Research directions

• Multiscale investigation of complex arrhythmias
  Atrial fibrillation (AF) is the most common heart rhythm disorder in the world and increases in prevalence with advancing age, with major public health impact especially due to increased risk of stroke and hospitalizations. AF is a complex multifactorial disease where several cardiac and non-cardiac predisposing factors, including genetics, age-/disease-associated remodeling and autonomic dysfunctions, concur to the formation of the arrhythmia triggers and substrates. The incomplete understanding of AF mechanisms and the multiplicity of factors promoting the arrhythmia in humans have hampered the development of effective therapeutic approaches. Our work encompasses the use of advanced signal analysis, multimodal imaging, computational models combined with structural/molecular analysis of cardiac tissue samples to investigate the mechanisms underlying AF initiation and perpetuation, with the ultimate aim to transfer the results to direct clinical application.

  .              

• New risk stratification markers of sudden cardiac death
  Sudden cardiac death (SCD), primarily caused by ventricular arrhythmias, is one of the leading causes of mortality in industrialized countries and is responsible for 60-70% of all deaths of cardiovascular origin. The prognostic stratification of sudden death represents an open challenge for modern cardiology. Current guidelines for the use of implantable cardioverter-defibrillators in primary prevention are mostly based on left ventricular ejection fraction, which is however a suboptimal SCD predictor. By using meta-analysis techniques, we are addressing our research to the identification of novel image-based/electrocardiographic markers to improve prediction and the risk stratification of sudden cardiac death.

• Proton radiosurgery as new ablation treatment of life-threatening arrhythmias
  Catheter ablation, which commonly uses radiofrequency or cryothermal energy, is an invasive procedure for the treatment of arrhythmias, often accompanied by procedure related complication and with still unsatisfactory efficacy outcomes. Proton beam therapy, most commonly used to treat tumors, offers radiophysical properties that are appealing for noninvasive ablation of arrhythmias. On the other hand, the use of multimodal imaging combined with electrocardiographic mapping can aid in the non-invasive identification of ablation targets in the individual patient. Within a research network that includes the Proton Therapy Center, the Cardiology and Radiology Divisions of the APSS of Trento, we will investigate the feasibility of image-guided proton radiosurgery as a new treatment option for otherwise untreatable patients suffering from ventricular tachycardia. Extending the use of proton therapy from oncological to cardiological applications could represent an open challenge for modern radiosurgery.

Group members

• Flavia Ravelli, PI
• Michela Masè, Postdoc collaborator
• Alessandro Cristoforetti, Postdoc collaborator

Collaborations

• Department of Cardiovascular Sciences, University of Leicester, UK (T. Almeida)
• BioMIT, Universitat Politècnica de València, Valencia (Spain) (J.J. Rieta)
• BIOtech - Department of Industrial Engineering, University of Trento, Italy (G. Nollo)
• Divisions of Cardiology, Cardiac Surgery and Radiology, APSS, Trento, Italy
• Proton Therapy Center (PTC), APSS, Trento, Italy
• Medicaltech s.r.l., Polo Tecnologico, Rovereto, Italy

Selected publications

Ravelli F., Masè M. MicroRNAs: new contributors to mechano-electric coupling and atrial fibrillation (2021) Progress in Biophysics & Molecular Biology, 159, pp 146-156

Almeida T, Soriano D, Masè M, Ravelli F., Bezerra A, Li X, Chu G, Salinet J, Stafford P, Andre Ng G, Schlindwein F, Yoneyama T. Unsupervised classification of atrial electrograms for electroanatomic mapping of human persistent atrial fibrillation (2021) IEEE Transactions on Biomedical Engineering 68(4), 9186302, pp 1131-1141

Disertori M, Masè M, Rigoni M, Nollo G, Ravelli F. Declining clinical benefit of ICD in heart failure patients: Temporal trend of mortality outcomes from randomized controlled trials (2020) Journal of Cardiology, 75 (2), pp. 148-154.

Marsili IA, Biasiolli L, Masè M, Adami A, Andrighetti AO, Ravelli F., Nollo G. Implementation and validation of real-time algorithms for atrial fibrillation detection on a wearable ECG device (2020) Computers in Biology and Medicine, 116, art. no. 103540

Masè, M, Grasso M, Avogaro L, Giacomaz MN, D'Amato E, Tessarolo F, Graffigna A, Denti MA, Ravelli F. Upregulation of mir-133b and mir-328 in patients with atrial dilatation: Implications for stretch-induced atrial fibrillation (2019) Frontiers in Physiology, 10, art. no. 1133

Cristoforetti A, Mase M, Bonmassari R, Dallago M, Nollo G, Ravelli F. A patient-specific mass-spring model for biomechanical simulation of aortic root tissue during transcatheter aortic valve implantation (2019) Physics in Medicine and Biology, 64 (8), art. no. 085014

Disertori M, Masè M, Ravelli F. Myocardial fibrosis predicts ventricular tachyarrhythmias (2017) Trends in Cardiovascular Medicine, 27 (5), pp. 363-372

Masè M, Grasso M, Avogaro L, D'Amato E, Tessarolo F, Graffigna A, Denti MA, Ravelli F. Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation (2017) Scientific Reports, 7, art. no. 41127

Disertori M, Masè M, Rigoni M, Nollo G, Ravelli F. Heart rate turbulence is a powerful predictor of cardiac death and ventricular arrhythmias in postmyocardial infarction and heart failure patients: a systematic review and meta-analysis (2016) Circulation: Arrhythmia and Electrophysiology, 9 (12), art. no. e004610

Disertori M, Rigoni M, Pace N, Casolo G, Masè M, Gonzini L, Lucci, D., Nollo, G., Ravelli F. Myocardial fibrosis assessment by LGE is a powerful predictor of ventricular tachyarrhythmias in ischemic and nonischemic LV dysfunction: a meta-analysis (2016) JACC: Cardiovascular Imaging, 9 (9), pp. 1046-1055

Ravelli F., Masè M. Computational mapping in atrial fibrillation: How the integration of signal-derived maps may guide the localization of critical sources (2014) Europace, 16 (5), pp. 714-723

Ravelli F., Masè M, Cristoforetti A, Marini M, Disertori M. The logical operator map identifies novel candidate markers for critical sites in patients with atrial fibrillation (2014) Progress in Biophysics and Molecular Biology, 115 (2-3), pp. 186-197.

Disertori M, Masè M, Marini M, Mazzola S, Cristoforetti A, Del Greco M, Kottkamp H, Arbustini E, Ravelli F. Electroanatomic mapping and late gadolinium enhancement MRI in a genetic model of arrhythmogenic atrial cardiomyopathy (2014) Journal of Cardiovascular Electrophysiology, 25 (9), pp. 964-970.

Rieta JJ, Ravelli F., Sörnmo L. Guest Editorial: Advances in modeling and characterization of atrial arrhythmias (2013), Biomedical Signal Processing and Control, 8 (6), pp. 956-957.

Disertori M, Quintarelli S, Grasso M, Pilotto A, Narula N, Favalli V, Canclini C, Diegoli M, Mazzola S, Marini M, Del Greco M, Bonmassari R, Masè M, Ravelli F., Specchia C, Arbustini E. Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A (2013) Circulation: Cardiovascular Genetics, 6 (1), pp. 27-36

Cristoforetti A, Mase M, Ravelli F. A fully adaptive multiresolution algorithm for atrial arrhythmia simulation on anatomically realistic unstructured meshes (2013) IEEE Transactions on Biomedical Engineering, 60 (9), art. no. 6514086, pp. 2585-2593.

Ravelli F., Masè M, Cristoforetti A, Del Greco M, Centonze M, Marini M, Disertori M. Anatomic localization of rapid repetitive sources in persistent atrial fibrillation: Fusion of biatrial CT images with wave similarity/cycle length maps (2012) JACC: Cardiovascular Imaging, 5 (12), pp. 1211-1220.

Masè M, Glass L, Disertori M, Ravelli F. Nodal recovery, dual pathway physiology, and concealed conduction determine complex AV dynamics in human atrial tachyarrhythmias (2012) American Journal of Physiology - Heart and Circulatory Physiology, 303 (10), pp. H1219-H1228.