Massimo Mancone

Thrombus Aspiration During Primary Percutaneous Coronary Intervention Improves Myocardial Reperfusion and Reduces Infarct Size. The EXPIRA (Thrombectomy With Export Catheter in Infarct-Related Artery During Primary Percutaneous Coronary Intervention) Prospective, Randomized Trial

OBJECTIVES The purpose of this study was to evaluate the impact on myocardial perfusion and infarct size as assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of a manual thrombectomy device, Export Medtronic (EM) (Medtronic Inc., Minneapolis, Minnesota), as adjunctive therapy in primary percutaneous coronary intervention (PPCI) in a subset of patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND PPCI may cause thrombus dislodgment, leading to microvascular damage. METHODS One hundred seventy-five STEMI patients were randomly assigned to standard percutaneous coronary intervention (PCI) (n = 87) or EM-PCI (n = 88). The primary end points were the occurrence of myocardial blush grade > or =2 and the rate of 90-min ST-segment resolution >70%. The CE-MRI substudy was performed in 75 patients with anterior STEMI to assess microvascular obstruction and infarct size. RESULTS Myocardial blush grade > or =2 and ST-segment resolution occurred more frequently in the EM-PCI group (88% vs. 60%, p = 0.001; and 64% vs. 39%, p = 0.001). In the acute phase, microvascular obstruction extent was significantly lower in the EM-PCI group and at 3 months, infarct size was significantly reduced only in the EM-PCI group. A lower incidence of cardiac death in the EM-PCI group (4.6% vs. 0%, log-rank test p = 0.02) was observed at 9 months. CONCLUSIONS Thrombectomy prevents thrombus embolization and preserves microvascular integrity reducing infarct size, and it therefore represents an useful adjunctive therapy in PPCI.

Impact of Primary Coronary Angioplasty Delay on Myocardial Salvage, Infarct Size, and Microvascular Damage in Patients With ST-Segment Elevation Myocardial Infarction : Insight From Cardiovascular Magnetic Resonance

OBJECTIVES We investigated the extent and nature of myocardial damage by using cardiovascular magnetic resonance (CMR) in relation to different time-to-reperfusion intervals. BACKGROUND Previous studies evaluating the influence of time to reperfusion on infarct size (IS) and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) have yielded conflicting results. METHODS Seventy patients with STEMI successfully treated with primary percutaneous coronary intervention within 12 h from symptom onset underwent CMR 3 +/- 2 days after hospital admission. Patients were subcategorized into 4 time-to-reperfusion (symptom onset to balloon) quartiles: < or =90 min (group I, n = 19), >90 to 150 min (group II, n = 17), >150 to 360 min (group III, n = 17), and >360 min (group IV, n = 17). T2-weighted short tau inversion recovery and late gadolinium enhancement CMR were used to characterize reversible and irreversible myocardial injury (area at risk and IS, respectively); salvaged myocardium was defined as the normalized difference between extent of T2-weighted short tau inversion recovery and late gadolinium enhancement. RESULTS Shorter time-to-reperfusion (group I) was associated with smaller IS and microvascular obstruction and larger salvaged myocardium. Mean IS progressively increased overtime: 8% (group I), 11.7% (group II), 12.7% (group III), and 17.9% (group IV), p = 0.017; similarly, MVO was larger in patients reperfused later (0.5%, 1.5%, 3.7%, and 6.6%, respectively, p = 0.047). Accordingly, salvaged myocardium markedly decreased when reperfusion occurred >90 min of coronary occlusion (8.5%, 3.2%, 2.4%, and 2.1%, respectively, p = 0.004). CONCLUSIONS In patients with STEMI treated with primary percutaneous coronary intervention, time to reperfusion determines the extent of reversible and irreversible myocardial injury assessed by CMR. In particular, salvaged myocardium is markedly reduced when reperfusion occurs >90 min of coronary occlusion.

Impact of intracoronary aspiration thrombectomy during primary angioplasty on left ventricular remodelling in patients with anterior ST elevation myocardial infarction

Objective: To evaluate prospectively the impact on left ventricular (LV) remodelling of an intracoronary aspiration thrombectomy device as adjunctive therapy in primary percutaneous coronary intervention (PCI) in patients with anterior ST elevation myocardial infarction (STEMI). Methods: 76 consecutive patients with anterior STEMI (65.3 (11.2) years, 48 men) were randomly assigned to intracoronary thrombectomy and stent placement (n  =  38) or to conventional stenting (n  =  38) of the infarct related artery. Each patient underwent transthoracic echocardiography immediately after PCI and at six months. At the time of echocardiographic control, major adverse cardiovascular events (MACE) in terms of death, new onset of myocardial infarction, and hospitalisation for heart failure were also evaluated. Results: After a successful primary PCI, patients in the thrombectomy group achieved a higher rate of post-procedure myocardial blush grade 3 (36.8% v 13.1%, p  =  0.03) and effective ST segment resolution at 90 minutes (81.6% v 55.3%, p  =  0.02). Six months after the index intervention, 19 patients (26.8%) developed LV dilatation, defined as an increase in end diastolic volume (EDV) ⩾ 20%: 15 in the conventional group and four in the thrombectomy group (p  =  0.006). Accordingly, at six months patients treated conventionally had significantly higher end systolic volumes (82 (7.7) ml v 75.3 (4.9) ml, p < 0.0001) and EDV (152.5 (18.1) ml v 138.1 (10.7) ml, p < 0.0001) than patients treated with thrombectomy. No differences in cumulative MACE were observed (10.5% in the conventional group v 8.6% in the thrombectomy group, not significant). Conclusion: Compared with conventional stenting, adjunctive aspiration thrombectomy in successful primary PCI seems to be associated with a significantly lower incidence of LV remodelling at six months in patients with anterior STEMI.

Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology) : safety, tolerability, clinical, and haemodynamic effect

Background: Oral bosentan is an established treatment for pulmonary arterial hypertension (PAH). Objective: To evaluate safety, tolerability, and clinical and haemodynamic effects of bosentan in patients with PAH related to congenital heart disease (CHD). Patients: 22 patients with CHD related PAH (8 men, 14 women, mean (SD) age 38 (10) years) were treated with oral bosentan (62.5 mg×2/day for the first 4 weeks and then 125 mg×2/day). Main outcome measures: Clinical status, liver enzymes, World Health Organisation (WHO) functional class, resting oxygen saturations and 6-min walk test (6MWT) were assessed at baseline and at 1, 3, 6, and 12 months. Haemodynamic evaluation with cardiac catheterisation was performed at baseline and at 12 month follow-up. Results: 12 patients had ventricular septal defect, 5 atrioventricular canal, 4 single ventricle, and 1 atrial septal defect. All patients tolerated bosentan well. No major side effects were seen. After a year of treatment, an improvement was seen in WHO functional class (2.5 (0.7) v 3.1 (0.7); p<0.05), oxygen saturation at rest (87 (6%) v 81 (9); p<0.001), heart rate at rest (81 (10) v 87 (14) bpm; p<0.05), distance travelled in the 6MWT (394 (73) v 320 (108) m; p<0.001), oxygen saturation at the end of the 6MWT (71 (14) v 63 (17%); p<0.05), Borg index (5.3 (1.8) v 6.5 (1.3); p<0.001), pulmonary vascular resistances index (14 (9) v 22 (12) WU m2; p<0.001), systemic vascular resistances index (23 (11) v 27 (10) WU.m2; p<0.01), pulmonary vascular resistances index/systemic vascular resistances index (0.6 (0.5) v 0.9 (0.6); p<0.05); pulmonary (4.0 (1.3) v 2.8 (0.9) l/min/m2; p<0.001) and systemic cardiac output (4.2 (1.4) v 3.4 (1.1) l/min/m2; p<0.05). Conclusions: Bosentan was safe and well tolerated in adults with CHD related PAH during 12 months of treatment. Clinical status, exercise tolerance, and pulmonary haemodynamics improved considerably.

Impact of Thrombectomy With EXPort Catheter in Infarct-Related Artery During Primary Percutaneous Coronary Intervention (EXPIRA Trial) on Cardiac Death

In ST-segment elevation myocardial infarction (STEMI) impairment of microcirculatory function is a negative independent predictor of myocardial function recovery. In the Impact of Thrombectomy with EXPort Catheter in Infarct-Related Artery during Primary Percutaneous Coronary Intervention (PCI; EXPIRA) trial we found that manual thrombectomy resulted in a better myocardial reperfusion expressed by an improved procedural outcome and a decrease of infarct size compared to conventional PCI. The aim of the present study was to investigate whether the early efficacy of thrombus aspiration translates into very long-term clinical benefit. We randomized 175 patients with STEMI with occlusive thrombus at baseline undergoing primary PCI to thromboaspiration with a manual device (Export Medtronic, n = 88) or standard PCI (n = 87). No differences in baseline, clinical, and angiographic preprocedural findings were observed between the 2 groups except for incidence of hypertension and cholesterol levels. After 24 months major adverse cardiac events were 13.7% versus 4.5% (p = 0.038, log-rank test) and cardiac death was 6.8% versus 0% (p = 0.012, log-rank test). A strict correlation was observed between cardiac death incidence and tissue reperfusion parameters (postprocedural myocardial blush grade and ST-segment resolution). In conclusion, manual thrombus aspiration before stenting of the infarct-related artery in selected patients with STEMI improving myocardial reperfusion significantly decrease cardiac death and major adverse cardiac events at 2 years.

Pharmacodynamic Effect of Switching Therapy in Patients With High On-Treatment Platelet Reactivity and Genotype Variation With High Clopidogrel Dose Versus Prasugrel The RESET GENE Trial

Background—High on-treatment platelet reactivity (HTPR) is associated with adverse outcomes. We aim to compare the novel thienopyridine prasugrel versus double-dose clopidogrel in patients with HTPR and explore the interaction between CYP2C19 genotype and both drugs. Methods and Results—Consecutive stable patients undergoing percutaneous coronary intervention were screened with the Multiplate Analyzer P2Y12 assay, defining HTPR as area under the curve >450. Those with HTPR were randomized to prasugrel (10 mg/day) or high-dose clopidogrel (150 mg/day) for 2 weeks and then crossed-over to, respectively, clopidogrel and prasugrel, repeating the P2Y12 assay at the end of each cycle. Clinical follow-up (until 3 months) and CYP2C19 genotyping was performed in all patients. The primary end point was platelet reactivity after 14 days of prasugrel versus high-dose clopidogrel. Thirty-two patients were randomized to prasugrel and then high-dose clopidogrel or to high-dose clopidogrel followed by prasugrel. Prasugrel was associated with a significantly lower platelet reactivity than high-dose clopidogrel was (325.8 versus 478.5 area under the curve, P=0.028). No patient treated with prasugrel exhibited HTPR, whereas 9 (28.1%) receiving high-dose clopidogrel still had prevalence of HTPR (P=0.001). Similar findings were obtained changing cutoffs or considering platelet reactivity as a continuous variable. Genotyping showed the same efficacy between high-dose clopidogrel and prasugrel in the 18 (56.3%) CYP2C19*2 noncarriers (HTPR in 12.5% versus 0, P=0.274), whereas it was significantly worse in the 14 (43.7%) carriers (HTPR in 43.7% versus 0, P=0.003). Conclusions—HTPR is successfully abolished by therapy with prasugrel irrespective of CYP2C19 genotype. Conversely, high-dose clopidogrel can address HTPR only in CYP2C19*2 noncarriers. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01465828.

The Effect of Thrombectomy on Myocardial Blush in Primary Angioplasty: The Randomized Evaluation of Thrombus Aspiration by Two Thrombectomy Devices in Acute Myocardial Infarction (RETAMI) Trial

Background: In patients with ST‐segment elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) may cause thrombus dislodgment leading to microvascular function impairment, which is a negative independent predictor of myocardial function recovery. Compared with conventional stenting, pretreatment with aspiration thrombectomy during primary PCI significantly improves coronary epicardial flow and myocardial tissue perfusion parameters. We sought to evaluate the angiographic findings of two different manual aspiration thrombectomy devices (Diver‐Invatec® (DI) and Export‐Medtronic®® (EM)) in STEMI patients undergoing primary angioplasty. Methods: We randomized 103 STEMI patients referred to our hospital to undergo primary PCI (<12 hr from symptoms onset) to DI (n = 52) and EM (n = 51) devices. The primary angiographic composite end‐points were the rates of post‐thrombectomy thrombus score (TS) ≤≤2, TIMI flow grade ≥≥2, and post‐stenting myocardial blush grade (MBG) ≥≥2 in the two groups. Results: Baseline, clinical, and angiographic preprocedural findings did not differ between the two groups. After aspiration thrombectomy, a TS ≤≤ 2 was more frequently present in EM group (92.3 vs. 69.3%, P = 0.0052). Also the rate of post‐thrombectomy TIMI ≥≥ 2 (69.3 vs. 92.2%, P = 0.0052) and post‐stenting MBG ≥≥2 (88.2 vs. 69.3%, P = 0.029) were significantly higher in EM group. No significative differences were observed in terms of clinical events at 1 and 12 months. Conclusions: In this single‐center, prospective, randomized study, a EM use before stenting in STEMI patients seems to remove more thrombotic burden compared with DI, providing a greater post‐thrombectomy epicardial flow and a better post‐stenting microvascular perfusion.

Prognostic factors in severe pulmonary hypertension patients who need parenteral prostanoid therapy: The impact of late referral

BACKGROUND Oral drugs have made the treatment of pulmonary hypertension (PH) feasible in non-expert centers, which could delay patient access to prostanoid therapy. METHODS Fifty-seven consecutive patients with precapillary PH received a prostanoid in our center. Data at prostanoid initiation included modality of center referral, medical history, New York Heart Association [NYHA] class, exercise capacity, echocardiographic parameters, and hemodynamics. RESULTS Overall survival at 1, 2, and 3 years was 85%, 69%, 55%, respectively. Non-survivors had worse NYHA class III/IV (17/12) than survivors (27/1; p < 0.01) and exercise capacity on 6-minute-walk distance (254 ± 114 vs 354 ± 91 meters; p < 0.01). Non-survivors were more frequently referred on oral therapy (83% vs 36%; p < 0.01) and had a higher rate of urgent prostanoid treatment (69% vs 17%; p < 0.0001). Multivariate analysis (hazard ratio [95% confidence interval]) found the independent prognostic factors were urgent prostanoid therapy (2.0 [1.1-3.9]) and NYHA class (3.5 [1.5-8.2]). Survivors had a significant response to prostanoid, improving NYHA class from 2.8 ± 0.4 to 2.3 ± 0.5 (p = 0.002), 6-minute walk distance from 354 ± 91 to 426 ± 82 meters (p = 0.0001), and pulmonary hemodynamics (pulmonary artery pressure from 56 ± 13 to 44 ± 18 mm Hg [p < 0.05]; cardiac index from 2.0 ± 1.2 to 3.1 ± 1.2 liters/min/m(2) [p = 0.002], and pulmonary vascular resistance from 17 ± 10 to 8 ± 6 WU [p = 0.001]). CONCLUSIONS Referral of patients on oral treatment to a tertiary PH center is delayed and significantly affects prognosis.

Incidence of contrast-induced acute kidney injury associated with diagnostic or interventional coronary angiography

BACKGROUND Contrast-induced acute kidney injury (CI-AKI) represents an important cause of hospital-acquired AKI. The aim of this study was to evaluate the incidence of CI-AKI after coronary angiography (CA) or percutaneous coronary intervention (PCI) and the role of patient-/procedure-related risk factors. METHODS For 11 months, patients undergoing CA or PCI were prospectively evaluated for CI-AKI, and factors possibly affecting CI-AKI were analyzed. Statistical analysis was completed using Students t-test, chi-square or Fisher exact test, and multivariate logistic regression. RESULTS Among 585 consecutive patients, incidence of CI-AKI was 5.1% (n=30) and renal replacement therapy was required in 10% of those (n=3). Incidence of CI-AKI was higher in patients with anemia or chronic kidney disease (CKD) associated with diabetes. Basal hemoglobin was significantly lower in CI-AKI patients while Mehran score, contrast medium (CM) volume, contrast ratio (CM volume / maximum contrast dose) and ratio glomerular filtration rate (CM volume / GFR) were significantly higher. Multivariate analysis selected a higher contrast ratio as a factor independently associated with a higher risk of CI-AKI which otherwise appeared to be lower with increasing basal hemoglobin. CONCLUSIONS The incidence of CI-AKI after CA or PCI was higher in patients with CKD associated with diabetes. Lower levels of basal hemoglobin appeared to be related to a higher risk of CI-AKI, and contrast media volume, especially if exceeding the dose adjusted for renal function, was a strong modifiable risk factor for CI-AKI.

Cardiovascular disease in HIV patients: from bench to bedside and backwards

HIV patients are exposed to a higher risk of adverse cardiovascular events, due to complex interactions between traditional risk factors and HIV infection itself in terms of ongoing endothelial dysfunctional immune activation/inflammation and increased risk of thrombosis. On the other hand, long-span antiretroviral therapy administration still raises questions on its long-term safety in an era in which life expectancy is becoming longer and longer while treatment of non-HIV-related serious events is increasingly raising concern. In this article, we will critically analyse the current knowledge of pathological and clinical aspects pertaining to the increased risk of cardiovascular events associated with HIV.