Publications by authors named "Piergiuseppe Agostoni"

280 Publications

"You can leave your mask on": effects on cardiopulmonary parameters of different airway protection masks at rest and during maximal exercise.

Eur Respir J 2021 Mar 7. Epub 2021 Mar 7.

Centro Cardiologico Monzino IRCCS, Milan, Italy

Background: During the COVID-19 pandemic, the use of protection masks is essential to reduce contagions. However, public opinion reports an associated subjective shortness of breath. We evaluated cardiorespiratory parameters at rest and during maximal exertion to highlight any differences with the use of protection masks.

Methods: Twelve healthy subjects underwent three cardiopulmonary exercise tests: without wearing protection mask, with surgical and with FFP2 mask. Dyspnea was assessed by Borg Scale. Standard pulmonary function tests were also performed.

Results: All the subjects (40.8±12.4 years; 6 males) completed the protocol with no adverse event. At spirometry, from no mask to surgical to FFP2, a progressive reduction of FEV and FVC was observed (3.94±0.91 l, 3.23±0.81 l, 2.94±0.98 l and 4.70±1.21 l, 3.77±1.02 l, 3.52±1.21 l, respectively, p<0.001). Rest ventilation, O uptake (V̇O) and CO production (VCO) were progressively lower with a reduction of respiratory rate. At peak exercise, subjects revealed a progressively higher Borg scale when wearing surgical and FFP2. Accordingly, at peak exercise, V̇O (31.0±23.4, 27.5±6.9, 28.2±8.8 ml/kg/min, p=0.001), ventilation (92±26, 76±22, 72±21 l, p=0.003), respiratory rate (42±8, 38±5, 37±4, p=0.04) and tidal volume (2.28±0.72, 2.05±0.60, 1.96±0.65 l, p=0.001) were gradually lower. We did not observed a significant difference in oxygen saturation.

Conclusions: Protection masks are associated with significant but modest worsening of spirometry and cardiorespiratory parameters at rest and peak exercise. The effect is driven by a ventilation reduction due to an increased airflow resistance. However, since exercise ventilatory limitation is far from being reached, their use is safe even during maximal exercise, with a slight reduction in performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.04473-2020DOI Listing
March 2021

In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies.

Antioxidants (Basel) 2021 Feb 27;10(3). Epub 2021 Feb 27.

Department of Pharmaceutical Sciences (DISFARM), Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy.

Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehensive identification and characterization of the plasma AGEs/ALEs involved in HF (untargeted approach). This work provides the first ex vivo high-resolution mass spectrometry (HR-MS) profiling of AGEs/ALEs occurring in human serum albumin (HSA), the most abundant protein in plasma, characterized by several nucleophilic sites and thus representing the main protein substrate for AGE/ALE formation. A set of AGE/ALE adducts in pooled HF-HSA samples was defined, and a semi-quantitative analysis was carried out in order to finally select those presenting in increased amounts in the HF samples with respect to the control condition. These adducts were statistically confirmed by monitoring their content in individual HF samples by applying a targeted approach. Selected AGEs/ALEs proved to be mostly CML derivatives on Lys residues (i.e., CML-Lys12, CML-Lys378, CML-Lys402), and one deoxy-fructosyl derivative on the Lys 389 (DFK-Lys 389). The nature of CML adducts was finally confirmed using immunological methods and in vitro production of such adducts further confirmed by mass spectrometry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox10030358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997412PMC
February 2021

The semantic of a pandemic: Are cardiovascular patients dying "with" or "from" COVID-19? Reflections from a case report.

Medicine (Baltimore) 2021 Mar;100(9):e25072

Centro Cardiologico Monzino IRCCS.

Rationale: Northern Italy has been particularly hit by the current Covid-19 pandemic. Italian deceased patients have a mean age of 78.5 years and only 1.2% have no comorbidities. These data started a public debate whether patients die "with" or "from" Covid-19. If on one hand the public opinion has been persuaded to believe that Covid-19 infection has poor outcomes just in elderly and/or fragile subjects, on the other hand, hospitals are admitting an increasing number of healthy young patients needing semi-intensive or intensive care units.

Patient Concerns: At the end of March 2020, a 79-year-old patient (M.G.) was admitted to the emergency department of our hospital with a 5 days history of fever, dyspnea, and cough. He was known for hypertension and coronary artery disease with a previous coronary artery stenting. Both the comorbidities were carried out without complications and the patient was previously asymptomatic and in good health. At admission, he was febrile and showed signs of respiratory failure with hypoxia and hypocapnia at blood gas analysis.

Diagnosis: The day after, he was tested for SARS-CoV-2 with a real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swab, which turned positive and a chest CT-Scan was consistent with the diagnosis of interstitial pneumonia.

Interventions: He was treated with i.v. diuretics, paracetamol, prolonged noninvasive ventilation (CPAP), and empiric antibiotic therapy on top of his chronic treatment.

Outcomes: A treatment with heparin and corticosteroids was started; however, he developed irreversible respiratory failure. Invasive ventilation was not considered appropriate due to his comorbidities, low chances of recovery, and intensive care unit overcrowding. The patient died 9 days after admission.

Lessons: Health conditions that are most reported as risk factors are common cardiovascular diseases that can be managed in modern clinical practice. Through a brief illustrative clinical case, we would like to underline how Covid-19 can be per se the cause of death in patients that would otherwise have had an acceptable life expectancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000025072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939151PMC
March 2021

Prognostic role of transferrin saturation in heart failure patients.

Eur J Prev Cardiol 2021 Feb 23. Epub 2021 Feb 23.

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

Aims: In heart failure (HF) iron deficiency (ID) is frequently observed and represents a major mortality risk factor. Purpose of this study was to evaluate the correlation between mortality and ID in a cohort of 661 consecutive patients hospitalized for HF worsening.

Methods And Results: Patients were grouped: (i)according to presence(+)/absence(-) of anaemia (A) and ID defined following World Health Organization (WHO) and European Society of Cardiology (ESC)-American College of Cardiology/American Heart Association/HF society of America (ACC/AHA/HFSA) definitions, respectively: Group A-ID- (n = 123), Group A+ID- (n = 80), Group A+ID+ (n = 247), and Group A-ID+ (n = 211); (ii) according to presence of absolute (serum ferritin < 100μg/L) and functional ID [ferritin between 100 and 300μg/L and transferrin saturation (TSAT) < 20%]; and (iii) according to TSAT <20% and ≥20%. Groups were not different for several clinical features but age, gender, kidney function, and chronic obstructive pulmonary disease. Average follow-up was 1.94 year (±420 days). Overall 5 years mortality rate was 29.5%. Only anaemia and functional ID but not ID as defined by guidelines showed an impact on prognosis. Transferrin saturation <20% (n = 360) patients showed worst prognosis compared to TSAT ≥20% (n = 301) patients. In addition, functional ID patients showed worse prognosis compared patients with ferritin <100μg/L and TSAT <20% or ≥20% likely due to more severe chronic inflammatory status [C-reactive protein, 7.4 (interquartile range 2.7-22.6) and 3.2 (1.4-8.7) mg/L, P < 0.0001 respectively].

Conclusion: We confirmed that in HF anaemia is associated to a poor prognosis. Moreover, we showed that patients with TSAT <20% had worse prognosis compared to those with TSAT ≥20% but the composite of ferritin between 100 and 300 μg/L and TSAT <20% identifies HF patients with the poorest survival rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurjpc/zwaa112DOI Listing
February 2021

Digital PCR for high sensitivity viral detection in false-negative SARS-CoV-2 patients.

Sci Rep 2021 02 22;11(1):4310. Epub 2021 Feb 22.

Unità di Ingegneria Tissutale Cardiovascolare, Centro Cardiologico Monzino, IRCCS, Via Carlo Parea, 4, 20138, Milan, Italy.

Patients requiring diagnostic testing for coronavirus disease 2019 (COVID-19) are routinely assessed by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) amplification of Sars-CoV-2 virus RNA extracted from oro/nasopharyngeal swabs. Despite the good specificity of the assays certified for SARS-CoV-2 molecular detection, and a theoretical sensitivity of few viral gene copies per reaction, a relatively high rate of false negatives continues to be reported. This is an important challenge in the management of patients on hospital admission and for correct monitoring of the infectivity after the acute phase. In the present report, we show that the use of digital PCR, a high sensitivity method to detect low amplicon numbers, allowed us to correctly detecting infection in swab material in a significant number of false negatives. We show that the implementation of digital PCR methods in the diagnostic assessment of COVID-19 could resolve, at least in part, this timely issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-83723-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900100PMC
February 2021

Non-invasive estimation of stroke volume during exercise from oxygen in heart failure patients.

Eur J Prev Cardiol 2020 Apr 29. Epub 2020 Apr 29.

Centro Cardiologico Monzino, IRCCS, Italy.

Aims: In heart failure, oxygen uptake and cardiac output measurements at peak and during exercise are important in defining heart failure severity and prognosis. Several cardiopulmonary exercise test-derived parameters have been proposed to estimate stroke volume during exercise, including the oxygen pulse (oxygen uptake/heart rate). Data comparing measured stroke volume and the oxygen pulse or stroke volume estimates from the oxygen pulse at different stages of exercise in a sizeable population of healthy individuals and heart failure patients are lacking.

Methods: We analysed 1007 subjects, including 500 healthy and 507 heart failure patients, who underwent cardiopulmonary exercise testing with stroke volume determination by the inert gas rebreathing technique. Stroke volume measurements were made at rest, submaximal (∼50% of exercise) and peak exercise. At each stage of exercise, stroke volume estimates were obtained considering measured haemoglobin at rest, predicted exercise-induced haemoconcentration and peripheral oxygen extraction according to heart failure severity.

Results: A strong relationship between oxygen pulse and measured stroke volume was observed in healthy and heart failure subjects at submaximal (R2 = 0.6437 and R2 = 0.6723, respectively), and peak exercise (R2 = 0.6614 and R2 = 0.5662) but not at rest. In healthy and heart failure subjects, agreement between estimated and measured stroke volume was observed at submaximal (-3 ± 37 and -11 ± 72 ml, respectively) and peak exercise (1 ± 31 and 6 ± 29 ml, respectively) but not at rest.

Conclusion: In heart failure patients, stroke volume estimation and oxygen pulse during exercise represent stroke volume, albeit with a relevant individual data dispersion so that both can be used for population studies but cannot be reliably applied to a single subject. Accordingly, whenever needed stroke volume must be measured directly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487320920755DOI Listing
April 2020

Minute ventilation/carbon dioxide production in chronic heart failure.

Eur Respir Rev 2021 Mar 2;30(159). Epub 2021 Feb 2.

Centro Cardiologico Monzino, IRCCS, Milan, Italy.

In chronic heart failure, minute ventilation (') for a given carbon dioxide production (' ) might be abnormally high during exercise due to increased dead space ventilation, lung stiffness, chemo- and metaboreflex sensitivity, early metabolic acidosis and abnormal pulmonary haemodynamics. The '' relationship, analysed either as ratio or as slope, enables us to evaluate the causes and entity of the '/perfusion mismatch. Moreover, the ' axis intercept, when ' is extrapolated to 0, embeds information on exercise-induced dead space changes, while the analysis of end-tidal and arterial CO pressures provides knowledge about reflex activities. The '' relationship has a relevant prognostic power either alone or, better, when included within prognostic scores. The '' slope is reported as an absolute number with a recognised cut-off prognostic value of 35, except for specific diseases such as hypertrophic cardiomyopathy and idiopathic cardiomyopathy, where a lower cut-off has been suggested. However, nowadays, it is more appropriate to report '' slope as percentage of the predicted value, due to age and gender interferences. Relevant attention is needed in '' analysis in the presence of heart failure comorbidities. Finally, '' abnormalities are relevant targets for treatment in heart failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/16000617.0141-2020DOI Listing
March 2021

Multiplexed MRM-Based Proteomics Identified Multiple Biomarkers of Disease Severity in Human Heart Failure.

Int J Mol Sci 2021 Jan 15;22(2). Epub 2021 Jan 15.

Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy.

Heart failure (HF) is a complex disease due to the intricate interplay of several mechanisms, which therefore implies the need for a multimarker strategy to better personalize the care of patients with HF. In this study, we developed a targeted mass spectrometry approach based on multiple reaction monitoring (MRM) to measure multiple circulating protein biomarkers, involved in cardiovascular disease, to address their relevance in the human HF, intending to assess the feasibility of the workflow in the disease monitoring and risk stratification. In this study, we analyzed a total of 60 plasma proteins in 30 plasma samples from eight control subjects and 22 age- and gender- matched HF patients. We identified a panel of four plasma proteins, namely Neuropilin-2, Beta 2 microglobulin, alpha-1-antichymotrypsin, and complement component C9, that were more abundant in HF patients in relation to disease severity and pulmonary dysfunction. Moreover, we showed the ability of the combination of these candidate proteins to discriminate, with sufficient accuracy, HF patients from healthy subjects. In conclusion, we demonstrated the feasibility and potential of a proteomic workflow based on MRM mass spectrometry for the evaluation of multiple proteins in human plasma and the identification of a panel of biomarkers of HF severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22020838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830442PMC
January 2021

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: the Multicenter Italian CORIST Study.

Authors:
Augusto Di Castelnuovo Simona Costanzo Andrea Antinori Nausicaa Berselli Lorenzo Blandi Marialaura Bonaccio Roberto Cauda Giovanni Guaraldi Lorenzo Menicanti Marco Mennuni Giustino Parruti Giuseppe Patti Francesca Santilli Carlo Signorelli Alessandra Vergori Pasquale Abete Walter Ageno Antonella Agodi Piergiuseppe Agostoni Luca Aiello Samir Al Moghazi Rosa Arboretti Marinella Astuto Filippo Aucella Greta Barbieri Alessandro Bartoloni Paolo Bonfanti Francesco Cacciatore Lucia Caiano Laura Carrozzi Antonio Cascio Arturo Ciccullo Antonella Cingolani Francesco Cipollone Claudia Colomba Crizia Colombo Francesca Crosta Gian Battista Danzi Damiano D'Ardes Katleen de Gaetano Donati Francesco Di Gennaro Giuseppe Di Tano Gianpiero D'Offizi Massimo Fantoni Francesco Maria Fusco Ivan Gentile Francesco Gianfagna Elvira Grandone Emauele Graziani Leonardo Grisafi Gabriella Guarnieri Giovanni Larizza Armando Leone Gloria Maccagni Ferruccio Madaro Stefano Maitan Sandro Mancarella Massimo Mapelli Riccardo Maragna Rossella Marcucci Giulio Maresca Silvia Marongiu Claudia Marotta Lorenzo Marra Franco Mastroianni Maria Mazzitelli Alessandro Mengozzi Francesco Menichetti Marianna Meschiari Jovana Milic Filippo Minutolo Beatrice Molena Arturo Montineri Cristina Mussini Maria Musso Daniela Niola Anna Odone Marco Olivieri Antonella Palimodde Roberta Parisi Emanuela Pasi Raffaele Pesavento Francesco Petri Biagio Pinchera Venerino Poletti Claudia Ravaglia Andrea Rognoni Marco Rossato Marianna Rossi Vincenzo Sangiovanni Carlo Sanrocco Laura Scorzolini Raffaella Sgariglia Paola Giustina Simeone Eleonora Taddei Carlo Torti Roberto Vettor Andrea Vianello Marco Vinceti Alexandra Virano Laura Vocciante Raffaele De Caterina Licia Iacoviello

Thromb Haemost 2021 Jan 7. Epub 2021 Jan 7.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy.

Introduction:  A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality.

Aim:  We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients.

Methods:  In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores.

Results:  Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation.

Conclusion:  In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1347-6070DOI Listing
January 2021

Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes.

Eur Heart J 2021 Feb;42(6):700-710

Department of Cardiology (CVK), Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Föhrer Str. 15, 13353 Berlin, Germany.

Aims: The EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and HF symptoms In patients with chronic heArt faiLure) trials evaluated the effects of empagliflozin on exercise ability and patient-reported outcomes in heart failure (HF) with reduced and preserved ejection fraction (EF), with and without type 2 diabetes (T2D), reporting, for the first time, the effects of sodium-glucose co-transporter-2 inhibition in HF with preserved EF (HFpEF).

Methods And Results: HF patients with reduced EF (HFrEF) (≤40%, N = 312, EMPERIAL-Reduced) or preserved EF (>40%, N = 315, EMPERIAL-Preserved), with and without T2D, were randomized to empagliflozin 10 mg or placebo for 12 weeks. The primary endpoint was 6-minute walk test distance (6MWTD) change to Week 12. Key secondary endpoints included Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnoea score. 6MWTD median (95% confidence interval) differences, empagliflozin vs. placebo, at Week 12 were -4.0 m (-16.0, 6.0; P = 0.42) and 4.0 m (-5.0, 13.0; P = 0.37) in EMPERIAL-Reduced and EMPERIAL-Preserved, respectively. As the primary endpoint was non-significant, all secondary endpoints were considered exploratory. Changes in KCCQ-TSS and CHQ-SAS dyspnoea score were non-significant. Improvements with empagliflozin in exploratory pre-specified analyses of KCCQ-TSS responder rates, congestion score, and diuretic use in EMPERIAL-Reduced are hypothesis generating. Empagliflozin adverse events were consistent with those previously reported.

Conclusion: The primary outcome for both trials was neutral. Empagliflozin was well tolerated in HF patients, with and without T2D, with a safety profile consistent with that previously reported in T2D. Hypothesis-generating improvements in exploratory analyses of secondary endpoints with empagliflozin in HFrEF were observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehaa943DOI Listing
February 2021

The MECKI score initiative: Development and state of the art.

Eur J Prev Cardiol 2020 12;27(2_suppl):5-11

Centro Cardiologico Monzino, IRCCS, Italy.

The high morbidity and poor survival rates associated with chronic heart failure still represent a big challenge, despite improvements in treatments and the development of new therapeutic opportunities. The prediction of outcome in heart failure is gradually moving towards a multiparametric approach in order to obtain more accurate models and to tailor the prognostic evaluation to the individual characteristics of a single subject. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was developed 10 years ago from 2715 patients and subsequently validated in a different population. The score allows an accurate evaluation of the risk of heart failure patients using only six variables that include the evaluation of the exercise capacity (peak oxygen uptake and ventilation/CO production slope), blood samples (haemoglobin, Na, Modification of Diet in Renal Disease) and echocardiography (left ventricular ejection fraction). Over the following years, the MECKI score was tested taking into account therapies and specific markers of heart failure, and it proved to be a simple, useful tool for risk stratification and for therapeutic strategies in heart failure patients. The close connection between the centres involved and the continuous updating of the data allow the participating sites to propose substudies on specific subpopulations based on a common dataset and to put together and develop new ideas and perspectives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487320959010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691632PMC
December 2020

Roles of periodic breathing and isocapnic buffering period during exercise in heart failure.

Eur J Prev Cardiol 2020 12;27(2_suppl):19-26

Cardiovascular Department, Ospedali Riuniti and University of Trieste, Italy.

In heart failure, exercise - induced periodic breathing and end tidal carbon dioxide pressure value during the isocapnic buffering period are two features identified at cardiopulmonary exercise testing strictly related to sympathetic activation. In the present review we analysed the physiology behind periodic breathing and the isocapnic buffering period and present the relevant prognostic value of both periodic breathing and the presence/absence of the identifiable isocapnic buffering period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487320952029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691624PMC
December 2020

Risk stratification in cardiomyopathy.

Eur J Prev Cardiol 2020 12;27(2_suppl):52-58

Centro Cardiologico Monzino, IRCCS, Italy.

Prognostic stratification of cardiomyopathies represents a cornerstone for the appropriate management of patients and is focused mainly on arrhythmic events and heart failure. Cardiopulmonary exercise testing provides additional prognostic information, particularly in the setting of heart failure. Cardiopulmonary exercise testing data, integrated in scores such as the Metabolism Exercise Cardiac Kidney Index score have been shown to improve the risk stratification of these patients. Cardiopulmonary exercise testing has been analysed as a potential supplier of prognostic parameters in the context of hypertrophic cardiomyopathy, for which it has been shown that a reduced oxygen consumption peak, an increased ventilation/carbon dioxide production slope and chronotropic incompetence correlate with a worse prognosis. To a lesser extent, in dilated cardiomyopathy, it has been shown that the percentage of oxygen consumption peak, not the pure value, and the ventilation/carbon dioxide production slope are associated with a greater cardiovascular risk. Few data are available about other cardiomyopathies (arrhythmogenic and restrictive). Cardiomyopathy patients should be early and routinely referred to heart failure advanced centres in order to perform a comprehensive risk stratification which should include a cardiopulmonary exercise test, with variables and cut-offs shown to improve their risk stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487320961898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691630PMC
December 2020

Role of comorbidities in heart failure prognosis Part 2: Chronic kidney disease, elevated serum uric acid.

Eur J Prev Cardiol 2020 12;27(2_suppl):35-45

Cardiology Dept, Guglielmo da Saliceto Hospital, AUSL Piacenza and University of Parma, Italy.

Despite improvements in pharmacotherapy, morbidity and mortality rates in community-based populations with chronic heart failure still remain high. The increase in medical complexity among patients with heart failure may be reflected by an increase in concomitant non-cardiovascular comorbidities, which are recognized as independent prognostic factors in this population. Heart failure and chronic kidney disease share many risk factors, and often coexist. The presence of kidney failure is associated with incremented risk of cardiovascular and non-cardiovascular mortality in heart failure patients. Chronic kidney disease is also linked with underutilization of evidence-based heart failure therapy that may reduce morbidity and mortality. More targeted therapies would be important to improve the prognosis of patients with these diseases. In recent years, serum uric acid as a determinant of cardiovascular risk has gained interest. Epidemiological, experimental and clinical data show that patients with hyperuricaemia are at increased risk of cardiac, renal and vascular damage and cardiovascular events. Moreover, elevated serum uric acid predicts worse outcome in both acute and chronic heart failure. While studies have raised the possibility of preventing heart failure through the use of uric acid lowering agents, the literature is still inconclusive on whether the reduction in uric acid will result in a measurable clinical benefit. Available evidences suggest that chronic kidney disease and elevated uric acid could worsen heart failure patients' prognosis. The aim of this review is to analyse a possible utilization of these comorbidities in risk stratification and as a therapeutic target to get a prognostic improvement in heart failure patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487320957793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691631PMC
December 2020

The MECKI score initiative: a successful and ongoing story.

Eur J Prev Cardiol 2020 12;27(2_suppl):3-4

Centro Cardiologico Monzino, IRCCS, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487320952692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691625PMC
December 2020

[Grey zones on diabetes in cardiovascular disease. Expert opinion].

G Ital Cardiol (Rome) 2020 Dec;21(12):916-922

Centro Studi ANMCO, Fondazione per il Tuo cuore - Heart Care Foundation Onlus, Firenze.

Clinical guidelines, while representing an objective reference to perform correct therapeutic choices, contain grey zones, where recommendations are not supported by solid evidence. In a conference held in Bergamo in October 2018, an attempt was made to highlight some of the main grey zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies in diabetes mellitus and cardiovascular disease. The first topic concerns the appropriateness of second level cardiovascular screening of the entire population of diabetic patients. The second gap in evidence concerns the validity of a target of glycated hemoglobin considering the last trials. The work has also been implemented with the evidences deriving from important randomized studies published after the date of the Conference.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1714/3472.34545DOI Listing
December 2020

How Patients With Heart Failure Perform Daily Life Activities: An Innate Energy-Saving Strategy.

Circ Heart Fail 2020 11 17;13(11):e007503. Epub 2020 Nov 17.

Centro Cardiologico Monzino, IRCCS, Milano, Italy (M.M., E.S., A.B., P.G., F.D.M., C.V., G.B., P.A.).

Background: Cardiopulmonary exercise test and 6-minute walking test are frequently used tools to evaluate physical performance in heart failure (HF), but they do neither represent activities of daily living (ADLs) nor fully reproduce patients' symptoms. We assessed differences in task oxygen uptake, both as absolute value and as percentage of peak oxygen consumption (peakVO), ventilation efficiency (VE/VCO ratio), and dyspnea intensity (Borg scale) in HF and healthy subjects during standard ADLs and other common physical actions.

Methods: Healthy and HF subjects (ejection fraction <45%, stable conditions) underwent cardiopulmonary exercise test. All of them, carrying a wearable metabolic cart, performed a 6-minute walking test, two 4-minute treadmill exercises (at 2 and 3 km/h), and ADLs: ADL1 (getting dressed), ADL2 (folding 8 towels), ADL3 (putting away 6 bottles), ADL4 (making a bed), ADL5 (sweeping the floor for 4 minutes), ADL6 (climbing 1 flight of stairs carrying a load).

Results: Sixty patients with HF (age 65.2±12.1 years; ejection fraction 30.4±6.7%, peakVO 14.2±4.0 mL/[min·kg]) and 40 healthy volunteers (58.9±8.2 years, peakVO 28.1±7.4 mL/[min·kg]) were enrolled. For each exercise, patients showed higher VE/VCO ratio, percentage of peakVO, and Borg scale value than controls, while absolute values of task oxygen uptake and exercise duration were lower and higher, respectively, in all activities, except for treadmill (fixed execution time and intensity). Differently from Borg Scale data, metabolic values and exercise time length changed in parallel with HF severity, except for ADL duration in very short (ADL3) and composite (ADL1) activities. Borg scale values correlated with percentage of peakVO.

Conclusions: During ADLs, patients self-regulated activities in parallel with HF severity by decreasing intensity (VO) and prolonging the effort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007503DOI Listing
November 2020

Cardiac output changes during exercise in heart failure patients: focus on mid-exercise.

ESC Heart Fail 2021 Feb 17;8(1):55-62. Epub 2020 Nov 17.

Centro Cardiologico Monzino, IRCCS, Milan, Italy.

Aims: Peak exercise oxygen uptake (VO ) and cardiac output (CO) are strong prognostic indexes in heart failure (HF) but unrelated to real-life physical activity, which is associated to submaximal effort.

Methods And Results: We analysed maximal cardiopulmonary exercise test with rest, mid-exercise, and peak exercise non-invasive CO measurements (inert gas rebreathing) of 231 HF patients and 265 healthy volunteers. HF patients were grouped according to exercise capacity (peak VO  < 50% and ≥50% pred, Groups 1 and 2). To account for observed differences, data regarding VO , CO, stroke volume (SV), and artero-venous O content difference [ΔC(a-v)O ] were adjusted by age, gender, and body mass index. A multiple regression analysis was performed to predict peak VO from mid-exercise cardiopulmonary exercise test and CO parameters among HF patients. Rest VO was lower in HF compared with healthy subjects; meanwhile, Group 1 patients had the lowest CO and highest ΔC(a-v)O . At mid-exercise, Group 1 patients achieved a lower VO , CO, and SV [0.69 (interquartile range 0.57-0.80) L/min; 5.59 (4.83-6.67) L/min; 62 (51-73) mL] than Group 2 [0.94 (0.83-1.1) L/min; 7.6 (6.56-9.01) L/min; 77 (66-92) mL] and healthy subjects [1.15 (0.93-1.30) L/min; 9.33 (8.07-10.81) L/min; 87 (77-102) mL]. Rest to mid-exercise SV increase was lower in Group 1 than Group 2 (P = 0.001) and healthy subjects (P < 0.001). At mid-exercise, ΔC(a-v)O was higher in Group 2 [13.6 (11.8-15.4) mL/100 mL] vs. healthy patients [11.6 (10.4-13.2) mL/100 mL] (P = 0.002) but not different from Group 1 [13.6 (12.0-14.9) mL/100 mL]. At peak exercise, Group 1 patients achieved a lower VO , CO, and SV than Group 2 and healthy subjects. ΔC(a-v)O was the highest in Group 2. At multivariate analysis, a model comprising mid-exercise VO , carbon dioxide production (VCO ), CO, haemoglobin, and weight predicted peak VO , P < 0.001. Mid-exercise VO and CO, haemoglobin, and weight added statistically significantly to the prediction, P < 0.050.

Conclusions: Mid-exercise VO and CO portend peak exercise values and identify severe HF patients. Their evaluation could be clinically useful.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835620PMC
February 2021

Impact of heart failure on the clinical course and outcomes of patients hospitalized for COVID-19. Results of the Cardio-COVID-Italy multicentre study.

Eur J Heart Fail 2020 12 27;22(12):2238-2247. Epub 2020 Nov 27.

Cardiology, ASST Spedali Civili di Brescia and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.

Aims: To assess the prognostic value of a history of heart failure (HF) in patients with coronavirus disease 2019 (COVID-19).

Methods And Results: We enrolled 692 consecutive patients admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. Mean age was 67.4 ± 13.2 years, 69.5% of patients were males, 90 (13.0%) had a history of HF, median hospitalization length was 14 days (interquartile range 9-24). In-hospital death occurred in 37 of 90 patients (41.1%) with HF history vs. 126 of those with no HF history (20.9%). The increased risk of death associated with HF history remained significant after adjustment for clinical variables related to COVID-19 and HF severity, including comorbidities, oxygen saturation, lymphocyte count and plasma troponin [adjusted hazard ratio (HR) for death: 2.25; 95% confidence interval (CI) 1.26-4.02; P = 0.006 at multivariable Cox regression model including 404 patients]. Patients with a history of HF also had more in-hospital complications including acute HF (33.3% vs. 5.1%, P < 0.001), acute renal failure (28.1% vs. 12.9%, P < 0.001), multiorgan failure (15.9% vs. 5.8%, P = 0.004) and sepsis (18.4% vs. 8.9%, P = 0.006). Other independent predictors of outcome were age, sex, oxygen saturation and oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen ratio (PaO /FiO ). In-hospital treatment with corticosteroids and heparin had beneficial effects (adjusted HR for death: 0.46; 95% CI 0.29-0.74; P = 0.001; n = 404 for corticosteroids, and adjusted HR 0.41; 95% CI 0.25-0.67; P < 0.001; n = 364 for heparin).

Conclusions: Hospitalized patients with COVID-19 and a history of HF have an extremely poor outcome with higher mortality and in-hospital complications. HF history is an independent predictor of increased in-hospital mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2052DOI Listing
December 2020

Pulmonary embolism in patients with COVID-19: characteristics and outcomes in the Cardio-COVID Italy multicenter study.

Clin Res Cardiol 2020 Nov 3. Epub 2020 Nov 3.

Cardiology, ASST Spedali Civili and Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.

Background: Pulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited.

Methods: Data were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between D-dimer levels and PE incidence was evaluated using restricted cubic splines models.

Results: The study included 689 patients (67.3 ± 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9-24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission D-dimer [4344 (1099-15,118) vs. 818.5 (417-1460) ng/mL, p < 0.001]. They also received more frequently darunavir/ritonavir, tocilizumab and ventilation support. Furthermore, they faced more bleeding episodes requiring transfusion (15.6% vs. 5.1%, p < 0.001) and non-significantly higher in-hospital mortality (34.6% vs. 22.9%, p = 0.06). In multivariate regression, only D-dimer was associated with PE (HR 1.72, 95% CI 1.13-2.62; p = 0.01). The relation between D-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline D-dimer < 500 ng/mL.

Conclusions: PE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of D-dimer in this population need to be clarified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00392-020-01766-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607374PMC
November 2020

Prognostic impact of admission high-sensitivity C-reactive protein in acute myocardial infarction patients with and without diabetes mellitus.

Cardiovasc Diabetol 2020 10 20;19(1):183. Epub 2020 Oct 20.

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

Background: High-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM.

Methods: We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint.

Results: Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients.

Conclusions: This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-020-01157-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576820PMC
October 2020

Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study.

Authors:
Augusto Di Castelnuovo Marialaura Bonaccio Simona Costanzo Alessandro Gialluisi Andrea Antinori Nausicaa Berselli Lorenzo Blandi Raffaele Bruno Roberto Cauda Giovanni Guaraldi Ilaria My Lorenzo Menicanti Giustino Parruti Giuseppe Patti Stefano Perlini Francesca Santilli Carlo Signorelli Giulio G Stefanini Alessandra Vergori Amina Abdeddaim Walter Ageno Antonella Agodi Piergiuseppe Agostoni Luca Aiello Samir Al Moghazi Filippo Aucella Greta Barbieri Alessandro Bartoloni Carolina Bologna Paolo Bonfanti Serena Brancati Francesco Cacciatore Lucia Caiano Francesco Cannata Laura Carrozzi Antonio Cascio Antonella Cingolani Francesco Cipollone Claudia Colomba Annalisa Crisetti Francesca Crosta Gian B Danzi Damiano D'Ardes Katleen de Gaetano Donati Francesco Di Gennaro Gisella Di Palma Giuseppe Di Tano Massimo Fantoni Tommaso Filippini Paola Fioretto Francesco M Fusco Ivan Gentile Leonardo Grisafi Gabriella Guarnieri Francesco Landi Giovanni Larizza Armando Leone Gloria Maccagni Sandro Maccarella Massimo Mapelli Riccardo Maragna Rossella Marcucci Giulio Maresca Claudia Marotta Lorenzo Marra Franco Mastroianni Alessandro Mengozzi Francesco Menichetti Jovana Milic Rita Murri Arturo Montineri Roberta Mussinelli Cristina Mussini Maria Musso Anna Odone Marco Olivieri Emanuela Pasi Francesco Petri Biagio Pinchera Carlo A Pivato Roberto Pizzi Venerino Poletti Francesca Raffaelli Claudia Ravaglia Giulia Righetti Andrea Rognoni Marco Rossato Marianna Rossi Anna Sabena Francesco Salinaro Vincenzo Sangiovanni Carlo Sanrocco Antonio Scarafino Laura Scorzolini Raffaella Sgariglia Paola G Simeone Enrico Spinoni Carlo Torti Enrico M Trecarichi Francesca Vezzani Giovanni Veronesi Roberto Vettor Andrea Vianello Marco Vinceti Raffaele De Caterina Licia Iacoviello

Nutr Metab Cardiovasc Dis 2020 10 31;30(11):1899-1913. Epub 2020 Jul 31.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy; Department of Medicine and Surgery, University of Insubria, Varese, Italy. Electronic address:

Background And Aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death.

Methods And Results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses.

Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2020.07.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833278PMC
October 2020

Association of Troponin Levels With Mortality in Italian Patients Hospitalized With Coronavirus Disease 2019: Results of a Multicenter Study.

JAMA Cardiol 2020 Nov;5(11):1274-1280

Cardiology Unit, Cardiovascular Department, Papa Giovanni XXIII Hospital-Bergamo, Bergamo, Italy.

Importance: Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19). However, the initial data were reported from single-center or 2-center studies in Chinese populations. Compared with these patients, European and US patients are older, with more comorbidities and higher mortality rates.

Objective: To evaluate the prevalence and prognostic value of myocardial injury, detected by elevated plasma troponin levels, in a large population of White Italian patients with COVID-19.

Design, Setting, And Participants: This is a multicenter, cross-sectional study enrolling consecutive patients with laboratory-confirmed COVID-19 who were hospitalized in 13 Italian cardiology units from March 1 to April 9, 2020. Patients admitted for acute coronary syndrome were excluded. Elevated troponin levels were defined as values greater than the 99th percentile of normal values.

Main Outcomes And Measures: Clinical characteristics and outcomes stratified as elevated or normal cardiac troponin levels at admission, defined as troponin T or troponin I at a level greater than the 99th percentile of normal values.

Results: A total of 614 patients with COVID-19 were included in this study (mean age [SD], 67 [13] years; 70.8% male), of whom 148 patients (24.1%) died during the hospitalization. Elevated troponin levels were found in 278 patients (45.3%). These patients were older (mean [SD] age, 64.0 [13.6] years vs 71.3 [12.0] years; P < .001) and had higher prevalence of hypertension (168 patients [50.5%] vs 182 patients [65.9%]; P < .001), heart failure (24 [7.2%]; 63 [22.8%]; P < .001), coronary artery disease (50 [15.0%] vs 87 [31.5%]; P < .001), and atrial fibrillation (33 [9.9%] vs 67 [24.3%]; P < .001). Elevated troponin levels were associated with an increased in-hospital mortality (37% vs 13%; HR, 1.71 [95% CI, 1.13-2.59]; P = .01 via multivariable Cox regression analysis), and this was independent from concomitant cardiac disease. Elevated troponin levels were also associated with a higher risk of in-hospital complications: heart failure (44 patients [19.2%] vs 7 patients [2.9%]; P < .001), sepsis (31 [11.7%] vs 21 [6.4%]; P = .03), acute kidney failure (41 [20.8%] vs 13 [6.2%]; P < .001), multiorgan failure (21 [10.9%] vs 6 [2.9%]; P = .003), pulmonary embolism (27 [9.9%] vs 17 [5.2%]; P = .04), delirium (13 [6.8%] vs 3 [1.5%]; P = .02), and major bleeding (16 [7.0%] vs 4 [1.6%]; P = .008).

Conclusions And Relevance: In this multicenter, cross-sectional study of Italian patients with COVID-19, elevated troponin was an independent variable associated with in-hospital mortality and a greater risk of cardiovascular and noncardiovascular complications during a hospitalization for COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2020.3538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450398PMC
November 2020

S-Thiolation Targets Albumin in Heart Failure.

Antioxidants (Basel) 2020 Aug 17;9(8). Epub 2020 Aug 17.

Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy.

Human serum albumin (HSA) is associated with several physiological functions, such as maintaining oncotic pressure and microvascular integrity, among others. It also represents the major and predominant antioxidant in plasma due to the presence of the Cys34 sulfhydryl group. In this study, we assessed qualitative and quantitative changes in HSA in patients with heart failure (HF) and their relationship with the severity of the disease. We detected by means of mass spectrometry a global decrease of the HSA content in the plasma of HF patients in respect to control subjects, a significant increase of thio-HSA with a concomitant decrease in the reduced form of albumin. Cysteine and, at a lesser extent, homocysteine represent the most abundant thiol bound to HSA. A strong inverse correlation was also observed between cysteine-HSA and peak VO/kg, an index of oxygen consumption associated with HF severity. Moreover, in HL-1 cardiomyocytes incubated with HO, we showed a significant decrease of cell viability in cells treated with thio-HSA in respect to restored native-HSA. In conclusion, we found for the first time that S-thiolation of albumin is increased in the plasma of HF patients and induced changes in the structure and antioxidant function of HSA, likely contributing to HF progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox9080763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463808PMC
August 2020

Rationale and design of the EPLURIBUS Study (Evidence for a comPrehensive evaLUation of left ventRicle dysfnctIon By a whole-heart coverage cardiac compUted tomography Scanner).

J Cardiovasc Med (Hagerstown) 2020 Oct;21(10):812-819

Cardiovascular Imaging Department, Centro Cardiologico Monzino, IRCCS.

Background: Cardiac magnetic resonance (CMR) is the standard of reference for myocardial fibrosis detection by late gadolinium enhancement. Cardiac computed tomography (CCT) is emerging as a promising alternative. The Evidence for a comPrehensive evaLUation of left ventRicle dysfnctIon By a whole-heart coverage cardiac compUted tomography Scanner study will assess the feasibility and diagnostic accuracy of a comprehensive functional and anatomical cardiac evaluation with CCT as compared with CMR and invasive coronary angiography as standard of reference.

Methods: Consecutive patients with a newly diagnosed left ventricle (LV) dysfunction (left ventricular ejection fraction <50%) and a clinical indication to CMR will be screened. Exclusion criteria will be contraindications to contrast agents and impaired renal function. CCT will be performed per protocol within 10 days from CMR. A total of 100 patients will be enrolled within 24 months. We will evaluate with CCT volume and ejection fraction of the LV and right ventricle, presence, extent and pattern of delayed enhancement and cardiac venous system. Moreover, presence and degree of coronary stenoses will be evaluated among patients undergoing invasive coronary angiography in the 6 months following CCT.

Results: The primary study endpoints will be: first, to assess the diagnostic performance of CCT vs. CMR to detect the delayed enhancement in a territory-based and patient-based analysis; second, to assess the agreement between CCT and CMR in the discrimination between ischemic vs. nonischemic delayed enhancement patters in a territory-based analysis; third, to assess the correlation between CCT and CMR for LV and right ventricle end-diastolic and end-systolic volumes and ejection fraction measurements.

Conclusion: The Evidence for a comPrehensive evaLUation of left ventRicle dysfnctIon By a whole-heart coverage cardiac compUted tomography Scanner study will assess the diagnostic performance of CCT using the latest scanner generation for a comprehensive evaluation of patients with new-onset LV dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2459/JCM.0000000000001051DOI Listing
October 2020

Sacubitril/valsartan use in a real-world population of patients with heart failure and reduced ejection fraction.

J Cardiovasc Med (Hagerstown) 2020 Nov;21(11):882-888

Centro Cardiologico Monzino, IRCCS, Heart Failure Unit.

Aims: Practice guidelines recommend sacubitril/valsartan for heart failure with reduced ejection fraction. The aim of our study was to describe the use of sacubitril/valsartan in real-world clinical practice to help identify patients best able to tolerate titration to higher doses.

Methods: We retrospectively analyzed clinical data for 201 patients with heart failure with reduced ejection fraction prescribed sacubitril/valsartan at our heart failure clinic (Centro Cardiologico Monzino) between September 2016/December 2018. Patients had a mean age of 67.2 years, mean left ventricular ejection fraction of 30.1%, New York Heart Association class II (65%), class III (35%), and poor cardiopulmonary exercise capacity. Median 2-year risk of death/urgent cardiac transplantation was 8.9% [Metabolic Exercise Cardiac Kidney Index (MECKI) score].

Results: After a median follow-up of 230 (interquartile interval: 105-366) days, 57 patients achieved higher-dose sacubitril/valsartan, 103 tolerated medium/low doses, nine died, and 20 interrupted treatment. The highest dose of sacubitril/valsartan was reached by younger patients with better hemoglobin (Hb) levels, renal function, and blood pressure (BP). Patients continuing on sacubitril/valsartan had significantly higher serum Hb and sodium, better BP, and lower MECKI scores than patients who discontinued treatment or died during follow-up. Our patients were older and frailer than those in the pivotal PARADIGM-HF trial.

Conclusion: In our experience, more than one-third of the patients were able to tolerate the higher dose of sacubitril/valsartan, and these patients were younger, had higher Hb, and better BP and renal function. MECKI score stratification was useful to discriminate patients who continued treatment from those who did not. Future prospective studies should test if these clinical variables can guide the up-titration of sacubitril/valsartan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2459/JCM.0000000000001018DOI Listing
November 2020

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use.

Card Fail Rev 2020 Mar 8;6:e19. Epub 2020 Jul 8.

Critical Care Proprietary Products, Orion Pharma Espoo, Finland.

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15420/cfr.2020.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374352PMC
March 2020

A new pathophysiology in heart failure patients.

Artif Organs 2020 Dec 12;44(12):1303-1305. Epub 2020 Aug 12.

Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, University of Rome "Sapienza", Policlinico Umberto I, Rome, Italy.

In the treatment of patients with severe heart failure, left ventricle assist device plays an important role, especially as a destination therapy. Nevertheless, even in successful cases, patients' progressive weaning is rarely taken into consideration. The recovery of more physiological circulation conditions is not a main goal. This hypothesis is discussed in this article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aor.13770DOI Listing
December 2020