Publications by authors named "Andrea Demarchi"

34 Publications

Transcatheter mitral valve repair with MitraClip in patients with pulmonary hypertension: hemodynamic and prognostic perspectives.

Rev Cardiovasc Med 2021 Mar;22(1):33-38

Division of Cardiology and Cardiac Intensive Care Unit, San Paolo Hospital, 17100 Savona, Italy.

Transcatheter mitral valve repair with MitraClip has emerged as a possible therapeutic option for patients with severe mitral regurgitation (MR) with high risk for surgical valve repair. MitraClip intervention has demonstrated to improve haemodynamics and clinical outcomes in selected patients in observational and randomized studies. Preoperative pulmonary hypertension (PH) is known to affect prognosis in patients undergoing surgical mitral valve intervention. The aim of the present review is to discuss the available literature focused on the haemodynamic and clinical effects of MitraClip in patients with severe MR and PH.
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http://dx.doi.org/10.31083/j.rcm.2021.01.214DOI Listing
March 2021

De Winter Pattern Caused by a Large Diagonal Branch Culprit Lesion.

J Invasive Cardiol 2021 Mar;33(3):E230

Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.

A 70-year-old man was referred to the emergency department for an episode of ongoing chest pain during physical activity. Urgent coronary angiogram revealed a 75% stenosis in the left anterior descending coronary artery and a total occlusion of a large diagonal branch. Both stenoses were treated successfully with percutaneous coronary intervention. After reperfusion, the ECG showed a "De Winter" pattern, which was the ECG expression of a culprit lesion located in a large diagonal branch rather than in the left anterior descending.
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March 2021

A Primary Prevention Clinical Risk Score Model for Patients With Brugada Syndrome (BRUGADA-RISK).

JACC Clin Electrophysiol 2021 02 28;7(2):210-222. Epub 2020 Oct 28.

Department of Cardiology, Santa Maria University Hospital, Lisbon Academic Medical Centre and Cardiovascular Centre of the University of Lisbon, Faculty of Medicine, Lisbon, Portugal.

Objectives: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS).

Background: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence.

Methods: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation.

Results: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country.

Conclusions: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription.
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http://dx.doi.org/10.1016/j.jacep.2020.08.032DOI Listing
February 2021

Incidence of Ventricular Arrhythmias and 1-Year Predictors of Mortality in Patients Treated With Implantable Cardioverter-Defibrillator Undergoing Generator Replacement.

J Am Heart Assoc 2021 Feb 30;10(4):e018090. Epub 2021 Jan 30.

Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology Fondazione IRCCS Policlinico San Matteo Pavia Italy.

Background When implantable cardioverter defibrillator (ICD) battery is depleted most patients undergo generator replacement (GR) even in the absence of persistent ICD indication. The aim of this study was to assess the incidence of ventricular arrhythmias and the overall prognosis of patients with and without persistent ICD indication undergoing GR. Predictors of 1-year mortality were also analyzed. Methods and Results Patients with structural heart disease implanted with primary prevention ICD undergoing GR were included. Patients were stratified based on the presence/absence of persistent ICD indication (left ventricular ejection fraction ≤35% at the time of GR and/or history of appropriate ICD therapies during the first generator's life). The study included 371 patients (82% male, 40% with ischemic heart disease). One third of patients (n=121) no longer met ICD indication at the time of GR. During a median follow-up of 34 months after GR patients without persistent ICD indication showed a significantly lower incidence of appropriate ICD shocks (1.9% versus 16.2%, <0.001) and ICD therapies. 1-year mortality was also significantly lower in patients without persistent ICD indication (1% versus 8.3%, =0.009). At multivariable analysis permanent atrial fibrillation, chronic advanced renal impairment, age >80, and persistent ICD indication were found to be significant predictors of 1-year mortality. Conclusions Patients without persistent ICD indication at the time of GR show a low incidence of appropriate ICD therapies after GR. Persistent ICD indication, atrial fibrillation, advanced chronic renal disease, and age >80 are significant predictors of 1-year mortality. Our findings enlighten the need of performing a comprehensive clinical reevaluation of ICD patients at the time of GR.
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http://dx.doi.org/10.1161/JAHA.120.018090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955330PMC
February 2021

Short P-Wave Duration is a Marker of Higher Rate of Atrial Fibrillation Recurrences after Pulmonary Vein Isolation: New Insights into the Pathophysiological Mechanisms Through Computer Simulations.

J Am Heart Assoc 2021 Jan 7;10(2):e018572. Epub 2021 Jan 7.

Division of Cardiology Cardiocentro Ticino Lugano Switzerland.

Background Short ECG P-wave duration has recently been demonstrated to be associated with higher risk of atrial fibrillation (AF). The aim of this study was to assess the rate of AF recurrence after pulmonary vein isolation in patients with a short P wave, and to mechanistically elucidate the observation by computer modeling. Methods and Results A total of 282 consecutive patients undergoing a first single-pulmonary vein isolation procedure for paroxysmal or persistent AF were included. Computational models studied the effect of adenosine and sodium conductance on action potential duration and P-wave duration (PWD). About 16% of the patients had a PWD of 110 ms or shorter (median PWD 126 ms, interquartile range, 115 ms-138 ms; range, 71 ms-180 ms). At Cox regression, PWD was significantly associated with AF recurrence (=0.012). Patients with a PWD <110 ms (hazard ratio [HR], 2.20; 95% CI, 1.24-3.88; =0.007) and patients with a PWD ≥140 (HR, 1.87, 95% CI, 1.06-3.30; =0.031) had a nearly 2-fold increase in risk with respect to the other group. In the computational model, adenosine yielded a significant reduction of action potential duration 90 (52%) and PWD (7%). An increased sodium conductance (up to 200%) was robustly accompanied by an increase in conduction velocity (26%), a reduction in action potential duration 90 (28%), and PWD (22%). Conclusions One out of 5 patients referred for pulmonary vein isolation has a short PWD which was associated with a higher rate of AF after the index procedure. Computer simulations suggest that shortening of atrial action potential duration leading to a faster atrial conduction may be the cause of this clinical observation.
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http://dx.doi.org/10.1161/JAHA.120.018572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955300PMC
January 2021

Elevated serum uric acid is associated with a greater inflammatory response and with short- and long-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Nutr Metab Cardiovasc Dis 2021 02 3;31(2):608-614. Epub 2020 Nov 3.

University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Coronary Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Background And Aims: Despite elevated serum uric acid (eSUA) has been identified as independent risk factor for cardiovascular diseases, its prognostic value in the setting of ST-segment elevation myocardial infarction (STEMI) is still controversial. Although the mechanisms of this possible relationship are unsettled it has been suggested that eSUA could trigger the inflammatory response. This study sought to investigate the association between eSUA with short- and long-term mortality and with inflammatory response in patients with STEMI treated with primary percutaneous coronary intervention (pPCI).

Methods And Results: Blood samples were collected on admission and at 24 and 48 h after pPCI: the inflammatory biomarkers C-reactive protein (CRP), neutrophil count and neutrophil to lymphocytes ratio (NLR) were considered. Baseline eSUA was defined as ≥6.8 mg/dl. Cumulative 30-days and 1-year mortalities were estimated using the Kaplan-Meyer analysis. Multivariable analyses were performed by Cox proportional hazard models. In the 2369 patients with STEMI considered, 30-day mortality was 5.8% among patients with eSUA and 2% among patient with normal SUA level (p < 0.001); 1-year mortality was 8.5% vs 4%, respectively (p < 0.001). At multivariable analyses eSUA was an independent predictor of 30-day mortality (HR 1.196, 95%CI 1.006-1.321, p = 0.042) and 1-year mortality (HR 1.178, 95%CI 1.052-1.320, p = 0.005). eSUA patients presented higher values in on admission CRP (p < 0.001) and in neutrophil count and NLR at 24 h (respectively, p = 0.020 and p < 0.001) and at 48 h (p = 0.018 and p < 0.001) compared to patients with normal SUA levels.

Conclusions: Elevated serum uric acid is associated with higher short- and long-term mortality and with a greater inflammatory response after reperfusion in patients with STEMI treated with primary PCI.
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http://dx.doi.org/10.1016/j.numecd.2020.10.020DOI Listing
February 2021

Challenges in activation of remote monitoring in patients with cardiac rhythm devices during the coronavirus (COVID-19) pandemic.

Int J Cardiol 2021 04 2;328:247-249. Epub 2020 Dec 2.

Division of Cardiology, Cardiocentro Ticino, Lugano, Switzerland.

Background: Remote monitoring (RM) technology embedded in cardiac rhythm devices permits continuous monitoring of device function, and recording of selected cardiac physiological parameters and cardiac arrhythmias and may be of utmost utility during Coronavirus (COVID-19) pandemic, when in-person office visit for regular follow-up were postponed. However, patients not alredy followed-up via RM represent a challenging group of patients to be managed during the lockdown.

Methods: We reviewed patient files scheduled for an outpatient visit between January 1, 2020 and May 11th, 2020 to assess the proportion of patients in whom RM activation was possible without office visit, and compared them to those scheduled for visit before the lockdown.

Results: During COVID-19 pandemic, RM activation was feasible in a minority of patients (7.8% of patients) expected at outpatient clinic for a follow-up visit and device check-up. This was possible in a good proportion of complex implantable devices such as cardiac resynchronization therapy and implantable cardioverter defibrillator but only in a minority of patients with a pacemaker the RM function could be activated during the period of restricted access to hospital.

Conclusions: Our experience strongly suggest to consider the systematic activation of RM function at the time of implantation or - by default programming - in all cardiac rhythm management devices.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709476PMC
April 2021

Peripheral Artery Disease in Diabetes Mellitus: Focus on Novel Treatment Options.

Curr Pharm Des 2020 ;26(46):5953-5968

Adult Intensive Care Unit, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom.

Diabetes mellitus (DM) and peripheral artery disease (PAD) are two clinical entities closely associated. They share many pathophysiological pathways such as inflammation, endothelial dysfunction, oxidative stress and pro-coagulative unbalance. Emerging data focusing on agents targeting these pathways may be promising. Moreover, due to the increased cardiovascular risk, there is a growing interest in cardiovascular and "pleiotropic" effects of novel glucose lowering drugs. This review summarizes the main clinical features of PAD in patients, the diagnostic process and current medical/interventional approaches, ranging from "classical treatment" to novel agents.
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http://dx.doi.org/10.2174/1389201021666201126143217DOI Listing
April 2021

Has hyperglycemia a different prognostic role in STEMI patients with or without diabetes?

Nutr Metab Cardiovasc Dis 2021 02 17;31(2):528-531. Epub 2020 Sep 17.

Ospedale "Città della Salute e della Scienza di Torino", Division of Cardiology and Department of Medical Sciences, University of Torino, Italy.

Background And Aims: Hyperglycemia at hospital admission is a common finding in patients with STEMI. However, whether elevated acute glycemia in these patients may have a direct impact on worsening prognosis or is just a marker of a greater neurohormonal activation in response to the infarction is still unsettled. We sought to investigate the prognostic impact of hyperglycemia at hospital admission in patients undergoing primary PCI (pPCI) for STEMI, and the influence of the presence of diabetes mellitus (DM) on its prognostic impact.

Methods: and Results, We enrolled 2958 consecutive STEMI patients treated by pPCI. Hyperglycemia was defined as plasma glucose >198 mg/dL (or >11 mmol/L). Patients with hyperglycemia showed a greater risk-profile; they also experienced a higher mortality both at univariable (17.6% vs 5.2%, p < 0.001) and multivariable (HR 1.9, 95%IC 1.5-2.9, p = 0.001) analysis. However, after stratification for DM presence, hyperglycemia resulted as an independent predictor of mortality only in patients without DM (HR 2, 95%IC 1.2-3.4, p = 0.01).

Conclusion: Hyperglycemia in the setting of myocardial infarction treated with primary PCI in an independent predictor of all-cause mortality in patients without diabetes; in patients with diabetes, its prognostic impact seems attenuated.
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http://dx.doi.org/10.1016/j.numecd.2020.09.005DOI Listing
February 2021

Very late stent expansion with intracoronary lithotripsy: a case report.

Eur Heart J Case Rep 2020 Oct 17;4(5):1-4. Epub 2020 Oct 17.

Division of Cardiology, S. Andrea Hospital, Corso Mario Abbiate 21, 13100 Vercelli, Italy.

Background: Underexpanded stent in heavily calcified coronary lesion is common and persists over years. It is related to long-term failure and negative outcomes. Treatment of this situation after many years with intracoronary lithotripsy (ICL-Shockwave) could be an option.

Case Summary: We report a case of a man with underexpanded coronary stent implanted 11 years earlier. Optical coherence tomography highlighted the mechanism of stent underexpansion showing the presence of calcium stones under the old struts. Intracoronary lithotripsy crushed calcium under the stent struts causing its geometric change (from elliptical to round shape) and a consequent better transmission of the true radial force of the old stent.

Discussion: Heavily calcified coronary lesions lead to stent underexpansion which persists over years. Intracoronary lithotripsy could be a very late option to manage this unfavourable common result.
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http://dx.doi.org/10.1093/ehjcr/ytaa228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649517PMC
October 2020

Long-term effects of intensive B cell depletion therapy in severe cases of IgG4-related disease with renal involvement.

Immunol Res 2020 12 10;68(6):340-352. Epub 2020 Nov 10.

Nephrology and Dialysis Universitary Unit, and Center of Research of Immunopathology and Rare Diseases (CMID) San Giovanni Bosco Hospital, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.

IgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20 B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.
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http://dx.doi.org/10.1007/s12026-020-09163-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674183PMC
December 2020

New Drugs and Interventional Strategies for the Management of Hypertension.

Curr Pharm Des 2020 Nov 5. Epub 2020 Nov 5.

Royal Brompton & Harefield NHS Foundation Trust, London. United Kingdom.

Essential hypertension is an important cause of cardiovascular morbidity and mortality worldwide with significant clinical and economical implications. The field of antihypertensive treatment already numbers numerous agents and class of drugs. However, despite these, patients are still developing uncontrolled hypertension hence the continuous need for novel agents, with good tolerability. Advances in this field are focussing both on pharmacotherapy, with developments in traditional and non-traditional targets, as well as interventional techniques such as renal denervation and baroreflex activation therapy. It is likely that future strategies may involve a tailored approach to the individual patient, with genetic modulation playing a key role.
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http://dx.doi.org/10.2174/1381612826666201106091527DOI Listing
November 2020

Long-term percentage of ventricular pacing in patients requiring pacemaker implantation after transcatheter aortic valve replacement: A multicenter 10-year experience.

Heart Rhythm 2020 11 5;17(11):1897-1903. Epub 2020 Jun 5.

Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Background: Recent studies suggest that atrioventricular (AV) conduction may recover after pacemaker (PM) implantation following transcatheter aortic valve replacement (TAVR), but little is known about long-term follow-up of such patients.

Objective: The purpose of this study was to evaluate the long-term percentage of right ventricular pacing in patients who underwent TAVR and required PM implantation stratified based on the indication for permanent pacing.

Methods: Retrospective analysis of all consecutive patients who underwent TAVR from February 2008 to August 2019 at 3 centers was performed. Patients already implanted with a PM/implantable cardioverter-defibrillator (ICD) before TAVR, implanted with a cardiac resynchronization therapy device, or implanted >30 days after TAVR were excluded. Eligible patients were divided into 2 groups based on the presence (persistent atrioventricular block [AVB] group) or absence (nonpersistent AVB group) of persistent third-degree AVB after TAVR.

Results: A total of 1594 patients underwent TAVR. Two hundred four patients were implanted with a PM or ICD after TAVR and 32 met exclusion criteria, so 172 patients were eligible (median time TAVR-PM implant 4 days) for a total of 352 follow-up visits analyzed. A significant difference in the percentage of ventricular pacing was observed at follow-up performed 7-90 days after implantation (98% persistent AVB group vs 8% nonpersistent AVB group; P <.001). This difference remained significant at follow-up performed 91-270 days (95% vs 3.5%; P <.001), 271-540 days (95.5% vs 3%; P = .006), and 541-900 days (97.4% vs 2.2%; P <.001) after implantation.

Conclusion: Patients requiring PM implantation due to persistent third-degree AVB after TAVR were less likely to show AV conduction recovery, whereas patients implanted for other indications showed a low percentage of pacing during follow-up.
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http://dx.doi.org/10.1016/j.hrthm.2020.05.040DOI Listing
November 2020

Leptin affects the inflammatory response after STEMI.

Nutr Metab Cardiovasc Dis 2020 06 21;30(6):922-924. Epub 2020 Feb 21.

Division of Cardiology, Ospedale "Città della Salute e della Scienza di Torino", Department of Medical Sciences, Università di Torino, Italy.

Leptin is an adipose tissue-derived hormone primarily involved in the regulation of food intake. Leptine has been shown to have a much broader role than just regulating body weight and appetite in response to food intake: among the others, it has been associated with increased ROS production and inflammation, factors involved in the restoration of an effective myocardial reperfusion after myocardial revascularization. Our study, to our best knowledge, is the first showing a direct relationship between leptin serum levels, inflammatory mediators of the ischemia reperfusion damage and effective myocardial reperfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention. Our findings suggest that leptin serum levels are directly associated with the inflammatory response during an acute myocardial infarction and may have a role in risk stratification in this clinical setting.
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http://dx.doi.org/10.1016/j.numecd.2020.02.004DOI Listing
June 2020

The unfavourable inflammatory response in elderly patients after myocardial infarction: should we talk of 'dysflammaging'?

J Cardiovasc Med (Hagerstown) 2020 04;21(4):340-342

Division of Cardiology, Città della Salute e della Scienza Hospital, Department of Medical Sciences, University of Torino, Torino, Italy.

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http://dx.doi.org/10.2459/JCM.0000000000000925DOI Listing
April 2020

Bail-out unexpanded stent implantation in acute left main dissection treated with intra coronary lithotripsy: a case report.

Eur Heart J Case Rep 2019 Dec 8;3(4):1-5. Epub 2019 Oct 8.

Division of Cardiology, S. Andrea Hospital, Corso Mario Abbiate 21, 13100 Vercelli, Italy.

Background: The percutaneous treatment of heavily calcified coronary lesions is challenging and presents high rate of complications. Unexpandable stent is one of the most serious complication. Both of these conditions may benefit from the intracoronary lithotripsy (ICL-Shockwave), a new coronary percutaneous technique.

Case Summary: This case report describes a man treated with percutaneous coronary intervention (PCI) for a left main (LM) severe calcified lesion. The PCI was complicated by a huge dissection of LM in a not completely expandable lesion. A bail-out stent implantation was performed with residual unexpansion. The ICL permitted to expand acutely the stent and obtain an optimal final result.

Discussion: Familiarity with dedicated techniques and devices to treat calcified coronary lesions is fundamental to perform high-risk complex PCI. This case emphasizes the potential usefulness of the new ICL technique to treat calcified lesions or related complications like unexpandable stent.
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http://dx.doi.org/10.1093/ehjcr/ytz172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939817PMC
December 2019

Reduced Cardio-Renal Function Accounts for Most of the In-Hospital Morbidity and Mortality Risk Among Patients With Type 2 Diabetes Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

Diabetes Care 2019 07 2;42(7):1305-1311. Epub 2019 May 2.

Centro Cardiologico Monzino Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.

Objective: ST-segment elevation myocardial infarction (STEMI) patients with type 2 diabetes mellitus (DM) have higher in-hospital mortality than those without. Since cardiac and renal functions are the main variables associated with outcome in STEMI, we hypothesized that this prognostic disparity may depend on a higher rate of cardiac and renal dysfunction in DM patients.

Research Design And Methods: We retrospectively analyzed 5,152 STEMI patients treated with primary angioplasty. Left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were evaluated at hospital admission. The primary end point was in-hospital mortality. A composite of in-hospital mortality, cardiogenic shock, and acute kidney injury was the secondary end point.

Results: There were 879 patients (17%) with DM. The incidence of LVEF ≤40% (30% vs. 22%), eGFR ≤60 mL/min/1.73 m (27% vs. 18%), or both (12% vs. 6%) was higher ( < 0.001 for all comparisons) in DM patients. In-hospital mortality was higher in DM patients than in non-DM patients (6.1% vs. 3.5%; = 0.002), with an unadjusted odds ratio (OR) of 1.81 (95% CI 1.31-2.49; < 0.001). However, DM was no longer associated with an increased mortality risk after adjustment for cardiac and renal function (OR 1.03, 95% CI 0.68-1.56; = 0.89). A similar behavior was observed for the secondary end point, with an unadjusted OR for DM of 1.52 (95% CI 1.25-1.85; < 0.001) and an OR after adjustment for cardiac and renal function of 1.07 (95% CI 0.85-1.36; = 0.53).

Conclusions: The study indicates that the increased in-hospital mortality and morbidity of DM patients with STEMI is mainly driven by their underlying cardio-renal dysfunction.
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http://dx.doi.org/10.2337/dc19-0047DOI Listing
July 2019

Smoker's paradox in ST-elevation myocardial infarction: Role of inflammation and platelets.

Hellenic J Cardiol 2019 Nov - Dec;60(6):397-399. Epub 2019 Apr 2.

Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology - Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, Unit of Cardiology, University of Pavia, Pavia, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.hjc.2019.03.004DOI Listing
October 2020

[Bleeding risk in patients with acute coronary syndromes treated with antiplatelet agents: incidence, prognosis and clinical evaluation. From research to clinical practice].

G Ital Cardiol (Rome) 2018 Nov;19(11):628-639

S.C. Cardiologia, Fondazione IRCCS Policlinico San Matteo, Pavia.

Dual antiplatelet therapy (DAPT) including aspirin and a P2Y12 inhibitor is the cornerstone for the treatment of patients with acute coronary syndrome (ACS). The introduction of more potent drugs significantly reduced ischemic events, but with an associated increased risk of bleeding. Although appropriate estimation of bleeding risk by comparing the single drugs is challenging, mainly because of differences in definitions, it has been consistently shown that bleeding events are associated with an adverse outcome, both at short and long-term follow-up.Current guidelines recommend a short DAPT in patients at high bleeding risk, making appropriate risk estimation of crucial importance. Several numerical scores have been proposed for use in daily clinical practice. Although an objective risk assessment provides superior risk discrimination compared to physician's estimation, none of these scores appear free from limitations, nor have been obtained from cohorts of patients on short-tern treatment with prasugrel or ticagrelor. In the present review, we report the rates of major bleeding observed in the main randomized clinical trials and registries, their association with mortality, differences in definitions when used as safety endpoint, and finally the scores currently used for evaluation in daily clinical practice.
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http://dx.doi.org/10.1714/3012.30110DOI Listing
November 2018

IgG4-related kidney disease: the effects of a Rituximab-based immunosuppressive therapy.

Oncotarget 2018 Apr 20;9(30):21337-21347. Epub 2018 Apr 20.

Nephrology and Dialysis Unit, San Giovanni Bosco Hospital, and University of Turin, Italy.

IgG4-related disease (IgG4-RD) is a recently recognized disorder, characterized by elevated serum IgG4 concentrations, dense tissue infiltration of IgG4-positive plasma cells and storiform fibrosis. Treatment is usually based on steroids, however, relapses and long-term adverse effects are frequent. We prospectively studied 5 consecutive patients with histologically-proven IgG4-RD and renal involvement, treated with an extended Rituximab protocol combined with steroids. Two doses of intravenous cyclophosphamide were added in 4 patients. Five patients with IgG-RD were investigated: three had tubulointerstitial nephritis (TIN), while two had retroperitoneal fibrosis (RPF). In the patients with TIN, renal biospy was repeated after 1 year. In the patients with TIN, estimated glomerular filtration rate (eGFR) at 12 months increased from 9 to 24 ml/min per 1.73 m; IgG/IgG4 decreased from 3,236/665 to 706/51 mg/dl; C3/C4 increased from 49/6 to 99/27 mg/dl; CD20 B-cells decreased from 8.7% to 0.5%; Regulatory T-cells decreased from 7.2% to 2.5%. These functional and immunologic changes persisted at 24 months and in two patients at 36 months. A repeat renal biopsy in the patients with TIN showed a dramatic decrease in interstitial plasma cell infiltrate with normalization of IgG4/IgG positive plasma cells. The patients with RPF showed a huge regression of retroperitoneal tissue. In this sample of patients with aggressive IgG4-RD and renal involvement, treatment aimed at depleting B cells and decreasing antibody and cytokine production was associated with a substantial, persistent increase in eGFR, and a definite improvement in immunologic, radiologic and histological parameters.
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http://dx.doi.org/10.18632/oncotarget.25095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940417PMC
April 2018

The paradox of clopidogrel use in patients with acute coronary syndromes and diabetes: insight from the Diabetes and Acute Coronary Syndrome Registry.

Coron Artery Dis 2018 06;29(4):309-315

SC Cardiologia Fondazione IRCCS Policlinico San Matteo, Pavia.

Background: Patients with diabetes mellitus (DM) and acute coronary syndromes have a greater level of platelet aggregation and a poor response to oral antiplatelet drugs. Clopidogrel is still widely used in clinical practice, despite the current evidence favoring ticagrelor and prasugrel.

Aim: The aim of this study was to investigate the determinants of clopidogrel use in the population of the multicenter prospective 'Acute Coronary Syndrome and Diabetes Registry' carried out during a 9-week period between March and May 2015 at 29 Hospitals.

Patients And Methods: A total of 559 consecutive acute coronary syndrome patients [mean age: 68.7±11.3 years, 50% ST-elevation myocardial infarction (STEMI)], with 'known DM' (56%) or 'hyperglycemia' at admission, were included in the registry; 460 (85%) patients received a myocardial revascularization.

Results: At hospital discharge, dual antiplatelet therapy was prescribed to 88% of the patients (clopidogrel ticagrelor and prasugrel to 39, 38, and 23%, respectively). Differences in P2Y12 inhibitor administration were recorded on the basis of history of diabetes, age, and clinical presentation (unstable angina/non-STEMI vs. non-STEMI). On univariate analysis, age older than 75 years or more, known DM, peripheral artery disease, previous myocardial infarction, previous revascularization, complete revascularization, previous cerebrovascular event, creatinine clearance, unstable angina/non-STEMI at presentation, Global Registry of Acute Coronary Events Score, EuroSCORE, CRUSADE Bleeding Score, and oral anticoagulant therapy were significantly associated with clopidogrel choice at discharge. On multivariate analysis, only oral anticoagulant therapy and the CRUSADE Bleeding Score remained independent predictors of clopidogrel prescription.

Conclusion: In the present registry of a high-risk population, clopidogrel was the most used P2Y12 inhibitor at hospital discharge, confirming the 'paradox' to treat sicker patients with the less effective drug. Diabetic status, a marker of higher thrombotic risk, did not influence this choice; however, bleeding risk was taken into account.
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http://dx.doi.org/10.1097/MCA.0000000000000601DOI Listing
June 2018

Management of diabetic patients hospitalized for acute coronary syndromes: a prospective multicenter registry.

J Cardiovasc Med (Hagerstown) 2017 Aug;18(8):572-579

aSC Cardiologia, Fondazione IRCCS, Policlinico San Matteo, Pavia bSC Cardiologia, Ospedale Santa Croce e Carle, Cuneo cDipartimento di Cardiologia, Grande Ospedale Metropolitano, Niguarda dASST Santi Paolo e Carlo, Milano, Ospedale San Carlo Borromeo eUnità Coronarica, LSR Sperimentazione Cardiologica, Fondazione IRCCS Policlinico San Matteo, Pavia fUOC Cardiologia e UTIC, Polo Universitario San Paolo, ASST Santi Paolo e Carlo, Milano gCardiologia ASST Bergamo Ovest, Treviglio hCardiologia e UTIC, ASST Cremona, Cremona iDivisione di Cardiologia, ASST Bergamo Est, Ospedale Bolognini, Seriate jUO Cardiologia ASST Valle Olona Presidio Gallarate kUSC Cardiologia, ASST Lodi, Lodi lUO Cardiologia, ASST Carlo Poma, Mantova mDipartimento di Cardiologia, ASST Papa Giovanni XXIII, Bergamo, Italy.

Background: Patients with diabetes mellitus and acute coronary syndrome (ACS) present an increased risk of adverse cardiovascular events. An Italian Consensus Document indicated 'three specific must' to obtain in this subgroup of patients: optimal oral antiplatelet therapy, early invasive approach and a tailored strategy of revascularization for unstable angina/non-ST-elevation-myocardial infarction (UA/NSTEMI); furthermore, glycemia at admission should be managed with dedicated protocols.

Aim: To investigate if previous recommendations are followed, the present multicenter prospective observational registry was carried out in Lombardia during a 9-week period between March and May 2015.

Methods And Results: A total of 559 consecutive ACS patients (mean age 68.7 ± 11.3 years, 35% ≥75 years, 50% STEMI), with 'known DM' (56%) or 'hyperglycemia', this last defined as blood glucose value ≥ 126 mg/dl at admission, were included in the registry at 29 hospitals with an on-site 24/7 catheterization laboratory. Patients with known diabetes mellitus received clopidogrel in 51% of the cases, whereas most patients with hyperglycemia (72%) received a new P2Y12 inhibitor: according to clinical presentation in case STEMI prasugrel/ticagrelor were more prescribed than clopidogrel (70 vs. 30%, P < 0.001); on the contrary, no significant difference was found in case of UA/NSTEMI (48 vs. 52%, P = 0.57).Overall, 96% of the patients underwent coronary angiography and 85% received a myocardial revascularization (with percutaneous coronary intervention in 92% of cases) that was however performed in fewer patients with known diabetes mellitus compared with hyperglycemia (79 vs. 90%, P = 0.001).Among UA/NSTEMI, 85% of patients received an initial invasive approach, less than 72 h in 80% of the cases (51% <24 h); no difference was reported comparing known diabetes mellitus to hyperglycemia. Despite similar SYNTAX score, patients with known diabetes mellitus had a higher rate of Heart Team discussion (29 vs. 12%, P = 0.03) and received a surgical revascularization in numerically more cases.Most investigators (85%) followed a local protocol for glycemia management at admission, but insulin was used in fewer than half of the cases; diabetes consulting was performed in 25% of the patients and mainly in case of known diabetes mellitus.

Conclusion: Based on data of the present real world prospective registry, patients with ACS and known diabetes mellitus are treated with an early invasive approach in case of UA/NSTEMI and with a tailored revascularization strategy, but with clopidogrel in more cases; glycemia management is taken into account at admission.
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http://dx.doi.org/10.2459/JCM.0000000000000523DOI Listing
August 2017

Comparison of Outcomes of Staged Complete Revascularization Versus Culprit Lesion-Only Revascularization for ST-Elevation Myocardial Infarction and Multivessel Coronary Artery Disease.

Am J Cardiol 2017 Feb 9;119(4):508-514. Epub 2016 Dec 9.

Department of Molecular Medicine, University of Pavia, Pavia, Italy; Coronary Care Unit and Laboratory for Clinical and Experimental Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Medicine, University of Cape Town, Cape Town, South Africa.

The management of noninfarct-related arteries in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary disease (MVD) is still debated. We evaluated the prognostic impact of staged complete revascularization with percutaneous coronary intervention (PCI) in STEMI patients with MVD admitted to our hospital from 2005 to 2013. Patients undergoing staged complete revascularization (n = 300) were compared with 1:1 propensity score-matched patients with culprit lesion-only treatment (n = 300). We considered a composite primary end point of all-cause death, myocardial infarction, and urgent PCI. Secondary end points included components of the primary, cardiovascular death, any PCI excluding staged PCI. We also performed an analysis including only patients surviving at least 5 days. The median follow-up was 553 days. The primary end point occurred in 10.3% of patients in the staged complete revascularization group and in 16.3% of patients in the culprit lesion-only group (hazard ratio 0.61, 95% CI 0.38 to 0.95, p = 0.031). Although this difference was no longer significant when considering only the survivors at day 5, all-cause and cardiovascular mortalities were still reduced in the staged complete revascularization group. Complete revascularization was associated with a better outcome (hazard ratio 0.35, 95% CI 0.17 to 0.63, p = 0.005) if performed within 30 days of STEMI. In conclusion, compared with culprit lesion-only revascularization, in STEMI patients with MVD undergoing primary PCI, an approach of staged complete revascularization was associated with a better outcome.
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http://dx.doi.org/10.1016/j.amjcard.2016.10.040DOI Listing
February 2017

Diagnosis of del(5q) MDS, 14 Years after JAK-2 Positive PV Appearance: Complete Remission of both Diseases with Lenalidomide Monotherapy.

Mediterr J Hematol Infect Dis 2016 20;8(1):e2016050. Epub 2016 Oct 20.

Rare Diseases, Immunology, Immunohaematology and Haematology Department, San Giovanni Bosco Hospital, Turin, Italy.

This is the report of the clinical case of a patient who presents the association of a JAK-2 positive chronic myeloproliferative neoplasia to a subsequent 5q- myelodysplastic syndrome, developed after about 14 years from the first diagnosis. Patient's symptoms had rapidly worsened, and she became transfusion-dependent. Therapy with low-dose Lenalidomide quickly reduced the splenomegaly and completely brought white cells counts, haemoglobin, and platelets back to normal. After more than one year from the start, blood cell count is still normal. As far as we know, this is the first case of an effective treatment with Lenalidomide reported in this clinical setting.
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http://dx.doi.org/10.4084/MJHID.2016.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111523PMC
October 2016

Thulium:yttrium-aluminum-garnet laser for en bloc resection of bladder cancer: clinical and histopathologic advantages.

Urology 2014 Apr 16;83(4):851-5. Epub 2014 Feb 16.

Department of Urology, San Giovanni Bosco Hospital, Turin, Italy. Electronic address:

Objective: To determine whether thulium:yttrium-aluminum-garnet laser resection of bladder tumor (TmLRBT) may offer advantages over classic resection.

Materials And Methods: From April 2011 to September 2012, 55 consecutive patients newly diagnosed with clinical stage ≤T2 bladder cancer were enrolled in a prospective study on TmLRBT. Neoplasm was removed en bloc in all cases. When the tumor size was >3 cm, it was necessary to incise longitudinally and/or across the lesion and the bladder wall at its the base into 2 or more parts. All cases of non-muscle-invasive bladder cancer underwent second look in 30-90 days.

Results: Pathology reported urothelial carcinoma with Ta low grade in 31 patients (56.4%), T1 high grade in 18 (32.7%), and T2 high grade in 6 (10.9%). Histopathologic evaluation showed that the bladder detrusor was provided in all cases. Hemostasis was excellent, and no postoperative hematuria was reported. In a case of T1 G3, endoscopic re-evaluation showed a focal infiltration of the bladder detrusor, so the patient underwent radical cystectomy. To date, with a mean follow-up of 16 months (range, 8-25), the recurrence rate in patients with superficial disease is 14.5%. All recurrences were outside the site of first resection, and there was no progression in tumor grade.

Conclusion: TmLRBT is a simple method that seems to overcome the "incise and scatter" problem associated with traditional transurethral resection of bladder tumor. Our initial data on staging accuracy and reduction of the local recurrence rate are encouraging.
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http://dx.doi.org/10.1016/j.urology.2013.12.022DOI Listing
April 2014

APP mutations in the Aβ coding region are associated with abundant cerebral deposition of Aβ38.

Acta Neuropathol 2012 Dec 13;124(6):809-21. Epub 2012 Nov 13.

Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Milan, Italy.

Aβ is the main component of amyloid deposits in Alzheimer disease (AD) and its aggregation into oligomers, protofibrils and fibrils is considered a seminal event in the pathogenesis of AD. Aβ with C-terminus at residue 42 is the most abundant species in parenchymal deposits, whereas Aβ with C-terminus at residue 40 predominates in the amyloid of the walls of large vessels. Aβ peptides with other C-termini have not yet been thoroughly investigated. We analysed Aβ38 in the brains of patients with Aβ deposition linked to sporadic and familial AD, hereditary cerebral haemorrhage with amyloidosis, or Down syndrome. Immunohistochemistry, confocal microscopy, immunoelectron microscopy, immunoprecipitation and the electrophoresis separation of low molecular weight aggregates revealed that Aβ38 accumulates consistently in the brains of patients carrying APP mutations in the Aβ coding region, but was not detected in the patients with APP mutations outside the Aβ domain, in the patients with presenilin mutations or in subjects with Down syndrome. In the patients with sporadic AD, Aβ38 was absent in the senile plaques, but it was detected only in the vessel walls of a small subset of patients with severe cerebral amyloid angiopathy. Our results suggest that APP mutations in the Aβ coding region favour Aβ38 accumulation in the brain and that the molecular mechanisms of Aβ deposition in these patients may be different from those active in patients with familial AD associated with other genetic defects and sporadic AD.
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http://dx.doi.org/10.1007/s00401-012-1061-xDOI Listing
December 2012