Michele Galli

Independent and incremental prognostic value of doppler-derived mitral deceleration time of early filling in both symptomatic and asymptomatic patients with left ventricular dysfunction

OBJECTIVES This study sought to investigate the relative and incremental prognostic value of demographic, historical, clinical, echocardiographic and mitral Doppler variables in patients with left ventricular systolic dysfunction. BACKGROUND The prognostic value of diastolic abnormalities as assessed by mitral Doppler echocardiography has yet to be defined. METHOD A total of 508 patients with left ventricular ejection fraction < or = 35% were followed up for a mean (+/- SD) period of 29 +/- 11 months. RESULTS During the follow-up period, 148 patients (29.1%) were admitted to the hospital for congestive heart failure, and 100 patients (19.7%) died. By Cox model analysis, Doppler-derived mitral deceleration time of early filling < or = 125 ms (relative risk [RR] 1.93, 95% confidence interval [CI] 1.4 to 3.7), New York Heart Association functional class III or IV (RR 1.49, 95% CI 1.4 to 2.3), ejection fraction < or = 25% (RR 1.85, 95% CI 1.6 to 2.9), third heart sound (RR 2.06, 95% CI 1.8 to 3.2), age > 60 years (RR 1.95, 95% CI 1.8 to 3.1) and left atrial area > 18 cm2 (RR 1.73, 95% CI 1.6 to 2.7) were all found to be independent and additional predictors of all-cause mortality, and deceleration time was the single best predictor (chi-square 37.80). When all these significant variables were analyzed in hierarchic order, after age, functional class, third sound, ejection fraction and left atrial area, deceleration time still added significant prognostic information (global chi-square from 9.2 to 104.7). Also, deceleration time was the strongest independent predictor of hospital admission for congestive heart failure (RR 4.88, 95% CI 3.7 to 6.9) and cumulative events (congestive heart failure or all-cause mortality, or both; RR 2.44, 95% CI 2.0 to 3.8) in both symptomatic and asymptomatic patients. CONCLUSIONS Deceleration time of early filling is a powerful independent predictor of poor prognosis in patients with left ventricular systolic dysfunction, whether symptomatic or asymptomatic. A short (< or = 125 ms) deceleration time by mitral Doppler echocardiography adds important prognostic information compared with other clinical, functional and echocardiographic variables.

No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age

Background—We investigated the association between 9 polymorphisms of genes encoding hemostasis factors and myocardial infarction in a large sample of young patients chosen because they have less coronary atherosclerosis than older patients, and thus their disease is more likely to be related to a genetic predisposition to a prothrombotic state. Methods and Results—This nationwide case-control study involved 1210 patients who had survived a first myocardial infarction at an age of <45 years who underwent coronary arteriography in 125 coronary care units and 1210 healthy subjects matched for age, sex, and geographical origin. None of the 9 polymorphisms of genes encoding proteins involved in coagulation (G-455A &bgr;-fibrinogen: OR, 1.0; CI, 0.8 to 1.2; G1691A factor V: OR, 1.1; CI, 0.6 to 2.1; G20210A factor II: OR, 1.0; CI, 0.5 to 1.9; and G10976A factor VII: OR, 1.0; CI, 0.8 to 1.3), platelet function (C807T glycoprotein Ia: OR, 1.1; CI, 0.9 to 1.3; and C1565T glycoprotein IIIa: OR, 0.9; CI, 0.8 to 1.2), fibrinolysis (G185T factor XIII: OR, 1.2; CI, 0.9 to 1.6; and 4G/5G plasminogen activator inhibitor type 1: OR, 0.9; CI, 0.7 to 1.2), or homocysteine metabolism (C677T methylenetetrahydrofolate reductase: OR, 0.9; CI, 0.8 to 1.1) were associated with an increased or decreased risk of myocardial infarction. Conclusions—This study provides no evidence supporting an association between 9 polymorphisms of genes encoding proteins involved in hemostasis and the occurrence of premature myocardial infarction or protection against it.

Spontaneous delayed recovery of perfusion and contraction after the first 5 weeks after anterior infarction. Evidence for the presence of hibernating myocardium in the infarcted area.

BackgroundIn patients with ventricular dysfunction caused by stunning or hibernation, it is not clear when complete recovery of the salvaged myocardium occurs after acute myocardial infarction. The purpose of this study was to determine whether a delayed recovery of perfusion and contraction continues even after the subacute phase. Methods and ResultsWe prospectively studied 71 consecutive male patients with first uncomplicated Q-wave anterior infarction. Resting regional blood flow distribution and contraction were assessed quantitatively 5 weeks and 7 months after the acute phase by serial sestamibi tomography and two-dimensional echocardiography. Coronary angiography also was performed in 52 patients. Overall, at 7 months there was an improvement in the perfusion defect severity (1019±811 versus 1365±821 at 5 weeks, P<.001) as well as in the extent of abnormal wall motion (28±19% versus 32±15%, P<.001) and left ventricular ejection fraction (53±14% versus 50±13%, P<.01). Among the 68 of 71 patients showing resting perfusion defects at 5 weeks, two groups were identified: 47 (group 1) who showed a significant (beyond the reproducibility limits) 7-month reduction of the resting perfusion defect, and 21 patients (group 2) in whom the perfusion defect remained unchanged. Ejection fraction and the extent of abnormal wall motion significantly (P<.01) improved in group 1 but not in group 2. Despite the presence of a comparable perfusion defect size between the two groups at 5 weeks after infarction, group 1 already showed a better regional and global ventricular function (P<.05). No significant differences were found between the two groups regarding age, medical therapy, the extent of underlying coronary disease, thrombolysis in the acute phase, Thrombolysis in Myocardial Infarction grade of the infarct-related vessel, and presence of collaterals on angiography. ConclusionsAfter anterior Q-wave infarction, the recovery of perfusion and wall motion may continue well after the subacute phase. Several patients exhibit relative hypoperfusion in viable tissue as late as 5 weeks after infarction, and a significant improvement of perfusion in the infarcted area commonly is observed between 5 weeks and 7 months. This delayed improvement of perfusion is associated with a delayed improvement of contractile function in the infarcted area after the first 5 weeks, which may continue for up to 7 months, suggesting the presence of hibemating myocardium in the infarcted area. Despite similar perfusion defect sizes, the level of regional function can be different at 5 weeks, and measurements taken around this time may not accurately estimate the eventual recovery of function.

Effects of nitroglycerin by technetium-99m sestamibi tomoscintigraphy on resting regional myocardial hypoperfusion in stable patients with healed myocardial infarction.

Myocardial sestamibi uptake reflects regional flow distribution and cellular integrity; however, some segments showing reduced tracer uptake at rest may consist of viable, although hypoperfused, myocardium. It is speculated that the administration of nitroglycerin (NTG) before the sestamibi injection would improve the tracer uptake in resting hypoperfused regions. Thirty-six stable patients with previous myocardial infarction (56 +/- 2 years; mean ejection fraction 42 +/- 2%), in whom perfusion defects could be seen at resting sestamibi tomography, repeated the scintigraphic study 2 to 6 days later, receiving NTG (0.3 to 0.6 mg sublingually) before the tracer injection. The size of the tracer uptake defect was quantified from circumferential profiles in 3 short-axis slices by integrating the area below the lower normal limit (mean -2 SD). After NTG, the mean perfusion defect significantly decreased (from 6,324 +/- 619 to 5,365 +/- 516, p < 0.01). The defect was reduced beyond the reproducibility limits in 20 patients (56%, group 1) and was unchanged or increased in 16 (44%, group 2). The resting sestamibi defect size was comparable between the 2 groups. The average percent reduction of the perfusion defect after NTG was 29 +/- 4% (range 7 to 74).(ABSTRACT TRUNCATED AT 250 WORDS)

Accuracy and safety of technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile (Sestamibi) myocardial scintigraphy with high dose dipyridamole test in patients with effort angina pectoris: A multicenter study

Clinical and physiologic evidence indicates that maximal coronary vasodilation is not achieved in a large number of patients with use of the standard dose of dipyridamole (0.56 mg/kg body weight over 4 min). The feasibility, safety and accuracy of technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile (Sestamibi) scintigraphy associated with intravenous high dose dipyridamole (0.56 mg/kg over 4 min followed 4 min later by an additional 0.28 mg/kg over 2 min) were evaluated in a multicenter study. Planar myocardial perfusion images were obtained at rest and after dipyridamole in 101 patients with effort chest pain and no prior myocardial infarction. High dose dipyridamole (62 patients) was used when typical chest pain or electrocardiographic (ECG) signs of ischemia, or both, did not occur during or after the standard dose (39 patients). With high dose dipyridamole, 34 patients had pain (18 patients) or ECG signs of ischemia (ST depression greater than or equal to 2 mm) (8 patients), or both (8 patients), whereas the other 28 patients had Sestamibi injection in the absence of symptoms or ECG changes. All patients underwent coronary angiography: 81 had significant coronary artery disease (greater than or equal to 50% reduction of lumen diameter) (affecting one vessel in 38, two vessels in 19 and three vessels in 24 patients) and 20 patients had normal coronary arteries. The overall sensitivity, specificity and predictive accuracy of Sestamibi scintigraphy were 81%, 90% and 83%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient left ventricular dilation at quantitative stress-rest sestamibi tomography: Clinical, electrocardiographic, and angiographic correlates

BackgroundFew data are available regarding the incidence and significance of transient left ventricular (LV) dilation on stress sestamibi single photon emission computed tomography (SPECT), which is different from thallium-201 studies because images are acquired late after tracer injection.MethodsWe studied 234 patients with ischemic heart disease and interpretable electrocardiograms undergoing stress-rest sestamibi SPECT on separate days. Sestamibi uptake defect extent was quantified on SPECT polar maps. Epicardial and endocardial transient dilation indexes (TDI) were also calculated.ResultsAccording to our normal TDI values, 148 patients (63%), had no dilation and 86 patients (37%) had abnormal endocardial TDI; a global LV dilation (abnormal endocardial and epicardial TDI) was observed in 19 patients (8%). ST-segment depression was more frequent in patients with transient LV dilation (55%) than in those without (36%; P<.01), as were the extent of stress hypoperfusion (13%±12% vs 6%±7% in patients with no dilation; P<.001) and the angiographic severity score (11.4±5.9 vs 9.2±3.7; P<.05). At multivariate analysis, stress hypoperfusion was the sole predictor of transient LV dilation.ConclusionsTransient LV cavity dilation is frequent on stress sestamibi SPECT. Ventricular cavity dilation is more common than global dilation and suggests subendocardial ischemia. It is related to a greater amount of jeopardized myocardium and is strongly associated with electrocardiographic signs of ischemia.

Tissue plasminogen activator antigen is strongly associated with myocardial infarction in young women

Summary.  Women who develop acute myocardial infarction (AMI) at a young age have fewer classical risk factors and less coronary stenosis than older women. In this rare population, it is plausible that a heightened hemostatic system may play an important mechanistic role in thrombus formation and in the development of AMI. We chose to investigate whether or not there is an association between premature AMI and the plasma concentrations of five hemostatic measurements that had been previously established as risk factors for AMI, and of the inflammation marker C‐reactive protein (CRP). Women who had survived AMI at the age of 45 years or less (n = 141) were drawn from those admitted to 125 Italian coronary care units over a 3‐year period. In them, and in an equal number of controls, plasma levels of immunoreactive tissue plasminogen activator (tPA), plasminogen activation inhibitor 1 (PAI‐1), von Willebrand factor (VWF), fibrinogen, D‐dimer and CRP were measured. Higher levels of VWF, fibrinogen, CRP and tPA were associated with AMI. After adjustment for both classical and hemostatic risk factors, only tPA maintained an independent association with AMI: the odds ratios (taken as an index of relative risk) for tPA values in the middle and higher tertiles were 2.86 (CI 1.63–5.02) and 8.18 (CI 2.66–25.20), respectively. In conclusion, there is a strong association between non‐fatal AMI and increased plasma levels of tPA antigen. This finding is thought to be the expression of a reduced rather than enhanced fibrinolytic activity.

Intracoronary ST-Segment Shift Soon After Elective Percutaneous Coronary Intervention Accurately Predicts Periprocedural Myocardial Injury

Background— Elevation of cardiac biomarkers after coronary angioplasty (percutaneous coronary intervention [PCI]) reflects periprocedural myocardial damage and is associated with adverse cardiac events. We assessed whether periprocedural myocardial damage that occurs despite successful PCI could be rapidly and easily identified by intracoronary ST-segment recording with the use of a catheter guidewire. Methods and Results— In 108 consecutive stable patients undergoing elective single-vessel PCI, we recorded unipolar ECG from the intracoronary guidewire in the distal coronary before PCI and 2 minutes after the last balloon inflation. After PCI, intracoronary ST-segment shift ≥1 mm from baseline was considered significant. Troponin I levels were measured at baseline and at 8 and 24 hours after intervention, and myocardial damage was defined as troponin I increase above the upper normal value after intervention. All patients had normal cardiac marker values before PCI, and PCI was successful in all (residual stenosis <20%, Thrombolysis in Myocardial Infarction grade 3 flow). After PCI, long-term follow-up data were collected; myocardial damage was detected in 50 patients (46%), although abnormal creatine kinase-MB values were documented in only 11 (10%). Significant intracoronary ST-segment shift after PCI was present in 40 patients (37%; group A) and absent in the remaining 68 (63%; group B). Procedural myocardial damage was documented in 37 group A patients (93%) and in 13 group B patients (19%; P<0.001); significant ECG changes were found on standard ECG after intervention in only 5 patients (13%) and 1 patient (1%) (P<0.05). Sensitivity of intracoronary ST-segment shift for predicting myocardial damage was 74%, and specificity was 95%, with positive and negative predictive values of 93% and 81%, respectively. On multivariate analysis, intracoronary ST-segment shift was the sole independent predictor of myocardial damage (odds ratio, 54.1; 95% confidence interval, 12.1 to 240; P<0.0001). At a median follow-up of 12±5 months, major coronary event–free survival was significantly worse in group A patients (log-rank test &khgr;2=4.0; P<0.05). Conclusions— After successful single-vessel PCI, intracoronary ST-segment shift allows the prompt and inexpensive identification of patients developing myocardial injury, who may require adjunctive therapy and longer in-hospital stay.

Ischemic burden in silent and painful myocardial ischemia: A quantitative exercise sestamibi tomographic study

OBJECTIVES We sought to determine whether the amount of myocardial ischemic burden differs in patients with painful or silent myocardial hypoperfusion during exercise testing. BACKGROUND Whether a lack of symptoms during ischemia reflects an alteration in pain perception or less myocardium in jeopardy remains a controversial issue. METHODS We studied 300 consecutive patients with a well established history of ischemic heart disease and reversible hypoperfusion on exercise sestamibi tomography. Rest and stress sestamibi defects were quantitatively assessed and indexes of exercise left ventricular dilation derived. RESULTS Painful and silent reversible ischemia was observed in 97 (32%) and 203 (68%) patients, respectively. Patients with painful ischemia had lower values for work load, exercise time and peak rate-pressure product (p < 0.01) and more frequently showed significant ST segment depression during exercise than did patients with silent ischemia (69% vs. 40%, p < 0.001). On sestamibi tomography, patients with painful ischemia had more reversible hypoperfusion than did patients with silent ischemia (mean +/- SD 16 +/- 10% vs. 11 +/- 7%, p < 0.001), despite a comparable extent of stress hypoperfusion (22 +/- 12% vs. 22 +/- 13%); they also had a higher endocardial dilation index (1.32 +/- 0.32 vs. 1.10 +/- 0.26, p < 0.001). By multivariate logistic analysis, the most powerful correlate of painful ischemia was a history of effort angina; the extent of reversible perfusion defect was the sole independent scintigraphic correlate of painful ischemia. CONCLUSIONS To our knowledge, this is the largest study comparing the degree of hypoperfusion and the presence of symptoms during exercise stress testing in a consecutive cohort of patients with ischemic heart disease and reversible hypoperfusion. The results suggest that the ischemic burden is greater in painful than in silent ischemia.

High dose dipyridamole myocardial imaging: simultaneous sestamibi scintigraphy and two-dimensional echocardiography in the detection and evaluation of coronary artery disease

BACKGROUND Dipyridamole stress combined with echocardiography or perfusion scintigraphy can be used to detect coronary artery disease, but head-to-head comparative data are lacking. The aim of this study was to compare the relative accuracy of high-dose dipyridamole stress imaging (up to 0.84 mg/kg over 10 min) with two-dimensional echocardiography and sestamibi perfusion scintigraphy in detecting coronary artery disease. METHODS One-hundred and one patients with a history of chest pain and no previous myocardial infarction, were studied simultaneously using planar perfusion scintigraphy and echocardiography during a high-dose dipyridamole stress, at seven different institutions. RESULTS During coronary angiography, 21 patients had non-significant lesions, and 80 had significant lesions (> or = 50% diameter reduction): 37 had single-, 19 double- and 24 triple-vessel disease. Sensitivity for disease detection was 78% [95% confidence interval (CI) 67-86%] for echocardiography and 79% (CI 68-87%) for scintigraphy. The specificity was 76% (CI 67-84%) for echocardiography and 90% (CI 83-95%) for scintigraphy. The inter-center variation in accuracy ranged from 50 to 100% for echocardiography (coefficient of variation 19.7%) and from 71 to 100% for scintigraphy (coefficient of variation 15%). The angiographically assessed extent and severity of coronary artery disease, evaluated using the Duke score, was correlated to the extent and severity of perfusion defects with scintigraphy (r = 0.65, P < 0.0001) and regional wall motion abnormalities by echocardiography (r = 0.57, P < 0.0001). CONCLUSIONS Perfusion scintigraphy and echocardiography have similar accuracies for the non-invasive identification of angiographically assessed coronary artery disease during high-dose dipyridamole stress. Inter-center variability in diagnostic accuracy is higher for echocardiography than scintigraphy. Both methods allow a reasonably accurate estimation of extent and severity of disease, via a semiquantitative assessment of extent and severity of perfusion of functional defects.