Claudio Michelassi

Predictive value of elevated neutrophil–lymphocyte ratio on cardiac mortality in patients with stable coronary artery disease

BACKGROUND An association between white blood cell count (WBC), severity of coronary artery disease (CAD) and survival has been described in patients with acute coronary syndrome. Our aim was to analyze the predictive ability for cardiac events of differential WBC, which is still not well characterized, against established risk factors in angiographically proven CAD patients. METHODS We prospectively evaluated complete blood count, biomarkers of inflammation [(C-reactive protein (CRP) and serum iron (SI)], glucose/lipid metabolism [(fasting glucose (FG), total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterol] and established risk factors in 422 consecutive ischemic patients with angiographically documented stable CAD. On a 3-year follow-up, cardiac death and non-fatal myocardial infarction (MI) were considered as end-points. RESULTS At multivariate analysis neutrophil to lymphocyte ratio (N/L) emerged as independent predictor of cardiac death (HR 8.13; p=0.02) together with CRP, left ventricular ejection fraction (LVEF), FG, HDL and SI. CRP, LVEF, and HDL showed an independent prognostic value for cardiac death and non-fatal MI. Event-free survival according to N/L tertiles was 99% for the first tertile (1.23+/-0.26), 96.5% for the second (2.05+/-0.29), and 88.8% for the third one (5.19+/-3.81). CONCLUSIONS N/L is an independent predictor of cardiac mortality in stable CAD patients.

Myocardial Blood Flow Response to Pacing Tachycardia and to Dipyridamole Infusion in Patients With Dilated Cardiomyopathy Without Overt Heart Failure A Quantitative Assessment by Positron Emission Tomography

BACKGROUND Myocardial blood flow (MBF) impairment has been documented in advanced dilated cardiomyopathy (DCM) in which hemodynamic factors, secondary to severe ventricular dysfunction, may limit myocardial perfusion. To assess whether MBF impairment in DCM may also be present independent of hemodynamic factors, the present study was designed to quantify myocardial perfusion in patients with mild disease without overt heart failure. METHODS AND RESULTS Absolute regional MBF (milliliters per minute per gram) was measured by positron emission tomography and 13N-ammonia in resting conditions, during pacing-induced tachycardia, and after dipyridamole infusion (0.56 mg/kg over 4 minutes) in 22 DCM patients and in 13 healthy subjects. Patients were in New York Heart Association functional class I-II and showed depressed left ventricular (LV) ejection fraction by radionuclide angiography (35 +/- 8%; range, 21% to 48%), normal coronary angiography, and normal or moderately increased LV end-diastolic pressure (9.2 +/- 5.5 mm Hg; range, 2 to 20 mm Hg). There were no differences in arterial blood pressure, heart rate, and rate-pressure product between patients and control subjects in the three study conditions. Compared with control subjects, DCM patients had lower mean MBF at rest (0.80 +/- 0.25 versus 1.08 +/- 0.20 mL.min-1.g-1, P < .01), during atrial pacing tachycardia (1.21 +/- 0.59 versus 2.03 +/- 0.64 mL.min-1.g-1, P < .01), and after dipyridamole infusion (1.91 +/- 0.76 versus 3.78 +/- 0.86 mL.min-1.g-1, P < .01). LV MBF values were related to baseline LV end-diastolic pressure at rest (r = -.57, P < .01) and during pacing (r = -.67, P < .01) but not after dipyridamole infusion (r = .19, P = .40). Five patients had LV end-diastolic pressure > 12 mm Hg; in 4, myocardial perfusion was severely depressed both at baseline and in response to stress. CONCLUSIONS In patients with DCM without overt heart failure, myocardial perfusion is impaired both at rest and in response to vasodilating stimuli. The abnormalities in vasodilating capability can be present despite normal hemodynamics; progression of the disease is associated with more depressed myocardial perfusion.

Prognostic value of dipyridamole echocardiography early after uncomplicated myocardial infarction: A large-scale, multicenter trial

PURPOSE To determine the prognostic capability of the dipyridamole echocardiography test (DET) early after an acute myocardial infarction. PATIENTS AND METHODS On the basis of 11 different echocardiographic laboratories, all with established experience in stress echocardiography and fulfilling quality-control requirements for stress echocardiographic readings, 925 patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months. RESULTS During the follow-up, there were 34 deaths and 37 nonfatal myocardial infarctions; 104 patients developed class III or IV angina and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction, and death), the most important univariate predictor was the presence of an inducible wall motion abnormality after dipyridamole administration (chi 2 = 45.8). With a Cox analysis, echocardiographic positivity, age, and male gender were found to have an independent and additive value. Considering survival (and, therefore, death as the only event), age was the most meaningful parameter, followed by the wall motion score index during dipyridamole administration (chi 2 = 12.1). Among other parameters, the resting wall motion score index was a significant predictor of death. In a multivariate analysis, the prognostic contributions of age (relative risk estimate = 1.08) and wall motion score index during dipyridamole administration (relative risk estimate = 4.1) were independent and additive. In particular, considering death only, the event rate was 2% in patients with negative DET results, 4% in patients with positive high-dose DET results, and 7% in patients with positive low-dose DET results. CONCLUSIONS DET is feasible and safe early after uncomplicated myocardial infarction and allows effective risk stratification on the basis of the presence, severity, extent, and timing of the induced dyssynergy.

Value of transthoracic echocardiography in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients

PURPOSE Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. The present study was undertaken to determine prospectively the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE. SUBJECTS AND METHODS We examined 110 consecutive patients with suspected PE. The study protocol included assessment of clinical probability, echocardiography, and perfusion lung scanning. Pulmonary angiography was performed in all patients with abnormal scans. As echocardiographic criteria to diagnose acute PE, we used the presence of any two of the following: right ventricular (RV) hypokinesis, RV end-diastolic diameter >27 mm (without RV wall hypertrophy), or tricuspid regurgitation velocity >2.7 m/sec. Clinical estimates of PE served as pretest probabilities in calculating, after echocardiography, the posttest probabilities of PE. RESULTS Pulmonary angiography confirmed PE in 43 (39%) of 110 patients. Echocardiographic diagnostic criteria for PE yielded a sensitivity of 56% and a specificity of 90%. For pretest probabilities of 10%, 50%, and 90%, the posttest probabilities of PE conditioned by a positive echocardiogram were 38%, 85%, and 98%, respectively. The posttest probabilities of PE conditioned by a negative echocardiogram were 5%, 33%, and 81%, respectively. CONCLUSIONS In unselected patients with suspected PE, transthoracic echocardiography fails to identify some 50% of patients with angiographically proven PE. Although echocardiographic findings of RV strain, paired with a high clinical likelihood, support a diagnosis of PE, the transthoracic echocardiography has to have a better sensitivity to be used as a screening test to rule out PE.

Prognostic importance of dipyridamole-echocardiography test in coronary artery disease.

We studied the value of dipyridamole-echocardiography test in comparison with clinical, resting electrocardiogram and echocardiogram variables in predicting cardiac events occurring in 539 consecutive patients referred for dipyridamole-echocardiography test from 1984 to 1987. There were 118 cardiac events: 11 cardiac deaths, 12 nonfatal myocardial infarctions, and 95 coronary revascularization (bypass or angioplasty) procedures. A Cox survival analysis identified echocardiographic positivity after dipyridamole administration as the best predictor of cardiac events (relative risk ratio, 2.7). The next most powerful predictor was angina after dipyridamole administration (relative risk ratio, 1.9). Cardiac events occurred in 14 (6%) of 253 patients with normal high-dose dipyridamole echocardiographic test results, in 21 (26%) of 82 patients with high-dose dipyridamole echocardiographic positivity (0.84 mg/kg during 10 minutes), and in 83 (41%) of 204 patients with low-dose dipyridamole echocardiographic positivity (0.56 mg/kg during 4 minutes) (p less than 0.0001). In a subset of 341 patients, exercise electrocardiography stress test and coronary angiography were also available. A Cox survival analysis again identified echocardiographic positivity after dipyridamole as the best predictor of cardiac events (relative risk ratio, 1.9) followed by a pathologic coronary arteriography (relative risk ratio, 1.2). We conclude that the presence and timing of a transient dyssynergy during dipyridamole stress are useful predictors of subsequent cardiac events.

Diagnostic and prognostic value of dipyridamole echocardiography in patients with suspected coronary artery disease. Comparison with exercise electrocardiography.

BACKGROUND Before any new diagnostic test is accepted in clinical practice, such a test should be compared with established diagnostic tools in an appropriately large series of patients encompassing the complete spectrum of challenges to which the test is exposed. The aim of the present study was to assess the relative diagnostic and prognostic accuracies of high-dose dipyridamole echocardiography (two-dimensional echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg over 10 hours) versus maximal symptom-limited bicycle exercise ECG test in patients with angina. METHODS AND RESULTS We studied 429 consecutive in-hospital patients who met the following inclusion criteria: history of chest pain, off antianginal therapy for at least 2 days (1 week for beta-blockers), no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction (akinesis or dyskinesis) at baseline, and acceptable acoustic window under resting conditions. All patients underwent dipyridamole echocardiography and exercise ECG--on different days and in random order--within 1 week of coronary angiography (which was performed independent of test results) and were followed up for 37.8 +/- 14 months (range, 1 to 73 months). Criteria of positivity were for dipyridamole echocardiography, a transient regional dyssynergy absent in the baseline examination; for exercise ECG, an ST-segment shift of > or = 0.1 mV from baseline; and for coronary angiography, a luminal reduction of > or = 75% in at least one major coronary vessel (50% for left main). There were 183 patients without and 246 with coronary artery disease; 132 had one-, 70 had two-, and 44 had three- and/or left main vessel disease. The specificity was higher for dipyridamole echocardiography than for exercise ECG (90% versus 51%, P < .001). The overall sensitivity of dipyridamole echocardiography was similar to that of exercise ECG (75% versus 74%, P = NS), with no significant differences in the subset with one- (67% versus 69%, P = NS), two- (79% versus 77%, P = NS), or three- (93% versus 86%, P = NS) vessel disease. During the follow-up, there were 20 deaths, 13 nonfatal myocardial infarctions, and 126 revascularization procedures. In the univariate analysis, dipyridamole resulted in higher chi 2 values than did exercise stress testing. A Cox forward stepwise survival analysis identified the dipyridamole time as the most powerful prognostic predictor of death (chi 2 = 19.4, P < .0001) of all invasive and noninvasive parameters. The dipyridamole time also provided independent and additional prognostic information when it was adjusted for age, diabetes, resting ECG, and exercise stress test according to a modified, interactive stepwise procedure. This is true when death only, death and myocardial infarction, and death, myocardial infarction, and revascularization procedures were considered end points. CONCLUSIONS In patients with no previous myocardial infarction and good resting left ventricular function, compared with exercise ECG, dipyridamole echocardiography has a similar sensitivity and a higher specificity for the noninvasive detection of angiographically assessed coronary artery disease. Dipyridamole echocardiography also provides information in addition to that provided by exercise ECG for predicting death, infarction, and all events when the presence as well as the timing, severity, and extension of dipyridamole-induced wall motion abnormalities are considered.

Vasospastic ischemic mechanism of frequent asymptomatic transient ST-T changes during continuous electrocardiographic monitoring in selected unstable angina patients☆

Asymptomatic episodes of ST segment and/or T wave changes are often reported during Holter monitoring in patients with angina pectoris. However, the interpretation of such changes is debated relative to silent myocardial ischemia. We studied 11 patients admitted to the CCU because of frequent episodes of unstable anginal attacks who had undergone repeated periods of Holter monitoring, characterized by predominantly occurring asymptomatic episodes of ST segment and/or T wave changes associated with less frequent typical anginal attacks. In a total of 89 days of Holter monitoring, the patients evidenced 520 episodes of transient ECG changes including 180 of ST elevation, 73 of ST depression, and 267 of T wave alterations. Only 12% of episodes were symptomatic. Coronary injection during asymptomatic ST-T changes was performed in eight patients. In six it was possible to document spontaneous coronary spasm. In seven patients ergonovine administration induced anginal pain, ST-T changes, and coronary spasm. In all patients the anginal attacks completely disappeared with medical treatment and the asymptomatic episodes were abolished in six and reduced in four. Our findings support the hypothesis that in certain selected unstable anginal patients, transient asymptomatic ECG changes are caused by acute myocardial ischemia.

Coronary reserve and exercise ECG in patients with chest pain and normal coronary angiograms.

BackgroundCoronary vasodilator reserve is reduced in some patients with a history of chest pain and angiographically normal coronary arteries. ECG changes suggestive of myocardial ischemia during exercise also can be demonstrated in a subset of these patients. Methods and ResultsWe have investigated the correlation between coronary vasodilator reserve, assessed with 13N-labeled ammonia and positron emission tomography, and the ECG during exercise stress in 45 patients with a history of chest pain, angiographically normal coronary arteries, and a negative ergonovine test. ST segment depression on the ECG during exercise was present in 29 of 45 patients. Mean resting left ventricular blood flow was 1.04±0.22 ml · min−1 · g−1; it increased to 1.32±0.47 ml · min−1 g−1 (p<0.01 versus baseline value) during atrial pacing and to 2.52±0.96 ml · min−1 · g−1 (p<0.01 versus baseline value) after dipyridamole (0.56 mg/kg i.v.). No regional flow defects could be demonstrated in any patient during pacing or after dipyridamole. Myocardial flows after dipyridamole, however, did not show a normal frequency distribution (Kolmogorov-Smirnov test), and two patient populations could be identified. Twenty-nine (67%) patients had a mean left ventricular flow of 3.02±0.33 ml · min−1 · g−1 after dipyridamole (range, 2.13–5.46 ml · min−1 · g−1), and 14 (33%) patients had a mean flow of 1.48±0.29 ml · min−1 · g−1 (range, 1.06–2.04 ml · min−1 · g−1, p<0.01 versus the “high-flow group”). ConclusionsApproximately one third of patients in our series showed a reduced coronary vasodilator reserve. Although 12 of 14 patients in the “low-flow group” had ST segment depression during exercise stress, 16 of 29 patients in the high-flow group also had ST segment depression during exercise stress. Therefore, despite a good sensitivity (86%) in identifying patients with a blunted increment of coronary flow, the ECG response during exercise stress appears to have a rather low specificity (45%). This suggests that factors other than reduced coronary reserve and myocardial ischemia may play a role in the genesis of the ST segment depression in these patients.

Clinical value of left atrial appendage flow for prediction of long-term sinus rhythm maintenance in patients with nonvalvular atrial fibrillation ☆

OBJECTIVES This study evaluated the role of various clinical and echocardiographic parameters, including the left atrial appendage (LAA) anterograde flow velocity, for prediction of the long-term preservation of sinus rhythm (SR) in patients with successful cardioversion (CV) of nonvalvular atrial fibrillation (AF). BACKGROUND Echocardiographic parameters for assessing long-term SR maintenance after successful CV of nonvalvular AF are not accurately defined. METHODS Clinical, transthoracic echocardiographic and transesophageal echocardiographic (TEE) data--measured in AF lasting >48 h--of 186 consecutive patients (116 men, mean age: 65 +/- 9 years) with successful CV (electrical or pharmacologic) were analyzed for assessment of one-year maintenance of SR. RESULTS At one-year follow-up, 91 of 186 (49%) patients who underwent successful CV continued to have SR. Mean LAA peak emptying flow velocity was higher in patients remaining in SR for one year than in those with AF relapse (41.7 +/- 20.2 cm/s vs. 27.7 +/- 17.0 cm/s; p < 0.001). On multivariate logistic regression analysis, only the mean LAA peak emptying velocity >40 cm/s (p = 0.0001; chi(2): 23.9, odds ratio [OR] = 5.2, confidence interval [CI] 95% = 2.7 to 10.1) and the use of preventive antiarrhythmic drug treatment (p = 0.0398; chi(2): 4.2; OR = 2.0, CI 95% = 1.0 to 3.8) predicted the continuous preservation of SR during one year, outperforming other univariate predictors such as absence of left atrial spontaneous echocardiographic contrast during TEE, the left atrial parasternal diameter <44 mm, left ventricular ejection fraction >46% and AF duration <1 week before CV. The negative and positive predictive values of the mean LAA peak emptying velocity >40 cm/s for assessing preservation of SR were 66% (CI 95% = 56.9 to 74.2) and 73% (CI 95% = 62.4 to 83.3), respectively. CONCLUSIONS In TEE-guided management of nonvalvular AF, high LAA flow velocity identifies patients with greater likelihood to remain in SR for one year after successful CV. Low LAA velocity is of limited value in identifying patients who will relapse into AF.

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.