Guido Parodi’s research while affiliated with Azienda Ospedaliera Universitaria Sassari and other places

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Publications (344)


Clinical characteristics and outcomes of patients with takotsubo syndrome and dynamic left ventricular outflow tract obstruction
  • Article

October 2024

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22 Reads

European Heart Journal

D Di Vece

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M Bellino

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A Silverio

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[...]

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Background Left ventricular outflow tract obstruction (LVOTO) is recognized as a serious complication of Takotsubo syndrome (TTS). However, its impact on patient prognosis remains insufficiently investigated. Purpose This study aimed to assess clinical characteristics and short- and long-term outcomes of patients with TTS complicated by LVOTO. Methods Patients with TTS were enrolled from the Takotsubo Italian Network (TIN). The primary outcome was the composite of acute heart failure, cardiogenic shock, and mortality during hospitalization. Secondary outcomes included the single components of the primary outcome and the occurrence of death or TTS recurrence during follow-up. Results Overall, 881 patients were included in the study [median age 72.0 (63.0–78.0) years; 91.3% female], with LVOTO detected in 59 patients (6.7%). Low diastolic blood pressure, ST-segment elevation, and moderate-to-severe mitral regurgitation were independently associated with occurrence of LVOTO. Propensity score weighting regression analysis revealed a significant higher risk of the primary outcome (OR, 2.99; 95% CI, 2.22–4.02), acute heart failure (OR, 2.19; 95% CI, 1.59–3.02), cardiogenic shock (OR, 4.56; 95% CI, 3.07–6.78), and in-hospital mortality (OR, 2.42; 95% CI, 1.13–5.21) in patients with TTS complicated by LVOTO. No significant association between LVOTO and long-term mortality or TTS recurrence was observed during follow-up. Conclusions In this real-world evidence study, LVOTO was detected in about 7% of TTS patients and was associated with a significantly higher risk of adverse events during hospitalization, including mortality. Early detection of LVOTO can aid in prognostic assessment and guide therapeutic management in patients with TTS.


Effects of cardiac resynchronization therapy and physiologicaL pacing on left atrioventricular coupling index: the REPHYL-LACI study

October 2024

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4 Reads

European Heart Journal

Introduction Cardiac dyssynchrony and right ventricular pacing are associated with left atrial (LA) remodeling and atrioventricular uncoupling. Cardiac resynchronization therapy -CRT and conduction system pacing –CSP are important therapeutic options. Left atrioventricular coupling index (LACI) is a novel imaging parameter useful to describe the relationship between LA and left ventricle (LV). It could be measured as the ratio between LA end-diastolic volume (EDV) and the LV EDV or, alternatively, as the LA volume indexed for body surface area (LAVi) divided for a’ measured by tissue Doppler imaging (TDI) at medial mitral annulus level. Higher values indicate greater impairment of atrioventricular coupling. However, LACI has not been investigated in patients treated with CRT or CSP, and there is no comparison data about the two different measurement methodologies with echocardiography. Purpose To study the effects of CRT/CSP on LACI. Methods We retrospectively collected clinical, ECG and echocardiographic data of patients treated with standard CRT or CSP. Changes between baseline and follow-up (i.e. before and after CRT/CSP) were tested for significance. Baseline features were compared with these of a control group of patients without established major cardiovascular diseases. Results We enrolled fifty-six patients (median age at first echo 78[72.5-82]years; males 70%) and 56 controls (median age 77[72.5-83]years, p=0.974; males 57%, p= 0.170). Main clinical/instrumental data are shown in Table 1 and 2. In patients treated with CRT/CSP baseline LACIv (LAVid/LV EDV) was significantly lower than in controls (31[21-44]%vs34[29-48]%, p=0.040), despite higher LAVi and LV volumes in the first group (p<0.0001 for both). Conversely, LACId (LAVi/TDI-a’) was significantly higher in the CRT/CSP (4.48[2.81-8.28]vs2.89[2.36-3.67]mlxsecond/cm-1, p<0.0001). After a median follow-up of 515[282-1326]days, patients treated with CRT/CSP showed a significant increase of both LACIv (40[29-50]%, p=0.004) and LACId (4.95[3.77-9.89], p<0.0001). This worsening of atrioventricular coupling was accompanied by a trending LA dilatation with significant reduction of its reservoir function compared to baseline (expansion index 0.58[0.38-1.30]vs0.43[0.29-0.58], p=0.0002), despite a tendency toward stability or improvement of LV size and systolic/diastolic parameters. Conclusions In patients treated with CRT/CSP there is a worsening of LACI over time. We can speculate that the detrimental effects of artificial pacing might not be adequately counterbalanced by CRT/CSP, or that LV and LA pathology follow alternative trajectories with different responses to treatments. Moreover, the measurement of LACId should be probably avoided in patients with conduction disorders or paced. Further larger case-control studies are needed to clarify the usefulness of LACI as a valid parameter to assess atrioventricular coupling and its changes over time in patients treated with CRT/CSP.


Impact of hypertension on mortality in patients with ST-elevation myocardial infarction undergoing primary angioplasty: insights from the international multicenter ISACS-STEMI registry

October 2024

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62 Reads

Journal of Hypertension

Background Hypertension is the most prevalent cardiovascular risk factor, with several detrimental effects on the cardiovascular system. Contrasting results have been reported so far on its prognostic role in patients admitted for ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated the impact of hypertension on short-term mortality in a large multicenter contemporary registry of STEMI patients, including patients treated during COVID-19 pandemic. Methods The ISACS-STEMI COVID-19 was a retrospective registry that included STEMI patients treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 in 109 high-volume primary PCI centers from 4 continents. We collected data on baseline, clinical and procedural characteristics, in-hospital outcome and 30-day mortality. For this analysis patients were grouped according to history of hypertension at admission. Results A total of 16083 patients were assessed, including 8813 (54.8%) with history of hypertension. These patients were more often elderly, with a worse cardiovascular risk profile, but were less frequently active smoker. Some procedural differences were observed between the two groups, including lower rate of thrombectomy and use of glycoprotein IIb/IIIa inhibitors or cangrelor but more extensive coronary disease in patients with hypertension. Between patients with and without hypertension, there was no significant difference in SARS-CoV-2 positivity. Hypertensive patients had a significantly higher in-hospital and 30-day mortality, similarly observed in both pre-COVID-19 and COVID-19 era, and confirmed after adjustment for main baseline differences and propensity score (in-hospital mortality: adjusted odds ratio (OR) [95% confidence interval (CI)] =1.673 [1.389–2.014], P < 0.001; 30-day mortality: adjusted hazard ratio (HR) [95% CI] = 1.418 [1.230–1.636], P < 0.001). Conclusion This is one of the largest and contemporary study assessing the impact of hypertension in STEMI patients undergoing primary angioplasty, including also the COVID-19 pandemic period. Hypertension was independently associated with significantly higher rates of in-hospital and 30-day mortality.




Unadjusted and adjusted analysis for the risk of the study outcomes in patients receiving cangrelor or tirofiban. aOR, adjusted odds ratio; BARC, Bleeding Academic Research Consortium; CI, confidence interval; MBG, myocardial blush grade; OR, odds ratio; TIMI; Thrombolysis in Myocardial Infarction
Intravenous antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention
  • Article
  • Publisher preview available

April 2024

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71 Reads

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2 Citations

Journal of Thrombosis and Thrombolysis

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. Graphical abstract

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

August 2023

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15 Reads

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5 Citations

European Heart Journal - Cardiovascular Pharmacotherapy

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 & 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™ฏ 1, 2, 4 and 6 hours after ticagrelor LD. The primary endpoint was residual platelet reactivity 1 hour 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-hour 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-hour 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 hours 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.


Echocardiographic heart ageing patterns predict cardiovascular and non-cardiovascular events and reflect biological age: the SardiNIA study

August 2023

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60 Reads

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10 Citations

European Journal of Preventive Cardiology

Aims: Age is a crucial risk factor for cardiovascular (CV) and non-CV diseases. As people age at different rates, the concept of biological age has been introduced as a personalized measure of functional deterioration. Associations of age with echocardiographic quantitative traits were analysed to assess different heart ageing rates and their ability to predict outcomes and reflect biological age. Methods: Associations of age with left ventricular mass, geometry, diastolic function, left atrial volume, and aortic root size were measured in 2614 healthy subjects. Based on the 95% two-sided tolerance intervals of each correlation, three discrete ageing trajectories were identified and categorized as "slow", "normal", and "accelerated" hearts ageing patterns. The primary endpoint included fatal and non-fatal CV events, and the secondary endpoint was a composite of CV and non-CV events and all-cause death. The heart phenotypic age (HeartPhAge) was estimated as a proxy of biological age. Results: The slow ageing pattern was found in 8.7% of healthy participants, the normal pattern in 76.8%, and the accelerated pattern in 14.3%. Kaplan-Meier curves of the heart ageing patterns diverged significantly (P=0.0001) for both primary and secondary endpoints, with the event rate being lowest in the slow, intermediate in the normal, and highest in the accelerated pattern. In Cox proportional-hazards model, heart aging patterns predicted both primary (P=0.01) and secondary (P=0.03 to <0.0001) endpoints, independent of chronological age and risk factors. Compared to chronological age, HeartPhAge was 9 years younger in slow, 4 years older in accelerated (both P<0.0001), and overlapping in normal ageing patterns. Conclusion: Standard Doppler-echocardiography detects slow, normal, and accelerated heart ageing patterns. They predict CV and non-CV events, reflect biological age, and provide a new tool to calibrate prevention timing and intensity.


Figure 2. Penalized Logistic Regression Features Importance. Coloured bars graphically represent the importance of the corresponding feature. The error bars correspond to the standard deviation over the multiple cross validation runs. The greater the magnitude of the importance, the stronger the impact of the variable on the prediction. The sign of the importance shows how the variable impacts the prediction. For categorical variable, the coefficient of the importance represents the increasing (or decreasing in accordance with the sign) of risk in presence of that variable. For continuous variable, the coefficient of the importance represents the increasing (or decreasing in accordance with the sign) of risk as the variable increases. CAD: coronary artery disease; TTS: takotsubo syndrome; AV: atrio-ventricular; COPD: chronic obstructive pulmonary disease; BMI: body mass index; BP: blood pressure; LVEF: left ventricular ejection fraction.
Machine learning‐based prediction of in‐hospital death for patients with takotsubo syndrome: The InterTAK‐ML model

July 2023

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278 Reads

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10 Citations

European Journal of Heart Failure

Aims: Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine-learning (ML) based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles. Methods and results: A Ridge Logistic Regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). 31 clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the receiver-operating characteristic curve (AUC), Sensitivity and Specificity. As secondary endpoint, a K-Medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the ten most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), Sensitivity 0.85 (0.78-0.95) and Specificity 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs 15.5% vs 5.4% vs 0.8% vs 0.5%) which were consistent also in the external cohort. Conclusion: A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death. This article is protected by copyright. All rights reserved.


Citations (60)


... In this issue of the Journal of Thrombosis and Thrombolysis, Silverio and colleagues from the INVEST-STEMI (Intravenous antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention) group conducted a prospective multicentre registry of 627 STEMI patients from seven Italian centres who received either cangrelor or tirofiban during PCI and reported procedural characteristics and inhospital ischemic and bleeding outcomes [4]. Intravenous antiplatelet therapy was administered after identifying the coronary anatomy on emergency angiography. ...

Reference:

Optimal intravenous antiplatelet therapy in patients with ST-elevation myocardial infarction: is the picture becoming clearer?
Intravenous antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Journal of Thrombosis and Thrombolysis

... This association was consistent in all studies, regardless of different strategies concerning the timing of the loading dose (prehospital or in the catheterization laboratory) as well as differences in administration of the loading dose (integral tablet or crushed/chewed tablet). 6,16,20,29,30 In the current study, despite significant differences in platelet aggregation and HTPR, we found no corresponding differences in biomarkers of platelet activity or coagulation between patients treated with morphine and those not treated. Soluble p-selectin, CD40 ligand, beta-TG, TAT, prothrombin fragment and D-dimer were all similar in the two groups. ...

Platelet inhibition with orodispersible ticagrelor in acute coronary syndromes according to morphine use: the TASTER study final results
  • Citing Article
  • August 2023

European Heart Journal - Cardiovascular Pharmacotherapy

... This eventually could be used to detect pronounced aging effects as subclinical indicators in common screening programs. Subsequently, cardiac remodeling could be diagnosed via cardiac ultrasound as hypertrophic myocardium, i.e., the heart muscle appears enlarged and thickened 8,12 . The gold standard to quantify cardiac fibrosis is the Late Gadolinium Enhancement, in which a contrast agent accumulates in the micro scars during a cardiac magnetic resonance imaging (MRI) 28 . ...

Echocardiographic heart ageing patterns predict cardiovascular and non-cardiovascular events and reflect biological age: the SardiNIA study
  • Citing Article
  • August 2023

European Journal of Preventive Cardiology

... Particularly in mortality prediction, research indicated that machine learning models significantly outperform conventional systems in terms of accuracy statistics for identification, calibration and evaluation [15]. Machine learning models have proven highly effective in prognostic prediction and decision-making across diverse analyses of extensive electronic health record data, showcasing immense potential in disease diagnosis [16,17] and prognosis prediction [18,19]. ...

Machine learning‐based prediction of in‐hospital death for patients with takotsubo syndrome: The InterTAK‐ML model

European Journal of Heart Failure

... Interestingly, in our population we observed the overall pharmacological undertreatment of COPD patients, who less often received a beta-blocker or a RAS inhibitor at discharge, similarly to what described in general heart failure patient populations [37,38]. Though few data are available regarding the appropriate long-term treatment of TTS after the acute phase, some studies suggest a potential benefit of ACE-inhibitors and beta-blockers [3,23,39], adding a further potential explanation to our study findings. ...

Arterial Hypertension in Patients with Takotsubo Syndrome: Prevalence, Long-Term Outcome, and Secondary Preventive Strategies. A Report from the Takotsubo Italian Network Register
  • Citing Article
  • July 2023

European Journal of Preventive Cardiology

... Previous studies have shown that inflammatory markers such as C-reactive protein and platelets can reflect the extent of the inflammatory response in patients with AMI and have been shown to be strongly correlated with the in-hospital mortality of such patients. 13,14 An increase in aspartate aminotransferase (AST) levels on admission is regarded as an independent predictor of AMI mortality. 15 The AST to lymphocyte ratio index (ALRI), which assesses the degree of systemic inflammation, is significantly correlated with survival outcomes in patients with hepatocellular carcinoma 16 and metastatic colorectal cancer. ...

Prognostic role of CRP-independent inflammatory patterns in patients undergoing primary percutaneous interventions
  • Citing Article
  • April 2023

European Journal of Clinical Investigation

... [4] Atherosclerotic cardiovascular diseases are the primary cause of mortality in the elderly population worldwide. [5,6] ST-segment elevation myocardial infarction (STEMI) is a significant complication of atherosclerotic heart disease. [6][7][8][9][10] Studies have shown that mortality rates were higher during the COVID-19 pandemic compared to the pre-pandemic or postpandemic period, despite management algorithms recommended by current guidelines for elderly patients hospitalized with STEMI. ...

Age-Related Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry

... TTS is frequently triggered by emotional or physical stress [2]. Recently some cases of neurally mediate reflex syncope (NMRS) triggering TTS have been described [3][4][5][6][7][8]. Our meta-summary of case reports aimed to characterize patients who experienced TTS following a NMRS episode. ...

946 TAKOTSUBO SYNDROME TRIGGERED BY REFLEX SYNCOPE: A POTENTIALLY FATAL COMPLICATION OF A BENIGN CONDITION
  • Citing Article
  • December 2022

European Heart Journal Supplements

... This is particularly true if the ejection fraction was reduced by a previous ACS. We also investigated whether the so-called "smoker's paradox" reported in some STEMI patients [17,18] could be reflected in our population. We found that smoke was not associated with higher mortality (HR 0.98; 95% CI: 0.80-1.21, ...

Impact of Smoking Status on Mortality in STEMI Patients Undergoing Mechanical Reperfusion for STEMI: Insights from the ISACS–STEMI COVID-19 Registry

... These findings are of interest for several reasons. The number of patients included is among the highest for studies that only included STEMI patients, providing robustness of the findings [18,33,34]. Patients with hypertension of this cohort displayed an increased cardiovascular risk profile as compared to patients without history of hypertension, including a higher rate of prior cardiovascular events. ...

SARS-CoV-2 Positivity, Stent Thrombosis, and 30-day Mortality in STEMI Patients Undergoing Mechanical Reperfusion
  • Citing Article
  • October 2022

Angiology