Maurizio Anselmi

Prediction of 1-year clinical outcomes using the SYNTAX score in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

OBJECTIVES This study sought to evaluate the impact of SYNTAX score (SXscore), and compare its performance in isolation and combination with the PAMI (The Primary Angioplasty in Myocardial Infarction Study) score, for the prediction of 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. BACKGROUND Patients with STEMI were excluded from the original SYNTAX score (SXscore) algorithm. Therefore, the utility of using the SXscore in this patient group remains undefined. METHODS SXscore was calculated retrospectively in 807 patients with STEMI enrolled in the randomized STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) clinical trials. Clinical outcomes of all-cause death, reinfarction, and clinically driven target vessel revascularization were subsequently stratified according to SXscore tertiles: SX(LOW) ≤ 9 (n = 311), 9 < SX(MID) ≤ 16 (n = 234), SX(HIGH) >16 (n = 262). RESULTS At 1-year follow-up, all clinical outcomes including mortality, mortality/reinfarction, major adverse cardiac events (MACE) (a composite of all-cause death, reinfarction and target vessel revascularization), and definite, definite/probable, and any stent thrombosis were all significantly higher in patients in the highest SXscore tertile. SXscore was identified as an independent predictor of mortality, MACE, and stent thrombosis out to 1-year follow-up. The combination SYNTAX-PAMI score led to a net reclassification improvement of 15.7% and 4.6% for mortality and MACE, respectively. The C-statistics for the SXscore, PAMI score, and the combined SYNTAX-PAMI score were 0.65, 0.81, and 0.73 for 1-year mortality, and 0.68, 0.64, and 0.69 for 1-year MACE, respectively. CONCLUSIONS SXscore does have a role in the risk stratification of patients with STEMI having primary percutaneous coronary intervention; however, this ability can be improved through a combination with clinical variables. (Multicentre 2×2 Factorial Randomised Study Comparing Tirofiban Versus Abciximab and SES Versus BMS in AMI; NCT00229515).

Prognostic value of detection of myocardial viability using low-dose dobutamine echocardiography in infarcted patients

Revascularization can improve ventricular function in patients with viable myocardium, but whether and how the presence of viable myocardium affects prognosis of infarcted patients is still far from clear. Thus, 202 patients (173 men, 59 +/- 9 years old) with a previous or recent myocardial infarction (MI) and regional asynergies underwent low-dose dobutamine echocardiography (5-15 microg/kg per min) to assess myocardial viability and were followed for a period of 16 +/- 11 months after revascularization (89 patients) or medical therapy (113 patients). Four groups of patients were defined: (1) patients with viability, revascularized (n = 64); (2) patients with viability, treated medically (n = 52); (3) patients without viability, revascularized (n = 25); and (4) patients without viability, treated medically (n = 61). Of these patients, 45 (23%) patients suffered 57 cardiac events: 18 cardiac deaths (9%), 7 MIs, 12 unstable angina, 9 heart failures, and 11 new revascularization procedures. Patients with viability, revascularized, experienced a slightly lower event rate (22%) compared with patients with viability, treated medically, patients without viability, treated medically and patients without viability, revascularized (29%, 31%, and 36%, respectively; p = not significant [NS]). The frequency of events was then evaluated in those 108 patients with an ejection fraction < or =33%, in whom 14 cardiac deaths occurred: the incidence of cardiac death was slightly lower in patients with viability, revascularized (3/37, 8%) than in the patients with viability, treated medically (4/26, 15%), patients without viability, revascularized (2/11, 18%), or patients without viability, treated medically (5/34, 15%) (p = NS). Nonfatal cardiac events were significantly fewer (p <0.05) in patients with viability, revascularized (8%) and in patients without viability, treated medically (6%) than in patients with viability, treated medically and patients without viability, revascularized (27%). In infarcted patients with severe left ventricular dysfunction, the presence of viable myocardium, if left unrevascularized, leads to further events. On the contrary, in the absence of myocardial viability, revascularization could lead to a worse prognosis than medical therapy.

Enhanced Levels of Oxidized Low-Density Lipoprotein Prime Monocytes to Cytokine Overproduction via Upregulation of CD14 and Toll-Like Receptor 4 in Unstable Angina

Objectives—The purpose of this study was to establish whether oxidized low-density lipoprotein (oxLDL) contributes to cytokine overproduction via upregulation of CD14 and toll-like receptor-4 (TLR-4) expression on circulating monocytes of unstable angina (UA) patients. Methods and Results—Expression of CD14 and TLR-4 on circulating monocytes, and the concentration of plasma oxLDL, (interleukin [IL])-6, IL-1 beta, IL-8, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1 (MCP-1) were measured in 27 control (C) subjects, 29 patients with stable angina (SA), and 27 with UA. CD14 and TLR-4 expression on monocytes and circulating IL-6, IL-1 beta, and oxLDL were higher in UA than in SA and C subjects (P<0.001). In in vitro experiments, oxLDL increased CD14 and TLR-4 expression (P<0.001) in control monocytes as well as IL-6, IL-1 beta, and at a lower extent TNF-&agr; and MCP-1 levels in the supernatant (P from <0.05 to <0.001). The preincubation of sera derived from UA patients but with control monocytes also induced a significant increase of CD14 and TLR-4 expression (P<0.001) and of IL-6 and IL-1 beta production (P<0.001) in the supernatant. Conclusions—In UA patients oxLDL may contribute to monocyte overproduction of some cytokines by upregulating CD14 and TLR-4 expression.

Primary cardiac leiomyosarcoma: seven-year survival with combined surgical and adjuvant therapy

Primary cardiac sarcomas constitute a rare entity that have been uniformly associated with poor long-term survival. A case of left atrial leiomyosarcoma involving the interatrial septum and the right atrial free wall and presenting with syncope and atrial fibrillation, is described. Two extensive surgical excisions followed by adjuvant radiation and chemotherapy improved survival with a good quality of life. This approach of combined surgical, medical and radiation therapy may offer better longterm outcome, since our patient is the longest survivor thus far reported.

Ventricular remodeling and infarct expansion.

Infarct expansion, defined as an alteration in the ventricular topography due to thinning and lengthening of the infarcted segment, develops within the first few hours of the acute symptoms, mostly in patients with a large, transmural, anterior myocardial infarction. Shape changes, peculiar to risk region location and due to disparity in regional ventricular architecture, could be posited as the first step in the process of infarct expansion, with various cellular mechanisms contributing to subsequent continued early and late ventricular dilation. Because the increase in left ventricular volume is expected to be linearly dependent on the extent of the infarction, limiting infarct size, by thrombolysis, would proportionally reduce enlargement of the cavity. The effect of thrombolysis on left ventricular volume, however, seems not to be completely accounted for by the lessening effect of reperfusion on infarct size, because data suggest a restraining effect of reperfusion on the process of ventricular dilation in addition to the lessening effect on infarct size. If this turns out to be true, then the achievement of a patent vessel even beyond the time period when that patency may be expected to salvage myocardium would be further justified. Theoretical predictions substantiate the potential effectiveness in restraining ventricular dilation of stiffening of the necrotic region alone, independently of myocardial salvage in infarcted patients. The process of progressive ventricular dilation involves not only a primary alteration in function of the infarcted region, but also a time-dependent secondary change in the noninfarcted tissue itself, finalized to restore stroke volume despite a persistently depressed ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Reperfusion reduces left ventricular dilatation by preventing infarct expansion in the acute and chronic phases of myocardial infarction

Reperfusion reduces left ventricular dilatation in patients with acute myocardial infarction, but it is unclear to what extent this is a primary effect or only a consequence of the limiting effect of reperfusion on infarct size. To address this issue, 56 consecutive patients were examined by means of two-dimensional echocardiography on day 1, on day 3, before discharge, and at 6 months after an acute myocardial infarction. From this population two groups of 12 patients each, perfectly matched for site of myocardial infarction, extent of ventricular asynergy at two-dimensional echocardiography (akinesis + dyskinesis), and clinical characteristics were identified according to the creatine kinase (CK) time to peak, which was regarded as a marker of spontaneous or induced reperfusion: (1) CK time to peak of 12 hours or less (reperfused patients, n = 12), and (2) CK time to peak of more than 12 hours (nonreperfused patients, n = 12). In these two groups of patients end-diastolic and end-systolic left ventricular volumes and endocardial lengths of asynergic and normal ventricular segments, imaged in a cross-sectional view at the level of the papillary muscles, were then computed. At the first examination end-diastolic volume, end-systolic volume, and endocardial segment lengths of normal and asynergic segments were similar in the two groups of patients. Patients with late CK time to peak, however, showed a progressive increase in left ventricular systolic volumes and in asynergic endocardial segment lengths between the first and third (predischarge) examinations (p < 0.05 for both), with no change in systolic length of the normal myocardium. The left ventricular end-systolic volume and the asynergic endocardial segment length of patients with early CK time to peak, however, did not increase during hospitalization. The increment in end-systolic volume and in systolic infarct segment length from the first to the third examinations was higher in nonreperfused patients (p = 0.018 and p = 0.04, respectively). Changes similar to those detected in systole were found for diastolic volume and diastolic infarcted and noninfarcted segment length in both groups, but they did not reach statistical significance. After 6 months, an increases in volume and endocardial length were found in both groups of patients. Relative to the first examination, however, the increase in systolic volume and in asynergic systolic endocardial lengths remained greater for nonreperfused patients (p = 0.077 and p = 0.01, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of Serum Creatinine and Cystatin-C for Early Diagnosis of Contrast-Induced Nephropathy after Coronary Angiography and Interventions

BACKGROUND The diagnostic accuracy of serum creatinine and cystatin C (Cys) as early predictors of contrast-induced nephropathy (CIN) has been debated. We investigated the diagnostic sensitivities, diagnostic specificities, and variations from baseline for serum creatinine and Cys in CIN. METHODS We prospectively evaluated 166 patients at risk for CIN at baseline, and at 12, 24, and 48 h after exposure to contrast media. CIN occurred in 30 patients (18%). Changes (Δ) compared to baseline in serum creatinine and Cys were evaluated at the predefined time points. ROC curve analysis was performed for the Δ 12-h basal serum creatinine and Cys. RESULTS The Δ serum creatinine at 12 h from baseline was the earliest predictor of CIN [area under the ROC curve (AUC) = 0.80; P < 0.001]. The Δ serum creatinine 15% variation [0.15 mg/dL (13.2 μmol/L)] yielded 43% diagnostic sensitivity and 93% diagnostic specificity. The ΔCys at 12 h from baseline performed significantly worse than serum creatinine (AUC = 0.48; P = 0.74). CONCLUSIONS Variations from the serum creatinine baseline offer better diagnostic accuracy for predicting CIN at an earlier stage than similar variations in Cys. An additional diagnostic value of Cys over the determination of serum creatinine in the setting of CIN was not observed.

Left atrial filling volume can be used to reliably estimate the regurgitant volume in mitral regurgitation

OBJECTIVES The objective was to analyze the accuracy and diagnostic value of the estimated regurgitant volume of mitral regurgitation using 1) left atrial volume variation during ventricular systole (left atrial filling volume) and 2) the percent of systolic pulmonary vein velocity integral compared with its total. BACKGROUND Left atrial filling volume (LAfill), which represents the atrial volume variation during ventricular systole, has been used for the assessment of mitral regurgitation severity. A good correlation with invasive semiquantitative evaluation was found, but with an unacceptable overlapping among grades. The reason could be the absence of information concerning the contribution of blood entering into the left atrium from the pulmonary veins. METHODS Doppler regurgitant volume (Dpl-RVol) (mitral stroke volume - aortic stroke volume) was measured in 30 patients with varying degrees and etiological causes of mitral regurgitation. In each patient atrial volumes were measured from the apical view, using the biplane area-length method. The systolic time-velocity integral of pulmonary vein flow was expressed as a percentage of the total (systolic-diastolic) time-velocity integral (PVs%). These parameters were used in this group of patients to obtain an equation whose reliability in estimating Dpl-RVol was tested in a second group of patients. RESULTS In the initial study group, with linear regression analysis the following parameters correlated with Dpl-RVol: end-systolic left atrial volume (R2=0.37, p=0.0004); LAfill (R2=0.45, p < 0.0001); PVs% (R2=0.56, p < 0.0001). In multiple regression analysis the combination of LAfill and the percent of the systolic pulmonary vein velocity integral (PVs%) provided a more accurate estimate of regurgitant volume (R2=0.88; SEE 10.6; p < 0.0001; Dpl-RV=6.18 + (1.01 x LAfill) - (0.783 x PVs%). The equation was subsequently tested in 54 additional patients with mitral regurgitation with a mean Dpl-RVol 27+/-37 ml. Estimated regurgitant volume and Dpl-RVol correlated well with each other (R2=0.90; SEE 12.1; p < 0.0001). In the test population, the equation was 100% sensitive and 98% specific in detecting a regurgitant volume higher than 55 ml. CONCLUSIONS Left atrial filling volume and pulmonary vein flow give a reliable estimate of regurgitant volume in mitral regurgitation.

Does the site of bleeding matter? A stratified analysis on location of TIMI-graded bleedings and their impact on 12-month outcome in patients with ST-segment elevation myocardial infarction

AIMS While bleeding in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI) is known to be associated with poor outcomes, the differential prognostic impact of access-site related versus non access-site related bleedings is unknown. We aimed to assess the relative impact of access-site related bleeding, as compared to non access-site related, on 12-month clinical outcome in patients undergoing intervention for STEMI. METHODS AND RESULTS Thirty-day bleeding endpoints, stratified into access-site versus non access-site, were examined according to the TIMI scale in 744 patients with STEMI enrolled in the MULTISTRATEGY trial. TIMI major or minor bleeding complications occurred in 56 (7.5%) patients within 30 days, 46% had an access-site related bleed and 34% required blood transfusion. Bleeding severity and the need for transfusion were equally distributed between site access- versus non-site access-related bleeds. After adjustment, patients with any TIMI rated bleed were more likely to die or develop recurrent MI within 12 months (HR 2.1 [95% CI: 1.13-3.8]; p=0.02). This ratio was entirely driven by non-site access-related bleeds (adjusted HR: 2.66 [95% CI: 1.21-5.8]; p=0.007), whereas site-access bleeds were not associated with worse outcomes (HR: 0.74 [95% CI: 0.16-3.4]; p=0.70). CONCLUSIONS While bleeds of any TIMI severity within 30 days were independently associated with worse cardiovascular outcomes at 12 months, thus confirming previous analyses, this relationship was entirely driven in our study by non access-site related haemorrhagic events. Investigation on whether the site of bleeding complications may preferentially impact cardiovascular outcomes is warranted.

Comparison of Left Ventricular Function and Volumes During Transesophageal Atrial Pacing Combined With Two-Dimensional Echocardiography in Patients With Syndrome X, Atherosclerotic Coronary Artery Disease, and Normal Subjects

Nine patients with syndrome X were compared with 2 groups of patients known to have coronary artery disease (CAD) (8 patients who developed regional wall motion abnormalities [group ECHO+] and 6 patients who showed only ST depression at echo-pacing [group ECG+]) and with 6 healthy volunteer control subjects. Left ventricular function at rest was normal in all patients. End-diastolic and end-systolic volumes (ml/m2) and ejection fraction were calculated at baseline and at peak of echo-pacing using a Simpsons biplane method. No regional wall motion abnormalities were observed during the echo-pacing in patients with syndrome X or in the volunteers. End-diastolic volume decreased in patients with syndrome X, in the volunteers (from 47 +/- 11 to 30 +/- 12 and from 72 +/- 7 to 38 +/- 6, respectively, p <0.01 for both), and in ECG+ patients (from 48 +/- 10 to 33 +/- 6, p <0.05), whereas it did not change in ECHO+ patients. End-systolic volume decreased in patients with syndrome X and in the volunteers (from 17 +/- 5 to 11 +/- 4 and from 28 +/- 6 to 16 +/- 4, respectively, p <0.01 for both), whereas it did not change or else slightly increased in patients with CAD (from 18 +/- 10 to 16 +/- 5 for ECG+ patients and from 19 +/- 5 to 24 +/- 9 for ECHO+ patients, p = NS for both), regardless of whether regional wall motion abnormalities appeared. Ejection fraction decreased in ECG+ and ECHO+ patients (from 64 +/- 12 to 52 +/- 11 and from 62 +/- 9 to 44 +/- 13, respectively, p <0.01 for both), whereas it did not change in patients with syndrome X and in the volunteers (from 64 +/- 8 to 61 +/- 8 and from 61 +/- 7 to 58 +/- 7, respectively, p = NS for both). During echo-pacing in syndrome X patients no regional wall motion was detected. Left ventricular volumes and ejection fraction showed the same patterns of variation in these patients as they did in the healthy control subjects, in contrast with those patients with CAD, whether or not regional wall motion abnormalities appeared in the latter.