Publications by authors named "Enrico G Caiani"

61 Publications

Evaluation of Cardiac Circadian Rhythm Deconditioning Induced by 5-to-60 Days of Head-Down Bed Rest.

Front Physiol 2020 13;11:612188. Epub 2021 Jan 13.

Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.

Head-down tilt (HDT) bed rest elicits changes in cardiac circadian rhythms, generating possible adverse health outcomes such as increased arrhythmic risk. Our aim was to study the impact of HDT duration on the circadian rhythms of heart beat (RR) and ventricular repolarization (QTend) duration intervals from 24-h Holter ECG recordings acquired in 63 subjects during six different HDT bed rest campaigns of different duration (two 5-day, two 21-day, and two 60-day). Circadian rhythms of RR and QTend intervals series were evaluated by Cosinor analysis, resulting in a value of midline (MESOR), oscillation amplitude (OA) and acrophase (φ). In addition, the QTc (with Bazett correction) was computed, and day-time, night-time, maximum and minimum RR, QTend and QTc intervals were calculated. Statistical analysis was conducted, comparing: (1) the effects at 5 (HDT5), 21 (HDT21) and 58 (HDT58) days of HDT with baseline (PRE); (2) trends in recovery period at post-HDT epochs (R) in 5-day, 21-day, and 60-day HDT separately vs. PRE; (3) differences at R + 0 due to bed rest duration; (4) changes between the last HDT acquisition and the respective R + 0 in 5-day, 21-day, and 60-day HDT. During HDT, major changes were observed at HDT5, with increased RR and QTend intervals' MESOR, mostly related to day-time lengthening and increased minima, while the QTc shortened. Afterward, a progressive trend toward baseline values was observed with HDT progression. Additionally, the φ anticipated, and the OA was reduced during HDT, decreasing system's ability to react to incoming stimuli. Consequently, the restoration of the orthostatic position elicited the shortening of RR and QTend intervals together with QTc prolongation, notwithstanding the period spent in HDT. However, the magnitude of post-HDT changes, as well as the difference between the last HDT day and R + 0, showed a trend to increase with increasing HDT duration, and 5/7 days were not sufficient for recovering after 60-day HDT. Additionally, the φ postponed and the OA significantly increased at R + 0 compared to PRE after 5-day and 60-day HDT, possibly increasing the arrhythmic risk. These results provide evidence that continuous monitoring of astronauts' circadian rhythms, and further investigations on possible measures for counteracting the observed modifications, will be key for future missions including long periods of weightlessness and gravity transitions, for preserving astronauts' health and mission success.
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http://dx.doi.org/10.3389/fphys.2020.612188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838678PMC
January 2021

Cardiac adaptations to 60 day head-down-tilt bed rest deconditioning. Findings from the AGBRESA study.

ESC Heart Fail 2021 Feb 15;8(1):729-744. Epub 2020 Nov 15.

Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany.

Aims: Reduced physical activity increases the risk of heart failure; however, non-invasive methodologies detecting subclinical changes in myocardial function are not available. We hypothesized that myocardial, left ventricular, systolic strain measurements could capture subtle abnormalities in myocardial function secondary to physical inactivity.

Methods And Results: In the AGBRESA study, which assessed artificial gravity through centrifugation as potential countermeasure for space travel, 24 healthy persons (eight women) were submitted to 60 day strict -6° head-down-tilt bed rest. Participants were assigned to three groups of eight subjects: a control group, continuous artificial gravity training on a short-arm centrifuge (30 min/day), or intermittent centrifugation (6 × 5 min/day). We assessed cardiac morphology, function, strain, and haemodynamics by cardiac magnetic resonance imaging (MRI) and echocardiography. We observed no differences between groups and, therefore, conducted a pooled analysis. Consistent with deconditioning, resting heart rate (∆8.3 ± 6.3 b.p.m., P < 0.0001), orthostatic heart rate responses (∆22.8 ± 19.7 b.p.m., P < 0.0001), and diastolic blood pressure (∆8.8 ± 6.6 mmHg, P < 0.0001) increased, whereas cardiac output (∆-0.56 ± 0.94 L/min, P = 0.0096) decreased during bed rest. Left ventricular mass index obtained by MRI did not change. Echocardiographic left ventricular, systolic, global longitudinal strain (∆1.8 ± 1.83%, P < 0.0001) decreased, whereas left ventricular, systolic, global MRI circumferential strain increased not significantly (∆-0.68 ± 1.85%, P = 0.0843). MRI values rapidly returned to baseline during recovery.

Conclusion: Prolonged head-down-tilt bed rest provokes changes in cardiac function, particularly strain measurements, that appear functional rather than mediated through cardiac remodelling. Thus, strain measurements are of limited utility in assessing influences of physical deconditioning or exercise interventions on cardiac function.
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http://dx.doi.org/10.1002/ehf2.13103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835618PMC
February 2021

Predictive Value of Pre-Operative 2D and 3D Transthoracic Echocardiography in Patients Undergoing Mitral Valve Repair: Long Term Follow Up of Mitral Valve Regurgitation Recurrence and Heart Chamber Remodeling.

J Cardiovasc Dev Dis 2020 Oct 20;7(4). Epub 2020 Oct 20.

Centro Cardiologico Monzino, IRCCS, 20138 Milan, Italy.

The "ideal" management of asymptomatic severe mitral regurgitation (MR) in valve prolapse (MVP) is still debated. The aims of this study were to identify pre-operatory parameters predictive of residual MR and of early and long-term favorable remodeling after MVP repair. We included 295 patients who underwent MV repair for MVP with pre-operatory two- and three-dimensional transthoracic echocardiography (2DTTE and 3DTTE) and 6-months (6M) and 3-years (3Y) follow-up 2DTTE. MVP was classified by 3DTTE as simple or complex and surgical procedures as simple or complex. Pre-operative echo parameters were compared to post-operative values at 6M and 3Y. Patients were divided into Group 1 (6M-MR < 2) and Group 2 (6M-MR ≥ 2), and predictors of MR 2 were investigated. MVP was simple in 178/295 pts, and 94% underwent simple procedures, while in only 42/117 (36%) of complex MVP a simple procedure was performed. A significant relation among prolapse anatomy, surgical procedures and residual MR was found. Post-operative MR ≥ 2 was present in 9.8%: complex MVP undergoing complex procedures had twice the percentage of MR ≥ 2 vs. simple MVP and simple procedures. MVP complexity resulted independent predictor of 6M-MR ≥ 2. Favorable cardiac remodeling, initially found in all cases, was maintained only in MR < 2 at 3Y. Pre-operative 3DTTE MVP morphology identifies pts undergoing simple or complex procedures predicting MR recurrence and favorable cardiac remodeling.
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http://dx.doi.org/10.3390/jcdd7040046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712008PMC
October 2020

Cardiovascular adaptation to simulated microgravity and countermeasure efficacy assessed by ballistocardiography and seismocardiography.

Sci Rep 2020 10 19;10(1):17694. Epub 2020 Oct 19.

LPHYS, Université Libre de Bruxelles, Brussels, Belgium.

Head-down bed rest (HDBR) reproduces the cardiovascular effects of microgravity. We tested the hypothesis that regular high-intensity physical exercise (JUMP) could prevent this cardiovascular deconditioning, which could be detected using seismocardiography (SCG) and ballistocardiography (BCG). 23 healthy males were exposed to 60-day HDBR: 12 in a physical exercise group (JUMP), the others in a control group (CTRL). SCG and BCG were measured during supine controlled breathing protocols. From the linear and rotational SCG/BCG signals, the integral of kinetic energy ([Formula: see text]) was computed on each dimension over the cardiac cycle. At the end of HDBR, BCG rotational [Formula: see text] and SCG transversal [Formula: see text] decreased similarly for all participants (- 40% and - 44%, respectively, p < 0.05), and so did orthostatic tolerance (- 58%, p < 0.01). Resting heart rate decreased in JUMP (- 10%, p < 0.01), but not in CTRL. BCG linear [Formula: see text] decreased in CTRL (- 50%, p < 0.05), but not in JUMP. The changes in the systolic component of BCG linear iK were correlated to those in stroke volume and V max (R = 0.44 and 0.47, respectively, p < 0.05). JUMP was less affected by cardiovascular deconditioning, which could be detected by BCG in agreement with standard markers of the cardiovascular condition. This shows the potential of BCG to easily monitor cardiac deconditioning.
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http://dx.doi.org/10.1038/s41598-020-74150-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573608PMC
October 2020

Mobile health applications for managing atrial fibrillation for healthcare professionals and patients: a systematic review.

Europace 2020 Aug 27. Epub 2020 Aug 27.

School of Medicine, University of Belgrade, Belgrade, Serbia.

Aims: A plethora of mobile health applications (m-health apps) to support healthcare are available for both patients and healthcare professionals (HCPs) but content and quality vary considerably and few have undergone formal assessment. The aim is to systematically review the literature on m-health apps for managing atrial fibrillation (AF) that examine the impact on knowledge of AF, patient and HCP behaviour, patients' quality-of-life, and user engagement.

Methods And Results: MEDLINE, EMBASE, CINAHL, and PsychInfo were searched from 1 January 2005 to 5 September 2019, with hand-searching of clinical trial registers and grey literature. Studies were eligible for inclusion if they reported changes in any of the following: (i) knowledge of AF; (ii) provider behaviour (e.g. guideline adherence); (iii) patient behaviour (e.g. medication adherence); (iv) patient quality-of-life; and (v) user engagement. Two reviewers independently assessed articles for eligibility. A narrative review was undertaken as included studies varied widely in their design, interventions, comparators, and outcomes. Seven studies were included; six m-health apps aimed at patients and one at HCPs. Mobile health apps ranged widely in design, features, and method of delivery. Four studies reported patient knowledge of AF; three demonstrated significant knowledge improvement post-intervention or compared to usual care. One study reported greater HCP adherence to oral anticoagulation guidelines after m-health app implementation. Two studies reported on patient medication adherence and quality-of-life; both showed improved quality-of-life post-intervention but only one observed increased adherence. Regarding user engagement, five studies reported patient perspectives on usability, three on acceptability, and one on feasibility; overall all m-health apps were rated positively.

Conclusion: Mobile health apps demonstrate improvements in patient knowledge, behaviour, and quality of life. Studies formally evaluating the impact of m-health on HCP behaviour are scarce and larger-scale studies with representative patient cohorts, appropriate comparators, and longer-term assessment of the impact of m-health apps are warranted.
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http://dx.doi.org/10.1093/europace/euaa269DOI Listing
August 2020

Analysis of changes in cardiac circadian rhythms of RR and QT induced by a 60-day head-down bed rest with and without nutritional countermeasure.

Eur J Appl Physiol 2020 Jul 3;120(7):1699-1710. Epub 2020 Jun 3.

Department of Electronics, Information and Bioengineering, Politecnico di Milano, P.zza L. da Vinci 32, 20133, Milan, Italy.

Purpose: Prolonged weightlessness exposure generates cardiovascular deconditioning, with potential implications on ECG circadian rhythms. Head-down (- 6°) tilt (HDT) bed rest is a ground-based analogue model for simulating the effects of reduced motor activity and fluids redistribution occurring during spaceflight. Our aim was to evaluate the impact of 60-day HDT on the circadianity of RR and ventricular repolarization (QTend) intervals extracted from 24-h Holter ECG recordings, scheduled 9 days before HDT (BDC-9), the 5th (HDT5), 21st (HDT21) and 58th (HDT58) day of HDT, the 1st (R + 0) and 8th (R + 7) day after HDT. Also, the effectiveness of a nutritional countermeasure (CM) in mitigating the HDT-related changes was tested.

Methods: RR and QTend circadian rhythms were evaluated by Cosinor analysis, resulting in maximum and minimum values, MESOR (a rhythm-adjusted mean), oscillation amplitude (OA, half variation within a night-day cycle), and acrophase (φ, the time at which the fitting sinusoid's amplitude is maximal) values.

Results: RR and QTend MESOR increased at HDT5, and the OA was reduced along the HDT period, mainly due to the increase of the minima. At R + 0, QTend OA increased, particularly in the control group. The φ slightly anticipated during HDT and was delayed at R + 0.

Conclusion: 60-Day HDT affects the characteristics of cardiac circadian rhythm by altering the physiological daily cycle of RR and QTend intervals. Scheduled day-night cycle and feeding time were maintained during the experiment, thus inferring the role of changes in the gravitational stimulus to determine these variations. The applied nutritional countermeasure did not show effectiveness in preventing such changes.
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http://dx.doi.org/10.1007/s00421-020-04404-7DOI Listing
July 2020

Implementing the new European Regulations on medical devices-clinical responsibilities for evidence-based practice: a report from the Regulatory Affairs Committee of the European Society of Cardiology.

Eur Heart J 2020 07;41(27):2589-2596

Cardiovascular Program and CiberCV, IR-Hospital de la Santa Creu i Sant Pau, Convent-ICCC, C/ Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.

The new European Union (EU) law governing the regulatory approval of medical devices that entered into force in May 2017 will now take effect from 26 May 2021. Here, we consider how it will change daily practice for cardiologists, cardiac surgeons, and healthcare professionals. Clinical evidence for any high-risk device must be reported by the manufacturer in a Summary of Safety and Clinical Performance (SSCP) that will be publicly available in the European Union Database on Medical Devices (Eudamed) maintained by the European Commission; this will facilitate evidence-based choices of which devices to recommend. Hospitals must record all device implantations, and each high-risk device will be trackable by Unique Device Identification (UDI). Important new roles are envisaged for clinicians, scientists, and engineers in EU Expert Panels-in particular to scrutinize clinical data submitted by manufacturers for certain high-risk devices and the evaluations of that data made by notified bodies. They will advise manufacturers on the design of their clinical studies and recommend to regulators when new technical specifications or guidance are needed. Physicians should support post-market surveillance by reporting adverse events and by contributing to comprehensive medical device registries. A second law on In Vitro Diagnostic Medical Devices will take effect from 2022. We encourage all healthcare professionals to contribute proactively to these new systems, in order to enhance the efficacy and safety of high-risk devices and to promote equitable access to effective innovations. The European Society of Cardiology will continue to advise EU regulators on appropriate clinical evaluation of high-risk devices.
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http://dx.doi.org/10.1093/eurheartj/ehaa382DOI Listing
July 2020

Long-Term Microgravity Exposure Increases ECG Repolarization Instability Manifested by Low-Frequency Oscillations of T-Wave Vector.

Front Physiol 2019 17;10:1510. Epub 2019 Dec 17.

BSICoS Group, Aragón Institute of Engineering Research, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.

Ventricular arrhythmias and sudden cardiac death during long-term space missions are a major concern for space agencies. Long-duration spaceflight and its ground-based analog head-down bed rest (HDBR) have been reported to markedly alter autonomic and cardiac functioning, particularly affecting ventricular repolarization of the electrocardiogram (ECG). In this study, novel methods are developed, departing from previously published methodologies, to quantify the index of Periodic Repolarization Dynamics (PRD), an arrhythmic risk marker that characterizes sympathetically-mediated low-frequency oscillations in the T-wave vector. PRD is evaluated in ECGs from 42 volunteers at rest and during an orthostatic tilt table test recorded before and after 60-day -6° HDBR. Our results indicate that tilt test, on top of enhancing sympathetic regulation of heart rate, notably increases PRD, both before and after HDBR, thus supporting previous evidence on PRD being an indicator of sympathetic modulation of ventricular repolarization. Importantly, long-term microgravity exposure is shown to lead to significant increases in PRD, both when evaluated at rest and, even more notably, in response to tilt test. The extent of microgravity-induced changes in PRD has been associated with arrhythmic risk in prior studies. An exercise-based, but not a nutrition-based, countermeasure is able to partially reverse microgravity-induced effects on PRD. In conclusion, long-term exposure to microgravity conditions leads to elevated low-frequency oscillations of ventricular repolarization, which are potentiated following sympathetic stimulation and are related to increased risk for repolarization instabilities and arrhythmias. Tested countermeasures are only partially effective in counteracting microgravity effects.
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http://dx.doi.org/10.3389/fphys.2019.01510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928004PMC
December 2019

Assessment of ventricular repolarization instability in terms of T-wave alternans induced by head-down bed-rest immobilization.

Physiol Meas 2019 10 30;40(10):104001. Epub 2019 Oct 30.

Department of Biomedical Engineering, Lund University, Lund, Sweden. BSICoS Group, Instituto de Investigación en Ingeniería de Aragón (I3A), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.

Objective: To assess the effects of different durations of simulated microgravity exposure on ventricular repolarization (VR) in terms of T-wave alternans (TWA) as well as to test whether an increase in VR heterogeneity could be detected once normal gravity was restored.

Approach: A total of 63 healthy volunteers were recruited in several head-down bed-rest (HDBR) experiments in the context of the European Space Agency bed-rest strategy. TWA is evaluated during the night period using ambulatory ECG recordings, before, during and after long- (60 d), mid- (21 d) and short- (5 d) duration HDBR by the long-term averaging technique.

Main Results: 5-21 d of exposure to simulated microgravity by means of the HDBR model do not lead to a significant increase of cardiac electrical instability in healthy myocardial substrates up to the point of eliciting TWA on the surface ECG. However, TWA indices increased after long-term HDBR exposure, once normal gravity was re-established, indicative of incipient electrical instability on VR at the conclusion of 60 d of HDBR.

Significance: The results of this work underline the importance of focusing future research on immediate effects after long-term microgravity exposure, both simulated by HDBR or from space mission scenarios, once partial gravity conditions are re-established. A deeper insight in the understanding of human body reactions in these scenarios results crucial in the design of future long-duration spaceflight missions, to mitigate any potential risk that can limit astronaut's performance.
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http://dx.doi.org/10.1088/1361-6579/ab4c18DOI Listing
October 2019

ESC e-Cardiology Working Group Position Paper: Overcoming challenges in digital health implementation in cardiovascular medicine.

Eur J Prev Cardiol 2019 07 27;26(11):1166-1177. Epub 2019 Mar 27.

8 Department of Cardiology, Leiden University Medical Centre (LUMC), The Netherlands.

Cardiovascular disease is one of the main causes of morbidity and mortality worldwide. Despite the availability of highly effective treatments, the contemporary burden of disease remains huge. Digital health interventions hold promise to improve further the quality and experience of cardiovascular care. This position paper provides a brief overview of currently existing digital health applications in different cardiovascular disease settings. It provides the reader with the most relevant challenges for their large-scale deployment in Europe. The potential role of different stakeholders and related challenges are identified, and the key points suggestions on how to proceed are given. This position paper was developed by the European Society of Cardiology (ESC) e-Cardiology working group, in close collaboration with the ESC Digital Health Committee, the European Association of Preventive Cardiology, the European Heart Rhythm Association, the Heart Failure Association, the European Association of Cardiovascular Imaging, the Acute Cardiovascular Care Association, the European Association of Percutaneous Cardiovascular Interventions, the Association of Cardiovascular Nursing and Allied Professions and the Council on Hypertension. It relates to the ESC's action plan and mission to play a pro-active role in all aspects of the e-health agenda in support of cardiovascular health in Europe and aims to be used as guiding document for cardiologists and other relevant stakeholders in the field of digital health.
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http://dx.doi.org/10.1177/2047487319832394DOI Listing
July 2019

The need for transparency of clinical evidence for medical devices in Europe.

Lancet 2018 08 17;392(10146):521-530. Epub 2018 Jul 17.

Department of Cardiovascular Sciences, Katholieke University Leuven, Leuven, Belgium.

To use medical devices rationally, health-care professionals must base their choices of which devices to recommend for individual patients on an objective appraisal of their safety and clinical efficacy. The evidence submitted by manufacturers when seeking approval of their high-risk devices must be publicly available, including technical performance and premarket clinical studies. Giving physicians access to this information supplements the peer-reviewed scientific literature and might be essential for comparing alternative devices within any class. Interested patients should be encouraged to review the evidence for any device that has been recommended for them. The new EU law on medical devices states that the manufacturer is to prepare a summary of the evidence for any implantable or high-risk device. Defining its content, however, has been delegated to implementing legislation, which is now being considered. From a clinical perspective, it is imperative that all evidence reviewed by notified bodies and regulatory authorities is disclosed-with the exception, if justified, only of technical specifications that are considered confidential or manufacturing details that are protected as intellectual property-and public access to this evidence must be guaranteed by EU law. From ethical and other perspectives, there are no grounds for less clinical evidence being available to health-care professionals about the medical devices that they use than is already available for new pharmaceutical products. Full transparency is needed; without it, informed decisions relating to the use of new medical devices will remain impossible.
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http://dx.doi.org/10.1016/S0140-6736(18)31270-4DOI Listing
August 2018

Quantification of Ventricular Repolarization Variation for Sudden Cardiac Death Risk Stratification in Atrial Fibrillation.

IEEE J Biomed Health Inform 2019 05 28;23(3):1049-1057. Epub 2018 Jun 28.

Objective: Atrial fibrillation (AF) rhythm gives rise to an irregular response in ventricular activity, preventing the use of standard ECG-derived risk markers based on ventricular repolarization heterogeneity under this particular condition. In this study, we proposed new indices to quantify repolarization variations in AF patients, assessing their stratification performance in a chronic heart failure population with AF.

Methods: We developed a method based on a selective bin averaging technique. Consecutive beats preceded by a similar RR interval were selected, from which the average variation within the ST-T complex for each RR range was computed. We proposed two sets of indices: 1) the 2-beat index of ventricular repolarization variation, ( I), computed from pairs of stable consecutive beats; and 2) the 3-beat indices of ventricular repolarization variation, computed in triplets of stable consecutive beats ( I).

Results: These indices showed a significant association with sudden cardiac death (SCD) outcome in the study population. In addition, risk assessment based on the combination of the proposed indices improved stratification performance compared to their individual potential.

Conclusion: Patients with enhanced ventricular repolarization variation computed in terms of the proposed indices were successfully associated to a higher SCD incidence in our study population, evidencing their prognostic value.

Significance: using a simple ambulatory ECG recording, it is possible to stratify AF patients at risk of SCD, which may help cardiologists in adopting most effective therapeutic strategies, with a positive impact in both the patient and healthcare systems.
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http://dx.doi.org/10.1109/JBHI.2018.2851299DOI Listing
May 2019

Post-Ventricular Premature Contraction Phase Correction Improves the Predictive Value of Average T-Wave Alternans in Ambulatory ECG Recordings.

IEEE Trans Biomed Eng 2018 03;65(3):635-644

Objective: We proposed and evaluated a method for correcting possible phase shifts provoked by the presence of ventricular premature contractions (VPCs) for a better assessment of T-wave alternans (TWA).  Methods: First, we synthesized ECG signals with artificial TWA in the presence of different noise sources. Then, we assessed the prognostic value for sudden cardiac death (SCD) of the long-term average of TWA amplitude (the index of average alternans, ) in ambulatory ECG signals from congestive heart failure (CHF) and evaluated whether it is sensitive to the presence of VPCs.

Results: The inclusion of the phase correction after VPC in the processing always improved estimation accuracy of the under different noisy conditions and regardless of the number of the VPCs included in the sequence. It also presented a positive impact on the prognostic value of with increased hazard ratios (from 17% to 29%, depending of the scenario) in comparison to the noninclusion of this step.

Conclusion: The proposed methodology for estimation, which corrects for the possible phase reversal on TWA after the presence of VPCs, represents a robust TWA estimation approach with a significant impact on the prognostic value of for SCD stratification in CHF patients.

Significance: An accurate TWA estimation has a potential direct clinical impact on noninvasive SCD stratification, allowing better identification of patients at higher risk and helping clinicians in adopting the most appropriate therapeutic strategy.
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http://dx.doi.org/10.1109/TBME.2017.2711645DOI Listing
March 2018

Human Pathophysiological Adaptations to the Space Environment.

Front Physiol 2017 2;8:547. Epub 2017 Aug 2.

MedLab, Institute of Life Sciences, Scuola Superiore Sant'AnnaPisa, Italy.

Space is an extreme environment for the human body, where during long-term missions microgravity and high radiation levels represent major threats to crew health. Intriguingly, space flight (SF) imposes on the body of highly selected, well-trained, and healthy individuals (astronauts and cosmonauts) pathophysiological adaptive changes akin to an accelerated aging process and to some diseases. Such effects, becoming manifest over a time span of weeks (i.e., cardiovascular deconditioning) to months (i.e., loss of bone density and muscle atrophy) of exposure to weightlessness, can be reduced through proper countermeasures during SF and in due time are mostly reversible after landing. Based on these considerations, it is increasingly accepted that SF might provide a mechanistic insight into certain pathophysiological processes, a concept of interest to pre-nosological medicine. In this article, we will review the main stress factors encountered in space and their impact on the human body and will also discuss the possible lessons learned with space exploration in reference to human health on Earth. In fact, this is a productive, cross-fertilized, endeavor in which studies performed on Earth yield countermeasures for protection of space crew health, and space research is translated into health measures for Earth-bound population.
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http://dx.doi.org/10.3389/fphys.2017.00547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539130PMC
August 2017

Anatomical Regurgitant Orifice Detection and Quantification from 3-D Echocardiographic Images.

Ultrasound Med Biol 2017 05 16;43(5):1048-1057. Epub 2017 Feb 16.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.

The vena contracta and effective regurgitant orifice area (EROA) are currently used for the clinical assessment of mitral regurgitation (MR) from 2-D color Doppler imaging. In addition to being highly user dependent and having low repeatability, these methods do not represent accurately the anatomic regurgitant orifice (ARO), which affects the adequate assessment of MR patients. We propose a novel method for semi-automatic detection and quantitative assessment of the 3-D ARO shape from 3-D transesophageal echocardiographic images. The algorithm was tested on a set of 25 patients with MR, and compared with EROA for validation. Results indicate the robustness of the proposed approach, with low variability in relation to different settings of user-defined segmentation parameters. Although EROA and ARO exhibited a good correlation (r = 0.8), relatively large biases were measured, indicating that EROA probably underestimates the real shape and size of the regurgitant orifice. Along with the higher reproducibility of the proposed approach, this highlights the limitations of current clinical approaches and underlines the importance of accurate assessment of the ARO shape for diagnosis and treatment in MR patients.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2016.12.017DOI Listing
May 2017

Discussion of "Computational Electrocardiography: Revisiting Holter ECG Monitoring".

Methods Inf Med 2016 Aug 13;55(4):312-21. Epub 2016 Jul 13.

Herbert Witte, Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Friedrich-Schiller University, Bachstraße 18, 07743 Jena, E-mail:

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Computational Electrocardiography: Revisiting Holter ECG Monitoring" written by Thomas M. Deserno and Nikolaus Marx. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the paper of Deserno and Marx. In subsequent issues the discussion can continue through letters to the editor.
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http://dx.doi.org/10.3414/ME15-15-0009DOI Listing
August 2016

Segmentation of the left ventricular endocardium from magnetic resonance images by using different statistical shape models.

J Electrocardiol 2016 May-Jun;49(3):383-91. Epub 2016 Mar 9.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Italy.

We evaluate in this paper different strategies for the construction of a statistical shape model (SSM) of the left ventricle (LV) to be used for segmentation in cardiac magnetic resonance (CMR) images. From a large database of LV surfaces obtained throughout the cardiac cycle from 3D echocardiographic (3DE) LV images, different LV shape models were built by varying the considered phase in the cardiac cycle and the registration procedure employed for surface alignment. Principal component analysis was computed to describe the statistical variability of the SSMs, which were then deformed by applying an active shape model (ASM) approach to segment the LV endocardium in CMR images of 45 patients. Segmentation performance was evaluated by comparing LV volumes derived by ASM segmentation with different SSMs and those obtained by manual tracing, considered as a reference. A high correlation (r(2)>0.92) was found in all cases, with better results when using the SSM models comprising more than one frame of the cardiac cycle.
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http://dx.doi.org/10.1016/j.jelectrocard.2016.03.017DOI Listing
November 2017

Comparison of Image Processing Techniques for Nonviable Tissue Quantification in Late Gadolinium Enhancement Cardiac Magnetic Resonance Images.

J Thorac Imaging 2016 May;31(3):168-76

*Centro Cardiologico Monzino, IRCCS †Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy.

Purpose: The aim of this study was to compare the performance of quantitative methods, either semiautomated or automated, for left ventricular (LV) nonviable tissue analysis from cardiac magnetic resonance late gadolinium enhancement (CMR-LGE) images.

Materials And Methods: The investigated segmentation techniques were: (i) n-standard deviations thresholding; (ii) full width at half maximum thresholding; (iii) Gaussian mixture model classification; and (iv) fuzzy c-means clustering. These algorithms were applied either in each short axis slice (single-slice approach) or globally considering the entire short-axis stack covering the LV (global approach). CMR-LGE images from 20 patients with ischemic cardiomyopathy were retrospectively selected, and results from each technique were assessed against manual tracing.

Results: All methods provided comparable performance in terms of accuracy in scar detection, computation of local transmurality, and high correlation in scar mass compared with the manual technique. In general, no significant difference between single-slice and global approach was noted. The reproducibility of manual and investigated techniques was confirmed in all cases with slightly lower results for the nSD approach.

Conclusions: Automated techniques resulted in accurate and reproducible evaluation of LV scars from CMR-LGE in ischemic patients with performance similar to the manual technique. Their application could minimize user interaction and computational time, even when compared with semiautomated approaches.
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http://dx.doi.org/10.1097/RTI.0000000000000206DOI Listing
May 2016

An in-silico analysis of the effect of heart position and orientation on the ECG morphology and vectorcardiogram parameters in patients with heart failure and intraventricular conduction defects.

J Electrocardiol 2015 Jul-Aug;48(4):617-25. Epub 2015 May 8.

Center for Computational Medicine in Cardiology, Institute of Computational Science, Università della Svizzera italiana, Lugano, Switzerland; Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland.

Aim: The aim of this study was to investigate the influence of geometrical factors on the ECG morphology and vectorcardiogram (VCG) parameters.

Methods: Patient-tailored models based on five heart-failure patients with intraventricular conduction defects (IVCDs) were created. The heart was shifted up to 6 cm to the left, right, up, and down and rotated ±30° around the anteroposterior axis. Precordial electrodes were shifted 3 cm down.

Results: Geometry modifications strongly altered ECG notching/slurring and intrinsicoid deflection time. Maximum VCG parameter changes were small for QRS duration (-6% to +10%) and QRS-T angle (-6% to +3%), but considerable for QRS amplitude (-36% to +59%), QRS area (-37% to +42%), T-wave amplitude (-41% to +36%), and T-wave area (-42% to +33%).

Conclusion: The position of the heart with respect to the electrodes is an important factor determining notching/slurring and voltage-dependent parameters and therefore must be considered for accurate diagnosis of IVCDs.
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http://dx.doi.org/10.1016/j.jelectrocard.2015.05.004DOI Listing
March 2016

Semi-automated segmentation and quantification of mitral annulus and leaflets from transesophageal 3-D echocardiographic images.

Ultrasound Med Biol 2015 Jan 22;41(1):251-67. Epub 2014 Oct 22.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy. Electronic address:

Quantification of three-dimensional (3-D) morphology of the mitral valve (MV) using real-time 3-D transesophageal echocardiography (RT3-D TEE) has proved to be a valuable tool for the assessment of MV pathologies, but of limited use in clinical practice because it relies on user-intensive approaches. This study presents a new algorithm for the segmentation and morphologic quantification of the mitral annulus (MA) and mitral leaflets (ML) in closed valve configuration from RT3-D TEE volumes. Following initialization, the MA and the ML and the coaptation line (CL) are automatically obtained in 3-D. Validation with manual tracings was performed on 33 patients, resulting in segmentation errors in the order of 0.7 mm and 0.6 mm for the MA and ML segmentation, in addition to good intra- and inter-observer reproducibility (coefficients of variation below 12% and 15%, respectively). The ability of the algorithm to assess different MV pathologies as well as repaired valves with implanted annular rings was also explored. The reported performance of the proposed fast, semi-automated MA and ML quantification makes it promising for future applications in clinical settings such as the operating room, where obtaining results in short time is important.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2014.09.001DOI Listing
January 2015

Three-dimensional left ventricular segmentation from magnetic resonance imaging for patient-specific modelling purposes.

Europace 2014 Nov;16 Suppl 4:iv96-iv101

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Piazza L. da Vinci, 32, 20133 Milan, Italy IRCCS Centro Cardiologico Monzino, 20138 Milan, Italy.

Aims: To propose a nearly automated left ventricular (LV) three-dimensional (3D) surface segmentation procedure, based on active shape modelling (ASM) and built on a database of 3D echocardiographic (3DE) LV surfaces, for cardiac magnetic resonance (CMR) images, and to test its accuracy for LV volumes computation compared with 'gold standard' manual tracings and discs-summation method.

Methods And Results: The ASM was created based on segmented LV surfaces (4D LV analysis, Tomtec) from 3DE datasets of 205 patients. Then, it was applied to the cardiac magnetic resonance imaging short-axis (SAX) images stack of 12 consecutive patients. After proper realignment using two- and four-chambers CMR long-axis views both as reference and for initializing LV apex and base (six points in total), the ASM was iteratively and automatically updated to match the information of all the SAX planes contemporaneously, resulting in an endocardial LV 3D mesh from which volume was directly derived. The same CMR images were analysed by an experienced cardiologist to derive end-diastolic and end-systolic volumes. Linear correlation and Bland-Altman analyses were applied vs. the manual 'gold standard'. Active shape modelling results showed high correlations with manual values both for LV volumes (r(2) > 0.98) and ejection fraction (EF) (r(2) > 0.90), non-significant biases and narrow limits of agreement.

Conclusion: The proposed method resulted in accurate detection of 3D LV endocardial surfaces, which lead to fast and reliable measurements of LV volumes and EF when compared with manual tracing of CMR SAX images. The segmented 3D mesh, including a realistic LV apex and base, could constitute a novel starting point for more realistic patient-specific finite element modelling.
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http://dx.doi.org/10.1093/europace/euu232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401081PMC
November 2014

Semiautomated detection and quantification of aortic plaques from three-dimensional transesophageal echocardiography.

J Am Soc Echocardiogr 2014 Jul 24;27(7):758-66. Epub 2014 Apr 24.

Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.

Background: Aortic atherosclerosis is a risk factor for cerebrovascular events. Two-dimensional transesophageal echocardiographic quantification of descending aortic plaques is time-consuming and underestimates plaque burden. The aim of this study was to assess the feasibility and accuracy of a novel semiautomated program that uses three-dimensional (3D) transesophageal echocardiography to identify and quantify aortic plaque severity as determined by plaque thickness, volume, and number. The relationship between maximum plaque thickness and volume was also examined.

Methods: Descending aortic 3D transesophageal echocardiographic images from 58 patients were analyzed for plaque thickness, volume, and number using semiautomated custom software. The reference standard was manual assessment by an expert reader using 3D multiplanar reconstructions. Agreement and κ values were calculated to determine the program's accuracy against the reference standard. Correlation and bias were examined using linear regression and Bland-Altman statistics. Pearson's correlation was used to examine the relationship between maximum plaque thickness and volume.

Results: Analysis was possible in all patients. Overall agreement for the absolute presence or absence of plaque per patient was 95%. Agreement regarding the number of plaques per patient and plaque severity was high at 95% and 85%, respectively. Plaque volume was slightly underestimated by the program compared with manual measurements. The correlation between plaque thickness and volume was 0.56.

Conclusions: The results of this study demonstrate that semiautomated plaque analysis of 3D transesophageal echocardiographic descending aortic data sets is feasible and accurate in determining plaque severity as measured by plaque thickness, volume, and number. This methodology allows the standardization of plaque quantification, which will improve its utility in clinical trials. A greater understanding of the importance of plaque thickness versus volume is needed.
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http://dx.doi.org/10.1016/j.echo.2014.03.003DOI Listing
July 2014

From Kepler's conjecture and fcc lattice to modelling of crowding in living matter.

Ital J Anat Embryol 2013 ;118(1):92-104

Department of Human Morphology and Biomedical Sciences - Città degli Studi, Università di Milano. Via L. Mangiagalli 31, 20133 Milano, Italy

Up to now, sphere packing has been investigated without any reference to living matter. This study focuses on the void space (VS) of sphere packing to mimic the extracellular spaces of living tissues. It was inspired by the importance of the extracellular matrix, the vehicle of micro and macromolecules involved in cell metabolism, intercellular communication and drug delivery. The analysis of sphere packing evidenced that in uniform random packing VS is about 1.9 times greater than in the face centered cubic (fcc) lattice (thus being very close to the 1.9 volume ratio of the cube to the sphere). This datum is a good reference for cell packing in vivo. The disproportionate increase of VS per sphere in loose packing in vitro is analyzed having in mind the variability in volume and composition of the interstitial spaces in vivo and cell trafficking. Arrangements of lymphocytes mimicking a two-dimensional hexagonal pattern and dense packing of disks generated by numerical procedures, are described in 7 micro m-thick haematoxylin and eosin-stained histological slices from a human lymph node. In narrow tubes simulating roundish cells arranged in limited compartments of the interstice, sphere packing is characterized by noticeable increases of VS. The VS of this packing in vitro is compatible with variability in volume and composition of the interstitial spaces and with cell trafficking in vivo. This paper stresses that in mammalian tissues and organs cells can be packed quite more densely than spheres in the fcc lattice. As to pathology, attention is focused: (i) on overcrowding of cell organelles in some diseases, (ii) on shrinking or swelling of high amplitude, whose opposite effects are to concentrate or dilute intracellular structures and crowding of macromolecules, and (iii) on neoplastic tissues.
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August 2013

Microgravity effects on ventricular response to heart rate changes.

Annu Int Conf IEEE Eng Med Biol Soc 2012 ;2012:3424-7

Communications Technology Group, Aragón Institute of Engineering Research (I3A), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain. jbolea@lagunaat unizar.es

The effect of simulated microgravity on ventricular repolarization (VR) has been evaluated on healthy volunteers by a 5-day Head Down (-6°) Bed Rest (HDBR) maneuver. QT to RR and QT(p) (measured until the peak of the T wave) to RR hystereses have been measured during a tilt table test, and differences between them have been studied to better understand possible changes in the final part of the repolarization. To characterize the hystereses, two indices have been computed: M(90), quantifying adaptation lag in beats, and α evaluating the slope of parabolic regression fitting. Significant differences between QT and QT(p) were found before, but not after HDBR. Specifically, before HDBR was considerable lower for QT(p) than for QT, while α was significantly higher. After HDBR, M(90) and a took essentially the same values for QT and QT(p). This fact evidenced the different effect of HDBR on QT to RR and QT(p) to RR adaptations, and suggest HDBR could lead to an impairment in ventricular repolarization dispersion.
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http://dx.doi.org/10.1109/EMBC.2012.6346701DOI Listing
July 2013

Three-dimensional dynamic assessment of tricuspid and mitral annuli using cardiovascular magnetic resonance.

Eur Heart J Cardiovasc Imaging 2013 Oct 22;14(10):986-95. Epub 2013 Jan 22.

Centro Cardiologico Monzino IRCCS, Via Parea 4, Milan 20138, Italy.

Aims: To explore the potentiality of cardiovascular magnetic resonance (CMR) in the quantitative evaluation of mitral valve annulus (MVA) and tricuspid valve annulus (TVA) morphology and dynamics.

Methods And Results: CMR was performed in 13 normal subjects and 9 patients with mitral (n = 7) or tricuspid regurgitation (n = 2), acquiring cine-images in 18 radial long-axis planes passing through the middle of MVA or TVA. A novel algorithm was used to obtain dynamic three-dimensional (3D) reconstruction of MVA and TVA. Analysis was feasible in all cases, allowing accurate 3D annular reconstruction and tracking. The 3D area increased from systole [MVA, median = 10.0 cm(2) (first quartile = 8.6, third quartile = 11.4); TVA, 11.2 cm(2) (8.8-13.2)] to diastole [MVA, 10.6 cm(2) (9.4, 11.7); TVA, 11.9 cm(2) (9.2-13.5)], with TVA larger than MVA. While the longest diameter showed similar systolic and diastolic values, the shortest diameter elongated from systole [MVA, 30 mm (29-33); TVA, 33 mm (31-36)] to diastole [MVA, 31 mm (29-32); TVA, 36 mm (33-39)]. Also, TVA became more circular than MVA. TVA showed lower peak systolic excursion in the septal [15.9 mm (13.0-18.5)] and anterior regions [17.9 mm (12.2-20.7)] compared with the posterior [21.9 mm (18.6-24.0)] segment. Values in MVA were smaller than in TVA, slightly higher in anterior [11.2 mm (9.5-13.0)] than in posterior [12.4 mm (10.2-14.6)] segments. Valvular regurgitation was associated with enlarged, flattened, and more circular annuli.

Conclusion: The applied method was feasible and accurate in normal and regurgitant valves, and may potentially have an impact on diagnosis, improvement of surgical techniques and design of annular prostheses.
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http://dx.doi.org/10.1093/ehjci/jet004DOI Listing
October 2013

Toward patient-specific simulations of cardiac valves: state-of-the-art and future directions.

J Biomech 2013 Jan 20;46(2):217-28. Epub 2012 Nov 20.

Bioengineering Department, Politecnico di Milano, Milano, Italy.

Recent computational methods enabling patient-specific simulations of native and prosthetic heart valves are reviewed. Emphasis is placed on two critical components of such methods: (1) anatomically realistic finite element models for simulating the structural dynamics of heart valves; and (2) fluid structure interaction methods for simulating the performance of heart valves in a patient-specific beating left ventricle. It is shown that the significant progress achieved in both fronts paves the way toward clinically relevant computational models that can simulate the performance of a range of heart valves, native and prosthetic, in a patient-specific left heart environment. The significant algorithmic and model validation challenges that need to be tackled in the future to realize this goal are also discussed.
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http://dx.doi.org/10.1016/j.jbiomech.2012.10.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552085PMC
January 2013

Evaluation of right ventricular systolic function after mitral valve repair: a two-dimensional Doppler, speckle-tracking, and three-dimensional echocardiographic study.

J Am Soc Echocardiogr 2012 Jul 25;25(7):701-8. Epub 2012 Apr 25.

Centro Cardiologico Monzino IRCCS, Milan, Italy.

Background: Conventional indices of right ventricular (RV) function are known to be reduced after cardiac surgery, as a consequence of geometric rather than functional alterations. New techniques, such as three-dimensional (3D) transthoracic and two-dimensional speckle-tracking echocardiography, may be useful in postsurgical RV assessment. The aim of this study was to compare indices of RV function obtained using different echocardiographic modalities, before and after surgery.

Methods: Forty-two patients were screened the day before and 6 months after mitral valve repair. Twenty healthy patients were also enrolled as controls. Tricuspid annular plane systolic excursion and peak systolic velocity were calculated from Doppler tissue imaging. Longitudinal and radial strain values were obtained from speckle-tracking echocardiography. RV ejection fraction was calculated from 3D transthoracic echocardiographic RV volumes, and similarly, fractional area change was computed from RV areas.

Results: Tricuspid annular plane systolic excursion (25 ± 4 vs 17 ± 3 mm), peak systolic velocity (17 ± 4 vs 12 ± 2 cm/sec), and fractional area change (43 ± 8% vs 39 ± 7%) significantly decreased after surgery (P < .01), while 3D RV ejection fraction was preserved (59 ± 7% vs 59 ± 6%). Speckle-tracking echocardiographic results were dependent on the considered direction, with preserved radial but decreased longitudinal strain values. All postoperative two-dimensional longitudinal indices were smaller than in controls. Preoperative parameters were not significantly correlated with RV functional changes.

Conclusions: Although 3D ejection fraction was preserved after surgery, in agreement with the lack of evidence of RV dysfunction, two-dimensional indices showed a functional loss in the longitudinal direction. Fractional area change, as a combination of radial and longitudinal properties, was slightly decreased. Speckle-tracking echocardiography could constitute a useful approach to relate local and space-dependent changes to the global RV function.
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http://dx.doi.org/10.1016/j.echo.2012.03.017DOI Listing
July 2012

Effect of mitral valve repair on mitral-aortic coupling: a real-time three-dimensional transesophageal echocardiography study.

J Am Soc Echocardiogr 2012 May 8;25(5):524-31. Epub 2012 Mar 8.

Cardiovascular Sciences, Università Degli Studi di Milano, Milan, Italy.

Background: The aortic valve and the mitral valve (MV) are coupled via fibrous tissue. Simultaneous dynamic analysis of the two valves' annuli has demonstrated that they have synchronous and reciprocal behavior. Accordingly, the aims of this study were to characterize mitral-aortic coupling (MAC) in three-dimensional space before and after MV repair and to identify the untoward effects of annuloplasty rings on MAC compared with normal valvular function.

Methods: Real-time three-dimensional transesophageal echocardiography was performed on 28 consecutive patients with degenerative MV disease and severe mitral regurgitation before and after MV repair and in 25 age-matched control subjects. Custom software was used to semiautomatically identify the mitral and aortic annuli throughout the cardiac cycle and to measure parameters describing valvular dynamics.

Results: Patients with mitral regurgitation before MV repair were characterized by altered morphology and function of the MV but preserved MAC because of the maintained ability of the mitral annulus to change size and position. MV repair together with annuloplasty ring implantation forced the mitral annulus to be smaller and less pulsatile, with decreased displacement ability compared with normal mitral annuli. Because of this alteration in MAC, the "unaffected" aortic annulus became less pulsatile and less mobile.

Conclusions: This study shows unwanted and unexpected changes in aortic annular function secondary to mitral valve repair with an annuloplasty ring due to altered MAC mechanisms. These changes may alter the dynamic mechanism of the aortic root that facilitates blood ejection, so MAC should be considered and evaluated from diagnosis to treatment in MV disease.
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http://dx.doi.org/10.1016/j.echo.2012.02.002DOI Listing
May 2012

Mid-term evaluation of the effects of dynamic neutralization system on lumbar intervertebral discs using quantitative molecular MR imaging.

J Magn Reson Imaging 2012 May 29;35(5):1145-51. Epub 2011 Nov 29.

IRCCS Istituto Ortopedico Galeazzi, via R. Galeazzi 4, Milan, Italy.

Purpose: To evaluate the mid-term effects of implant of dynamic neutralization system (Dynesys) on disc tissue in patients with lumbar discopathy, through the quantification of glycosaminoglycans (GAG) concentration, both in treated and adjacent levels, by analysis of delayed gadolinium-enhanced MRI contrast (dGEMRIC) images.

Materials And Methods: Ten patients with low back pain underwent the dGEMRIC diagnostic protocol before, 6-months and after 2 years from surgery. Each patient was also evaluated with visual analog (VAS), Oswestry, and Prolo scales both at presurgery and during follow-up. From dGEMRIC images, a ΔT1 parametric map was obtained for each disc, as quantitative indicator of its GAG concentration, and divided in 13 sectors, which were classified at presurgery as normal or abnormal, based on a 70-ms threshold. Evolution of ΔT1 was studied during the follow-up.

Results: Nine of ten patients completed the follow-up. VAS, Oswestry, and Prolo grades showed an improvement. This was accompanied by a reduction of ΔT1 in abnormal segments while normal segments showed a pattern of initial worsening at 6 months, followed by an improvement after 2 years.

Conclusion: Our study confirmed the improvement in clinical evaluation, and for the first time related this to the changes in discs GAG concentration.
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http://dx.doi.org/10.1002/jmri.23525DOI Listing
May 2012

Trends in biomedical engineering: focus on Patient Specific Modeling and Life Support Systems.

J Appl Biomater Biomech 2011 May-Aug;9(2):109-17

Department of Structural Engineering, Politecnico di Milano, Milano, Italy.

Over the last twenty years major advancements have taken place in the design of medical devices and personalized therapies. They have paralleled the impressive evolution of three-dimensional, non invasive, medical imaging techniques and have been continuously fuelled by increasing computing power and the emergence of novel and sophisticated software tools. This paper aims to showcase a number of major contributions to the advancements of modeling of surgical and interventional procedures and to the design of life support systems. The selected examples will span from pediatric cardiac surgery procedures to valve and ventricle repair techniques, from stent design and endovascular procedures to life support systems and innovative ventilation techniques.
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http://dx.doi.org/10.5301/JABB.2011.8585DOI Listing
March 2013