Nazario Carrabba

Impact of Microvascular Dysfunction on Left Ventricular Remodeling and Long-Term Clinical Outcome After Primary Coronary Angioplasty for Acute Myocardial Infarction

Background—We hypothesized that preserved microvascular integrity in the area at risk would favorably influence left ventricular (LV) remodeling and long-term outcome after acute myocardial infarction. Methods and Results—Before and after successful primary angioplasty (percutaneous transluminal coronary angioplasty [PTCA]), 124 patients with acute myocardial infarction underwent intracoronary myocardial contrast echo (MCE). An MCE score index (MCESI) was derived by averaging the single-segment score (0=not visible, 1=patchy, 2=homogeneous contrast effect) within the area at risk. An MCESI ≥1 was considered adequate reperfusion. Mean follow-up was 46±32 months. After PTCA, 100 patients showed adequate reperfusion (no microvascular dysfunction, NoMD), whereas 24 did not (MD). MD patients had a higher mean creatine kinase (4153±2422 versus 2743±1774 U/L; P =0.002) and baseline wall-motion score index (2.61±0.31 versus 2.25±0.42; P <0.001) and a lower baseline ejection fraction (33±8% versus 40±7%; P <0.001). From day 1 on, LV volumes progressively increased in the MD patients (n=19) and were larger than those of NoMD patients (n=85) at 6 months (end-diastolic volume 170±55 versus 115±29 mL; P <0.001). MCESI was the most important independent predictor of LV dilation (OR 0.61, 95% CI 0.52 to 0.71, P <0.000001). By Cox analysis, MD represented the only predictor of cardiac death (OR 0.26, 95% CI 0.09 to 0.72, P =0.010) and combined events (cardiac death, reinfarction, and heart failure; OR 0.44, 95% CI 0.23 to 0.85, P =0.014). MD patients showed worse survival in terms of cardiac death (P <0.0001) and combined events (P <0.0001). Conclusions—In reperfused acute myocardial infarction, MD within the risk area is an important predictor of both LV remodeling and unfavorable long-term outcome.

Comparison of Prasugrel and Ticagrelor Loading Doses in ST-Segment Elevation Myocardial Infarction Patients RAPID (Rapid Activity of Platelet Inhibitor Drugs) Primary PCI Study

OBJECTIVES This study sought to compare the action of prasugrel and ticagrelor in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). BACKGROUND It has been documented that prasugrel and ticagrelor are able to provide effective platelet inhibition 2 h after a loading dose (LD). However, the pharmacodynamic measurements after prasugrel and ticagrelor LD have been provided by assessing only healthy volunteers or subjects with stable coronary artery disease. METHODS Fifty patients with STEMI undergoing PPCI with bivalirudin monotherapy were randomized to receive 60 mg prasugrel LD (n = 25) or 180 mg ticagrelor LD (n = 25). Residual platelet reactivity was assessed by VerifyNow at baseline and 2, 4, 8, and 12 h after LD. RESULTS Platelet reactivity units (PRU) 2 h after the LD (study primary endpoint) were 217 (12 to 279) and 275 (88 to 305) in the prasugrel and ticagrelor groups, respectively (p = NS), satisfying pre-specified noninferiority criteria. High residual platelet reactivity (HRPR) (PRU ≥240) was found in 44% and 60% of patients (p = 0.258) at 2 h. The mean time to achieve a PRU <240 was 3 ± 2 h and 5 ± 4 h in the prasugrel and ticagrelor groups, respectively. The independent predictors of HRPR at 2 h were morphine use (odds ratio: 5.29; 95% confidence interval: 1.44 to 19.49; p = 0.012) and baseline PRU value (odds ratio: 1.014; 95% confidence interval: 1.00 to 1.03; p = 0.046). CONCLUSIONS In patients with STEMI, prasugrel showed to be noninferior as compared with ticagrelor in terms of residual platelet reactivity 2 h after the LD. The 2 drugs provide an effective platelet inhibition 2 h after the LD in only a half of patients, and at least 4 h are required to achieve an effective platelet inhibition in the majority of patients. Morphine use is associated with a delayed activity of these agents. (Rapid Activity of Platelet Inhibitor Drugs Study, NCT01510171).

Impact of complete revascularization with percutaneous coronary intervention on survival in patients with at least one chronic total occlusion

AIMS This study sought to determine the impact on survival of successful drug-eluting stent-supported percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). METHODS AND RESULTS Comparison of long-term cardiac survival of consecutive patients who underwent PCI for at least one CTO and who were stratified into successful and failure procedures. From 2003 to 2006, 486 patients underwent PCI for 527 CTO. CTO-PCI was successful in 344 patients (71%) and 361 lesions (68%). Multivessel PCI was performed in 62% in the CTO-PCI failure group and in 71% in the CTO-PCI success group (P = 0.062). Cardiac survival rate was higher in the CTO-PCI success group compared with CTO-PCI failure group (91.6 +/- 2.0 vs. 87.4 +/- 2.9%; P = 0.025), in patients with multivessel disease and CTO-PCI success compared with CTO-PCI failure (91.4 +/- 2.2 vs. 86.6 +/- 3.1%; P = 0.021), and in patients with complete revascularization when compared to patients with incomplete revascularization (94.0 +/- 1.7 vs. 83.8 +/- 3.6%; P < 0.001). CONCLUSION Successful CTO-PCI confers a long-term survival benefit. Improvement in survival is driven by the differences in the outcome of patients with multivessel disease and who were completely revascularized.

Doppler-Derived Mitral Deceleration Time An Early Strong Predictor of Left Ventricular Remodeling After Reperfused Anterior Acute Myocardial Infarction

BACKGROUND The relation between remodeling and left ventricular (LV) diastolic function has not yet been fully investigated. The aim of this study was to determine whether early assessment of Doppler-derived mitral deceleration time (DT), a measure of LV compliance and filling, may predict progressive LV dilation after acute myocardial infarction (AMI). METHODS AND RESULTS Fifty-one patients (aged 61+/-11 years; 6 women) with anterior AMI successfully treated with direct coronary angioplasty underwent 2-dimensional and Doppler echocardiographic examinations within 24 hours of admission, at days 3, 7, and 30 and 6 months after the index infarction. Mitral flow velocities were obtained from the apical 4-chamber view with pulsed Doppler. End-diastolic volume index (EDVI) and end-systolic volume index (ESVI) were calculated with the Simpsons rule algorithm. Patients were divided according to the DT duration assessed at day 3 in 2 groups: group 1 (n=33) with DT >130 ms and group 2 (n=18) with DT </=130 ms. Patency and restenosis rate at 6 months were similar between the 2 groups (94% group 1 vs 89% group 2; P=0.52; 27% group 1 vs 33% group 2; P=0.64, respectively). LV volume indexes were similar in both groups at baseline (EDVI: 71+/-3 group 1 vs 70+/-3 mL/m2 group 2, P=0.42; ESVI: 43+/-3 group 1 vs 48+/-3 mL/m2 group 2, P=0.13, respectively). From day 3 on, LV volume indexes progressively increased in group 2 and were significantly larger than those of group 1 at 6 months (LVEDVI 61+/-3 group 1 vs 104+/-6 mL/m2 group 2, P=0.00001; LVESVI 31+/-3 group 1 vs 73+/-6 mL/m2 group 2, P=0.00001, respectively). A significant inverse correlation was found between DT and changes in EDVI at 6 months (r=-0.68; P<0.0000001). By stepwise multiple regression analysis among several clinical, demographic, angiographic, and echocardiographic variables, DT was the most powerful predictor of EDVI changes at 6 months (P=0.02). CONCLUSIONS These data suggest that early estimation (day 3) of Doppler-derived mitral DT provides a simple and accurate mean to predict late LV dilation after reperfused AMI.

High Residual Platelet Reactivity After Clopidogrel Loading and Long-Term Clinical Outcome After Drug-Eluting Stenting for Unprotected Left Main Coronary Disease

Background— No data exist about the impact of high residual platelet reactivity (HRPR) after clopidogrel loading on long-term clinical outcome in patients undergoing drug-eluting stent (DES) implantation for unprotected left main disease (ULMD). Methods and Results— Consecutive patients who underwent percutaneous coronary intervention for ULMD had prospective platelet reactivity assessment by light transmittance aggregometry after a loading dose of 600 mg of clopidogrel. The primary end point of the study was cardiac mortality, and the secondary end point was stent thrombosis. From January 2005 to September 2008, 215 consecutive patients were treated with DES for ULMD. The incidence of HRPR after clopidogrel loading was 18.6%. The median follow-up was 19.3 months. The overall estimated 1-, 2- and 3-year cardiac mortality rate was 3.9±1.3%, 7.5±2.2%, and 12.2±3.4%, respectively. The 3-year cardiac mortality rate was 8.0±3.1% in the low residual platelet reactivity (LRPR) group and 28.3±10.4% in the HRPR group (P=0.005). The 3-year stent thrombosis rate was 4.2±1.8% in the low residual platelet reactivity group and 16.0±7.3% in the HRPR group (P=0.021). By forward stepwise regression analysis, HRPR after clopidogrel loading was the only independent predictor of cardiac death (hazard ratio, 3.82; 95% confidence interval,1.38 to 10.54; P=0.010) and stent thrombosis (hazard ratio, 3.69; 95% confidence interval, 1.12 to 12.09; P=0.031). Conclusions— HRPR after 600-mg clopidogrel loading is a strong marker of increased risk of cardiac death and DES thrombosis in patients receiving DES stenting for ULMD. Routine assessment of in vitro residual platelet reactivity after clopidogrel loading in patients with ULMD potentially suitable for DES-supported percutaneous coronary intervention should be considered to guide patient care decisions.

Prognostic implications of restrictive left ventricular filling in reperfused anterior acute myocardial infarction

OBJECTIVES We sought to assess the relative prognostic role of a restrictive left ventricular (LV) filling pattern after a first anterior acute myocardial infarction (AMI) in patients treated with primary percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND In thrombolized patients, a short Doppler-derived mitral deceleration time (DT) of early filling is a powerful independent predictor of heart failure and death. However, it is still unknown whether the outcome of patients with AMI with a short DT may be improved by a more aggressive treatment. METHODS In 104 patients, two-dimensional and Doppler echocardiograms were obtained three days after the index AMI. Coronary angiography was performed in all patients one and six months after PTCA. The patients were classified into two groups according to the DT duration: group 1 (n = 34) with DT < or = 130 ms and group 2 (n = 70) with DT >130 ms. All patients were followed-up for a mean (+/- SD) period of 32 +/- 10 months. RESULTS During the follow-up period, 14 patients (13%) were admitted to the hospital for congestive heart failure, and 9 patients (9%) died. All cardiac deaths (n = 7) occurred in group 1. The survival rate at mean follow-up was 79% in group 1 and 97.2% in group 2 (p = 0.003). Multivariate Cox analysis showed that only age and restrictive filling were independent predictors of event-free survival. Furthermore, when survival with no cardiovascular events was analyzed, a short DT still emerged as the most powerful independent predictor. CONCLUSIONS Patients with a restrictive LV filling pattern early after anterior AMI have a poor clinical outcome, even if treated with primary PTCA.

Predictors of Reocclusion After Successful Drug-Eluting Stent–Supported Percutaneous Coronary Intervention of Chronic Total Occlusion

OBJECTIVES This study sought to assess the incidence of reocclusion and identification of predictors of angiographic failure after successful chronic total occlusion (CTO) drug-eluting stent-supported percutaneous coronary intervention (PCI). BACKGROUND Large registries have shown a survival benefit in patients with successful CTO PCI. Intuitively, sustained vessel patency may be considered as a main variable related to long-term survival. Very few data exist about the angiographic outcome after successful CTO PCI. METHODS The Florence CTO PCI registry started in 2003 and included consecutive patients treated with drug-eluting stents for at least 1 CTO (>3 months). The protocol treatment included routine 6- to 9-month angiographic follow-up. Clinical, angiographic, and procedural variables were included in the model of multivariable binary logistic regression analysis for the identification of the predictors of reocclusion. RESULTS From 2003 to 2010, 1,035 patients underwent PCI for at least 1 CTO. Of these, 802 (77%) had a successful PCI. The angiographic follow-up rate was 82%. Reocclusion rate was 7.5%, whereas binary restenosis (>50%) or reocclusion rate was 20%. Everolimus-eluting stents were associated with a significantly lower reocclusion rate than were other drug-eluting stents (3.0% vs. 10.1%; p = 0.001). A successful subintimal tracking and re-entry technique was associated with a 57% of reocclusion rate. By multivariable analysis, the subintimal tracking and re-entry technique (odds ratio [OR]: 29.5; p < 0.001) and everolimus-eluting stents (OR: 0.22; p = 0.001) were independently related to the risk of reocclusion. CONCLUSIONS Successful CTO-PCI supported by everolimus-eluting stents is associated with a very high patency rate. Successful subintimal tracking and re-entry technique is associated with a very low patency rate regardless of the type of stent used.

Left Ventricular Remodeling and Heart Failure in Diabetic Patients Treated With Primary Angioplasty for Acute Myocardial Infarction

Background—Diabetes mellitus has been recognized as a strong predictor of heart failure (HF) in patients with acute myocardial infarction (AMI). However, considerable controversy exists regarding the pathogenetic mechanisms of HF after AMI in diabetic patients. We hypothesized that the increased incidence of HF in diabetic patients was associated with a greater propensity for left ventricular (LV) remodeling. Methods and Results—A series of 325 patients (42 diabetics) with AMI successfully treated with primary angioplasty underwent serial 2D echocardiography from admission to 1 and 6 months and 6-month angiography. No significant difference was found between diabetics and nondiabetics regarding baseline clinical, angiographic, and echocardiographic characteristics, as well as 6-month restenosis and reocclusion rates. At 6 months, a similar incidence of LV remodeling was observed in diabetics and nondiabetics (33% versus 25%; P=0.234), with similar patterns of changes in LV volumes and LV global and regional systolic function. At 5 years, the incidence of HF was higher in the diabetics (43% versus 20%, P=0.001). Diabetes was found to be an independent predictor of HF at 5 years (hazard ratio, 1.8; P=0.0366). However, LV remodeling was predictive of HF in the nondiabetics (P=0.023) but not in the diabetics (P=0.123). In a subgroup of patients, higher LV chamber stiffness (as assessed by echocardiography) was detected in the diabetics with HF. Conclusions—The more frequent progression to HF in the diabetics after AMI is not explained by a greater propensity for LV remodeling. Other factors, such as diastolic dysfunction, may play a role.

Drug-eluting stent-supported percutaneous coronary intervention for chronic total coronary occlusion.

This study sought to determine the clinical and angiographic outcomes after drug‐eluting stent (DES)‐supported percutaneous coronary intervention (PCI) for chronic total coronary occlusion (CTO).

Determinants of treatment strategies and survival in acute myocardial infarction: a population-based study in the Florence district, Italy: results of the acute myocardial infarction Florence registry (AMI-Florence).

AIMS The Florence Acute Myocardial Infarction Registry is a prospective, observational study aimed at identifying the determinants of use of primary PCI and of prognosis in patients with STE-AMI, in an unselected population-based setting. METHODS AND RESULTS Nine hundred and thirty cases of STE-AMI (mean age: 70.5 years) were prospectively recorded. Factors associated with use of revascularization, or influencing survival were identified through multivariate analyses (respectively: logistic and Cox regression). Primary PCI was the preferred reperfusion therapy in the study district, with 50% of STE-AMI cases admitted within 24h, and 58% of those admitted within 12h from symptom onset treated; about 5% of patients undergone fibrinolysis (overall revascularization being 55% and 63%, respectively). Availability of PCI facilities at admission hospital was the strongest independent positive predictor of subsequent primary PCI. Advanced age, comorbidities, Killip class 3, delayed hospitalisation and other factors independently reduced the probability of receiving reperfusion. In the whole series, in-hospital mortality was 6.6% for revascularization and 15.6% for conservative therapy, 6-month mortality was 10.1% and 26.0% respectively. The independent, protective effect of primary PCI persisted at the multivariate analysis, being 44% the reduction in the risk of death at 6 months. CONCLUSION In this unselected series of patients, primary PCI, routinely performed in high volume centres, achieved good results in terms of survival even outside the setting of a randomised clinical trial. However, the relatively high number of untreated subjects and the tendency to select less severe cases of AMI for reperfusion treatment confirm the need for an accurate reassessment of behavioural patterns in selecting patients for revascularization.