Publications by authors named "Sabino Iliceto"

328 Publications

Using high sensitivity cardiac troponin values in patients with SARS-CoV-2 infection (COVID-19): The Padova experience.

Clin Biochem 2021 Apr 30;90:8-14. Epub 2021 Jan 30.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: The spectrum of Coronavirus Disease 2019 (COVID-19) is broad and thus early appropriate risk stratification can be helpful. Our objectives were to define the frequency of myocardial injury using high-sensitivity cardiac troponin I (hs-cTnI) and to understand how to use its prognostic abilities.

Methods: Retrospective study of patients with COVID-19 presenting to an Emergency Department (ED) in Italy in 2020. Hs-cTnI was sampled based on clinical judgment. Myocardial injury was defined as values above the sex-specific 99th percentile upper reference limits (URLs). Most data is from the initial hospital value.

Results: 426 unique patients were included. Hs-cTnI was measured in 313 (73.5%) patients; 85 (27.2%) had myocardial injury at baseline. Patients with myocardial injury had higher mortality during hospitalization (hazard ratio = 9 [95% confidence interval (CI) 4.55-17.79], p < 0.0001). Multivariable analysis including clinical and laboratory variables demonstrated an AUC of 0.942 with modest additional value of hs-cTnI. Myocardial injury was associated with mortality in patients with low APACHE II scores (<13) [OR (95% CI): 4.15 (1.40, 14.22), p = 0.014] but not in those with scores > 13 [OR (95% CI): 0.48 (0.08, 2.65), p = 0.40]. Initial hs-cTnI < 5 ng/L identified 33% of patients that were at low risk with 97.8% sensitivity (95% CI 88.7, 99.6) and 99.2% negative predictive value. Type 1 myocardial infarction (MI) and type 2 MI were infrequent.

Conclusions: hs-cTnI at baseline is a significant predictor of mortality in COVID-19 patients. A value < 5 ng/L identified patients at low risk.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847286PMC
April 2021

Atrial fibrillation after orthotopic heart transplantatation: Pathophysiology and clinical impact.

Int J Cardiol Heart Vasc 2021 Feb 12;32:100710. Epub 2021 Jan 12.

Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.

Background: Atrial fibrillation (AF) is a well-established post-cardiac surgery complication. Orthotopic heart transplantation (OHT) represents a peculiar condition where surgical thoracic veins isolation and autonomic denervation occur. This study aims at investigating AF incidence in OHT in order to define its risk factors and to evaluate its prognostic impact.

Methods: 278 patients affected by OHT were recruited in our Cardiac Surgery Unit and retrospectively analyzed, using clinical, surgical and instrumental data.

Results: The patients cohort showed 45 post-operative (16.5%) and 20 late AF cases (7.2%). Only paroxysmal AF episodes were observed. Elderly donors and acute rejection resulted as risk factors in patients with post-operative AF episodes, who presented higher all-cause mortality at 11 years post-OHT (p < 0.001, Kaplan Meier analysis). The majority of late AF episodes occurred during hospitalization, due to renal failure or infections and more frequently in male patients; no significant correlation was observed with acute or chronic rejection or other characteristics.

Conclusion: Pulmonary vein isolation and vagal denervation lead to low AF incidence in OHT recipients. Acute rejection and graft status are the main risk factors for post-operative AF episodes, while other systemic conditions act as late AF triggers. The occurrence of AF episodes is associated with poor outcome and AF should be considered as a marker of clinical frailty.
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http://dx.doi.org/10.1016/j.ijcha.2020.100710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811113PMC
February 2021

Subcutaneous implantable cardioverter-defibrillator and left ventricular assist devices for refractory heart failure: attention to possible interference.

J Cardiovasc Med (Hagerstown) 2021 Jan 4;Publish Ahead of Print. Epub 2021 Jan 4.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.

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http://dx.doi.org/10.2459/JCM.0000000000001148DOI Listing
January 2021

Right atrial volume is a major determinant of tricuspid annulus area in functional tricuspid regurgitation: a three-dimensional echocardiographic study.

Eur Heart J Cardiovasc Imaging 2020 Dec 2. Epub 2020 Dec 2.

Department of Medicine, Section of Cardiology, University of Chicago, 5801 S Ellis Ave, Chicago 60637, IL, USA.

Aims: The aim of this study is to explore the relationships of tricuspid annulus area (TAA) with right atrial maximal volume (RAVmax) and right ventricular end-diastolic volume (RVEDV) in healthy subjects and patients with functional tricuspid regurgitation (FTR) of different aetiologies and severities.

Methods And Results: We enrolled 280 patients (median age 66 years, 59% women) with FTR due to left heart disease (LHD), pulmonary hypertension (PH), corrected tetralogy of Fallot (TOF), chronic atrial fibrillation (AF), and 210 healthy volunteers (45 years, 53% women). We measured TAA at mid-systole and end-diastole, tenting volume of tricuspid leaflets, RAVmax, and RVEDV by 3D echocardiography. Irrespective of TA measurement timing, TAA correlated more closely with RAVmax than with RVEDV in both controls and FTR patients. On multivariable analysis, RAVmax was the most important determinant of TAA, accounting for 41% (normals) and 56% (FTR) of TAA variance. In FTR patients, age, RVEDV, and left ventricular ejection fraction were also independently correlated with TAA. RAVmax (AUC = 0.81) and TAA (AUC = 0.78) had a greater ability than RVEDV (AUC = 0.72) to predict severe FTR (P < 0.05). Among FTR patients, those with AF had the largest RAVmax and smallest RVEDV. RAVmax and TA were significantly dilated in all FTR groups, except in TOF. PH and TOF had largest RVEDV, yet tenting volume was increased only in PH and LHD.

Conclusion: RA volume is a major determinant of TAA, and RA enlargement is an important mechanism of TA dilation in FTR irrespective of cardiac rhythm and RV loading conditions.
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http://dx.doi.org/10.1093/ehjci/jeaa286DOI Listing
December 2020

Sounds Stimulation on In Vitro HL1 Cells: A Pilot Study and a Theoretical Physical Model.

Int J Mol Sci 2020 Dec 25;22(1). Epub 2020 Dec 25.

Department of Cardiac, Thoracic and Vascular Sciences, Padua University Medical School,35100 Padua, Italy.

Mechanical vibrations seem to affect the behaviour of different cell types and the functions of different organs. Pressure waves, including acoustic waves (sounds), could affect cytoskeletal molecules via coherent changes in their spatial organization and mechano-transduction signalling. We analyzed the sounds spectra and their fractal features. Cardiac muscle HL1 cells were exposed to different sounds, were stained for cytoskeletal markers (phalloidin, beta-actin, alpha-tubulin, alpha-actinin-1), and studied with multifractal analysis (using FracLac for ImageJ). A single cell was live-imaged and its dynamic contractility changes in response to each different sound were analysed (using Musclemotion for ImageJ). Different sound stimuli seem to influence the contractility and the spatial organization of HL1 cells, resulting in a different localization and fluorescence emission of cytoskeletal proteins. Since the cellular behaviour seems to correlate with the fractal structure of the sound used, we speculate that it can influence the cells by virtue of the different sound waves' geometric properties that we have photographed and filmed. A theoretical physical model is proposed to explain our results, based on the coherent molecular dynamics. We stress the role of the systemic view in the understanding of the biological activity.
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http://dx.doi.org/10.3390/ijms22010156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796405PMC
December 2020

'Hot phase' clinical presentation in arrhythmogenic cardiomyopathy.

Europace 2020 Dec 13. Epub 2020 Dec 13.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Via Giustiniani, 2, 35121 Padua, Italy.

Aims: The aim of this study is to evaluate the clinical features of patients affected by arrhythmogenic cardiomyopathy (AC), presenting with chest pain and myocardial enzyme release in the setting of normal coronary arteries ('hot phase').

Methods And Results: We collected detailed anamnestic, clinical, instrumental, genetic, and histopathological findings as well as follow-up data in a series of AC patients who experienced a hot phase. A total of 23 subjects (12 males, mean age at the first episode 27 ± 16 years) were identified among 560 AC probands and family members (5%). At first episode, 10 patients (43%) already fulfilled AC diagnostic criteria. Twelve-lead electrocardiogram recorded during symptoms showed ST-segment elevation in 11 patients (48%). Endomyocardial biopsy was performed in 11 patients, 8 of them during the acute phase showing histologic evidence of virus-negative myocarditis in 88%. Cardiac magnetic resonance was performed in 21 patients, 12 of them during the acute phase; oedema and/or hyperaemia were detected in 7 (58%) and late gadolinium enhancement in 11 (92%). At the end of follow-up (mean 17 years, range 1-32), 12 additional patients achieved an AC diagnosis. Genetic testing was positive in 77% of cases and pathogenic mutations in desmoplakin gene were the most frequent. No patient complained of sustained ventricular arrhythmias or died suddenly during the 'hot phase'.

Conclusion: 'Hot phase' represents an uncommon clinical presentation of AC, which often occurs in paediatric patients and carriers of desmoplakin gene mutations. Tissue characterization, family history, and genetic test represent fundamental diagnostic tools for differential diagnosis.
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http://dx.doi.org/10.1093/europace/euaa343DOI Listing
December 2020

Reduction in all-cause mortality in COVID-19 patients on chronic oral anticoagulation: A population-based propensity score matched study.

Int J Cardiol 2021 04 11;329:266-269. Epub 2020 Dec 11.

Cardiology Clinic, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Padua University Hospital, Padua, Italy. Electronic address:

Background: Coronavirus disease 2019 (COVID-19) global pandemic has strikingly high mortality rate with hypercoagulability state being part of the imputed mechanisms. We aimed to compare the rates of in hospital mortality in propensity score matched cohorts of COVID-19 patients in chronic anticoagulation versus those that were not.

Methods: In this population-based study in the Veneto Region, we retrospectively reviewed all patients aged 65 years or older, with a laboratory-confirmed COVID-19 diagnosis. We compared, after propensity score matching, those who received chronic anticoagulation for atrial fibrillation with those who did not.

Results: Overall, 4697 COVID-19 patients fulfilled inclusion criteria, and the propensity score matching yielded 559 patients per arm. All-cause mortality rate ratio was significantly higher among non-anticoagulated patients (32.2% vs 26.5%, p = 0.036). On time to event analysis, all-cause mortality was found lower among anticoagulated patients, although the estimate was not statistically significant. (HR 0.81, 95%CI 0.65-1.01, p = 0.054).

Conclusion: Among elderly patients with COVID-19, those on chronic oral anticoagulant treatment for atrial fibrillation seem to be at lower risk of all-cause mortality compared to their propensity score matched non-anticoagulated counterpart. This finding needs to be confirmed in further studies.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833678PMC
April 2021

Toward a Unified View of Cognitive and Biochemical Activity: Meditation and Linguistic Self-Reconstructing May Lead to Inflammation and Oxidative Stress Improvement.

Entropy (Basel) 2020 Jul 27;22(8). Epub 2020 Jul 27.

Department of Physics "E.R. Caianiello", Salerno University, Via Giovanni Paolo II, 132, 84084 Fisciano (Salerno), Italy.

Stress appears to be the basis of many diseases, especially myocardial infarction. Events are not objectively "stressful" but what is central is how the individual structures the experience he is facing: the thoughts he produces about an event put him under stress. This cognitive process could be revealed by language (words and structure). We followed 90 patients with ischemic heart disease and 30 healthy volunteers, after having taught them the Relaxation Response (RR) as part of a 4-day Rational-Emotional-Education intervention. We analyzed with the Linguistic Inquiry and Word Count software the words that the subjects used across the study following the progression of blood galectin-3 (inflammation marker) and malondialdehyde (oxidative stress marker). During the follow-up, we confirmed an acute and chronic decrease in the markers of inflammation and oxidative stress already highlighted in our previous studies together with a significant change in the use of language by the subjects of the RR groups. Our results and the precise design of our study would seem to suggest the existence of an intimate relationship and regulatory action by cognitive processes (recognizable by the type of language used) on some molecular processes in the human body.
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http://dx.doi.org/10.3390/e22080818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517388PMC
July 2020

Efficacy of immunosuppressive therapy in myocarditis: A 30-year systematic review and meta analysis.

Autoimmun Rev 2021 Jan 13;20(1):102710. Epub 2020 Nov 13.

Cardiology, Dept of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Padova, Italy. Electronic address:

Aims: Myocarditis is an inflammation of the heart muscle, due to infectious, toxic or autoimmune causes. Literature reported controversial results in relation to the effect of immunosuppression (IS)/immunomodulation (IM). We aimed at assessing the effect of IS/IM by meta analysis.

Methods And Results: Using the P.R.I.S.M.A. approach, two researchers searched for relevant studies on PubMed, Embase, and the Central Registry of Controlled Trials of the Cochrane Library. Proposed MeSH terms were: "immunotherapy OR immune therapy OR immune modeling OR Immunosuppressive Agents" AND "combination OR combined with OR plus" AND "myocarditis OR cardiomyopathies OR inflammatory cardiomyopathy". The language was restricted to English. Reference lists of included articles and those relevant to the topic were hand searched for the identification of additional, potentially relevant articles. The cutoff date was from 1987 until 30th Nov 2019. Reported survival or mortality events or change of left ventricular ejection fraction (LVEF) after IS/IT were primary outcomes of the study; in addition, improvement of New York Heart Association class, follow-up biopsy (Bx) findings, viral genome clearance on Bx and recurrence of myocarditis were recorded if reported. Statistical analysis was conducted using Review Manager 5.3; 5452 studies were screened, of these 73 were assessed for eligibility, including 8 randomized control studies, 26 retrospective studies, 2 prospective studies and 1 case control study, 34 case reports and 2 case series. In prospective studies, the difference in mortality between the IS and control groups tended to be lower in the combined IS groups (12.5% vs. 18.2%) (95% CI of odds ratio 0.7(0.3, 1.64)) and the pooled difference of the increase of LVEF between the IS and control groups tended to be higher in the combined IS groups (95% CI 7.26 (-2.29, 16.81)). In retrospective studies, the difference of survival between the IS and control group was significantly in favor of IS (95%CI Hazard ratio 0.82(0.69, 0.96)).

Conclusions: A tailored IS may be considered in myocarditis, depending on the phase of the disease, and the type of underlying autoimmune or immune-mediated form.
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http://dx.doi.org/10.1016/j.autrev.2020.102710DOI Listing
January 2021

Characteristics and hospital course of patients admitted for acute cardiovascular diseases during the coronavirus disease-19 outbreak.

J Cardiovasc Med (Hagerstown) 2021 01;22(1):29-35

Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Padua, Italy.

Introduction: During the coronavirus disease-19 (COVID-19) outbreak in spring 2020, people may have been reluctant to seek medical care fearing infection. We aimed to assess the number, characteristics and in-hospital course of patients admitted for acute cardiovascular diseases during the COVID-19 outbreak.

Methods: We enrolled all consecutive patients admitted urgently for acute myocardial infarction, heart failure or arrhythmias from 1 March to 31 May 2020 (outbreak period) and 2019 (control period). We evaluated the time from symptoms onset to presentation, clinical conditions at admission, length of hospitalization, in-hospital medical procedures and outcome. The combined primary end point included in-hospital death for cardiovascular causes, urgent heart transplant or discharge with a ventricular assist device.

Results: A similar number of admissions were observed in 2020 (N = 210) compared with 2019 (N = 207). Baseline characteristics of patients were also similar. In 2020, a significantly higher number of patients presented more than 6 h after symptoms onset (57 versus 38%, P < 0.001) and with signs of heart failure (33 versus 20%, P = 0.018), required urgent surgery (13 versus 5%, P = 0.004) and ventilatory support (26 versus 13%, P < 0.001). Hospitalization duration was longer in 2020 (median 10 versus 8 days, P = 0.03). The primary end point was met by 19 (9.0%) patients in 2020 versus 10 (4.8%) in 2019 (P = 0.09).

Conclusion: Despite the similar number and types of unplanned admissions for acute cardiac conditions during the 2020 COVID-19 outbreak compared with the same period in 2019, we observed a higher number of patients presenting late after symptoms onset as well as longer and more complicated clinical courses.
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http://dx.doi.org/10.2459/JCM.0000000000001129DOI Listing
January 2021

Cardiac injury and mortality in patients with Coronavirus disease 2019 (COVID-19): insights from a mediation analysis.

Intern Emerg Med 2021 Mar 27;16(2):419-427. Epub 2020 Sep 27.

Department of Medicine, University of Padova, Via Giustiniani, 2, Padua, 35128, Italy.

Backgrounds: Patients at greatest risk of severe clinical conditions from coronavirus disease 2019 (COVID-19) and death are elderly and comorbid patients. Increased levels of cardiac troponins identify patients with poor outcome. The present study aimed to describe the clinical characteristics and outcomes of a cohort of Italian inpatients, admitted to a medical COVID-19 Unit, and to investigate the relative role of cardiac injury on in-hospital mortality.

Methods And Results: We analyzed all consecutive patients with laboratory-confirmed COVID-19 referred to our dedicated medical Unit between February 26th and March 31st 2020. Patients' clinical data including comorbidities, laboratory values, and outcomes were collected. Predictors of in-hospital mortality were investigated. A mediation analysis was performed to identify the potential mediators in the relationship between cardiac injury and mortality. A total of 109 COVID-19 inpatients (female 36%, median age 71 years) were included. During in-hospital stay, 20 patients (18%) died and, compared with survivors, these patients were older, had more comorbidities defined by Charlson comorbidity index ≥ 3(65% vs 24%, p = 0.001), and higher levels of high-sensitivity cardiac troponin I (Hs-cTnI), both at first evaluation and peak levels. A dose-response curve between Hs-cTnI and in-hospital mortality risk up to 200 ng/L was detected. Hs-cTnI, chronic kidney disease, and chronic coronary artery disease mediated most of the risk of in-hospital death, with Hs-cTnI mediating 25% of such effect. Smaller effects were observed for age, lactic dehydrogenase, and D-dimer.

Conclusions: In this cohort of elderly and comorbid COVID-19 patients, elevated Hs-cTnI levels were the most important and independent mediators of in-hospital mortality.
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http://dx.doi.org/10.1007/s11739-020-02495-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520162PMC
March 2021

Screening of unknown atrial fibrillation through handheld device in the elderly.

J Geriatr Cardiol 2020 Aug;17(8):495-501

Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Objective: To estimate the prevalence of unknown atrial fibrillation (AF) in the elderly population of the Veneto Region, Italy.

Methods: 1820 patients aged ≥ 65 years with no history of AF and not anticoagulated were enrolled in primary-care settings. They underwent an opportunistic electrocardiogram screening with a handheld device (MyDiagnostick) designed to specifically detect AF. The electrocardiogram recordings were reviewed by the researchers, who confirmed the presence of AF.

Results: The device detected an arrhythmia in 143 patients, which was confirmed as AF in 101/143 (70.6%), with an overall prevalence of AF of 5.5% (101/1820). Prevalence of unknown AF resulted in 3.6% in patients aged 65-74 years, and 7.5% in patients age 75 or older, and increased according to CHADS-VASc score: 3.5% in patients with a score of 1 or 2, 5.6% in patients with a score of 3, 7.0% in patients with a score of 4, and 7.2% in patients with a score ≥ 5. The detection rate was significantly higher in patients with mild symptoms compared to asymptomatic counterparts (24.1% 4.0%, < 0.0001). At multivariate analysis, congestive heart failure and age ≥ 75 years-old were independent predictors for screen-detected AF.

Conclusions: An opportunistic screening with handheld device revealed an unexpectedly high prevalence of unknown AF in elderly patients with mild symptoms. Prevalence increased with age and CHADS-VASc score.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475215PMC
August 2020

Modulation of TRPV-1 by prostaglandin-E and bradykinin changes cough sensitivity and autonomic regulation of cardiac rhythm in healthy subjects.

Sci Rep 2020 09 16;10(1):15163. Epub 2020 Sep 16.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.

A neurogenic pathway, involving airway TRPV-1, has been implicated in acute cardiovascular events occurring after peaks of air pollution. We tested whether inhaled prostaglandin-E (PGE) and bradykinin (BK) regulate TRPV-1 activity in vivo by changing cough response to capsaicin (CPS) and affecting heart rate variability (HRV), while also taking into account the influence of TRPV-1 polymorphisms (SNPs). Moreover, we assessed the molecular mechanism of TRPV-1 modulation in vitro. Seventeen healthy volunteers inhaled 100 μg PGE, 200 μg BK or diluent in a randomized double-blind fashion. Subsequently, the response to CPS was assessed by cough challenge and the sympathetic activity by HRV, expressed by low (nLF) and high (nHF) normalized frequency components, as well as nLF/nHF ratio. Intracellular [Ca] was measured in HeLa cells, transfected with wild-type TRPV-1, pre-treated with increasing doses of PGE, BK or diesel exhaust particulate (DEP), after CPS stimulation. Six functional TRPV-1 SNPs were characterized in DNA from each subject. Inhalation of PGE and BK was associated with significant increases in cough response induced by 30 μM of CPS (cough number after PGE = 4.20 ± 0.42; p < 0.001, and after BK = 3.64 ± 0.37; p < 0.01), compared to diluent (2.77 ± 0.29) and in sympathetic activity (nLF/nHF ratio after PGE = 6.1; p < 0.01, and after BK = 4.2; p < 0.05), compared to diluent (2.5-3.3). No influence of SNPs was observed on autonomic regulation and cough sensitivity. Unlike PGE and BK, DEP directly activated TRPV-1. Inhalation of PGE and BK sensitizes TRPV-1 and is associated with autonomic dysregulation of cardiac rhythm in healthy subjects.
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http://dx.doi.org/10.1038/s41598-020-72062-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494872PMC
September 2020

Daily Exposure to Air Pollution Particulate Matter Is Associated with Atrial Fibrillation in High-Risk Patients.

Int J Environ Res Public Health 2020 08 19;17(17). Epub 2020 Aug 19.

Division of Cardiology, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35128 Padua, Italy.

Several epidemiological studies found an association between acute exposure to fine particulate matter of less than 2.5 μm and 10 μm in aerodynamic diameter (PM and PM) and cardiovascular diseases, ventricular fibrillation incidence and mortality. The effects of pollution on atrial fibrillation (AF) beyond the first several hours of exposure remain controversial. A total of 145 patients with implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy defibrillators (ICD-CRT), or pacemakers were enrolled in this multicentric prospective study. Daily levels of PM and PM were collected from monitoring stations within 20 km of the patient's residence. A Firth Logistic Regression model was used to evaluate the association between AF and daily exposure to PM and PM. Exposure levels to PM and PM were moderate, being above the World Health Organization (WHO) PM and PM thresholds of 25 μg/m and 50 μg/m, respectively, on 26% and 18% of the follow-up days. An association was found between daily levels of PM and PM and AF (95% confidence intervals (CIs) of 1.34-2.40 and 1.44-4.28, respectively) for an increase of 50 µg/m above the WHO threshold. Daily exposure to moderate PM and PM levels is associated with AF in patients who are not prone to AF.
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http://dx.doi.org/10.3390/ijerph17176017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504134PMC
August 2020

"Stay home stay safe?" Systemic inflammation in subjects undergoing routine hematology tests during the lockdown period of COVID-19.

Clin Chem Lab Med 2020 08 19;58(12):e315-e316. Epub 2020 Aug 19.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University Hospital of Padova, Padova, Italy.

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http://dx.doi.org/10.1515/cclm-2020-1016DOI Listing
August 2020

Echocardiography and cardiac magnetic resonance in children with repaired tetralogy of Fallot: New insights in cardiac mechanics and exercise capacity.

Int J Cardiol 2020 Dec 21;321:144-149. Epub 2020 Jul 21.

Department of Paediatric Cardiology, Royal Brompton Hospital, Sydney Street, London SW36NP, United Kingdom; Department of Child and Woman's Health, Paediatric Cardiology Unit, University of Padua, Padua, Italy. Electronic address:

Background: Pulmonary regurgitation (PR) and right ventricular (RV) dilatation and disfunction are common in patients with repaired Tetralogy of Fallot (r-TOF).

Aims: To compare Echo data with the gold standard CMR in a paediatric population of r-TOF with significant PR, to assess the reliability of standard and advanced echo parameters. In addition, to evaluate their correlation with peak oxygen consumption (VO).

Methods And Results: All patients underwent standard echo-Doppler study, speckle tracking analysis, and CMR to assess PR and RV size and function. Thirty-six patients underwent also cardiopulmonary exercise test. Fourty-six patients (aged 13.7 ± 3.0) were included. Echo derived RV areas correlated with CMR RV volumes (p < .0001, r = 0.72). RV end-diastolic area > 21.9 cm/m had a good sensitivity (83.3%) and specificity (73.5%) to identify a RV end-diastolic volume ≥ 150 ml/m. RVEF was preserved in all patients, while TAPSE was reduced in 78.2% and RVGLS in 60.8%. Flow-reversal in pulmonary branches showed a sensitivity of 95.8% and a specificity of 59.1% to identify CMR pulmonary regurgitant fraction (RF) ≥ 35%. None of the CMR parameters correlated with peak VO. Among the Echo data only right atrial strain (RAS) correlated with peak VO CONCLUSION: In children, flow-reversal in pulmonary branches identifies hemodynamically significant RF with a good sensitivity but poor specificity. RV area by echocardiogram is a valid first-line parameter to screen RV dilation. RV longitudinal systolic dysfunction coexists with a still preserved EF. RAS correlates strongly with peak VO and should be added in their follow up.
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http://dx.doi.org/10.1016/j.ijcard.2020.07.026DOI Listing
December 2020

Relation of Mitral Annulus and Left Atrial Dysfunction to the Severity of Functional Mitral Regurgitation in Patients with Dilated Cardiomyopathy.

Cardiol Res Pract 2020 9;2020:3261714. Epub 2020 Jul 9.

Istituto Auxologico Italiano IRCCS, Department of Cardiovascular Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy.

Methods: 56 patients (58 ± 17 years, 42 men) with DCM and FMR and 52 controls, prospectively enrolled, underwent 3DTTE dedicated for mitral valve (MV), LA, and left ventricle (LV) quantitative analysis.

Results: Patients with FMR vs. controls presented increased MA size and sphericity during the entire systole, whereas MA fractional area change (MAFAC) and MA displacement were decreased (15 ± 5 vs. 28 ± 5%; and 5 ± 3 vs. 10 ± 2 mm, < 0.001). In patients with moderate/severe FMR, MA diameters correlated with PISA radius, EROA, and regurgitant volume (Rvol), as also did the MA area (with PISA radius, EROA, and Rvol:  = 0.48,  = 0.58, and  = 0.47, < 0.05). MAFAC correlated inversely with EROA and Rvol ( = -0.32 and  = -0.35, < 0.05), with both active and total LA emptying fractions and with LV ejection fraction as well. In a stepwise multivariate regression model, decreased MAFAC and increased LA volume independently predicted patients with severe FMR.

Conclusions: Patients with DCM and FMR have MA geometry remodeling and contractile dysfunction, correlated with the severity of FMR. MA contractile dysfunction correlated with both LA and left LV pumps dysfunctions and predicted patients with severe FMR. Our results provide new insights that might help with better selection of patients for MV transcatheter procedures.
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http://dx.doi.org/10.1155/2020/3261714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368231PMC
July 2020

Evaluation of mexiletine effect on conduction delay and bradyarrhythmic complications in patients with myotonic dystrophy type 1 over long-term follow-up.

Heart Rhythm 2020 11 7;17(11):1944-1950. Epub 2020 Jun 7.

Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Background: Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by progressive cardiac conduction impairment, arrhythmias, and sudden death. Mexiletine is a sodium channel blocker drug used by patients with DM1 for treatment of myotonia, even though definitive proof of its safety over long-term follow-up is lacking.

Objective: The purpose of this study was to assess the impact of mexiletine for treatment of neurological symptoms on the composite endpoint of significant electrocardiogram modification (new onset or worsening of atrioventricular [AV] or intraventricular conduction delay) and bradyarrhythmic complications requiring pacemaker (PM) implantation (advanced AV block, symptomatic sinus pause >3 seconds).

Methods: This retrospective longitudinal study included a series of consecutive patients with genetically confirmed DM1 evaluated at our neurology and cardiology clinics from January 1, 2011, to January 1, 2020, who received mexiletine 200 mg twice daily. Patients with a PM, implantable cardioverter-defibrillator, or severe conduction abnormality (PQ interval ≥230 ms, complete bundle branch block, or atrial fibrillation) at enrollment were excluded.

Results: The study comprised 18 mexiletine-treated patients and 68 mexiletine-free controls. Over median follow-up of 53 months, the endpoint was reached by 4 (22%) mexiletine-treated patients and 23 (33%) non-mexiletine-treated patients (log-rank P = .45). In 3 non-mexiletine-treated patients, bradyarrhythmic complications requiring PM implantation were observed. At univariable analysis, only the presence of mild conduction delay (first-degree AV block with PQ interval <230 ms or left anterior fascicular block) at baseline predicted the endpoint (hazard ratio 2.22; 95% confidence interval 1.04-4.76).

Conclusion: Mexiletine 200 mg twice daily is safe in patients with DM1 and no severe conduction abnormality.
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http://dx.doi.org/10.1016/j.hrthm.2020.05.043DOI Listing
November 2020

Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin.

Int J Cardiol 2020 10 19;316:280-284. Epub 2020 May 19.

Department of Medicine, University of Padua Medical School, Padua, Italy.

Background: Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established.

Methods: We performed 12‑lead ECGs and 12‑lead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control.

Results: Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p = .02). Four patients had a QTc ≥ 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p = .03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms. At 24-h Holter ECG monitoring, 1 COVID-19 patient and no control had ≥1 run of non-sustained ventricular tachycardia (p = .4). No patients showed "R on T" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability.

Conclusion: Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID-19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable.
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http://dx.doi.org/10.1016/j.ijcard.2020.05.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235573PMC
October 2020

Axillary vein access for permanent pacemaker and implantable cardioverter defibrillator implantation: Fluoroscopy compared to ultrasound.

Pacing Clin Electrophysiol 2020 06 29;43(6):566-572. Epub 2020 May 29.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.

Background: Axillary vein access (AVA) using fluoroscopic landmarks is an effective and safe approach for cardiac implantable electronic devices (CIEDs) implantation. However, it may result in a higher radiation exposure. Ultrasound-guided axillary access (USAA) is an effective alternative technique to conventional subclavian access for CIEDs implantation. Studies comparing USAA and AVA using fluoroscopic landmarks are lacking. The purpose of this study was to compare the safety, efficacy, and radiation exposure data of the USAA approach with the AVA using fluoroscopic landmarks.

Methods: The study population included 95 consecutive patients (61% male, median age 78 years [71-85 years]) referred for CIEDs implantation using AVA with fluoroscopic landmark (n = 46) or USAA (n = 49). Baseline characteristics and radiation exposure data (Air-Kerma [mGy], DAP [Gy-cm ], fluoroscopy time [seconds], and X-rays emission time [seconds]) were compared according to the technique used for the AVA.

Results: Axillary vein was successfully accessed in 45 of 49 (92%) patients using ultrasound and in 42 of 46 (91%) patients using fluoroscopic landmarks (P = 1.00). Air-Kerma, DAP, fluoroscopy time, and X-rays emission time were shorter for USAA group compared with AVA using fluoroscopic landmarks (11 mGy [8-20] vs 37 mGy [24-81], P < .00001; 3 Gy-cm [2-5] vs 10 Gy-cm [6-16], P < .00001; 97 seconds [62-163] vs 271 seconds [185-365], P < .00001; and 7 seconds [4-10] vs 21 seconds [13-39], P < .00001). There were no significant differences between the two groups in median implant procedure time (P = .55). We did not encounter any acute or long-term complications in both groups.

Conclusions: Ultrasound-guided axillary vein cannulation for CIEDs implantation is a feasible and safe alternative approach and offers a significant reduction in fluoroscopy times without increasing procedural time.
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http://dx.doi.org/10.1111/pace.13940DOI Listing
June 2020

Dietary and Lifestyle Patterns are Associated with Heart Rate Variability.

J Clin Med 2020 Apr 14;9(4). Epub 2020 Apr 14.

Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Loredan, 18, 35131 Padova, Italy.

Assessment of heart rate variability (HRV) and cardiac ectopic beats is a clinically relevant topic. The present exploratory observational study aimed to inspect the relationships of lifestyle, dietary patterns, and anthropometrics with HRV, premature ventricular complexes (PVCs), and supraventricular premature complexes (SVPCs). A cross-sectional study enrolling subjects undergoing Holter monitoring was performed. Sociodemographic and clinical characteristics, body composition (full-body bio-impedentiometry), dietary patterns (validated food frequency questionnaire and 24 h dietary recall), and quality of life were assessed. Generalized additive models were estimated to evaluate the relationships between outcomes of interest and variables collected. The study enrolled 121 consecutive patients undergoing 24 h Holter monitoring. Upon univariable analysis, HRV was found to have an inverse association with mass of body fat (MBF) (-value 0.015), while doing physical activity was associated with a significantly higher HRV (-value 0.036). Upon multivariable analysis, fruit consumption in the 24 h dietary recall was found to be directly associated with HRV (-value 0.044). The present findings might be useful for improving the management of patients attending cardiac rhythm labs, and to tailor ad hoc prevention strategies (modification of lifestyle and eating habits) based on Holter parameters.
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http://dx.doi.org/10.3390/jcm9041121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230664PMC
April 2020

Arrhythmogenic Right Ventricular Cardiomyopathy: Characterization of Left Ventricular Phenotype and Differential Diagnosis With Dilated Cardiomyopathy.

J Am Heart Assoc 2020 03 2;9(5):e014628. Epub 2020 Mar 2.

Department of Cardio-Thoraco-Vascular Sciences and Public Health University of Padua Italy.

Background This study assessed the prevalence of left ventricular (LV) involvement and characterized the clinical, electrocardiographic, and imaging features of LV phenotype in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Differential diagnosis between ARVC-LV phenotype and dilated cardiomyopathy (DCM) was evaluated. Methods and Results The study population included 87 ARVC patients (median age 34 years) and 153 DCM patients (median age 51 years). All underwent cardiac magnetic resonance with quantitative tissue characterization. Fifty-eight ARVC patients (67%) had LV involvement, with both LV systolic dysfunction and LV late gadolinium enhancement (LGE) in 41/58 (71%) and LV-LGE in isolation in 17 (29%). Compared with DCM, the ARVC-LV phenotype was statistically significantly more often characterized by low QRS voltages in limb leads, T-wave inversion in the inferolateral leads and major ventricular arrhythmias. LV-LGE was found in all ARVC patients with LV systolic dysfunction and in 69/153 (45%) of DCM patients. Patients with ARVC and LV systolic dysfunction had a greater amount of LV-LGE (25% versus 13% of LV mass; <0.01), mostly localized in the subepicardial LV wall layers. An LV-LGE ≥20% had a 100% specificity for diagnosis of ARVC-LV phenotype. An inverse correlation between LV ejection fraction and LV-LGE extent was found in the ARVC-LV phenotype (=-0.63; <0.01), but not in DCM (=-0.01; =0.94). Conclusions LV involvement in ARVC is common and characterized by clinical and cardiac magnetic resonance features which differ from those seen in DCM. The most distinctive feature of ARVC-LV phenotype is the large amount of LV-LGE/fibrosis, which impacts directly and negatively on the LV systolic function.
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http://dx.doi.org/10.1161/JAHA.119.014628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335583PMC
March 2020

Evidence From Family Studies for Autoimmunity in Arrhythmogenic Right Ventricular Cardiomyopathy: Associations of Circulating Anti-Heart and Anti-Intercalated Disk Autoantibodies With Disease Severity and Family History.

Circulation 2020 04 2;141(15):1238-1248. Epub 2020 Mar 2.

I Cardiology Division, San Camillo Hospital, Rome, Italy (F.R., A.A., P.B., E.Z.).

Background: Serum anti-heart autoantibodies (AHAs) and anti-intercalated disk autoantibodies (AIDAs) are autoimmune markers in myocarditis. Myocarditis has been reported in arrhythmogenic right ventricular cardiomyopathy (ARVC). To provide evidence for autoimmunity, we searched for AHAs and AIDAs in ARVC.

Methods: We studied: 42 ARVC probands, 23 male, aged 42, interquartile range 33-49, 20 from familial and 22 nonfamilial pedigrees; 37 clinically affected relatives (ARs), 24 male aged 35, interquartile range 18-46; and 96 healthy relatives, 49 male, aged 27, interquartile range 17-45. Serum AHAs and AIDAs were tested by indirect immunofluorescence on human myocardium and skeletal muscle in 171 of the 175 ARVC individuals and in controls with noninflammatory cardiac disease (n=160), ischemic heart failure (n=141), and healthy blood donors (n=270). Screening of 5 desmosomal genes was performed in probands; when a sequence variant was identified, cascade family screening followed, blind to immunologic results.

Results: AHA frequency was higher (36.8%) in probands, ARs (37.8%), and healthy relatives (25%) than in noninflammatory cardiac disease (1%), ischemic heart failure (1%), or healthy blood donors (2.5%; =0.0001). AIDA frequency was higher in probands (8%, =0.006), in ARs (21.6%, =0.00001), and in healthy relatives (14.6%, =0.00001) than in noninflammatory cardiac disease (3.75%), ischemic heart failure (2%), or healthy blood donors (0.3%). AHA-positive status was associated with higher frequency of palpitation (=0.004), implantable cardioverter defibrillator implantation (=0.021), lower left ventricular ejection fraction (=0.004), AIDA-positive status with both lower right ventricular and left ventricular ejection fractions (=0.027 and =0.027, respectively). AHA- and/or AIDA-positive status in the proband and at least one of the respective relatives was more common in familial (17/20, 85%) than in sporadic (10/22, 45%) pedigrees (=0.007).

Conclusions: The presence of AHAs and AIDAs provides evidence of autoimmunity in the majority of familial and in almost half of sporadic ARVC. In probands and in ARs, these antibodies were associated with features of disease severity. Longitudinal studies are needed to clarify whether they may predict ARVC development in healthy relatives or if they be a result of manifest ARVC.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043931DOI Listing
April 2020

Novel Missense Variant in Gene Associated With Hypertrophic Cardiomyopathy Showing High Incidence of Restrictive Physiology.

Circ Genom Precis Med 2020 04 31;13(2):e002824. Epub 2020 Jan 31.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health (R.V., C.B., A.A., P.M., G.T., D.C., S.I., C.C.), University of Padua, Italy.

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http://dx.doi.org/10.1161/CIRCGEN.119.002824DOI Listing
April 2020

Ultrasound-guided serratus anterior plane block for subcutaneous implantable cardioverter defibrillator implantation using the intermuscular two-incision technique.

J Interv Card Electrophysiol 2020 Mar 3;57(2):303-309. Epub 2020 Jan 3.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via N. Giustiniani 2, 35121, Padova, Italy.

Purpose: Operative anaesthetic requirements and perioperative discomfort are barriers to wide adoption of the subcutaneous implantable cardioverter defibrillator (S-ICD) system, especially when the intermuscular technique is used because of the greater amount of tissue dissection. The procedure is most commonly performed under general anaesthesia (GA). There is growing interest in transitioning away from the routine use of GA and towards several alternative anaesthesia modalities for the S-ICD implant procedure without the involvement of an anaesthesiologist. We assessed the feasibility of ultrasound-guided serratus anterior plane block (US-SAPB) in patients undergoing S-ICD implantation with the intermuscular two-incision technique.

Methods: The study population included 38 consecutive patients (84% male; median, 53 [46-62] years) who received S-ICD implantation using the intermuscular two-incision technique. All procedures were performed under US-SAPB and conscious sedation without the involvement of an anaesthesiologist.

Results: The average procedure time was 67 ± 14 min. No patient experienced significant haemodynamic changes or oxygen desaturation during the period of the US-SAPB procedure and sedation; there was no need for pharmacological interventions. The entire procedure was well tolerated without discomfort or complications and with no need for GA, except in one (2.6%) patient who received GA with a laryngeal mask airway. Patients always remained able to respond appropriately to neurological monitoring during the S-ICD implantation procedure. There were no procedure-related complications.

Conclusions: US-SAPB and the intermuscular two-incision technique may be a promising safe and feasible combination for S-ICD implantation, overcoming the potential barrier to wider S-ICD adoption in clinical practice.
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http://dx.doi.org/10.1007/s10840-019-00669-xDOI Listing
March 2020

Clinical predictors of pocket hematoma after cardiac device implantation and replacement.

J Cardiovasc Med (Hagerstown) 2020 Feb;21(2):123-127

Department of Cardiac, Thoracic and Vascular Sciences, University of Padua.

Aims: Pocket hematoma is a common complication of cardiac implantable electronic device (CIED) procedures. the aim of the study was to research the clinical factors associated with pocket hematoma formation after CIED implantation or replacement and to identify the best perioperative antithrombotic management.

Methods: We retrospectively analyzed 500 consecutive patients who underwent to CIED implantation or replacement at our center from November 2014.

Results: Among our population, 206 patients (41.2%) were on anticoagulant therapy at the time of the intervention: 68 (13.6%) on ongoing Warfarin; 111 (22.2%) on low-molecular-weight heparin (LMWH); and 27 (5.4%) on ongoing direct oral anticoagulants. Antiplatelet therapy was present in 262 (52.4%) patients: in particular, 50 (10%) were on dual antiplatelet therapy, 64 (12.8%) were on single antiplatelet therapy and anticoagulant therapy, whereas 12 (2.4%) were on anticoagulant with dual antiplatelet therapy.Incidence of pocket hematoma after CIEDs implantation was of 4.6%. Considering the different perioperative anticoagulant strategies, patients on LMWH presented the higher hematoma rate [11/100 patients (11.0%), P < 0.001]. At the multivariate analysis, anticoagulant with dual antiplatelet therapy (P = 0.021, OR 6.3, IC 1.3-30.8), left ventricular ejection fraction (LVEF) less than 30% (P < 0.001, OR 7.4, IC 2.7-20.4), and use of LMWH (P = 0.008, OR 3.8, IC 1.4-10.6) resulted the strongest predictors of pocket hematoma (Hosmer test = 0.899).Considering replacement procedures, incidence of pocket hematoma was of 4.4%. The incidence was higher after ICD/CRT-D replacement. The majority of pocket hematoma occurred in patients with mechanical valve prosthesis (3/4 cases, 75%, P < 0.001).

Conclusion: The use of LMWH and a low LVEF expose patients to a higher risk of pocket hematoma after CIED procedures. Anticoagulant with dual antiplatelet therapy and LMWH should be avoided.
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http://dx.doi.org/10.2459/JCM.0000000000000914DOI Listing
February 2020

Functional Regurgitation of Atrioventricular Valves and Atrial Fibrillation: An Elusive Pathophysiological Link Deserving Further Attention.

J Am Soc Echocardiogr 2020 01 1;33(1):42-53. Epub 2019 Nov 1.

Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico, Department of Cardiovascular, Neural and Metabolic Sciences, S. Luca Hospital, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy. Electronic address:

In patients with structurally normal atrioventricular valvular apparatus, functional regurgitation of the mitral or tricuspid valves has been attributed mainly to ventricular dilation and/or dysfunction, through a combination of annulus dilation and tethering of the valve leaflets. The occurrence of functional regurgitation of atrioventricular valves in patients with long-standing persistent atrial fibrillation and atrial dilation but normal ventricular size and function has received much less attention, and its peculiar mechanisms still remain to be understood. This distinct form of functional regurgitation (i.e., "atrial functional regurgitation") may require different treatment and interventional repair approaches than the classical functional regurgitation due to ventricular dilatation and dysfunction ("ventricular functional regurgitation"), and current guideline recommendations do not yet address this distinction. Clarifying the differences in the pathophysiology of atrial functional regurgitation and its management implications is of paramount importance. This review describes briefly the comparative anatomy of mitral and tricuspid apparatus and the pathophysiology and typical echocardiographic features of atrial functional regurgitation compared with ventricular functional regurgitation, as well as the added value of three-dimensional echocardiography as an essential imaging tool to clarify the mechanisms involved in its development.
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http://dx.doi.org/10.1016/j.echo.2019.08.016DOI Listing
January 2020