Simone Biscaglia

Chronic obstructive pulmonary disease and ischemic heart disease comorbidity: overview of mechanisms and clinical management.

In the last few years, many studies focused their attention on the relationship between chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD), showing that these diseases are mutually influenced. Many different biological processes such as hypoxia, systemic inflammation, endothelial dysfunction, heightened platelet reactivity, arterial stiffness and right ventricle modification interact in the development of the COPD-IHD comorbidity, which therefore deserves special attention in early diagnosis and treatment. Patients with COPD-IHD comorbidity have a worst outcome, when compared to patients with only COPD or only IHD. These patients showed a significant increase on risk of adverse events and of hospital readmissions for recurrent myocardial infarction, heart failure, coronary revascularization, and acute exacerbation of COPD. Taken together, these complications determine a significant increase in mortality. In most cases death occurs for cardiovascular cause, soon after an acute exacerbation of COPD or a cardiovascular adverse event. Recent data regarding incidence, mechanisms and prognosis of this comorbidity, along with the development of new drugs and interventional approaches may improve the management and long-term outcome of COPD-IHD patients. The aim of this review is to describe the current knowledge on COPD-IHD comorbidity. Particularly, we focused our attention on underlying pathological mechanisms and on all treatment and strategies that may improve and optimize the clinical management of COPD-IHD patients.

Prospective validation of the bleeding academic research consortium classification in the all-comer PRODIGY trial

AIMS The Bleeding Academic Research Consortium (BARC) classification has been proposed by consensus to standardize bleeding endpoint definition and reporting in cardiovascular clinical trials. There are no prospective studies on its prognostic impact. METHODS AND RESULTS We explored the association of BARC-defined bleeding with mortality and compared its prognostic value against two validated bleeding scales: the Thrombolysis in Myocardial Infarction (TIMI) and the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) scales. Non-coronary artery bypass graft (CABG)-related bleedings within the PRODIGY trial were prospectively adjudicated by a blinded Clinical Event Committee and analysed according to multiple statistical modelling. At 2 years, bleeding occurred in 143 patients (7.1%) according to BARC Type 2, 3, or 5; in 50 patients (2.5%) according to TIMI minor or major; and in 61 patients (3.1%) according to GUSTO moderate or severe. One hundred sixty-three patients died (8.1%). After multivariable modelling, BARC Type 2, 3, or 5 bleeding was associated with increased 2-year mortality [hazard ratio (HR): 3.77; 95% confidence interval (CI): 2.37-5.98]. Bleeding Academic Research Consortium Type 3 or 5 was associated with an increased mortality rate at 2 years (adjusted HR: 7.72; 95% CI: 4.75-12.54) similar to that provided by TIMI (HR: 7.64, 95% CI: 4.53-12.87) or GUSTO (HR: 7.36, 95% CI: 4.38-12.34) criteria. CONCLUSIONS In a contemporary, all-comer percutaneous coronary intervention trial actionable BARC bleedings were associated with increased risk of mortality with BARC Type 3 or 5 bleedings providing a similar mortality risk to that posed by TIMI or GUSTO scales.

Cardiac troponin elevation predicts all-cause mortality in patients with acute exacerbation of chronic obstructive pulmonary disease: Systematic review and meta-analysis

BACKGROUND Cardiovascular disease, especially ischemic heart disease, is a major comorbidity in chronic obstructive pulmonary disease (COPD) patients. Several studies suggested that after acute exacerbation of COPD (AECOPD), there is a significant increase of mortality (cardiac and all-cause) and of myocardial infarction. Whether cardiac troponin (Tn) elevation during AECOPD could be considered a prognostic marker of all-cause mortality is still debated. METHODS To assess the prognostic role of cardiac Tn elevation during AECOPD, we performed a systematic review and meta-analysis. We included studies with patients admitted to the hospital for AECOPD, with at least one Tn assessment and reporting the relationship (after multivariable analysis) between Tn elevation and all-cause mortality. Secondarily, studies were stratified according to: i) type of troponin (Tn I or Tn T), and ii) follow-up length (≤6 months vs. >6 months). RESULTS Ten studies were included in the systematic review and 8 in the meta-analysis. Cardiac Tn elevation ranges from 18% to 73%. We found that cardiac Tn elevation was significantly related to an increased risk for all-cause mortality (OR 1.69; 95% CI 1.25-2.29; I(2) 40%). This finding was independent to the follow-up length of studies (≤6 months: OR 3.22; 95% CI 1.31-7.91; >6 months: OR 1.38; 95% CI 1.02-1.86). Finally, Tn T seems to be more helpful in predicting all-cause mortality as compared to Tn I (OR 1.54; 95% CI 1.2-1.96 vs. OR 3.39, 95% CI 0.86-13.36, respectively). CONCLUSIONS In patients admitted to the hospital for AECOPD, cardiac Tn elevation emerged as an independent predictor of increased risk of all-cause mortality.

Bioresorbable Scaffold vs. Second Generation Drug Eluting Stent in Long Coronary Lesions requiring Overlap: A Propensity-Matched Comparison (the UNDERDOGS study).

BACKGROUND Randomized clinical trials on bioresorbable scaffolds (BRS) enrolled patients with simple coronary lesions. The present study was sought to give preliminary findings about safety of BRS implantation in overlap in long coronary lesions. METHODS From June 2012 to January 2015, we prospectively collected data from 162 consecutive patients receiving overlapping BRS implantation in the 16 participating institutions. We applied a propensity-score to match BRS-treated patients with 162 patients receiving second generation drug eluting stents (DES) in overlap. The primary endpoint was a device-oriented endpoint (DOCE), including cardiac death, target vessel myocardial infarction, and target lesion revascularization. RESULTS DOCE rate did not significantly differ between the two groups (5.6% in BRS group vs. 7.4% in DES group, HR 0.79, 95%CI 0.37-3.55, p=0.6). Also stent/scaffold thrombosis did not differ between groups (1.2% in BRS group vs. 1.9% in DES group, p=0.6). Occurrence of procedural-related myocardial injury was significantly higher in the BRS group (25% vs. 12%, p=0.001), although it was not related to DOCE (HR 1.1, 95%CI 0.97-1.2, p=0.2). Imaging techniques and enhanced stent visualization systems were significantly more employed in the BRS group (p=0.0001 for both). Procedure length, fluoroscopy time and contrast dye amount were significantly higher in the BRS group (p=0.001, p=0.001 and p=0.01, respectively). CONCLUSIONS Overlapping BRS utilization in long coronary lesions showed a comparable DOCE rate at 1year if compared to second generation DES. Further and larger studies are on demand to confirm our findings.

Fractional flow reserve evaluation and chronic kidney disease: Analysis from a multicenter Italian registry (the FREAK study)

To establish if the presence of chronic kidney disease (CKD) influences fractional flow reserve (FFR) value in patients with intermediate coronary stenosis.

Uric acid and coronary artery disease: An elusive link deserving further attention

Uric acid is the final product of purine metabolism. Classically it is recognized as the cause of gouty arthritis and kidney stones. Western civilization has increased serum levels of uric acid which is no longer considered a benign plasma solute. It has been postulated and recently demonstrated that it can penetrate cell membrane and exerts damaging intracellular actions such as oxidation and inflammation. These observations have stimulated several epidemiological researches suggesting that hyperuricemia is linked or even provokes hypertension and coronary artery disease. In this review we summarize the current evidences regarding uric acid which contribute in the pathophysiology of coronary artery disease.

Occurrence, causes, and outcome after switching from ticagrelor to clopidogrel in a real-life scenario: data from a prospective registry

Abstract In randomized clinical trials, ticagrelor has been substituted in roughly one-third of the patients during follow-up. To date, there are no studies addressing safety and modalities of switching from ticagrelor to clopidogrel. The aim of our study is to describe the occurrence, causes, and outcome of the switch from ticagrelor to clopidogrel in a real-life scenario. From June 2013 to March 2015, 586 patients were treated with ticagrelor in our centre. Overall, 101 (17%) patients were switched to clopidogrel through a standardized protocol, and they were followed-up for 12 months. Ischemic and bleeding events were prospectively recorded. The switch from ticagrelor to clopidogrel occurred mostly after discharge (69 ± 40 days), and the most frequent cause was the need of oral anticoagulation treatment, followed by bleeding events. Patients requiring ticagrelor discontinuation were older, more frequently female, with lower body mass index and creatinine clearance if compared to the “non-switched” group. In the 10 days after the switch, we did not observe ischemic adverse events. No definite/probable stent thrombosis was recorded. Before the switch, there was a significant higher occurrence of BARC bleedings in the “switched” group, particularly BARC 1 and 2. Our data confirm that the switch from ticagrelor to clopidogrel is common, and it occurs for several reasons. Our analysis did not demonstrate a significant increase in adverse cardiovascular events in the days following the switch from ticagrelor to clopidogrel, although larger studies are needed to validate our findings.

Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial.

BACKGROUND Proton pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy (DAPT) with clopidogrel plus aspirin. METHODS AND RESULTS In the PRODIGY trial, 1,970 patients were randomized to 6- or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. Proton pump inhibitor users were older, were most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome, and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy end point (composite of all-cause death, myocardial infarction, and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%, adjusted hazard ratio [HR] 1.051, 95% CI 0.788-1.400, P = .736). Bleeding rates did not differ between the 2 groups (Bleeding Academic Research Consortium type 2, 3, or 5: adjusted HR 0.996, 95% CI 0.672-1.474, P = .980). Net clinical adverse events were also similar in no PPI and PPI patients (12.9% vs 14.9%, adjusted HR 0.99, 95% CI 0.772-1.268, P = .93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration. CONCLUSIONS The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome.

Overview of the pharmacological challenges facing physicians in the management of patients with concomitant cardiovascular disease and chronic obstructive pulmonary disease

Cardiovascular disease (CVD), including ischaemic heart disease (IHD) and heart failure (HF), and chronic obstructive pulmonary disease (COPD) are often concomitant because they share both risk factors (smoke) and pathological pathways (systemic inflammation). Cardiovascular disease and COPD association is increasing overtime. Several registries clearly showed a negative impact on the clinical outcome of the concomitant presence of CVD and COPD. Patients with CVD and COPD present an increased risk for myocardial infarction, HF, and hospital admission for acute exacerbation of COPD, with a negative impact on prognosis. To reduce the effect of this negative association, it is of paramount importance the pharmacological treatment with both cardiovascular and respiratory drugs, according to current guidelines. Nevertheless, several registries and studies showed that evidence-based drugs (both cardiovascular and respiratory) are often under administered in this subset of patients. In this overview, we summarize the available data regarding the use of cardiovascular drugs (antiplatelet agents, angiotensin converting enzyme inhibitors, β-blockers, and statins) in COPD patients, with or without concomitant IHD. Furthermore, we report advantages and disadvantages of respiratory drugs (β2 agonists, anti-cholinergics, and corticosteroids) administration in COPD patients with CVD.

Effects of pre-hospital clopidogrel administration on early and late residual platelet reactivity in ST-segment elevation myocardial infarction patients undergoing primary intervention.

TAFI levels influence the clot lysis time in healthy individuals in the presence of an intact intrinsic pathway of coagulation. Thromb Haemost 1998; 80: 829–35. 12 Declerck PJ. Thrombin activatable fibrinolysis inhibitor. Hamostaseologie 2011; 31: 165–73. 13 ColucciM, SemeraroN. Thrombin activatable fibrinolysis inhibitor: at the nexus of fibrinolysis and inflammation. Thromb Res 2012; 129: 314–9. 14 Mutch NJ, Robbie LA, Booth NA. Human thrombi contain an abundance of active thrombin. Thromb Haemost 2001; 86: 1028–34. 15 Guimaraes AHC, Barrett-Bergshoeff MM, Gils A, Declerck PJ, Rijken DC. Migration of the activation peptide of thrombin-activatable fibrinolysis inhibitor (TAFI) during SDS-polyacrylamide gel electrophoresis. J Thromb Haemost 2004; 2: 780–4. 16 Mutch NJ, Koikkalainen JS, Fraser SR, Duthie KM, Griffin M, Mitchell J, Watson HG, Booth NA. Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis. J Thromb Haemost 2010; 8: 2017–24. 17 Valnickova Z, Enghild JJ. Human procarboxypeptidase U, or thrombin-activable fibrinolysis inhibitor, is a substrate for transglutaminases – evidence for transglutaminase-catalyzed cross-linking to fibrin. J Biol Chem 1998; 273: 27220–4.