Guido Parodi

Left ventricular remodeling after primary coronary angioplasty: patterns of left ventricular dilation and long-term prognostic implications.

Background—We prospectively evaluated the prevalence, pattern, and prognostic impact of left ventricular (LV) remodeling after acute myocardial infarction (AMI) successfully treated with primary PTCA. The prevalence, course, and prognostic value of LV remodeling after primary PTCA are still to be clarified. Methods and Results—In 284 consecutive patients with AMI treated with primary PTCA, serial echocardiographic and angiographic studies, within 24 hours (T1), at 1 (T2) and 6 months (T3) after AMI were performed. Long-term (61±14 months) clinical follow-up data were collected for 98.6% patients enrolled in the study. Overall, 85 (30%) patients showed LV dilation (>20% end-diastolic volume increase) at T3 as compared with T1. Early (from T1 to T2), late (from T2 to T3), and progressive dilation patterns (from T1 to T2 to T3) were detected in 42 (15%), 41 (14%), and 36 (13%) patients, respectively. Cardiac death and combined events rate was significantly higher among patients with than among those without LV dilation (P =0.005 and P =0.025, respectively). The pattern of LV dilation during 6 months did not significantly affect survival. Cox survival analysis identified end-systolic volume at T1 and age as baseline predictors and end-systolic volume at T3 and age as 6-month predictors of cardiac death, respectively. Conclusions—LV remodeling after successful PTCA occurs despite sustained patency of the infarct-related artery and preservation of regional and global LV function. LV dilation at 6 months after AMI but not the specific pattern of LV dilation is clearly associated with worse long-term clinical outcome.

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.

Left Ventricular Remodeling After Primary Coronary Angioplasty

Background— We prospectively evaluated the prevalence, pattern, and prognostic impact of left ventricular (LV) remodeling after acute myocardial infarction (AMI) successfully treated with primary PTCA. The prevalence, course, and prognostic value of LV remodeling after primary PTCA are still to be clarified. Methods and Results— In 284 consecutive patients with AMI treated with primary PTCA, serial echocardiographic and angiographic studies, within 24 hours (T1), at 1 (T2) and 6 months (T3) after AMI were performed. Long-term (61±14 months) clinical follow-up data were collected for 98.6% patients enrolled in the study. Overall, 85 (30%) patients showed LV dilation (>20% end-diastolic volume increase) at T3 as compared with T1. Early (from T1 to T2), late (from T2 to T3), and progressive dilation patterns (from T1 to T2 to T3) were detected in 42 (15%), 41 (14%), and 36 (13%) patients, respectively. Cardiac death and combined events rate was significantly higher among patients with than among those withou...

High Residual Platelet Reactivity After Clopidogrel Loading and Long-term Cardiovascular Events Among Patients With Acute Coronary Syndromes Undergoing PCI

CONTEXT High residual platelet reactivity (HRPR) in patients receiving clopidogrel has been associated with high risk of ischemic events after percutaneous coronary intervention (PCI). OBJECTIVE To test the hypothesis that HRPR after clopidogrel loading is an independent prognostic marker of risk of long-term thrombotic events in patients with acute coronary syndromes (ACS) undergoing an invasive procedure and antithrombotic treatment adjusted according to the results of platelet function tests. DESIGN, SETTING, AND PATIENTS Prospective, observational, referral center cohort study of 1789 consecutive patients with ACS undergoing PCI from April 2005 to April 2009 at the Division of Cardiology of Careggi Hospital, Florence, Italy, in whom platelet reactivity was prospectively assessed by light transmittance aggregometry. INTERVENTIONS All patients received 325 mg of aspirin and a loading dose of 600 mg of clopidogrel followed by a maintenance dosage of 325 mg/d of aspirin and 75 mg/d of clopidogrel for at least 6 months. Patients with HRPR as assessed by adenosine diphosphate test (≥70% platelet aggregation) received an increased dose of clopidogrel (150-300 mg/d) or switched to ticlopidine (500-1000 mg/d) under adenosine diphosphate test guidance. MAIN OUTCOME MEASURES The primary end point was a composite of cardiac death, myocardial infarction, any urgent coronary revascularization, and stroke at 2-year follow-up. Secondary end points were stent thrombosis and each component of the primary end point. RESULTS The primary end point event rate was 14.6% (36/247) in patients with HRPR and 8.7% (132/1525) in patients with low residual platelet reactivity (absolute risk increase, 5.9%; 95% CI, 1.6%-11.1%; P = .003). Stent thrombosis was higher in the HRPR group compared with the low residual platelet reactivity group (6.1% [15/247] vs 2.9% [44/1525]; absolute risk increase, 3.2%; 95% CI, 0.4%-6.7%; P = .01). By multivariable analysis, HRPR was independently associated with the primary end point (hazard ratio, 1.49; 95% CI, 1.08-2.05; P = .02) and with cardiac mortality (hazard ratio, 1.81; 95% CI, 1.18-2.76; P = .006). CONCLUSION Among patients receiving platelet reactivity-guided antithrombotic medication after PCI, HRPR status was significantly associated with increased risk of ischemic events at short- and long-term follow-up. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01231035.

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).

Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology

Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision‐making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed.

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.

Abciximab-Supported Infarct Artery Stent Implantation for Acute Myocardial Infarction and Long-Term Survival A Prospective, Multicenter, Randomized Trial Comparing Infarct Artery Stenting Plus Abciximab With Stenting Alone

Background—The impact on survival of routine use of abciximab as adjunctive treatment to routine infarct artery stenting for acute myocardial infarction is not defined. We sought to determine the effect of abciximab on 1-year survival and other major adverse cardiac events of patients with acute myocardial infarction undergoing routine infarct artery stenting. Methods and Results—The Abciximab and Carbostent Evaluation (ACE) Trial is an unblinded, randomized, controlled trial that compared abciximab with placebo in patients undergoing routine infarct artery stent implantation for acute myocardial infarction. At 1 year, the survival rate was 95±2% in the abciximab group and 88±2% in the stent-alone group (P =0.017). The reinfarction rate was 1% in the abciximab group and 6.0% in the stent-alone group, whereas there were no differences between groups in target vessel revascularization rate (16.5% in the abciximab group, 17.5% in the stent-alone group). Conclusions—Abciximab as adjunctive treatment to routine infarct artery stenting for acute myocardial infarction resulted in improved 1-year survival and lower reinfarction rates.

Comparison of AngioJet rheolytic thrombectomy before direct infarct artery stenting with direct stenting alone in patients with acute myocardial infarction. The JETSTENT trial.

OBJECTIVES The aim of this study was to determine whether rheolytic thrombectomy (RT) before direct infarct artery stenting as compared with direct stenting (DS) alone results in improved myocardial reperfusion and clinical outcome in patients with acute myocardial infarction. BACKGROUND The routine removal of thrombus before infarct artery stenting is still a matter of debate. METHODS This is a multicenter, international, randomized, 2-arm, prospective study. Eligible patients were patients with acute myocardial infarction, angiographic evidence of thrombus grade 3 to 5, and a reference vessel diameter ≥2.5 mm. Coprimary end points were early ST-segment resolution and (99m)Tc-sestamibi infarct size. An α value = 0.05 achieved by both coprimary surrogate end points or an α value = 0.025 for a single primary surrogate end point would be considered evidence of statistical significance. Other surrogate end points were Thrombolysis In Myocardial Infarction (TIMI) flow grade 3, corrected TIMI frame count, and TIMI grade 3 blush. Clinical end points were a composite of major adverse cardiovascular events at 1, 6, and 12 months. RESULTS From December 2005 to September 2009, 501 patients were randomly allocated to RT before DS or to DS alone. The ST-segment resolution was more frequent in the RT arm as compared with the DS alone arm: 85.8% and 78.8%, respectively (p = 0.043), while no difference between groups were revealed in the other surrogate end points. The 6-month major adverse cardiovascular events rate was 11.2% in the thrombectomy arm and 19.4% in the DS alone arm (p = 0.011). The 1-year event-free survival rates were 85.2 ± 2.3% for the RT arm, and 75.0 ± 3.1% for the DS alone arm (p = 0.009). CONCLUSIONS Although the primary efficacy end points were not met, the results of this study support the use of RT before infarct artery stenting in patients with acute myocardial infarction and evidence of coronary thrombus. (AngioJet Rheolytic Thrombectomy Before Direct Infarct Artery Stenting in Patients Undergoing Primary PCI for Acute Myocardial Infarction [JETSTENT]; NCT00275990).

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.