Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
20
Scopus Publications
Scopus Publications
MAD or MADness? Francesco Fulvio Faletra, Giuseppe Sgarito, Francesca Parisi, Eluisa La Franca, Massimiliano Mulè, Alessandra Carvelli, Giovanni Di Stefano, Rita Laura Borrello, Vincenzo Nuzzi, Paolo Manca, Manlio Cipriani Cardiovascular Ultrasound, 2025 Mitral valve prolapse (MVP) is a common condition affecting approximately 3% of the population, typically with a benign clinical course. However, a small subset of patients (5-10%) may develop severe mitral regurgitation or arrhythmias, which can lead to sudden cardiac death (SCD). Among the morphological features of MVP, mitral annular disjunction (MAD) has emerged as a potential marker of malignant MVP, with some studies suggesting an association with ventricular arrhythmias and SCD. MAD refers to a structural abnormality where there is a separation between the posterior mitral annulus and the ventricular myocardium, particularly during systole. Initially described in the 1980s, MAD has been primarily studied through echocardiography, although its dynamic nature during the cardiac cycle has complicated its diagnosis. The clinical significance of MAD has been debated, as its presence is not exclusive to pathological MVP, being observed in structurally normal mitral valves as well. Recent research, using advanced imaging techniques such as three-dimensional echocardiography, cardiac magnetic resonance and computed tomography, has provided a more refined understanding of MAD. These studies suggest that MAD can be found in normal hearts, particularly in the posterior mitral annulus, and is often considered a benign anatomical variant. However, the occurrence of MAD in patients with MVP, especially those with leaflet redundancy, has been linked to an increased risk of arrhythmias and SCD. The exact role of MAD in arrhythmogenesis remains unclear, but it is hypothesized that MAD may contribute to electrical instability by altering the mechanical properties of the mitral valve, potentially promoting fibrosis in the surrounding myocardium. Despite these associations, the direct causal role of MAD in SCD requires further investigation, and it may ultimately prove to be an innocent bystander rather than the primary cause of fatal arrhythmias.
The role of left atrio-ventricular coupling index and left atrial ejection fraction in predicting onset of atrial fibrillation and adverse cardiac events in hypertrophic cardiomyopathy Parisi Francesca, La Franca Eluisa, Pistelli Lorenzo, Gentile Giovanni, Bellavia Diego, Nuzzi Vincenzo, Manca Paolo, Massimiliano Mulè, Zito Concetta, Di Bella Gianluca, Scipione Carerj, Cipriani Manlio, Francesco F. Faletra Cardiovascular Ultrasound, 2025 BACKGROUND: Several predictors of atrial fibrillation (AF) onset in patients with hypertrophic cardiomyopathy (HCM) have been proposed, however, all of them showed limited accuracy. This study aims to assess the role of new echographic parameters in predicting AF onset and major adverse cardiovascular outcomes (cardiovascular death or heart transplantation). METHODS: Clinical and imaging data from 141 patients with HCM and without a history of AF were retrospectively analyzed over a 5-year period. Patients who developed AF during the study were compared to those who did not. The analysis focused on key atrial parameters, including the Left Atrial Contraction Index (LACI) and Left Atrial Ejection Fraction (LAEF). LACI was defined as the ratio of left atrial end-diastolic volume to left ventricular end-diastolic volume. Echocardiographic measurements were standardized using cardiac magnetic resonance (CMR) as the reference. Regarding statistical analysis, each significant continuous variable was categorized by identifying a cut-off value using the Youden index. Independent associations with outcomes and cumulative survival were assessed using Cox regression analysis. RESULTS: Thirty-five patients developed AF, at a mean time of 4 years. The HCM-AF group had significantly higher values of LACI, left atrial diameter (LAD), and left atrial minimum volume (LAVmin). A LACI > 43% on echocardiography and LACI > 44% on CMR showed the best performance in identifying patients at risk for AF. In multivariate analysis, an echocardiographic LAEF < 43% was independently associated with the occurrence of AF (HR 2.9, 95% CI: 1.2-6.9). Additionally, a LAD > 40.5 mm was independently associated with AF onset, with a hazard ratio of 2.5 (95% CI 1.1-5.5). Eleven patients experienced the composite outcome of cardiovascular death or heart transplant, and a LACI > 60% was associated with this outcome. CONCLUSION: In patients with HCM, both LACI and LAEF were significantly associated with the occurrence of AF over a 4-year period, demonstrating higher sensitivity and specificity compared to other parameters. A LACI > 60% was also found to be associated with cardiovascular death or heart transplant in this population.
Contemporary medical therapy for heart failure across the ejection fraction spectrum: The OPTIPHARM-HF registry Riccardo M. Inciardi, Maurizio Volterrani, Gianluigi Savarese, Muthiah Vaduganathan, Chiara Oriecuia, Carlo M. Lombardi, Cristina Gussago, Piergiuseppe Agostoni, Pietro Ameri, Giuseppe Armentaro, Chiara Arzilli, Nadia Aspromonte, Andrea Attanasio, Roberto Badagliacca, Lucia Barbieri, Pier Paolo Bocchino, Francesca Bursi, Matteo Cameli, Martino Canonero, Jeness S. Campodonico, Teresa Capovilla, Erberto Carluccio, Stefano Carugo, Vincenzo Castiglione, Dario Catapano, Manlio Cipriani, Michele Correale, Domenico D'Amario, Raffaele De Caterina, Gaetano M. De Ferrari, Emilia D'Elia, Luca Di Odoardo, Michele Emdin, Luigi Falco, Giulia Ferrante, Alessandra Fornaro, Paolo Fornaro, Gionata Guastamiglio, Marco Guazzi, Massimo Iacoviello, Massimo Imazio, Enrico Incaminato, Maria Teresa La Rovere, Sergio Leonardi, Marta Maccallini, Giulia E. Mandoli, Daniele Masarone, Marco Masetti, Alberto Mazzoni, Marta Mazzotta, Marco Merlo, Luigi Moschini, Filippo Novarese, Alberto Palazzuoli, Maria C. Pastore, Giuseppe Patti, Roberto F.E. Pedretti, Stefano Pidello, Massimo F. Piepoli, Giuseppe Pinto, Luciano Potena, Claudia Raineri, Filippo M. Rubbo, Mario Sabatino, Andrea Salzano, Angela Sciacqua, Michele Senni, Paolo Severino, Gianfranco Sinagra, Barbara Sposato, Stefano Taddei, Alessandro Valleggi, Carlo Vignati, Dario Vizza, Claudia Specchia, Giuseppe Rosano, Marco Metra, the OPTIPHARM-HF investigators European Journal of Heart Failure, 2025 Aims Despite guideline recommendations, guideline-directed medical therapy (GDMT) remains underused and underdosed in patients with heart failure (HF) across the ejection fraction (EF) spectrum. The aim of this study was to evaluate GDMT use, dosing, and implementation in a contemporary, nationwide HF cohort. Methods and results The OPTIPHARM-HF (NCT06192524) is a prospective, multicentre, observational study enrolling adult patients with HF, across 32 Italian HF centres. Clinical characteristics, medical therapy prevalence and change after first visit have been assessed in patients with reduced (HFrEF: EF ≤40%), mildly reduced (HFmrEF: EF 40–49%), and preserved EF (HFpEF: EF ≥50%). From September 2022 to December 2024, 3054 patients (mean age 69 ± 12 years, 25% female) were enrolled: 56% with HFrEF, 21% with HFmrEF, and 23% with HFpEF. Among HFrEF, prescription frequencies were: 90% for beta-blockers; 19% for angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARB); 61% for angiotensin receptor–neprilysin inhibitors (ARNI); 72% for mineralocorticoid receptor antagonists (MRA); and 69% for sodium–glucose co-transporter 2 inhibitors (SGLT2i). Less than 60% achieved ≥50% of target doses. Quadruple therapy was received by 47% of the patients. After first visit, there was an increase in prescription of all classes of drugs, and titration to quadruple therapy was attained in 64% (p < 0.001). Among HFmrEF, 88% were on beta-blockers, 34% on ACEi/ARB, 49% on ARNI, 63% on MRA, and 59% on SGLT2i. In the HFpEF group, 76% were on beta-blockers, 49% on ACEi/ARB, 18% on ARNI, 49% on MRA and 40% on SGLT2i. After the first visit, SGLT2i prescription significantly increased both in HFmrEF (74%, p < 0.001) and HFpEF (54%, p < 0.001). Conclusions Use of GDMT remains suboptimal across the EF spectrum although the adoption of quadruple GDMT in HFrEF and of SGLT2i in HFmrEF and HFpEF increased in recent years.
Right ventricular global work efficiency: A reliable non-invasive estimate of right ventricular contractility Paolo Manca, Vincenzo Nuzzi, Alessandro Lucchino, Gerardo Rugiano, Massimiliano Mulè, Alessandra Carvelli, Stefano Cannata, Sergio Sciacca, Francesca Parisi, Sabato Sorrentino, Francesco Fulvio Faletra, Paolo C. Colombo, Manlio Gianni Cipriani Esc Heart Failure, 2025 Background Right ventricular (RV) myocardial work (RVMW) recently emerged as a non-invasive alternative for the assessment of RV contractility. However, none of the prior studies assessed its variations under different haemodynamic conditions. We aimed to evaluate the variations of the components of RVMW in heart failure (HF) patients with pulmonary hypertension (PH) undergoing a reversibility test. Methods Consecutive HF patients with reduced ejection fraction who underwent right heart catheterization and echocardiography at our institution were prospectively enrolled. Patients with PH and augmented pulmonary vascular resistance who achieved normalization of pulmonary pressures after the reversibility test using vasodilators underwent a second echocardiographic assessment under the same haemodynamic conditions. Four components of RVMW were analysed: (1) RV global work index (mmHg%); (2) RV global constructive work (mmHg%); (3) RV global wasted work (RVGWW) (mmHg%); (4) RV global work efficiency (RVGWE) (%). Results One hundred two patients were enrolled (53 with PH and 49 without). Global RVMW was higher in patients with PH, due to a significantly higher RVGWW [81 (55–119) mmHg% vs. 49 (28–72) mmHg%; P = 0.013], while RVGWE was similar between the two groups (80 ± 10% vs. 82 ± 12%; P = 0.332). In patients with PH, 27/52 (51.9%) had combined PH, while 25/52 (48.1%) had isolated post-capillary PH. A reversibility test was performed in 26/27 (96.2%) patients with combined PH and pulmonary pressure normalization was observed in 16/26 (61.5%) subjects. In patients with PH normalization, RVGWE remained almost unchanged (from 82.8 ± 6.9% to 85.3 ± 6.6%; P = 0.596), while RVGWW significantly decreased [from 60 (49–90) mmHg% to 41 (31–53) mmHg%; P = 0.027]. Among all the echocardiographic and haemodynamic parameters adopted for assessing RV function, RVGWE was the least variable during the reversibility test (mean variation 3 ± 10%). Conclusions RVGWE is comparable between HF patients with and without PH and remains stable across different haemodynamic conditions. This consistency suggests that it can be a reliable parameter for assessing RV contractility. Larger studies are needed to confirm this hypothesis and to test its prognostic significance.
ISMETT experience with long-term left ventricular assist devices Vincenzo Nuzzi, Sergio Sciacca, Alessandro Lucchino, Paolo Manca, Giovanna Panarello, Matteo Rossetti, Alessandra Fontana, Simona Leone, Maria Scarlata, Eleonora Bonicolini, Massimiliano Mulè, Giuseppe Raffa, Marco Morsolini, Francesca Parisi, Stefano Cannata, Caterina Gandolfo, Gaetano Burgio, Francesco Musumeci, Francesco F. Faletra, Antonio Arcadipane, Michele Pilato, Manlio G. Cipriani Giornale Italiano Di Cardiologia, 2025 Razionale. L’insufficienza cardiaca avanzata rappresenta una condizione in cui le terapie farmacologiche hanno un impatto sulla prognosi limitato. I dispositivi di assistenza ventricolare sinistra (LVAD) hanno dimostrato di prolungare la sopravvivenza e migliorare la qualità di vita in questo scenario, in pazienti ben selezionati. La tecnologia degli LVAD si è evoluta, rendendo i dispositivi progressivamente più efficienti e gravati da meno complicanze.Materiali e metodi. Questo studio retrospettivo monocentrico analizza i risultati di impianti LVAD presso ISMETT, confrontando l’utilizzo di due dispositivi: HeartWare (HVAD) e HeartMate 3 (HM3). Le analisi sugli eventi sono state condotte considerando il primo anno di follow-up. L’evento primario considerato è la mortalità, mentre gli eventi secondari includono eventi avversi quali ictus, infezioni della driveline, scompenso cardiaco e trombosi di pompa.Risultati. Tra il 2010 e il 2024 sono stati impiantati 109 LVAD (10.75 impianti/anno). Il tasso di sopravvivenza a 1 anno è risultato superiore nei pazienti con HM3 (84.6%) rispetto a quelli con HVAD (78.6%). Gli eventi cerebrovascolari sono risultati significativamente meno frequenti nel gruppo HM3. Le infezioni della driveline sono risultate simili tra i due dispositivi. Il 15.7% dei pazienti portatori di HVAD è andato incontro a trombosi di pompa, mentre non sono state registrate trombosi di pompa nei pazienti HM3. Il rischio di sanguinamenti gastrointestinali è risultato significativamente più alto nei pazienti HVAD, mentre il rischio di insufficienza ventricolare destra era sovrapponibile tra i due gruppi.Conclusioni. Gli LVAD HM3 offrono un profilo di sicurezza superiore, con una riduzione della mortalità e delle complicanze rispetto ai dispositivi HVAD, riflettendo il progresso tecnologico nel supporto meccanico nell’insufficienza cardiaca avanzata. Lo studio fornisce nuovi dati sugli esiti dei pazienti con LVAD in Italia, contribuendo a migliorare le prospettive di trattamento per questa popolazione ad alto rischio.
Functional Mitral Valve Regurgitation, Pathophysiology, Leaflet ReModeling, and the Role of Imaging Francesco Fulvio Faletra, Eluisa La Franca, Massimiliano Mulè, Alessandra Carvelli, Francesca Parisi, Giovanni Di Stefano, Rita Laura Borrello, Vincenzo Nuzzi, Paolo Manca, Manlio Cipriani Echocardiography, 2025 Functional mitral regurgitation (FMR) is a complex left ventricle (LV) and left atrium (LA) disorder in which mitral valve regurgitation is just the “tip of the iceberg.” Unlike primary mitral cvalve regurgitation, in which regurgitation occurs due to anatomic abnormalities of the valve itself, the etiology of FMR is multifactorial. Regional and global LV dysfunction, extent and location of fibrotic myocardium (subendocardial/transmural scar), and annulus enlargement are the leading causes of valve regurgitation. A comprehensive understanding of the causes, mechanisms, severity, and clinical consequences of FMVR relies primarily on noninvasive imaging techniques. Echocardiography is the first‐line and most commonly used imaging technique. Cardiac magnetic resonance (CMR) has gained growing consensus mainly because it can precisely identify the extent and location of fibrotic myocardium. This review aims to: (a) describe the pathophysiology of the most common phenotypes of FMR, (b) challenge the paradigm that mitral leaflets are structurally normal in FMR, and (c) illustrate the critical role of both echocardiography and CMR in the comprehensive assessment of FMR.
MI2AMI-CS: A meta-analysis comparing Impella and IABP outcomes in Acute Myocardial Infarction-related Cardiogenic Shock Tommaso De Ferrari, Lorenzo Pistelli, Marco Franzino, Agustin Ezequiel Molinero, Giulia Azzurra De Santis, Alessandro Di Carlo, Giampaolo Vetta, Antonio Parlavecchio, Luigi Fimiani, Andrea Picci, Giuseppe Certo, Francesca Parisi, Giuseppe Venuti International Journal of Cardiology, 2024 BACKGROUND: Cardiogenic Shock (CS) complicating acute myocardial infarction (AMI) poses a significant mortality risk, suggesting the opportunity to implement effective mechanical circulatory support strategies. The comparative efficacy of Intra-Aortic Balloon Pump (IABP) and Impella in managing CS-AMI remains a subject of investigation. OBJECTIVE: This meta-analysis aims to evaluate the comparative effectiveness of Impella and IABP in managing CS-AMI, exploring mortality and adverse events. METHODS: A systematic search of major databases from inception to November 2023 identified eight studies, comprising 10,628 patients, comparing Impella and IABP in CS-AMI. Retrospective studies (preferably Propensity-matched) and Randomized Clinical Trials (RCTs) were included. RESULTS: Impella use exhibited significantly higher mortality (57% vs. 46%; OR: 1.44, 95% CI: 1.29-1.60; p < 0.001) and major bleeding (30% vs 15%; OR: 2.93, 95% CI: 1.67-5.13; p < 0.001). CONCLUSIONS: In unselected CS-AMI patients, Impella usage is associated with significantly higher mortality and major bleeding.
Ranolazine Unveiled: Rediscovering an Old Solution in a New Light Giulia Azzurra De Santis, Tommaso De Ferrari, Francesca Parisi, Marco Franzino, Agustin Ezequiel Molinero, Alessandro Di Carlo, Lorenzo Pistelli, Giampaolo Vetta, Antonio Parlavecchio, Marco Torre, Matteo Parollo, Giacomo Mansi, Pietro Paolo Tamborrino, Antonio Canu, Gino Grifoni, Luca Segreti, Andrea Di Cori, Stefano Marco Viani, Giulio Zucchelli Journal of Clinical Medicine, 2024 Ranolazine is an anti-anginal medication that has demonstrated antiarrhythmic properties by inhibiting both late sodium and potassium currents. Studies have shown promising results for ranolazine in treating both atrial fibrillation and ventricular arrhythmias, particularly when used in combination with other medications. This review explores ranolazine’s mechanisms of action and its potential role in cardiac arrhythmias treatment in light of previous clinical studies.
Arrhythmic risk profile in mitral valve prolapse: A systematic review and metanalysis of 1715 patients Lorenzo Pistelli, Giampaolo Vetta, Antonio Parlavecchio, Pasquale Crea, Francesca Parisi, Michele Magnocavallo, Rodolfo Caminiti, Simone Frea, Alessandro Vairo, Paolo Desalvo, Riccardo Faletti, Marco Gatti, Giuseppe Dattilo, Matteo Parollo, Andrea Di Cori, Maria Grazia Bongiorni, Giulia De Santis, Marco Borgi, Marco Franzino, Roberto Licordari, Giulio Zucchelli, Giovanni Domenico Della Rocca, Carla Giustetto Journal of Cardiovascular Electrophysiology, 2024 IntroductionMitral valve prolapse (MVP) is a common clinical condition in the general population. A subgroup of patients with MVP may experience ventricular arrhythmias and sudden cardiac death (“arrhythmic mitral valve prolapse” [AMVP]) but how to stratify arrhythmic risk is still unclear. Our meta‐analysis aims to identify predictive factors for arrhythmic risk in patients with MVP.MethodsWe systematically searched Medline, Cochrane, Journals@Ovid, Scopus electronic databases for studies published up to December 28, 2022 and comparing AMVP and nonarrhythmic mitral valve prolapse (NAMVP) for what concerns history, electrocardiographic, echocardiographic and cardiac magnetic resonance features. The effect size was estimated using a random‐effect model as odds ratio (OR) and mean difference (MD).ResultsA total of 10 studies enrolling 1715 patients were included. Late gadolinium enhancement (LGE) (OR: 16.67; p = .005), T‐wave inversion (TWI) (OR: 2.63; p < .0001), bileaflet MVP (OR: 1.92; p < .0001) and mitral anulus disjunction (MAD) (OR: 2.60; p < .0001) were more represented among patients with AMVP than in NAMVP. Patients with AMVP were shown to have longer anterior mitral leaflet (AML) (MD: 2.63 mm; p < .0001), posterior mitral leaflet (MD: 2.96 mm; p < .0001), thicker AML (MD: 0.49 mm; p < .0001), longer MAD length (MD: 1.24 mm; p < .0001) and higher amount of LGE (MD: 1.41%; p < .0001) than NAMVP. AMVP showed increased mechanical dispersion (MD: 8.04 ms; 95% confidence interval: 5.13–10.96; p < .0001) compared with NAMVP.ConclusionsOur meta‐analysis proved that LGE, TWI, bileaflet MVP, and MAD are predictive factors for arrhythmic risk in MVP patients.
