Intravenous antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention : A report from the INVEST-STEMI group.

The use of intravenous antiplatelet therapy during primary percutaneous coronary intervention (PPCI) is not fully standardized. The aim is to evaluate the effectiveness and safety of periprocedural intravenous administration of cangrelor or tirofiban in a contemporary ST-segment elevation myocardial infarction (STEMI) population undergoing PPCI. This was a multicenter prospective cohort study including consecutive STEMI patients who received cangrelor or tirofiban during PPCI at seven Italian centers. The primary effectiveness measure was the angiographic evidence of thrombolysis in myocardial infarction (TIMI) flow < 3 after PPCI. The primary safety outcome was the in-hospital occurrence of BARC (Bleeding Academic Research Consortium) 2-5 bleedings. The study included 627 patients (median age 63 years, 79% males): 312 received cangrelor, 315 tirofiban. The percentage of history of bleeding, pulmonary edema and cardiogenic shock at admission was comparable between groups. Patients receiving cangrelor had lower ischemia time compared to tirofiban. TIMI flow before PPCI and TIMI thrombus grade were comparable between groups. At propensity score-weighted regression analysis, the risk of TIMI flow < 3 was significantly lower in patients treated with cangrelor compared to tirofiban (adjusted OR: 0.40; 95% CI: 0.30-0.53). The risk of BARC 2-5 bleeding was comparable between groups (adjusted OR:1.35; 95% CI: 0.92-1.98). These results were consistent across multiple prespecified subgroups, including subjects stratified for different total ischemia time, with no statistical interaction. In this real-world multicenter STEMI population, the use of cangrelor was associated with improved myocardial perfusion assessed by coronary angiography after PPCI without increasing clinically-relevant bleedings compared to tirofiban.

Platelet inhibition with orodispersible ticagrelor in acute coronary syndromes according to morphine use: the TASTER study final results.

AIM: To date, it is still unknown whether orodispersible tablet (ODT) ticagrelor might represent a suitable way to reach a proper antiaggregation in acute coronary syndrome (ACS) patients receiving morphine. Aim of the present study was to evaluate platelet inhibition with 180 mg ticagrelor loading dose (LD) administered as ODT compared with standard coated tablet ticagrelor formulation in ACS patients undergoing percutaneous coronary intervention (PCI) according to morphine use. METHODS AND RESULTS: One-hundred and 30 patients presenting with STEMI or very high-risk NSTE-ACS were randomly assigned to receive ODT or standard ticagrelor LD. Potential morphine-ticagrelor interaction was assessed by stratified randomization according to morphine use. Platelet reactivity was evaluated by Platelet Reactivity Units (PRU) VerifyNow™ 1, 2, 4, and 6 h after ticagrelor LD. The primary endpoint was residual platelet reactivity 1 h after LD across the two ticagrelor formulation and according to morphine use. Safety endpoints were major bleedings and other in-hospital ticagrelor administration-related adverse events. One hour after LD, PRU median value was higher in morphine-treated patients (N = 32) as compared with patients not receiving morphine (N = 98; PRU = 187 [70-217]) vs. 73 [7-187]; P = 0.012). In patients with morphine, 1-h PRU values were similar between study groups (192 [114-236] vs. 173 [16-215] in ODT and standard tablet ticagrelor, respectively). Similarly, in patients without morphine, 1-h PRU values were not significantly different between study groups (69 [8-152] vs. 110 [6-193] in ODT and standard tablet ticagrelor, respectively). Platelet reactivity appeared similar in the 2 study arms at 2, 4, and 6 h after LD. No significant difference was observed among patients with or without morphine regarding in-hospital adverse events or drug side-effects, even if a reinfarction due to acute stent thrombosis was observed in a patient treated with morphine. CONCLUSIONS: There was no difference between ODT and standard ticagrelor tablets in terms of post-LD residual platelet reactivity, percentage of platelet inhibition or safety regardless to morphine use.

Dual Antiplatelet Therapy with 3rd Generation P2Y12 Inhibitors in STEMI Patients: Impact of Body Mass Index on Loading Dose-Response.

PURPOSE: This study aims to assess the association between body mass index (BMI) and platelet reactivity in STEMI patients treated with oral 3rd generation P2Y12 inhibitors. METHODS: Overall, 429 STEMI patients were enrolled in this study. Patients were divided into two groups according to BMI (BMI < 25 vs ≥ 25 kg/m2). A propensity score matching (1:1) was performed to balance potential confounders in patient baseline characteristics. Platelet reactivity was assessed by VerifyNow at baseline and after 3rd generation P2Y12 inhibitor (ticagrelor or prasugrel) loading dose (LD). Blood samples were obtained at baseline (T0), 1 h (T1), 2 h (T2), 4-6 h (T3), and 8-12 h (T4) after the LD. High on-treatment platelet reactivity (HTPR) was defined as a platelet reactivity unit value ≥ 208 units. RESULTS: After propensity score matching, patients with BMI ≥ 25 had similar values of baseline platelet reactivity, while they had higher level of platelet reactivity at 1 and 2 h after the LD and higher rate of HRPT. Furthermore, multivariate analysis demonstrated that BMI ≥ 25 was an independent predictor of HTPR at 2 h (OR 2.01, p = .009). Conversely, starting from 4 h after the LD, platelet reactivity values and HRPT rates were comparable among the two study groups. CONCLUSIONS: A BMI ≥ 25 kg/m2 is associated with delayed pharmacodynamic response to oral 3rd generation P2Y12 inhibitor LD, and it is a strong predictor of HTPR in STEMI patients treated by dual antiplatelet therapy with ticagrelor or prasugrel.

Left atrial remodeling in heart failure: the role of sphericity index (the SPHERICAT-HF study).

Left atrial sphericity index (LASI) is an echocardiographic index easily obtained; its use in patients with heart failure (HF) has never been investigated so far. This single-centre study aimed to investigate the usefulness of LASI in an unselected cohort of patients hospitalized for acute HF, and its potential correlation with the amino-terminal portion of pro-B-type natriuretic peptide (NT-proBNP) levels and with New York Heart Association (NYHA) functional class. Ninety-four consecutive HF patients underwent a transthoracic echocardiogram with a detailed study of the left atrium (LA) including LASI (calculated from the apical four-chamber view as the ratio between the transverse and longitudinal diameters), and blood tests (including NT-proBNP) on the same day. Median age was 75.5 (interquartile range-IQR 62-82) years and 55% were males, 58.5% had a NYHA class III-IV, and median NT-proBNP was 3284 (IQR 1215-7055) pg/ml. The LA was dilated in 94%, and median biplane LA volume index was 62 ml/m2. Patients with advanced NYHA class showed more advanced LA remodeling. Mean LASI was 0.78 ± 0.09 and did not correlate with NT-proBNP levels (r 0.03; p 0.75) or with patient NYHA class (R2 0.011; p 0.287). None of the echocardiographic indices of LA structural and functional remodeling proved to be independently associated with a high NYHA class on multivariate regression analysis. In conclusion, LA remodeling is almost invariably present in patients with HF. LASI does not correlate with NT-proBNP levels or with NYHA functional class. Further studies are needed to describe the complex patterns of atrial remodeling in HF.

Prevalence, clinical and instrumental features of left bundle branch block-induced cardiomyopathy: the CLIMB registry.

AIMS: Although increasingly recognized as a distinct pathological entity, left bundle branch block-induced cardiomyopathy (LBBB-ICMP) is not included among the possible aetiologies of acquired dilated cardiomyopathies (DCM). While diagnostic criteria have been proposed, its recognition remains principally retrospective, in the presence of clinical and instrumental red flags. We aimed to assess the prevalence and clinical and instrumental features of LBBB-ICMP in a large cohort of patients with DCM. METHODS AND RESULTS: We analysed a cohort of 242 DCM patients from a two-centre registry. Inclusion criteria were age > 18, non-ischaemic or non-valvular DCM, and LBBB on electrocardiogram. LBBB-ICMP was defined according to previously proposed diagnostic criteria: (i) neither family history nor clinically identifiable potential causes for DCM; (ii) negative genetic testing; (iii) echocardiographic features including non-severe chamber dilation, normal absolute and relative wall thickness, marked dyssynchrony, and normal right ventricular function; and (iv) absence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). From the entire cohort, we identified 30 subjects (similar in terms of New York Heart Association class I or II in 80% vs. 75%, P = 0.56; QRS width of 150 ± 22 vs. 151 ± 24 ms, P = 0.82; and cardiac remodelling of baseline end-diastolic diameter 66 ± 8 vs. 65 ± 10 mm, P = 0.53) with a comprehensive dataset including CMR and genetic testing, required to verify the presence of the diagnostic criteria proposed for LBBB-ICMP. The main characteristics of this subgroup were 73% males, age 45 ± 13 years, left ventricular ejection fraction (LVEF) 30 ± 10%, LGE in 38% of patients, and QRS complex of 150 ± 22 ms. Patients were under guideline-directed medical therapy, and 57% of them were treated with cardiac resynchronization therapy (CRT). Two patients (6.67%, 50% males, age 53 ± 13 years) fulfilled the diagnostic criteria proposed for LBBB-ICMP. After a follow-up of 44 (12-76) months, LVEF was normal and QRS width significantly reduced (from 154 ± 25 to 116 ± 52 ms) in patients with LBBB-ICMP. Both patients were under optimal medical treatment, and one was implanted with CRT-D. Neither of the two patients experienced death, malignant ventricular arrhythmia, or heart failure hospitalization at follow-up. CONCLUSIONS: Left bundle branch block-induced cardiomyopathy emerges as a distinct pathological entity, promptly identifiable in a minority but not negligible proportion of patients with newly diagnosed DCM and LBBB, using a series of diagnostic criteria including CMR and genetic testing. Further studies are needed to better elucidate the clinical course of LBBB-ICMP.

Single, Dual, and Triple Antithrombotic Therapy in Cancer Patients with Coronary Artery Disease: Searching for Evidence and Personalized Approaches.

Improvement in life expectancy of patients suffering from oncohematologic disorders has turned cancer from an acute into a chronic condition, making the management of comorbidities problematic, especially when it comes to both acute and chronic cardiovascular diseases. Treatment-related adverse events and drug-drug interactions often influence the therapeutic approach of patients with active malignancies and cardiovascular disease. Furthermore, tumor cells and platelets maintain a complex crosstalk that on one hand enhances tumor dissemination and on the other hand induces hemostasis abnormalities. Hence, clinicians should move carefully in the intricate land mines established by patients with active cancer under antithrombotic therapy. To date, there is no consensus on the antithrombotic treatment of patients with cardiovascular diseases and concomitant malignancies. The aim of this review is to collect the available scientific evidence, including the latest clinical trials and guidelines, in order to provide guidance on the management of antithrombotic treatment (both antiplatelet and anticoagulant therapy) in cancer patients with either pre-existent or new-onset coronary artery disease. Randomized-controlled trials on antithrombotic treatment in oncologic populations, which by far have thus far been excluded, have to be promoted to supply recommendations in the oncohematologic setting.

The Controversial Role of Glucose-6-Phosphate Dehydrogenase Deficiency on Cardiovascular Disease: A Narrative Review.

Cardiovascular disorders (CVD) are highly prevalent and the leading cause of death worldwide. Atherosclerosis is responsible for most cases of CVD. The plaque formation and subsequent thrombosis in atherosclerosis constitute an ongoing process that is influenced by numerous risk factors such as hypertension, diabetes, dyslipidemia, obesity, smoking, inflammation, and sedentary lifestyle. Among the various risk and protective factors, the role of glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common inborn enzyme disorder across populations, is still debated. For decades, it has been considered a protective factor against the development of CVD. However, in the recent years, growing scientific evidence has suggested that this inherited condition may act as a CVD risk factor. The role of G6PD deficiency in the atherogenic process has been investigated using in vitro or ex vivo cellular models, animal models, and epidemiological studies in human cohorts of variable size and across different ethnic groups, with conflicting results. In this review, the impact of G6PD deficiency on CVD was critically reconsidered, taking into account the most recent acquisitions on molecular and biochemical mechanisms, namely, antioxidative mechanisms, glutathione recycling, and nitric oxide production, as well as their mutual interactions, which may be impaired by the enzyme defect in the context of the pentose phosphate pathway. Overall, current evidence supports the notion that G6PD downregulation may favor the onset and evolution of atheroma in subjects at risk of CVD. Given the relatively high frequency of this enzyme deficiency in several regions of the world, this finding might be of practical importance to tailor surveillance guidelines and facilitate risk stratification.

Spontaneous Device Detachment After its Partial Deployment During Left Atrial Appendage Occlusion: A Nightmare in the Cath Lab.

To date, this is the first description of a spontaneous unscrewing of an Amplatzer Amulet device from its delivery cable while its lobe was partially deployed within the left atrial appendage. In such cases, the device should be pushed forward to complete the deployment and to rescrew the device to the DC in order to prevent an unavoidable cardiac surgery.

Efficacy and safety of alternative oral administrations of P2Y12-receptor inhibitors: Systematic review and meta-analysis.

BACKGROUND: Early administration of P2Y12-receptor inhibitors is recommended in all patients with acute coronary syndrome undergoing invasive management, with the aim to achieve the fastest and most effective platelet inhibition. Several trials investigated alternative methods of P2Y12-receptor inhibitor administration (mainly chewed or crushed) aimed at ensuring faster and higher platelet inhibition. Thus, we decided to perform a systematic review and meta-analysis analyzing efficacy and safety of alternative P2Y12-receptor inhibitor administration strategies. METHODS: Systematic research was performed on Pubmed, Cochrane Library, Biomed Central, and Web of Science databases. We included randomized or observational trials testing at least one P2Y12-receptor inhibitor alternative administration. The primary outcome of the study was the value of the platelet reactivity unit (PRU) at 1 h after drug administration, assessed by VerifyNow P2Y12 test (Accumetrics, Inc., San Diego, CA). Secondary outcomes were adverse bleeding events (safety outcome). RESULTS AND DISCUSSION: Fourteen studies were selected for qualitative analysis. Five studies, all focused on ticagrelor, were selected for quantitative efficacy analyses. These five studies compared the administration of crushed/chewed ticagrelor 180 mg loading dose (LD) with the standard whole tablets LD. The pooled mean difference between the two administrations was -59.24 PRU (95% CI from -30.61 to -87.87 PRU) in favor of the crushed/chewed administration, corresponding to a 25% mean relative PRU reduction between alternative and standard P2Y12-receptor inhibitor administrations at 1 h after drug intake. A similar relationship was found in other studies on alternative administration of clopidogrel and prasugrel, not included in the quantitative analysis.

Glucose-6-phosphate dehydrogenase deficiency and risk of cardiovascular disease: A propensity score-matched study.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is associated with high morbidity and mortality. Studies in animal models and humans suggested that glucose‒6‒phosphate dehydrogenase (G6PD) deficiency, a genetically inherited condition causing haemolytic anemia, may be a risk factor for CVD. This hypothesis was tested in a large cohort from Northern Sardinia, where the population prevalence of G6PD deficiency is the highest in the Mediterranean area. METHODS: A retrospective observational case‒control study was performed using clinical records of 9604 patients undergoing digestive endoscopy between 2002 and 2017, with a known G6PD status and a complete clinical history including CVD and leading CVD risk factors. To circumvent covariates imbalance between cases and controls, a 1:2 propensity score‒matched analysis was performed. RESULTS: Major predictors of CVD, as expected, were age (OR 1.07; 95%CI 1.06-1.08), male sex (1.63; 95%CI 1.29-2.06), high blood pressure (OR 1.46; 95%CI 1.16-1.84), smoking (OR 3.03; 95%CI 2.42-3.79), diabetes (OR 1.65; 95%CI 1.23-2.21) and hypercholesterolemia (OR 2.20; 95%CI 1.71-2.84). The propensity score matching procedure resulted in 1123 G6PD deficient patients and 2246 patients with normal enzyme activity. When G6PD status was regressed on the CVD, including propensity score as a continuous covariate, an OR of 1.71 (95%CI 1.17-2.49; p = 0.006) was obtained. CONCLUSIONS: G6PD deficiency is significantly associated with increased risk of CVD, although the underlying mechanisms are still poorly understood. The loss of important protective pathways against oxidative stress, especially in the early stages of atherogenesis, might play a crucial role.

Cardiac Abnormalities in Alzheimer Disease: Clinical Relevance Beyond Pathophysiological Rationale and Instrumental Findings?

OBJECTIVES: This case control study sought to assess the presence and characteristics of cardiac abnormalities in patients with Alzheimer disease (AD). BACKGROUND: Protein misfolding is involved in the pathophysiology of neurodegenerative disorders such as AD. Recently, amyloid-beta (Aß) aggregates were identified within the cardiomyocytes and interstitium of patients with AD, suggesting that Aß oligomers may reach and damage the heart. METHODS: The authors studied 32 patients with AD and 34 controls matched by age and sex, all of whom were free from cardiac or systemic diseases. A clinical evaluation, an electrocardiogram, and an echocardiogram were performed in all subjects. Furthermore, patients with AD underwent genetic analyses (of the PSEN1, PSEN2, APP, and APOE genes). RESULTS: Compared to the control group, patients with AD had a higher prevalence of low-voltage electrocardiographic QRS complexes (28% vs. 3%, respectively; p = 0.004), a lower voltage/mass ratio (p = 0.05), a greater echocardiographic interventricular septum (10.1 ± 1.3 mm vs. 9.3 ± 1.1 mm, respectively; p = 0.01), a greater maximum wall thickness (10.8 ± 1.7 mm vs. 9.3 ± 1.1 mm, respectively; p = 0.0001), and a 2-fold higher prevalence of diastolic dysfunction (70% vs. 35%, respectively; p = 0.007). Symptoms and signs of heart failure were absent in all patients with AD. CONCLUSIONS: This study shows that electrocardiographic and echocardiographic abnormalities, including diastolic dysfunction, are present in patients with AD and that these studies reproduce the pattern of cardiac amyloidosis. These findings suggest that, in AD, there may be subclinical cardiac involvement likely associated with Aß amyloid deposition. The clinical relevance of these cardiac abnormalities should be evaluated in larger prospective studies.

APpropriateness Assessment in Antiplatelet THerapY (APATHY) registry: Insight from current clinical practice.

BACKGROUND: In clinical practice there is a gap between guidelines recommendation and antiplatelet strategies used for acute coronary syndrome (ACS). We sought to evaluate appropriateness of antiplatelet strategies employed in a tertiary center. METHODS AND RESULTS: From January to June 2014, 430 ACS were treated with percutaneous coronary intervention by 3 groups of interventional cardiologists. Aspirin and clopidogrel (52%) were the most commonly used antiplatelet therapies, being prasugrel associated with aspirin in 110 (25.5%) and ticagrelor in 97 (22.5%) ACS. Inappropriate use of prasugrel (Tia/Ictus) was found in 2 (1.8%) patients and not recommended use (>75years, without diabetes or previous myocardial infarction) in 11 (10%). Not recommended use of ticagrelor (plus warfarin) was found in 4 (4.4%). Switching from clopidogrel to prasugrel occurred in 29% [28 showing high residual platelet reactivity (HRPR: ADP 10µmol>70%), and 4 left main stenting], while from clopidogrel to ticagrelor occurred in 13.4% (all showing HRPR, but 1). The most powerful predictor for prescription of 3rd generation P2Y12 inhibitors was the HRPR (OR 5.473, 95%CI 2.41-12.43, p<0.0001), whereas the behavior of attending cardiologist (HR 0.674, 95%CI 0.573-0.847, p=0.001) and the older age reduced the probability of receiving it (OR0.963, 95%CI 0.943-0.984, p=0.001). CONCLUSIONS: Clopidogrel remained the most common P2Y12 inhibitor employed for ACS. Third generation P2Y12 inhibitor prescription was lower than the one expected by guidelines recommendations, and the switching was largely based on clopidogrel HRPR. These findings suggest the need for a greater effort to improve adherence of cardiology community to current guidelines.

Incidence and outcome of switching of oral platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: the SCOPE registry.

AIMS: In patients with acute coronary syndromes (ACS) undergoing a percutaneous coronary intervention (PCI), switching of oral P2Y12 receptor inhibitors may frequently occur. We aimed to assess the current incidence of switching of oral P2Y12 receptor inhibitors and its safety in consecutive ACS patients undergoing PCI over a three-month period. METHODS AND RESULTS: The SCOPE registry was a multicentre, observational, prospective study. A total of 1,363 consecutive patients were enrolled in 39 PCI centres across Italy. Switching of oral antiplatelet therapies occurred in 2.3% in the cathlab, 3.3% at discharge and 5.1% at follow-up. The cumulative incidence of major adverse cerebrovascular events (MACE) and net adverse cerebrovascular events (NACE: a combination of MACE and bleeding events) was 1.6% and 5.6%, respectively. Among patients receiving an upgrade switching (change from old to novel P2Y12 receptor inhibitors), no ischaemic or bleeding events occurred during the whole study period. On the other hand, downgrade switching (from novel to old P2Y12 receptor inhibitors) was an independent predictor of NACE (OR 5.3; CI: 2.1-18.2; p=0.04). CONCLUSIONS: Switching of oral antiplatelet therapies is not uncommon among ACS patients undergoing PCI. Notably, switching from clopidogrel to novel P2Y12 receptor inhibitors appears safe, while a downgrade switching in early phases of ACS is associated with adverse clinical events.

Long-Term Primary Patency Rate After Nitinol Self-Expandable Stents Implantation in Long, Totally Occluded Femoropopliteal (TASC II C & D) Lesions.

BACKGROUND: Endovascular therapy for long femoropopliteal lesions using percutaneous transluminal balloon angioplasty or first-generation of peripheral stents has been associated with unacceptable one-year restenosis rates. However, with recent advances in equipment and techniques, a better primary patency rate is expected. This study was conducted to detect the long-term primary patency rate of nitinol self-expandable stents implanted in long, totally occluded femoropopliteal lesions TransAtlantic Inter-Society Census (TASC II type C & D), and determine the predictors of reocclusion or restenosis in the stented segments. METHODS: The demographics, clinical, anatomical, and procedural data of 213 patients with 240 de novo totally occluded femoropopliteal (TASC II type C & D) lesions treated with nitinol self-expandable stents were retrospectively analysed. Of these limbs, 159 (66.2%) presented with intermittent claudication, while 81 (33.8%) presented with critical limb ischaemia. The mean-time of follow-up was 36±22.6 months, (range: 6.3-106.2 months). Outcomes evaluated were, primary patency rate and predictors of reocclusion or restenosis in the stented segments. RESULTS: The mean age of the patients was 70.9±9.3 years, with male gender 66.2%. Mean pre-procedural ABI was 0.45±0.53. One-hundred-and-seventy-five (73%) lesions were TASC II type C, while 65 (27%) were type D lesions. The mean length of the lesions was 17.9±11.3mm. Procedure related complications occurred in 10 (4.1%) limbs. There was no periprocedural mortality. Reocclusion and restenosis were detected during follow-up in 45 and 30 limbs respectively, and all were re-treated by endovascular approach. None of the patients required major amputation. Primary patency rates were 81.4±1.1%, 77.7±1.9% and 74.4±2.8% at 12, 24, and 36 months respectively. Male gender, severe calcification, and TASC II D lesion were independent predictors for reocclusion, while predictors of restenosis were DM, smoking and TASC II D lesions. CONCLUSIONS: Treatment of long, totally occluded femoropopliteal (TASC II C & D) lesions with nitinol self-expandable stents is safe and is associated with highly acceptable long-term primary patency rates.