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Dott. Francesco Tosello

  • Dottorato: 30° ciclo
  • Matricola: 222483

Attività di ricerca

Valutazione pressione centrale, metodica di misurazione, implicazione cliniche

Validazione modello matematico di interazione cuore-albero arterioso


Leone D* (first author), Tosello F* (first author), Faletti R, Schivazappa G, Bruno G, Avenatti E, Ravera A, Veglio F, Milan A. 

Accuracy of transthoracic echocardiography in the assessment of proximal aortic diameter in hypertensive patients: comparison with cardiac magnetic resonance.

J Hypertens. 2017 Aug;35(8):1626-1634


Accurate and reproducible measurements of proximal thoracic aorta diameters are essential in the diagnosis and follow-up of patients with aortic dilatation, a condition particularly common in hypertensive patients. 



to evaluate the accuracy of transthoracic echocardiography (TTE) in comparison with cardiac magnetic resonance (CMR) for the assessment of proximal thoracic aorta diameters in a cohort of hypertensive patients. 



A total of 75 essential hypertensive outpatients previously evaluated by TTE and than by CMR were included in the study. We specifically compared the two techniques at the level of sinuses of Valsalva (SoV) and ascending aorta (Asc) diameter. For the TTE images, the inner edge-to-inner edge and leading edge-to-leading edge conventions were compared. 



TTE and CMR diameters were significantly related (SoV: r 0.931, P < 0.001; Asc: r 0.949, P < 0.001) when the leading edge-to-leading edge convention was used. Mean difference between CMR and TTE diameters was 2.49 ± 2.01 mm at the level of SoV and 1.13 ± 1.77 mm at the level of Asc. Correlation was good also for the TEE diameters measured by inner edge-to-inner edge convention (SoV: r 0.936, P < 0.001; Asc: r 0.947, P < 0.001). Comparing the two approaches in the evaluation of Asc, inner edge-to-inner edge showed a trend to a better correlation with CMR measurements than leading edge-to-leading edge, with a good interobserver and intraobserver agreement. 



The results of the current study suggest that TTE could be a reliable tool to assess proximal aorta diameters in hypertensive patients


De Nicolò A, Avataneo V, Rabbia F, Sciandra M, Tosello F, Cusato J, Perlo E, Mulatero P, Veglio F, Di Perri G, D'Avolio A.

UHPLC-MS/MS method with sample dilution to test therapeutic adherence through quantification of ten antihypertensive drugs in urine samples.

J Pharm Biomed Anal. 2017 Aug 5;142:279-285

Abstract: Nowadays, hypertension represents an important health problem, particularly in developed countries. In some cases the standard therapeutic approaches are not able to reestablish the normal blood pressure values: this condition is called "resistant hypertension". However, a fraction of cases of resistant hypertension are actually due to poor adherence to the prescribed therapy. Therapeutic Drug Monitoring could represent a direct and useful tool to correctly identify non-compliant patients. Nevertheless, high throughput methods for the simultaneous monitoring of a wide panel of drugs in the same analysis are lacking and, furthermore, there is not a generally acknowledged "standard" matrix for this test (plasma or urine). In this work, we validated a UHPLC-MS/MS assay to quantify ten among the most used antihypertensive agents in urine samples, covering all the current classes: amlodipine, atenolol, clonidine, chlortalidone, doxazosin, hydrochlorothiazide, nifedipine, olmesartan, ramipril and telmisartan. Both standards and quality controls were prepared in urine matrix. Only 100μL of each sample were added with 40μL of internal standard and 860μL of water:acetonitrile 90:10, acidified with 0.05% formic acid. Chromatographic separation was performed on an Acquity® UPLC HSS T3 1.8μm 2.1×150mm column, with a gradient of water and acetonitrile, both added with 0.05% formic acid. Accuracy, intra-day and inter-day precision fitted FDA guidelines for all analytes, while matrix effects resulted reproducible among different urine lots. Method performances were tested on urine samples from hypertensive patients with good results. This simple analytical method could represent a useful tool for the management of antihypertensive therapy


Tosello F, Leone D, Laurent S, Veglio F, Milan A. Out of proportion proximal aortic remodeling: a subclinical marker of early vascular ageing? A systematic review Int J Cardiol. 2016 Nov 15;223:999-1006 

Abstract: Proximal aorta stiffens and dilates with aging. Aortic stiffening is a well known process, carrying prognostic implications. On the contrary, few data are available about proximal aorta dilatation. It is not known if "out of proportion" aortic remodeling, i.e. in excess for age, sex and body size, could be a marker of early vascular ageing; there is controversy on how it would be accelerated by classical risk factors or would associate with validated markers of cardiovascular organ damage. We conducted a systematic review in order to evaluate the determinants of proximal aortic dimensions, focusing on the association with arterial hypertension, cardiovascular risk factors and markers of organ damage. Age, gender and body size explain 40-50% of the variability of aortic dimensions; genetic predisposition accounts for nearly 20%. Among cardiovascular risk factors obesity and hypertension seem to be associated with faster outward aortic remodeling. Arterial hypertension would account for a 0.60-0.78 mm greater diameter at the ascending aorta. Moreover, in hypertension, left ventricular mass showed a strict association with aortic diameter in nearly all studies. Other classical risk factors for atherogenesis such as dyslipidemia and smoking showed a weak influence on proximal aortic dimensions. No study reported a greater aortic remodeling in diabetics. "Out of proportion" proximal aortic remodeling, could represent a subclinical marker of early vascular ageing, describing the cumulative influence of genetic predisposition, arterial hypertension and obesity.


Tosello F, Guala A, Leone D, Camporeale C, Bruno G, Ridolfi L, Veglio F, Milan A.       Central pressure appraisal: clinical validation of a subject-specific mathematical model.  PLoS One. 2016 Mar 4;11(3)

Abstract: Current evidence suggests that aortic blood pressure has a superior prognostic value with respect to brachial pressure for cardiovascular events, but direct measurement is not feasible in daily clinical practice. The aim of the present study is the clinical validation of a multiscale mathematical model for non-invasive appraisal of central blood pressure from subject-specific characteristics. A total of 51 young male were selected for the present study. Aortic systolic and diastolic pressure were estimated with a mathematical model and were compared to the most-used non-invasive validated technique (SphygmoCor device, AtCor Medical, Australia). SphygmoCor was calibrated through diastolic and systolic brachial pressure obtained with a sphygmomanometer, while model inputs consist of brachial pressure, height, weight, age, left-ventricular end-systolic and end-diastolic volumes, and data from a pulse wave velocity study. Model-estimated systolic and diastolic central blood pressures resulted to be significantly related to SphygmoCor-assessed central systolic (r = 0.65 p <0.0001) and diastolic (r = 0.84 p<0.0001) blood pressures. The model showed a significant overestimation of systolic pressure (+7.8 (-2.2;14) mmHg, p = 0.0003) and a significant underestimation of diastolic values (-3.2 (-7.5;1.6), p = 0.004), which imply a significant overestimation of central pulse pressure. Interestingly, model prediction errors mirror the mean errors reported in large meta-analysis characterizing the use of the SphygmoCor when non-invasive calibration is performed. In conclusion, multi-scale mathematical model predictions result to be significantly related to SphygmoCor ones. Model-predicted systolic and diastolic aortic pressure resulted in difference of less than 10 mmHg in the 51% and 84% of the subjects, respectively, when compared with SphygmoCor-obtained pressures.


Guala A, Camporeale C, Tosello F, Canuto C, Ridolfi L. Modelling and subject specific validation of the heart-arterial tree system Ann Biomed Eng 2015 jan; 43 (1):222-37


A modeling approach integrated with a novel subject-specific characterization is here proposed for the assessment of hemodynamic values of the arterial tree. A 1D model is adopted to characterize large-to-medium arteries, while the left ventricle, aortic valve and distal micro-circulation sectors are described by lumped submodels. A new velocity profile and a new formulation of the non-linear viscoelastic constitutive relation suitable for the {Q, A} modeling are also proposed. The model is firstly verified semi-quantitatively against literature data. A simple but effective procedure for obtaining subject-specific model characterization from non-invasive measurements is then designed. A detailed subject-specific validation against in vivo measurements from a population of six healthy young men is also performed. Several key quantities of heart dynamics-mean ejected flow, ejection fraction, and left-ventricular end-diastolic, end-systolic and stroke volumes-and the pressure waveforms (at the central, radial, brachial, femoral, and posterior tibial sites) are compared with measured data. Mean errors around 5 and 8%, obtained for the heart and arterial quantities, respectively, testify the effectiveness of the model and its subject-specific characterization

______________________________________________________________________________________________________________________________________________________________________________Tosello F, Florens E, Caruba T, Lebeller C, Mimoun L, Milan A, Fabiani JN, Boutouyrie P, Menasché P,Lillo-Lelouet A Atrial fibrillation at mid term afer bioprosthetic aortic valve replacement-implications for anti-thrombotic therapy Circ J. 2015;79(1):70-6 

Abstract BACKGROUND: Little is known about mid-term (3-month) postoperative atrial fibrillation (MT-POAF) in patients treated with bioprosthetic aortic valve replacement (BAVR). The aim of this study was to describe the natural history, identify the predictors and investigate the potential consequences in terms of anti-thrombotic therapy. METHODS AND RESULTS: During a longitudinal, prospective study, 219 patients were treated with BAVR early (7 days) and at mid-term postoperatively (30 and 90 days). POAF was monitored and risk factors were identified on logistic regression analysis. History of previous AF (OR, 3.08; 95% CI: 1.35-6.98), early POAF (OR, 5.93; 95% CI: 2.96-11.8), and BMI (per 5 kg/m(2): OR, 1.46; 95% CI: 1.03-2.09), were independent predictors for MT-POAF whereas sex, age and Euroscore were not. Results were identical when restricted to the 176 patients free from preoperative AF. In this subgroup, 36 patients (20.4%) had MT-POAF; 33 out of 174 (18.7%) would have required anticoagulation (CHA2DS2VASc score ≥ 1). Conversely, patients with BMI <27.7 and sinus rhythm at early follow-up had a very low risk of MT-POAF (OR, 0.16; 95% CI: 0.06-0.42). CONCLUSIONS: There was a higher than expected occurrence of MT-POAF in patients treated with BAVR, particularly in overweight patients with early POAF. This raises the question of implementing an anti-thrombotic therapy in these patients at higher risk of delayed atrial arrhythmia

______________________________________________________________________________________________________________________________________________________________________________ Milazzo V, Maule S, Di Stefano C, Tosello F, Totaro S, Veglio F, Milan A. Cardiac Organ Damage and arterial stiffness in autonomic failure: comparison with essential hypertension. Hypertension 2015 Dec;66(6):1168-75


Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m(2), P=0.59) and carotid-femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four-hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.


CONGRESSO SIIA Bologna 24-26 setttembre 2015  

Tosello F.; Leone D; Bruno G; Milan A; Veglio F. Pressione centrale, marker di "invecchiamento vascolare precoce": differenza in termini predittivi di danno d'organo rispetto alle pressioni periferiche in una coorte di ipertesi.  Università di Torino, Dipartimento di Scienze Mediche, Centro Ipertensione arteriosa, Ambulatorio di ecocardiografia

Background  Secondo la fisiopatologia e la visione corrente, le pressioni centrali sono una migliore stima del carico pressorio avvertito dal ventricolo di sinistra, dall'aorta prossimale, dal circolo cerebrale. La pressione centrale meglio descriverebbe l'effetto dell'invecchiamento vascolare precoce a livello degli organi bersaglio dell'ipertensione arteriosa. Aim Scopo di questa analisi è stato confrontare il potere predittivo delle pressioni centrale (cSBP, cPP) e periferica (pSBP, pPP) per danno d'organo cardio-vascolare in termini di massa ventricolare sinistra (MVS) e pulse wave velocity (cPWV). La popolazione è stata suddivisa in due fasce di età (cut off 40 anni) per indagare un eventuale effetto dell'età nel influenzare la differenza in termini di predittività tra i valori pressori centrali e periferici. Metodi Sono stati inclusi 854 ipertesi consequenzialmente valutati nel Laboratorio di Ecocardiografia del Centro Ipertensione dell'Università di Torino. Nella stessa seduta sono state valutate le pressioni a livello brachiale e stimate le pressioni a livello centrale tramite metodica validata con funzione di trasferimento applicata alla forma d'onda pressoria registrata a livello radiale (SphygmoCor). I soggetti sono stati sottoposti nell'arco della stessa sessione ad un ecocardiogramma TT per la valutazione del danno d'organo cardiaco e alla valutazione tonometrica carotidea e femorale per la stima della velocità dell'onda di polso carotido-femorale. Le pressioni sistolica centrale e periferica sono state alternativamente cimentate in modelli statistici di regressione multipla basali e corretti per età, sesso, peso, altezza, frequenza cardiaca, terapia antipertensiva, fumo, diabete, dislipidemia, confrontando i valori predittivi dei modelli (R2) con test Z. Risultati L'età media della popolazione era di 52.7±13.5 anni, con pressione periferica di 139.1±18.1/81.8±11.6 mmHg, e pPP di 57.3±13 mmHg; l'amplificazione dell'onda pulsatoria media era del 31.7±15.8%: tale dato deriva dalla stima delle pressioni aortiche di 127.1±17.7/83±11.7 mmHg, con una cPP di 44±12.1 mmHg. Il 77% della popolazione era in terapia antipertensiva attiva (607 pts). La MVS media era di 90.3±23.4  g/m2, e la velocità dell'onda pulsatoria di 7.82±1.9  m/s. Il 16.3% della popolazione (139 pz) era caratterizzato da ipertrofia ventricolare sinistra e l'11.6% aveva una cfPWV > 10 m/s (99 pz). La differenza in termini predittivi di danno d'organo emerge nelle analisi sulla sottopopolazione dei giovani (<40 anni, 154 ipertesi). In questa coorte  la cSBP arriva a spiegare il 3.6% in più (rispetto ai modelli includenti la pSBP) della variabilità della MVS (R2 0.52 vs 0.48; Z=2.14, p=0.031) e il 4.1% in più della variabilità della cfPWV (R2 0.24 vs 0.20; Z=2.28, p=0.022). La differenza in termini predittivi di danno d'organo tra pressioni pulsatorie centrali e periferiche è ancora maggiore: la  cPP spiega il 5.7% in più del danno in termini di MVS (R2 0.44 vs 0.38; Z=2.2; p=0.028); e il 4.7% in più in termini di cfPWV (Z 1.99; p=0.045). Conclusioni Abbiamo dimostrato una miglior predittività delle pressioni centrali sistolica e pulsatoria per danno d'organo cardiaco e vascolare nella coorte di soggetti ipertesi al di sotto dei 40 anni, coorte nella quale è maggiore l'amplificazione dell'onda pressoria. La valutazione dell'emodinamica centrale come marker di "early vascular ageing" in ipertesi giovani adulti, permette di identificare più accuratamente i soggetti portatori  di danno d'organo. 


Relatore a "XVIII CORSO DI PERFEZIONAMENTO CLINICO SULL'IPERTENSIONE ARTERIOSA 25-27 ottobre 2017 Aula Lenti Città della salute e della Scienza "Misurazione pressione centrale e stiffness arteriosa"

Relatore Corso di Ecocardiografia di base  novembre 2016 Torino Segreteria Scientifica Dr Alberto Milan

RElatore Relatore Corso Ecografia in Emergenza Urgenza SIMEU Cuneo 1-2 dicembre 2016 e marzo 2017

Relatore a "XVII CORSO DI PERFEZIONAMENTO CLINICO SULL'IPERTENSIONE ARTERIOSA" 26-27-28 ottobre 2016  Aula Lenti Città della Scienza e della Salute "Misurazione pressione centrale e stiffness arteriosa"

Relatore Corso di Ecocardiografia di base 26-27 maggio 2016 Torino Segreteria Scientifica Dr Alberto Milan

Relatore Mountain School Medicina Interna SIMI 19-20-21 maggio 2016 Camoglieres Cuneo

Relatore Corso Ecografia in Emergenza Urgenza SIMEU Cuneo 10-11 giugno 2016 direttore Drssa Paola CAsoli

Relatore a Congresso SIIA (Società Italiana Ipertensione Arteriosa) 2015 Bologna Presentazione orale II° Premio Giovani Ricercatori "Pressione centrale, marker di "invecchiamento vascolare precoce": differenza in termini predittivi di danno d'organo rispetto alle pressioni periferiche in una coorte di ipertesi"

Relatore a "XVI CORSO DI PERFEZIONAMENTO CLINICO SULL'IPERTENSIONE ARTERIOSA" 28-29-30 ottobre 2015  Centro Congressi Torino Incontra sessione "Misurazione pressione centrale"

Relatore Corso di Ecocardiografia di base 12-13 novembre 2015 Torino Segreteria Scientifica Dr Alberto Milan

Relatore Corso Ecografia in Emergenza Urgenza SIMEU Cuneo 27-28 novembre 2015 direttore Drssa Paola Molino


D-Day 2016 dottorato di Fisiopatologia Medica, 3 Febbraio 2016, Aula Lenti. AOU Città della Salute e della Scienza

D-Day 2015 dottorato di Fisiopatologia Medica, Febbraio 2015, Aula Favretto. AOU Città della Salute e della Scienza

Ultimo aggiornamento: 06/11/2017 11:27
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