Publications by authors named "Filippo Crea"

1,004 Publications

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Atrioventricular conduction in PM recipients after transcatheter aortic valve implantation: Implications using Wenckebach point measurement.

Front Cardiovasc Med 2022 22;9:904828. Epub 2022 Jul 22.

Department of Cardiovascular Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

Background: Atrioventricular (AV) conduction disturbances requiring permanent pacemaker implantation (PPI) are a common complication after transcatheter aortic valve implantation (TAVI). However, a significant proportion of patients might recover AV conduction at follow-up.

Objectives: The aim of our study was to evaluate the recovery of AV conduction by determination through Wenckebach point in patients with PPI and therefore identify patients who could benefit from device reprogramming to avoid unnecessary RV pacing.

Methods: We enrolled 43 patients that underwent PM implantation after TAVI at our Department from January 2018 to January 2021. PM interrogation was performed at follow-up and patients with native spontaneous rhythm were further assessed for AV conduction through WP determination.

Results: A total of 43 patients requiring a PM represented the final study population, divided in patients with severely impaired AV conduction (no spontaneous valid rhythm or WP < 100; 26) and patients with valid AV conduction (WP ≥ 100; 17). In the first group patients had a significantly higher number of intraprocedural atrioventricular block (AVB) (20 vs. 1, < 0.005), showed a significant higher implantation depth in LVOT (7.7 ± 2.2 vs. 4.4 ± 1.1, < 0.05) and lower ΔMSID (-0.28 ± 3 vs. -3.94 ± 2, < 0.05).

Conclusion: AV conduction may recover in a significant proportion of patients. In our study, valve implantation depth in the LVOT and intraprocedural AV block are associated with severely impaired AV conduction. Regular PM interrogation and reprogramming are required to avoid unnecessary permanent right ventricular stimulation in patients with AV conduction recovery.
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http://dx.doi.org/10.3389/fcvm.2022.904828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353552PMC
July 2022

The burden of cardiovascular risk factors: a global perspective.

Authors:
Filippo Crea

Eur Heart J 2022 Aug;43(30):2817-2820

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac430DOI Listing
August 2022

Myocardial infarction with non-obstructive coronary arteries in hypertrophic cardiomyopathy vs Fabry disease.

Int J Cardiol 2022 Aug 2. Epub 2022 Aug 2.

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy.

Background: Little is known about prevalence and predictors of myocardial infarction with non-obstructive coronary arteries (MINOCA) in Fabry disease (FD) and hypertrophic cardiomyopathy (HCM). We assessed and compared the prevalence and predictors of MINOCA in a large cohort of HCM and FD patients.

Methods: In this multicenter, retrospective study we enrolled 2870 adult patients with HCM and 267 with FD. The only exclusion criterion was documented obstructive coronary artery disease. MINOCA was defined according to guidelines. For each patient we collected clinical, ECG and echocardiographic data recorded at initial evaluation.

Results: Overall, 36 patients had MINOCA during a follow-up period of 4.5 ± 11.2 years, MINOCA occurred in 16 patients with HCM (0.5%) and 20 patients with FD (7.5%; p < 0.001). The difference between the 2 groups was highly significant, also after adjustment for the main clinical, ECG and echocardiographic variables (OR 6.12;95%CI:2.80-13.3;p < 0.001). In the FD population MINOCA occurred in 17 out of 96 patients with left ventricle hypertrophy (LVH, 17.7%) and in 3 out of 171 patients without LVH (1.7%; OR 12.0;95%CI 3.43-42.3;p < 0.001). At multivariable analysis, voltage criteria for LVH at ECG (OR 7.3;95%CI 1.93-27.7;p = 0.003) and maximal LV wall thickness at echocardiography (OR 1.15; 95%CI 1.05-1.27;p = 0.002) maintained an independent association with MINOCA. No major significant differences were found in clinical, ECG and echocardiographic findings between HCM patients with or without MINOCA.

Conclusions: MINOCA was rare in HCM patients, and 6-fold more frequent in FD patients. MINOCA may be considered a red flag for FD and aid in the differential diagnosis from HCM.
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http://dx.doi.org/10.1016/j.ijcard.2022.07.046DOI Listing
August 2022

Successful ventricular tachycardia radioablation in a patient with previous chemical pleurodesis: A case report.

Front Cardiovasc Med 2022 18;9:937090. Epub 2022 Jul 18.

Department of Cardiovascular Sciences, Agostino Gemelli University Polyclinic (Istituto di Ricovero e Cura a Carattere Scientifico), Rome, Italy.

Introduction: Stereotactic arrhythmia radioablation (STAR) is a novel technique for the ablation of ventricular tachycardia in patients with contraindications to standard procedures, i.e., radiofrequency ablation.

Case Presentation: We report the case of a 73-year-old man with non-ischemic dilated cardiomyopathy and recurrent VT episodes. Electroanatomic mapping showed VT prevalently of epicardial origin, but direct epicardial access through subxyphoid puncture could not be performed due to pleuropericardial adhesions from a past history of chemical pleurodesis. STAR was performed, with no VT recurrence at 6 months follow-up.

Conclusions: Previous experiences with STAR have demonstrated its importance in the management of patients with refractory VT in whom other ablation strategies were not successful. Our case report highlights the use of STAR as a second choice in a patient with an unfavorable VT anatomical location and technical limitations to an optimal radiofrequency ablation. Moreover, it confirms STAR's effectiveness in the ablation of complex transmural lesions, which are more often associated with non-ischemic structural heart disease.
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http://dx.doi.org/10.3389/fcvm.2022.937090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339650PMC
July 2022

Challenges in the management of aortic stenosis, multiple valve disease, culture-negative endocarditis, and cardiac surgery during pregnancy.

Authors:
Filippo Crea

Eur Heart J 2022 Aug;43(29):2715-2719

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac381DOI Listing
August 2022

Pre-existing Psychiatric Morbidity Is Strongly Associated to Takotsubo Syndrome: A Case-Control Study.

Front Cardiovasc Med 2022 12;9:925459. Epub 2022 Jul 12.

Catholic University of the Sacred Heart, Rome, Italy.

Background: Takotsubo syndrome (TTS) is an emerging disease characterized by an acute and reversible myocardial dysfunction which may have an influence on clinical status and prognosis. Despite extensive research, its pathophysiology has not been completely elucidated; among other hypothesis, a heart-brain interaction has been proposed.

Methods: The aim of this study was to assess the impact of psychiatric disorders and of some personality types on the pathogenesis of TTS. We conducted a retrospective observational case-control study. We enrolled a total of 50 patients, 25 with a previous diagnosis of TTS and 25 patients with a history of acute coronary syndrome (ACS), that underwent a comprehensive lifetime psychiatric assessment.

Results: We found no significant difference between TTS and ACS patients in cardiovascular risk profile. The frequency of lifetime psychiatric disorders was significantly greater in TTS. In particular, in the univariate analysis, TTS group showed a higher prevalence of mood disorders (Major Depressive Disorder, Bipolar Disorder, Dysthymia; 16 vs. 2, < 0.001) and anxiety disorder (Generalized Anxiety Disorder, Panic Disorder, Agoraphobia; 20 vs. 8, = 0.001) compared with ACS group. There was also a significant tendency in TTS patients to psychotropic medication use, substance abuse, and psychologist or psychiatrist consulting. However, there was no difference between the groups in previous stressful events and Type D personality. Moreover, the multivariate analysis showed that mood disorders were independently associated with TTS (OR 16.9, 95% CI, 2.2-127).

Conclusion: Our study demonstrated that pre-existing anxiety disorders and mostly mood disorders were significantly higher in TTS patients than in ACS group, suggesting the role of psychiatric disorders as possible pathophysiological substrate of TTS.
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http://dx.doi.org/10.3389/fcvm.2022.925459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314861PMC
July 2022

Perspectives in noninvasive imaging for chronic coronary syndromes.

Int J Cardiol 2022 Jul 25. Epub 2022 Jul 25.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future.
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http://dx.doi.org/10.1016/j.ijcard.2022.07.038DOI Listing
July 2022

Comparative analysis of right ventricular strain in Fabry cardiomyopathy and sarcomeric hypertrophic cardiomyopathy.

Eur Heart J Cardiovasc Imaging 2022 Jul 28. Epub 2022 Jul 28.

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy.

Aims: To perform a comparative analysis of right ventricle (RV) myocardial mechanics, assessed by 2D speckle-tracking echocardiography (2D-STE), between patients with Fabry disease and patients with sarcomeric disease.

Methods And Results: Patients with Fabry cardiomyopathy (FC) (n = 28) were compared with patients with sarcomeric hypertrophic cardiomyopathy (HCM), matched for degree of left ventricle hypertrophy (LVH) and demographic characteristics (n = 112). In addition, patients with Fabry disease and no LVH [phenotype-negative carriers of pathogenic α-galactosidase gene mutations (GLA LVH-)] (n = 28) were compared with age and sex-matched carriers of sarcomeric gene mutations without LVH [Phenotype-negative carriers of pathogenic sarcomeric gene mutations (Sarc LVH-)] (n = 56). Standard echocardiography and 2D-STE were performed in all participants. Despite a subtle impairment of RV global longitudinal strain (RV-GLS) was common in both groups, patients with FC showed a more prominent reduction of RV free wall longitudinal strain (RV-FWS) and lower values of difference between RV-FWS and RV-GLS (ΔRV strain), in comparison to individuals with HCM (P < 0.001 and P = 0.002, respectively). RV-FWS and ΔRV strain demonstrated an independent and additive value in discriminating FC from HCM, over the presence of symmetric LVH, systolic anterior motion of the mitral valve and RV hypertrophy. Similar results were found in GLA LVH- patients: they had worse RV-FWS and lower values of ΔRV strain as compared to Sarc LVH- patients (both P < 0.001).

Conclusion: Patients with FC show a specific pattern of RV myocardial mechanics, characterized by a larger impairment of RV-FWS and lower ΔRV strain in comparison to patients with HCM, which may be helpful in the differential diagnosis between these two diseases.
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http://dx.doi.org/10.1093/ehjci/jeac151DOI Listing
July 2022

Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment Elevation Myocardial Infarction Patients.

Front Immunol 2022 8;13:845526. Epub 2022 Jul 8.

Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Aims: Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression.

Methods And Results: We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS ( < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences.

Conclusions: Our study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies.
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http://dx.doi.org/10.3389/fimmu.2022.845526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307872PMC
July 2022

A focus on congenital heart disease and neonatal cardiac regeneration: an exciting future.

Authors:
Filippo Crea

Eur Heart J 2022 Jul;43(28):2643-2646

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac379DOI Listing
July 2022

'Here comes the story of the Hurricane': a case report of AL cardiac amyloidosis and myocardial bridging.

Eur Heart J Case Rep 2022 Jul 31;6(7):ytac225. Epub 2022 May 31.

Department of Cardiovascular Sciences, Catholic University of the Sacred Heart (UCSC), Rome, Italy.

Background: Cardiac amyloidosis (CA) is a rapidly progressive infiltrative cardiomyopathy, whose role is emerging as a not-so-rare disorder leading to heart failure (HF). Myocardial bridge (MB) is the most common inborn coronary artery variant, and its clinical relevance is still matter of debate. The exceptional coexistence of these two conditions could accelerate disease progression and worsen the already compromised clinical conditions.

Case Summary: We present the case of a 76-year-old female patient experiencing relapsing HF decompensation and presenting to our centre with dyspnoea at rest and severe peripheral congestion. Echocardiogram showed severe concentric hypertrophy, severe biventricular contractile dysfunction, and third-degree diastolic dysfunction. Coronary angiography excluded epicardial atherosclerotic disease, though displaying a long intramyocardial course of left anterior descending artery. Physiological invasive test was achieved in terms of instantaneous wave-free ratio (iFR), both at baseline and after inotropic and chronotropic stimuli, and attested haemodynamic significance. Concurrently, the diagnostic flow chart for CA was accomplished, by means of both invasive (periumbilical fat biopsy, bone marrow aspiration) and non-invasive tests (Tc-diphosphonate scintigraphy, serum-urine immunofixation) that confirmed the suspect of primary amyloidosis. Acute HF therapy was personalized according to the singularity of the case, avoiding both nitrates and beta-blockers, then first cycle of chemotherapy was started.

Discussion: Our clinical case shows a unique interaction between infiltrative cardiomyopathy and coronary artery abnormality. Amyloidosis can contribute to the ischaemic burden of the MB and this may, in turn, abbreviate the path to HF decompensation.
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http://dx.doi.org/10.1093/ehjcr/ytac225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280548PMC
July 2022

Heart failure: how to optimize guideline-directed medical therapy.

Authors:
Filippo Crea

Eur Heart J 2022 Jul;43(27):2533-2537

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac356DOI Listing
July 2022

Cardiac magnetic resonance: challenges, opportunities, and developments.

Authors:
Filippo Crea

Eur Heart J 2022 07;43(26):2427-2431

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac355DOI Listing
July 2022

The challenge of risk stratification in aortic aneurysms, congenital heart disease, and coronary bypass surgery.

Authors:
Filippo Crea

Eur Heart J 2022 07;43(25):2343-2346

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac334DOI Listing
July 2022

A 3-Year Single Center Experience With Left Atrial Pressure Remote Monitoring: The Long and Winding Road.

Front Cardiovasc Med 2022 13;9:899656. Epub 2022 Jun 13.

Department of Cardiovascular and Pulmonary Sciences, Catholic University of the Sacred Heart, Rome, Italy.

Background: Despite continuous advancement in the field, heart failure (HF) remains the leading cause of hospitalization among the elderly and the overall first cause of hospital readmission in developed countries. Implantable hemodynamic monitoring is being tested to anticipate the clinical exacerbation onset, potentially preventing an emergent acute decompensation. To date, only pulmonary artery pressure (PAP) sensor received the approval to be implanted in symptomatic heart failure patients with reduced ejection fraction. However, PAP's indirect estimation of left ventricular filling pressure can be inaccurate in some contexts.

Methods: The VECTOR-HF study (NCT03775161) is examining the safety, usability and performance of the V-LAP system, a latest-generation device capable of continuously monitoring left atrial pressure (LAP). In our center, five advanced HF patients have been enrolled. After confirmation of the transmitted data reliability, LAP trends and waveforms have guided therapy optimization. The aim of this work is to share clinical insights from our center preliminary experience with V-LAP application.

Results: Over a median follow-up time of 18 months, LAP-based therapy optimization managed to reduce intracardiac pressure over time and no hospital readmission occurred. This result was paralleled by an improvement in both functional capacity (6MWT distance 352.5 ± 86.2 meters at baseline to 441.2 ± 125.2 meters at last follow-up) and quality of life indicators (KCCQ overall score 63.82 ± 16.36 vs. 81.92 ± 9.63; clinical score 68.47 ± 19.48 vs. 83.70 ± 15.58).

Conclusion: Preliminary evidence from V-LAP application at our institution support a promising efficacy. However, further study is needed to confirm the technical reliability of the device and to exploit the clinical benefit of left-sided hemodynamic remote monitoring.
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http://dx.doi.org/10.3389/fcvm.2022.899656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236153PMC
June 2022

Precision medicine versus standard of care for patients with myocardial infarction with non-obstructive coronary arteries (MINOCA): rationale and design of the multicentre, randomised PROMISE trial.

EuroIntervention 2022 Jun 23. Epub 2022 Jun 23.

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents about 6-8% of patients presenting with myocardial infarction (MI), and it is associated with a significant risk of mortality, rehospitalisation, and angina burden, with high associated socioeconomic costs. It is important to note that multiple mechanisms may be responsible for MINOCA. However, to date, there are few prospective clinical trials on MINOCA and the treatment of these patients is still not defined, most likely because of the multiple underlying pathogenic mechanisms. The PROMISE trial is a randomised, multicentre, prospective, superiority, phase IV trial that will include 180 MINOCA patients randomised 1:1 to a "precision-medicine approach", consisting of a comprehensive diagnostic workup and pharmacological treatment specific for the underlying cause, versus a "standard of care" approach, consisting of routine diagnostic workup and standard medical treatment for acute coronary syndrome. The aim of this study is to evaluate if the "precision-medicine approach" will improve the angina status, evaluated using the Seattle Angina Questionnaire summary score, at 12 months (primary endpoint). Secondary endpoints include the rate of major adverse cardiovascular events at 12-month follow-up, the related primary and secondary healthcare costs, and the ability of cardiac magnetic resonance to evaluate the different mechanisms of MINOCA. Of importance, the results derived from this trial may pave the way for a new pathophysiology-driven approach with cause-target therapies personalised for the mechanisms of MINOCA (ClinicalTrials.gov: NCT05122780).
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http://dx.doi.org/10.4244/EIJ-D-22-00178DOI Listing
June 2022

Antiplatelet treatment of acute coronary syndromes: novel clinical and translational perspectives.

Authors:
Filippo Crea

Eur Heart J 2022 06;43(24):2253-2256

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac311DOI Listing
June 2022

Optical coherence tomography-derived lipid core burden index and clinical outcomes: results from the CLIMA registry.

Eur Heart J Cardiovasc Imaging 2022 Jun 20. Epub 2022 Jun 20.

Centro per la Lotta Contro L'Infarto - CLI Foundation, Rome, Italy.

Aims: The aim of this study was to assess the morphological characteristics and prognostic implications of the optical coherence tomography (OCT)-derived lipid core burden index (LCBI).

Methods And Results: OCT-LCBI was assessed in 1003 patients with 1-year follow-up from the CLIMA multicentre registry using a validated software able to automatically obtain a maximum OCT-LCBI in 4 mm (maxOCT-LCBI4mm). Primary composite clinical endpoint included cardiac death, myocardial infarction, and target-vessel revascularization. A secondary analysis using clinical outcomes of CLIMA study was performed. Patients with a maxOCT-LCBI4mm ≥ 400 showed higher prevalence of fibrous cap thickness (FCT) <75 μm [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.03-1.99; P = 0.034], lipid pool arc >180° (OR 3.93, 95%CI 2.97-5.21; P < 0.001), minimum lumen area <3.5 mm2 (OR 1.5, 95%CI 1.16-1.94; P = 0.002), macrophage infiltration (OR 2.38, 95%CI 1.81-3.13; P < 0.001), and intra-plaque intimal vasculature (OR 1.34, 95%CI 1.05-1.72; P = 0.021). A maxOCT-LCBI4mm ≥400 predicted the primary endpoint [adjusted hazard ratio (HR) 1.86, 95%CI 1.1-3.2; P = 0.019] as well as the CLIMA endpoint (HR 2.56, 95%CI 1.24-5.29; P = 0.011). Patients with high lipid content and thin FCT < 75 µm were at higher risk for adverse events (HR 4.88, 95%CI 2.44-9.72; P < 0.001).

Conclusions: A high maxOCT-LCBI4mm was related to poor outcome and vulnerable plaque features. This study represents a step further in the automated assessment of the coronary plaque risk profile.
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http://dx.doi.org/10.1093/ehjci/jeac110DOI Listing
June 2022

Left atrioventricular coupling index in hypertrophic cardiomyopathy and risk of new-onset atrial fibrillation.

Int J Cardiol 2022 Sep 15;363:87-93. Epub 2022 Jun 15.

Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Hospital University Germans Trias i Pujol, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain. Electronic address:

Backgrounds: This study aimed to investigate the association between left atrioventricular coupling index (LACI) and the occurrence of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM).

Methods: A total of 373 patients with HCM and no history of AF were evaluated by transthoracic echocardiography. LACI was defined by the ratio of left atrial (LA) end-diastolic volume divided by left ventricular (LV) end-diastolic volume. The cut-off value for LACI (≥40%) to identify LA-LV uncoupling was chosen based on the risk excess of new-onset AF described with a spline curve analysis.

Results: The median LACI was 37.5% (IQR: 24.4-56.7) and LA-LV uncoupling (LACI ≥40%) was observed in 171 (45.8%) patients. During a median follow-up of 11 (IQR 7-15) years, 118 (31.6%) subjects developed new-onset AF. The cumulative event-free survival at 10 years was 53% for patients with LA-LV uncoupling versus 94% for patients without LA-LV uncoupling (p < 0.001). Multivariable Cox regression analyses performed separately for each LA parameter showed an independent association between new-onset AF and LACI (hazard ratio [HR], 1.021; 95% CI, 1.017-1.026), LA maximum volume indexed (HR, 1.028; 95% CI, 1.017-1.039), LA minimum volume indexed (HR, 1.047; 95% CI, 1.037-1.060) and LA emptying fraction (HR, 0.967; 95% CI, 0.959-0.977, all p < 0.001). The inclusion of LACI in the multivariate model provided a larger improvement in the risk stratification for new-onset AF, as compared to conventional LA parameters.

Conclusion: In patients with HCM, LACI was more predictive of the occurrence of new-onset AF than conventional LA parameters.
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http://dx.doi.org/10.1016/j.ijcard.2022.06.017DOI Listing
September 2022

Methylation of the Hippo effector YAP by the methyltransferase SETD7 drives myocardial ischemic injury: a translational study.

Cardiovasc Res 2022 Jun 16. Epub 2022 Jun 16.

Center for Molecular Cardiology, University of Zürich, Switzerland.

Aims: Methylation of non-histone proteins is emerging as a central regulatory mechanism in health and disease. The methyltransferase SETD7 has shown to methylate and alter the function of a variety of proteins in vitro, however its function in the heart is poorly understood. The present study investigates the role of SETD7 in myocardial ischemic injury.

Methods And Results: Experiments were performed in neonatal rat ventricular myocytes (NRVMs), SETD7 knockout mice (SETD7-/-) undergoing myocardial ischemia-reperfusion (I/R) injury, left ventricular (LV) myocardial samples from patients with ischemic cardiomyopathy (ICM) and peripheral blood mononuclear cells (PBMCs) from patients with ST-elevation MI (STEMI). We show that SETD7 is activated upon energy deprivation in cultured NRVMs and methylates the Hippo pathway effector YAP, leading to its cytosolic retention and impaired transcription of antioxidant genes manganese superoxide dismutase (MnSOD) and catalase (CAT). Such impairment of antioxidant defense was associated with mitochondrial reactive oxygen species (mtROS), organelle swelling and apoptosis. Selective pharmacological inhibition of SETD7 by (R)-PFI-2 restored YAP nuclear localization thus preventing mtROS, mitochondrial damage and apoptosis in NRVMs. In mice, genetic deletion of SETD7 attenuated myocardial I/R injury, mtROS and LV dysfunction by restoring YAP-dependent transcription of MnSOD and CAT. Moreover, in cardiomyocytes isolated from I/R mice and ICM patients (R)-PFI-2 prevented mtROS accumulation while improving Ca2+-activated tension. Finally, SETD7 was upregulated in PBMCs from STEMI patients and negatively correlated with MnSOD and CAT.

Conclusions: We show a methylation-dependent checkpoint regulating oxidative stress during myocardial ischemia. SETD7 inhibition may represent a valid therapeutic strategy in this setting.
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http://dx.doi.org/10.1093/cvr/cvac102DOI Listing
June 2022

The complex link among heart failure, atrial fibrillation, and lung diseases, and an update on cardiac transplantation.

Authors:
Filippo Crea

Eur Heart J 2022 06;43(23):2165-2169

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac297DOI Listing
June 2022

Clinical impact of the extent of jeopardized myocardium in patients undergoing transcatheter aortic valve intervention.

Rev Esp Cardiol (Engl Ed) 2022 Jun 9. Epub 2022 Jun 9.

Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Dipartimento di Scienze Cardiovascolari, Università Cattolica del Sacro Cuore, Rome, Italy.

Introduction And Objectives: Coronary artery disease (CAD) is found in 30%-50% of patients with severe aortic stenosis (AS) undergoing treatment. The best management of CAD in AS patients undergoing transcatheter aortic valve implantation (TAVI) is still unclear. We investigated the clinical impact of the extent of jeopardized myocardium in patients with concomitant CAD and severe AS treated by TAVI.

Methods: Consecutive patients who underwent TAVI procedures at our hospital were identified. In the presence of CAD, the myocardium jeopardized before TAVI was graded using the British Cardiovascular Intervention Society (BCIS) jeopardy score (JS). The study population was divided in 3 groups: patients without concomitant CAD (no-CAD), patients with CAD and BCIS-JS ≤ 4 (CAD BCIS-JS ≤ 4) and patients with concomitant CAD and BCIS-JS> 4 (CAD BCIS-JS> 4). The primary study endpoint was major adverse cardiovascular and cerebrovascular events (MACCE).

Results: A total of 403 patients entered the study: 223 no-CAD, 94 CAD BCIS-JS ≤ 4 and 86 CAD BCIS-JS> 4. At> 3 months of follow-up [range 104-3296 days], patients without CAD and CAD patients with BCIS-JS ≤ 4 had better survival free from MACCE compared with those with less extensive revascularization (BCIS-JS> 4) (P=.049). This result was driven by a significant reduction in death (P=.031). On multivariate analysis, residual BCIS-JS ≤ 4 and NYHA class III-IV independently predicted MACCE.

Conclusions: In patients with concomitant CAD and severe AS, the extent of jeopardized myocardium before TAVI impacts on clinical outcomes.
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http://dx.doi.org/10.1016/j.rec.2022.05.020DOI Listing
June 2022

New avenues in the prevention of sudden cardiac death.

Authors:
Filippo Crea

Eur Heart J 2022 06;43(22):2083-2086

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac277DOI Listing
June 2022

Attilio Maseri: scientist, clinician, mentor, and gentleman.

Cardiovasc Res 2022 06;118(8):e57-e58

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Largo Gemelli 8, 00168 Rome, Italy.

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http://dx.doi.org/10.1093/cvr/cvac063DOI Listing
June 2022

The fingerprints of plaque rupture healing as detected by serial optical coherence tomography imaging.

EuroIntervention 2022 08 5;18(5):e405-e406. Epub 2022 Aug 5.

Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

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http://dx.doi.org/10.4244/EIJ-D-22-00007DOI Listing
August 2022

The challenge of cardiovascular prevention in the elderly: importance of randomized clinical trials.

Authors:
Filippo Crea

Eur Heart J 2022 06;43(21):1997-2000

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac273DOI Listing
June 2022

Clinical Impact of Heart Team Decisions for Patients With Complex Valvular Heart Disease: A Large, Single-Center Experience.

J Am Heart Assoc 2022 06 27;11(11):e024404. Epub 2022 May 27.

Fondazione Policlinico Universitario A. Gemelli IRCCS Roma Italia.

Background A multidisciplinary approach might be pivotal for the management of patients with valvular heart disease (VHD), but clinical outcome data are lacking. Methods and Results At our institution, since 2014, internal guidelines recommended heart team consultations for patients with VHD. The clinical/echocardiographic characteristics, treatment recommendations, performed treatment, and early clinical outcomes of consecutive, hospitalized patients with VHD undergoing heart team evaluation were collected. Surgical risk was prospectively assessed by the EuroSCORE II and STS-PROM. The primary end point of the study was early mortality. A total of 1004 patients with VHD with high clinical complexity (mean age, 75 years; mean EuroSCORE II, 9.4%; mean STS-PROM, 5.6%; 48% ischemic heart disease; 29% chronic kidney disease, 9% oncologic/hematologic diseases) were enrolled. The heart team recommended an interventional treatment for 807 (80%) patients and conservative management for 197 (20%) patients. Management crossovers occurred in only 5% of patients. The recommended intervention was cardiac surgery for 230 (23%) patients, percutaneous treatment in 516 (51%) patients, and hybrid treatment in 61 (6%) patients. Early mortality occurred in 24 patients (2.4%) and was independently predicted by aortic stenosis, left ventricular ejection fraction, pulmonary artery systolic pressure, and conservative management recommendation. In patients referred to treatment, observed early mortality (1.7%) was significantly lower (<0.001) than expected on the bases of both the STS-PROM (5.2%) and EuroSCORE II (9.7%). Conclusions Within the limitations of its single-center and observational design, the present study suggests that heart team-based management of patients with complex VHD is feasible and allows referral to a wide spectrum of interventions with promising early clinical results.
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http://dx.doi.org/10.1161/JAHA.121.024404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238748PMC
June 2022

Breast cancer chemotherapy induces vascular dysfunction and hypertension through a NOX4-dependent mechanism.

J Clin Invest 2022 07;132(13)

Department of Medicine, Jagiellonian University Medical College, Krakow, Poland.

Cardiovascular disease is the major cause of morbidity and mortality in breast cancer survivors. Chemotherapy contributes to this risk. We aimed to define the mechanisms of long-term vascular dysfunction caused by neoadjuvant chemotherapy (NACT) and identify novel therapeutic targets. We studied arteries from postmenopausal women who had undergone breast cancer treatment using docetaxel, doxorubicin, and cyclophosphamide (NACT) and from women with no history of such treatment matched for key clinical parameters. We explored mechanisms in WT and Nox4-/- mice and in human microvascular endothelial cells. Endothelium-dependent, NO-mediated vasodilatation was severely impaired in patients after NACT, while endothelium-independent responses remained normal. This was mimicked by a 24-hour exposure of arteries to NACT agents ex vivo. When applied individually, only docetaxel impaired endothelial function in human vessels. Mechanistic studies showed that NACT increased inhibitory eNOS phosphorylation of threonine 495 in a Rho-associated protein kinase-dependent (ROCK-dependent) manner and augmented vascular superoxide and hydrogen peroxide production and NADPH oxidase activity. Docetaxel increased expression of the NADPH oxidase NOX4 in endothelial and smooth muscle cells and NOX2 in the endothelium. A NOX4 increase in human arteries may be mediated epigenetically by diminished DNA methylation of the NOX4 promoter. Docetaxel induced endothelial dysfunction and hypertension in mice, and these were prevented in Nox4-/- mice and by pharmacological inhibition of Nox4 or Rock. Commonly used chemotherapeutic agents and, in particular, docetaxel alter vascular function by promoting the inhibitory phosphorylation of eNOS and enhancing ROS production by NADPH oxidases.
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http://dx.doi.org/10.1172/JCI149117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246378PMC
July 2022

Challenges in heart failure: from actionability of genetic variants in cardiopmyopathies to new therapeutic targets.

Authors:
Filippo Crea

Eur Heart J 2022 05;43(20):1887-1890

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehac243DOI Listing
May 2022
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