Daniele Rovai

Myocardial Contrast Echocardiography Versus Dobutamine Echocardiography for Predicting Functional Recovery After Acute Myocardial Infarction Treated With Primary Coronary Angioplasty

OBJECTIVES We sought to compare myocardial contrast echocardiography with low dose dobutamine echocardiography for predicting 1-month recovery of ventricular function in acute myocardial infarction treated with primary coronary angioplasty. BACKGROUND The relation between myocardial perfusion and contractile reserve in patients with acute myocardial infarction, in whom anterograde flow is fully restored without significant residual stenosis, is still unclear. METHODS Thirty patients with acute myocardial infarction treated successfully with primary coronary angioplasty underwent intracoronary contrast echocardiography before and after angioplasty and dobutamine echocardiography 3 days after the index infarction. One month later, two-dimensional echocardiography and coronary angiography were repeated in all patients and contrast echocardiography in 18 patients. RESULTS After coronary recanalization, 26 patients showed myocardial reperfusion within the risk area, although 4 did not. At 1-month follow-up, all patients had a patient infarct-related artery without significant restenosis. Both left ventricular ejection fraction and wall motion score index within the risk area significantly improved in the patients with reperfusion ([mean +/- SD] 38 +/- 8% vs. 48 +/- 12%, p < 0.005; and 2.35 +/- 0.5 vs. 2 +/- 0.6, p < 0.001, respectively), but not in those with no reflow. Of the 72 nonperfused segments before angioplasty, 27 showed functional improvement at follow-up. Myocardial contrast echocardiography had a sensitivity and a negative predictive value similar to dobutamine echocardiography in predicting late functional recovery (96% vs. 89% and 89% vs. 93%, respectively), but a lower specificity (18% vs. 91%, p < 0.001), positive predictive value (41% vs. 86%, p < 0.001) and overall accuracy (47% vs. 90%, p < 0.001). CONCLUSIONS Microvascular integrity is a prerequisite for myocardial viability after acute myocardial infarction. However, contrast enhancement shortly after recanalization does not necessarily imply a late functional improvement. Thus, contractile reserve elicited by low dose dobutamine is a more accurate predictor of regional functional recovery after reperfused acute myocardial infarction than microvascular integrity.

Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.

Background—The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. Methods and Results—A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ⩽0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88–0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69–0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65–0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001). Conclusions—In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979199.

Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplasty.

AIM To investigate the effect of abciximab on microvascular integrity and left ventricular (LV) functional recovery in patients with acute myocardial infarction (MI) treated by primary coronary angioplasty (PTCA). METHODS AND RESULTS Thirty-one patients (27 males; age 39-76 years) with first, acute MI (<6 h after onset) were randomized to receive either abciximab+primary PTCA (n=17) or primary PTCA alone (n=14). Baseline characteristics of the two groups were similar. Myocardial reperfusion was studied shortly after PTCA by corrected TIMI frame count (cTFC) and intracoronary myocardial contrast echocardiography (MCE), after 48 h by intravenous MCE using intermittent, harmonic power Doppler, and after 1 month by intravenous MCE and 99 mTc-tetrofosmin SPECT. The patients treated with abciximab showed a shorter cTFC (23+/-4 vs 30+/-9 frames; P<0.05), a more preserved microvascular integrity shortly after PTCA (77% vs 55%; P<0.01), after 48 h (86% vs 50%; P<0.005) and at 1-month follow-up (86% vs 54% by MCE, P<0.001, and 68% vs 60% by SPECT, P<0.005) than patients treated with PTCA alone. Abciximab patients also showed a better recovery of LV function, as demonstrated by greater reduction in wall motion score index (1.4+/-0.3 vs 1.5+/-0.2; P<0.05) and increase in LV ejection fraction (53+/-7% vs 48+/-5%; P<0.001). CONCLUSIONS Abciximab improves microvascular perfusion and LV functional recovery in primary PTCA.

Prognostic value of pulmonary venous flow Doppler signal in left ventricular dysfunction: contribution of the difference in duration of pulmonary venous and mitral flow at atrial contraction.

OBJECTIVES We assessed the contribution of difference in duration of pulmonary venous and mitral flow at atrial contraction (ARd-Ad) for prognostic stratification of patients with left ventricular (LV) systolic dysfunction. BACKGROUND Although pulmonary venous flow (PVF) variables may supplement mitral flow patterns in evaluating left ventricular (LV) diastolic function, their value to the prognostic stratification of patients has not been investigated. METHODS Pulsed wave Doppler mitral and PVF velocity curves were recorded in 145 patients (mean age: 70 years) with LV systolic dysfunction secondary to ischemic or nonischemic cardiomyopathy who were followed for 15 +/- 8 months. In 38% of patients, PVF signal was enhanced by the intravenous (IV) administration of a galactose-based echo-contrast agent. Based on E-wave deceleration time < or = or >130 ms and ARd-Ad, patients were grouped into restrictive (group 1, n = 40), nonrestrictive with ARd-Ad > or =30 ms (group 2, n = 55) and nonrestrictive with ARd-Ad <30 ms (group 3, n = 50). RESULTS During follow-up, 29 patients died from cardiac causes and 28 were hospitalized for worsening heart failure (HF). On multivariate Cox model, ARd-Ad > or =30 ms provided important prognostic information with regard to cardiac mortality and emerged as the single best predictor of cardiac events (cardiac mortality, hospitalization). The 24-month cardiac event-free survival was best (86.3%) for group 3; it was intermediate (37.9%) for group 2; and it was worst (22.9%) for group 1 (p < 0.0002 group 1 vs. 3; p < 0.0005 group 2 vs. 3; p < 0.0003 group 1 vs. group 2). CONCLUSIONS Assessment of ARd-Ad exhibited an independent value in the prognostic evaluation of patients with LV systolic dysfunction. Moreover, it contributed to identify patients at low, intermediate and high risk of cardiac events.

Stress/Rest Myocardial Perfusion Abnormalities by Gated SPECT: Still the Best Predictor of Cardiac Events in Stable Ischemic Heart Disease

The prognostic power of myocardial perfusion imaging in patients with ischemic heart disease (IHD) has been demonstrated since planar imaging. We aimed to investigate whether gated SPECT retains this value in current cardiology if compared with a complete diagnostic work-up and with more recent prognostic indicators. Methods: We selected from our database a cohort of 676 consecutive inpatients who underwent a complete diagnostic work-up that included gated SPECT and coronary arteriography for known or suspected IHD. Patients with acute myocardial infarction (MI), previous coronary artery bypass surgery, or overt hyperthyroidism and patients who were undergoing dialysis treatment were excluded. During follow-up (median, 37 mo), 24 patients died from cardiac causes and 19 experienced a nonfatal MI. Results: The following were determined to be independent predictors of event-free survival (cardiac death and nonfatal MI) in the different phases of diagnostic work-up using Cox proportional hazards regression analysis: among clinical variables, a previous MI; among laboratory examinations, serum creatinine and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels; among electrocardiographic and echocardiographic variables, left ventricular ejection fraction; and among SPECT variables, summed rest score (SRS) and summed difference score (SDS). In addition, a score of coronary stenoses at angiography was an independent predictor. When the above predictors were tested together, SRS (P < 0.0001), SDS (P = 0.0108), and serum creatinine (P = 0.0186) and LDL and HDL cholesterol levels (P = 0.0222) were the final independent predictors of event-free survival. When gated SPECT was added to the clinical, laboratory, electrocardiographic, and echocardiographic variables, the prognostic stratification significantly improved (P < 0.05); when coronary arteriography was added to gated SPECT, prognostic stratification did not further improve (P > 0.25). If the information provided by gated SPECT was made available after clinical, laboratory, electrocardiographic, echocardiographic, and angiographic variables, the prognostic stratification still improved significantly (P < 0.05). In 492 of these patients with ascertained IHD, SRS and SDS were the final independent predictors of survival. Medical treatment and coronary revascularization did not affect the prognostic information of gated SPECT. Conclusion: Myocardial perfusion abnormalities at rest and after stress are still the best predictors of cardiac event–free survival in patients with known or suspected IHD, even when compared with an extensive diagnostic work-up.

Contrast echo washout curves from the left ventricle: application of basic principles of indicator-dilution theory and calculation of ejection fraction

Time-intensity curves can be obtained from contrast echocardiography of the left ventricle. The purposes of this study were: 1) to verify whether these curves conform to the basic principles of indicator-dilution theory; and 2) to derive indexes of left ventricular ejection fraction from curve analysis. In seven closed chest dogs, 31 doses of the polysaccharide agent SHU-454 were injected into the left ventricular cavity during apical four chamber two-dimensional echocardiography. Data were obtained at different levels of ejection fraction, which were induced by changes in preload, afterload and contractility, and measured by single plane Simpsons rule analysis of digital subtraction left ventriculograms. In a subset of two dogs, eight incremental doses (from 1 to 8 ml) of SHU were injected in the basal state. Contrast echocardiograms were digitized off-line, the mean gray level/pixel of a region of interest inside the left ventricular cavity was measured, and the average value for three systolic frames of each beat was used to obtain time-intensity curves. A good correlation was observed between the peak of the time-intensity curve and the quantity of contrast injected (correlation coefficient r = 0.91 by a logarithmic fit). The echo intensities observed in each animal were subsequently transformed in quantity of contrast according to these functions and their natural logarithm was calculated both with and without background subtraction. All curves relating time and the natural logarithm of the corrected intensity exhibited a descending rectilinear portion (washout) in which the correlation was very good (r = 0.97 +/- 0.02 = mean +/- SD) and which was not significantly affected by background subtraction. The validity of this fit was also unaffected by heart rate (55 to 158 beats/min) and angiographic ejection fraction (22 to 74%), and only minimally influenced by duration of contrast washout (3.3 to 14.6 seconds). Ejection fraction was calculated by an algorithm derived from indicator-dilution theory: ejection fraction = [1 - e(-bd)] X 100, where b = slope of the curve and d = cardiac cycle duration. Linear regression analysis between values of ejection fraction derived by angiography and contrast echo yielded r = 0.73. A second index, based on b and d, was derived by multiple regression analysis. Linear regression analysis of this index and angiographic ejection fraction yielded a correlation of r = 0.87.(ABSTRACT TRUNCATED AT 400 WORDS)

Q-wave prediction of myocardial infarct location, size and transmural extent at magnetic resonance imaging.

ObjectiveWe investigated how pathologic Q waves or equivalents predict location, size and transmural extent of myocardial infarction (MI). MethodsMI characteristics, detected by contrast-enhanced magnetic resonance imaging, were compared with 12-lead electrocardiogram in 79 patients with previous first MI. ResultsQ waves involved only the anterior leads (V1–V4) in 13 patients: in all patients MI involved the anterior and anteroseptal walls and apex; 81% of scar tissue was within these regions. Q waves involved only the inferior leads (II, III, aVF) in 13 patients: in 12 of these patients MI involved the inferior and inferoseptal walls; however, only 59% of scar occupied these regions. Q waves involved only lateral leads (V5, V6, I, aVL) in 11 patients: in nine of these patients MI involved the lateral wall but only 27% of scar tissue was within this wall. Q waves involved two electrocardiogram locations in 42 patients. In the 79 patients as a whole, the number of anterior Q waves was related to anterior MI size (r=0.70); however, the number of inferior and lateral Q waves was only weakly related to MI size in corresponding territories (r=0.35 and 0.33). A tall and broad R wave in V1–V2 was a more powerful predictor of lateral MI size than Q waves. Finally, the number of Q waves accurately reflected the transmural extent of the infarction (r=0.70) only in anterior infarctions. ConclusionQ waves reliably predict MI location, size and transmural extent only in patients with anterior infarction. A tall and broad R wave in V1–V2 reflects a lateral MI.

Structural Abnormalities of the Coronary Arterial Wall—in Addition to Luminal Narrowing—Affect Myocardial Blood Flow Reserve

Multislice CT provides information on coronary luminal narrowing and on the structural abnormalities of the coronary arterial wall using densitometric analysis. We sought to investigate the effects of coronary luminal narrowing, structural abnormalities of the coronary arterial wall, and cardiovascular risk factors on regional and global myocardial blood flow (MBF) reserve. Methods: We studied 68 patients (mean age ± SD, 61 ± 10 y; 41 men, 27 women) with an intermediate probability of coronary artery disease. We measured the severity of coronary stenoses and the fibroadipose, fibromuscular, and calcium components of the coronary arterial wall by 64-row multislice CT coronary angiography. We also measured regional and global MBF reserve by PET using 13N-ammonia as a flow tracer at rest and after dipyridamole. Results: One or more significant coronary stenoses (≥50% luminal narrowing) was present in 32 patients (47%), and nonsignificant stenoses were present in 15 patients (22%). Regional MBF reserve was significantly different in the territories perfused by normal coronary arteries, nonsignificant coronary stenoses, and significant coronary stenoses (P < 0.001). Calcium content was higher in the coronary arteries with significant or nonsignificant stenoses (0.95% ± 1.08% and 0.73% ± 0.93%, respectively) than in those without stenoses (0.11% ± 0.38%, P < 0.001). Significant coronary stenosis (P = 0.047) and calcium content (P = 0.017) were the only independent determinants of impaired regional MBF reserve using multivariate analysis. At multiple logistic regression analysis, the Framingham risk score, an index of global cardiovascular risk burden, was the only significant determinant of global MBF reserve (P = 0.028). Conclusion: Coronary stenoses and coronary calcium content independently affect regional MBF reserve. Framingham risk score is the only significant determinant of global MBF reserve.

Therapeutic effect of diagnostic ultrasound on enzymatic thrombolysis An in vitro study on blood of normal subjects and patients with coronary artery disease

If delivered at elevated intensity, ultrasound potentiates enzymatic clot dissolution; however, an elevated acoustic intensity damages vascular wall and favors reocclusion. This studys aim was to investigate whether exposure to high-frequency, low-intensity ultrasound - generated by a diagnostic scanner -enhances enzymatic thrombolysis, and if this effect differs in clots from blood of normal subjects and of patients with coronary artery disease (CAD). Venous blood samples were drawn from 10 healthy volunteers and from 10 CAD patients on chronic medical treatment, which also included aspirin. Each sample generated 2 radiolabelled clots, which were positioned in 2 in vitro models filled with human plasma recirculating at 37 degrees. One clot was exposed to acetyl salicylic acid (60 microg/ml), tissue plasminogen activator (3 microg/ml) and heparin (1 IU/ml), while the other was exposed to the same medications plus ultra-sound (2.5 MHz, mechanical index = 1.0) for 3 hours. Enzymatic thrombolysis was measured as solubilization of radiolabel. Normal subjects and patients did not significantly differ as to coagulation parameters, weight, volume and density of the clots, and fibrinolytic activity (p = 0.794). Ultrasound exposure did not influence thrombolysis in clots of normal subjects (p = 0.367), while it enhanced the dissolution of clots of CAD patients (p = 0.013). The enhancement was equal to 51% at 5 minutes, 32% at 15 minutes, 27% at 30 minutes, 20% at 1 hour and 19% at 3 hours (p < 0.05). Diagnostic ultrasound enhances enzymatic dissolution of clots generated from the blood of CAD patients, likely due to chronic treatment and in particular to aspirin.

Impact of Blunted Pulmonary Venous Flow on the Outcome of Patients With Left Ventricular Systolic Dysfunction Secondary to Either Ischemic or Idiopathic Dilated Cardiomyopathy

The intravenous administration of echo contrast agents enhances the Doppler signal and makes the study of pulmonary venous flow (PVF) easily achievable by transthoracic echocardiography. The aim of this study was to evaluate whether PVF patterns play a role in predicting the outcome of patients with left ventricular (LV) systolic dysfunction. Thus, 115 patients (79 men, mean age 69 years) with LV dysfunction (ejection fraction [EF] <45%) due to either ischemic or idiopathic dilated cardiomyopathy were studied and followed-up for 1 year. A quantitative interrogation of all components of PVF was feasible in 69% of patients at standard transthoracic examination; after contrast enhancement, anterograde and retrograde flow velocities were measurable in 100% and 92% of patients, respectively. A blunted PVF (defined by a systolic-to-diastolic peak velocity ratio <1) was identified in 48 patients (42%), who had a worse clinical status, a lower LVEF, and a more severe pulmonary hypertension. Thirty-six patients had cardiac events at follow-up: sudden death in 4, progressive heart failure in 12, and hospitalization for worsening heart failure in 20 patients. Multivariate Cox proportional-hazards analysis revealed that advanced New York Heart Association class, male gender, and older age were independent predictors of mortality. However, blunted PVF, reduced LVEF, older age, and increased heart rate in descending order of power were independent predictors of heart failure hospitalizations and deaths from end-stage heart failure. In conclusion, the assessments of PVF may effectively contribute to the characterization of patients with LV dysfunction and to the prediction of their outcome.