. Inhibition of coronary prostaglandin biosynthesis by ketoprofen (1 mg/kg) or aspirin (15 mg/kg) administered intravenously did not significantly change coronary hemodynamics in resting conditions. In all patients cold pressor tests induced significant increases in coronary blood flow (p less than 0.001) and decreases in coronary vascular resistance (p less than 0.001) without changes in cardiac oxygen extraction and with consequent increases in calculated myocardial oxygen consumption. Simultaneously, a marked increase in coronary PGI2 (as 6-keto-PGF1 alpha) and PGE2 formation was observed (p less than 0.001). Both ketoprofen (1 mg/kg) and aspirin (15 mg/kg) administration completely abolished PGI2 and PGE2 formation that was induced by cold pressor test and caused a paradoxical increase in coronary vascular resistance (ketoprofen: p less than 0.02; aspirin: p less than 0.05). The results of this study support a physiologic role for the coronary prostaglandins in modulating coronary vascular response to sympathetic stimulation in nonischemic patients.