[ANMCO Position paper: States General 2023 - Digital medicine in cardiology: evidence and state of progress in Italy]. / Position paper ANMCO: Stati Generali 2023 ­ La medicina digitale in cardiologia: evidenze e stato di avanzamento in Italia.

Technological innovation provides easily accessible tools capable of simplifying healthcare processes. Notably, digital technology application in the cardiology field can improve prognosis, reduce costs, and lead to an overall improvement in healthcare. The digitization of health data, with the use of electronic health records and of electronic health files in Italy, represents one of the fields of application of digital technologies in medicine. The 2023 States General of the Italian Association of Hospital Cardiologists (ANMCO) provided an opportunity to focus attention on the potential benefits and critical issues associated with the implementation of the aforementioned digital tools, artificial intelligence, and telecardiology. This document summarizes key aspects that emerged during the event.

[ANMCO Position paper: Choosing Wisely - ANMCO proposals for 2023]. / Position paper ANMCO: Choosing Wisely ­ le proposte dell'ANMCO nel 2023.

Nowadays, a progressive and exponential increase in the use of invasive and non-invasive instrumental diagnostics and therapeutic services has been shown. Although unnecessary, instrumental examinations are often largely prescribed, replacing clinical evaluation. Their correct use, on the contrary, would address precise epidemiological and clinical contexts. Therefore identifying whether a test or procedure is appropriate or not plays a crucial role in clinical practice. Several documents from scientific societies and expert groups indicate the most appropriate cardiovascular diagnostic and therapeutic procedures. The international Choosing Wisely campaign invited the main scientific societies to identify five techniques or treatments used in their field that are often unnecessary and may potentially damage patients. The Italian Association of Hospital Cardiologists (ANMCO) joined the project identifying the five cardiological practices in our country at greater risk of inappropriateness in 2014. This list has recently been updated. Moreover, possible solutions to this problem have been proposed.

The influence of pectus excavatum on cardiac kinetics and function in otherwise healthy individuals: A systematic review.

BACKGROUND: A number of anterior chest wall deformities, most notably pectus excavatum (PE), may have a detrimental effect on cardiac motion and function. Interpretation of transthoracic echocardiography (TTE) and speckle-tracking echocardiography (STE) results may be hampered by the possible influence of PE on cardiac kinetics. METHODS: A comprehensive search of all articles assessing cardiac function in PE individuals was carried out. Inclusion criteria were: 1) individuals aged >10 years; 2) studies providing objective assessment of chest deformity (Haller index). Studies that measured myocardial strain parameters in PE patients were also included. RESULTS: The search (EMBASE and Medline) yielded a total of 392 studies, 36 (9.2%) of which removed as duplicates; a further 339 did not meet inclusion criteria. The full-texts of 17 studies were then analyzed. All studies concordantly reported impaired right ventricular volumes and function. With respect to left ventricle (LV), TTE studies uniformly demonstrated a significant impairment in conventional echoDoppler indices in PE individuals, whereas STE studies provided conflicting results. Importantly, LV functional alterations promptly reverted upon surgical correction of chest defect. In subjects with PE of mild-to-moderate severity, we observed that degree of anterior chest wall deformity, as noninvasively assessed by modified Haller index (MHI), was strongly associated with myocardial strain magnitude, in heterogenous cohorts of otherwise healthy PE individuals. CONCLUSIONS: Clinicians should be aware that in PE individuals, TTE and STE results may not always be indicative of intrinsic myocardial dysfunction, but may be, at least in part, influenced by artifactual and/or external chest shape determinants.

Impact of the COVID-19 pandemic on prescription of sacubitril/valsartan in Italy.

AIMS: The present study sought to examine the effect of the COVID-19 pandemic and lockdown measures on the prescription of sacubitril/valsartan in patients with heart failure (HF) in Italy. METHODS AND RESULTS: Data from Italian Medicines Agency (AIFA) monitoring registries were analysed. The sacubitril/valsartan monitoring registry is based on 6-month prescriptions. A monthly aggregation on new activations throughout the observational period was computed. From March to December 2020, the initiation of new HF patients on sacubitril/valsartan decreased by nearly 40% with prescriptions dropping to values similar to 2018 when the registry was still operated off-line. A slight increase in prescriptions was observed after the lockdown measures were lifted, but prescriptions remained constantly below the pre-lockdown period. CONCLUSION: A marked and worrisome decline during the COVID-19 pandemic in the activation of a life-saving treatment such as sacubitril/valsartan was observed. This decline was clearly linked to the lockdown measures instated to counteract the COVID-19 pandemic. Upcoming studies should analyse the occurrence of new cases of HF as well as the severity of patients admitted to hospitals and their mortality compared to pre-pandemic levels.

Anthraquinone laxatives use and colorectal cancer: A systematic review and meta-analysis of observational studies.

This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase, Google Scholar, and CENTRAL from inception until March 2021, for randomized controlled trials (RCTs) and observational studies. Through the systematic review, we identified 8 observational studies evaluating AQ laxatives use as a risk factor for CRC development, and 5 studies on CRC risk were included in the meta-analysis using a random-effects model. Through the meta-analysis, we found that a history of AQ laxatives use compared with "other" and "no laxatives" use was associated with CRC development (OR: 1.41; 95% CI: 0.94-2.11), although not at a statistically significant level. The possible association persists even after removal of the outlier studies (OR: 1.51; 95% CI: 0.97-2.34). Selection of cases and controls was judged at low or unclear risk of bias across almost all studies, and the quality of evidence was from moderate to low. In conclusion, it is not possible to associate the use of AQ laxatives with the development of CRC. However, the trend toward an increased risk of CRC provides a strong indication for investigating this issue by performing further high-quality studies.

Mechanical concordance between left atrium and left atrial appendage in nonvalvular atrial fibrillation: can it be exploited to avoid transesophageal echocardiography prior to electrical cardioversion during Covid-19 pandemic?

Transesophageal echocardiography (TEE) is the gold standard for assessing left atrial appendage (LAA) mechanic and thrombosis (LAAT); however, TEE is a high-risk procedure for viral transmission during coronavirus disease 2019 (COVID-19) pandemic. We investigated whether deformation indices of left atrium (LA) at transthoracic echocardiography (TTE) correlate with those of LAA assessed by TEE in nonvalvular atrial fibrillation (NVAF) patients undergoing electrical cardioversion (ECV). Consecutive patients with NVAF of ≥ 48 h or unknown duration, who underwent TEE and TTE at our Institution before ECV were retrospectively investigated. Standard echo-Doppler and LA and LAA myocardial strain and strain rate parameters were analyzed. A total of 115 NVAF patients (71.3 ± 8.1 yr/o, 59.1% men) were included: LAAT was diagnosed in 25 (21.7%) patients. Compared to patients without LAAT, those with LAAT had significantly higher CHA2DS2-VASc Risk score (4.5 ± 1.4 vs. 3.5 ± 1.1, p < 0.001), and lower ejection fraction (46.0 ± 14.8 vs. 57.6 ± 8.6%, p < 0.001). In LAAT patients, global strain of LA (8.7 ± 2.6 vs. 16.3 ± 4.5%, p < 0.001) and LAA (7.0 ± 1.7 vs. 11.7 ± 2.0%, p < 0.001) was significantly reduced compared to non-LAAT patients. A close relationship between left atrial strain reservoir (LASr) and LAA-global strain was demonstrated (r = 0.81). By univariable analysis, CHA2DS2-VASc Risk Score (OR 2.01, 95%CI 1.34-3.00), NT-proBNP (OR 1.36, 95%CI 1.19-1.54), ejection fraction (OR 0.92, 95%CI 0.88-0.96), E/e' ratio (OR 2.07, 95%CI 1.51-2.85), and LASr (OR 0.39, 95%CI 0.25-0.62) were strongly associated with LAAT presence at TEE. By multivariable analysis, only LASr (OR 0.40, 95%CI 0.24-0.70) retained statistical significance. ROC curve analysis revealed that an LASr cut-off value ≤ 9.3% had 98.9% sensibility and 100% specificity to identify LAAT by TEE (AUC = 0.98). In patients with NVAF of ≥ 48 h or unknown duration, scheduled to undergo ECV, LA deformation assessment by TTE might substitute invasive measurement of LAA function by TEE, simplifying diagnostic approach and possibly contributing to reduce COVID-19 infection diffusion.

Does chest shape influence exercise stress echocardiographic results in patients with suspected coronary artery disease?

Despite the good specificity of exercise stress echocardiography (ESE) for the detection of coronary artery disease (CAD), false positive (FP) results may occur. We have previously reported that chest abnormalities may affect parameters of cardiac contractility. The influence of chest shape on ESE results has never been previously investigated. We retrospectively analyzed 160 consecutive patients (64.4 ± 13.0-year old, 91 women) who had undergone coronary angiography at our Institution because of positive ESE, between June 2014 and May 2020. Modified Haller index (MHI; chest transverse diameter over the distance between sternum and spine) was assessed in all patients. Obstructive CAD was diagnosed by ≥ 70% stenosis in any epicardial coronary artery. Outcome was false-positivity at ESE. 80.6% of patients were diagnosed with obstructive CAD, while 19.4% had no CAD (FP). We separately analyzed patients with normal chest shape (MHI ≤ 2.5) and those with concave-shaped chest wall (MHI > 2.5). These latter were mostly women with small cardiac chambers, mitral valve prolapse (MVP) and exercise-induced ST-segment changes. Likelihood of false-positivity was significantly higher in subjects with MHI > 2.5 than those with MHI ≤ 2.5 (30.7% vs 9.4%, p = 0.001). By multivariate logistic regression analysis, MHI > 2.5 (OR 4.04, 95%CI 1.45-11.2, p = 0.007), MVP (OR 3.47, 95%CI 1.32-9-12, p = 0.01) and dyssynergy in the left circumflex territory (OR = 3.35, 95%CI 1.26-8.93, p = 0.01) were independently associated with false-positivity. Concave-shaped chest wall (MHI > 2.5) may be associated with false-positive stress echocardiographic result. Mechanisms underpinning this finding need to be further explored.

Chest conformation spuriously influences strain parameters of myocardial contractile function in healthy pregnant women.

AIMS: Left ventricular (LV) contractility during noncomplicated pregnancy has been previously investigated by two-dimensional speckle-tracking echocardiography (2D-STE), with conflicting results. Chest abnormalities might affect myocardial strain parameters, yet this issue has not been previously investigated during pregnancy. We evaluated the influence of chest conformation on myocardial strain parameters in healthy pregnant women. METHODS: Between October 2019 and February 2020, 50 healthy pregnant women (32.3 ±â€Š4.0 years old) were consecutively studied. They underwent obstetric visit, assessment of chest shape by modified Haller index (MHI; chest transverse diameter over the distance between sternum and spine) and transthoracic echocardiography implemented with 2D-STE analysis of all myocardial strain parameters in the first trimester (12-14 weeks), third trimester (36-38 weeks) and 6-9 weeks after delivery. RESULTS: LV ejection fraction remained substantially unchanged (P = 0.13), while on the average all myocardial strain parameters showed a small but significant decrease during pregnancy, and recovered postpartum (all P < 0.001). Women with concave-shaped chest wall (MHI > 2.5, n = 29), and those with normal chest conformation (MHI ≤ 2.5, n = 21) were then separately analyzed. Pregnant women with MHI above 2.5, but not those with MHI 2.5 or less, showed a progressive but reversible decrease in all myocardial strain parameters (all P < 0.001). MHI was strongly correlated with LV global longitudinal strain (r = -0.87) and LV global circumferential strain (r = -0.83) in the third trimester of pregnancy. CONCLUSION: Myocardial strain impairment during healthy pregnancy may not reflect intrinsic myocardial dysfunction but rather intraventricular dyssynchrony related to a narrow antero-posterior chest diameter and rise in the diaphragm, with consequent extrinsic myocardial compression.

Unity Is Intelligence: A Collective Intelligence Experiment on ECG Reading to Improve Diagnostic Performance in Cardiology.

Medical errors have a huge impact on clinical practice in terms of economic and human costs. As a result, technology-based solutions, such as those grounded in artificial intelligence (AI) or collective intelligence (CI), have attracted increasing interest as a means of reducing error rates and their impacts. Previous studies have shown that a combination of individual opinions based on rules, weighting mechanisms, or other CI solutions could improve diagnostic accuracy with respect to individual doctors. We conducted a study to investigate the potential of this approach in cardiology and, more precisely, in electrocardiogram (ECG) reading. To achieve this aim, we designed and conducted an experiment involving medical students, recent graduates, and residents, who were asked to annotate a collection of 10 ECGs of various complexity and difficulty. For each ECG, we considered groups of increasing size (from three to 30 members) and applied three different CI protocols. In all cases, the results showed a statistically significant improvement (ranging from 9% to 88%) in terms of diagnostic accuracy when compared to the performance of individual readers; this difference held for not only large groups, but also smaller ones. In light of these results, we conclude that CI approaches can support the tasks mentioned above, and possibly other similar ones as well. We discuss the implications of applying CI solutions to clinical settings, such as cases of augmented 'second opinions' and decision-making.

When a Friend Becomes Your Enemy: Natural Killer Cells in Atherosclerosis and Atherosclerosis-Associated Risk Factors.

Atherosclerosis (ATS), the change in structure and function of arteries with associated lesion formation and altered blood flow, is the leading cause of cardiovascular disease, the number one killer worldwide. Beyond dyslipidemia, chronic inflammation, together with aberrant phenotype and function of cells of both the innate and adaptive immune system, are now recognized as relevant contributors to atherosclerosis onset and progression. While the role of macrophages and T cells in atherosclerosis has been addressed in several studies, Natural Killer cells (NKs) represent a poorly explored immune cell type, that deserves attention, due to NKs' emerging contribution to vascular homeostasis. Furthermore, the possibility to re-polarize the immune system has emerged as a relevant tool to design new therapies, with some succesfull exmples in the field of cancer immunotherapy. Thus, a deeper knowledge of NK cell pathophysiology in the context of atherosclerosis and atherosclerosis-associated risk factors could help developing new preventive and treatment strategies, and decipher the complex scenario/history from "the risk factors for atherosclerosis" Here, we review the current knowledge about NK cell phenotype and activities in atherosclerosis and selected atherosclerosis risk factors, namely type-2 diabetes and obesity, and discuss the related NK-cell oriented environmental signals.

Influence of chest conformation on myocardial strain parameters in healthy subjects with mitral valve prolapse.

Chest shape might affect myocardial strain parameters. However, the relationship between myocardial strain parameters and chest conformation has not been previously investigated in subjects with mitral valve prolapse (MVP). Between April 2019 and May 2020, 60 healthy subjects (50.1 ± 8.6 year/old, 46.6% females) with MVP and mild-to-moderate mitral regurgitation, and 60 controls matched by age, sex, and cardiovascular risk factors were consecutively studied. Participants underwent modified Haller index (MHI) assessment (ratio of chest transverse diameter over the distance between sternum and spine), and transthoracic echocardiography implemented with 2D-speckle tracking analysis. MHI was significantly greater in MVP group than controls (2.6 ± 0.35 vs 2.1 ± 0.23, p < 0.0001). Left ventricular (LV) ejection fraction was similar in MVP and controls (63.5 ± 3.7% vs 64.3 ± 3.9%, p = 0.25). LV regional and global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) parameters and LV peak twist were all significantly lower in MVP compared to controls (all p < 0.0001). MVP subjects with a tight chest (MHI > 2.5, n = 30), and those with MHI ≤ 2.5 (n = 30) were then separately analyzed. A significant impairment in myocardial strain parameters and LV peak twist was documented in MVP subjects with MHI > 2.5, but not in those with MHI ≤ 2.5. MHI showed a strong inverse correlation with LV-GLS (r = - 0.85), GCS (r = - 0.84), GRS (r = - 0.84) and LV peak twist (r = - 0.94). In MVP subjects, impairment of myocardial strain parameters is not due to intrinsic reduction of cardiac contractility function, but it appears to be related to the degree of chest deformity.

Personalized-medicine on carotid endarterectomy and stenting.

Evidence based medicine (EBM) is the core of current clinical guidelines and is considered as the gold standard of clinical practice. Despite this, a number of limitations and criticisms are moved to EBM. The major one is that this method privileges randomized controlled trials (RCTs), in which the selection of patients is often based on rigid inclusion criteria. The lack of "pragmatism" of some RCTs sometimes makes it difficult to apply guidelines that derive from them to patients observed in clinical practice, who are often affected by comorbidities and disabilities. The new paradigm to overcome this limitation is personalized medicine (PM), which aims to take into account the particular characteristics displayed by the individual. In order to tailor the best treatment for the patient, PM uses EBM but emphasizes the person's specific information from the assessment of the clinic, lifestyle and risk/benefit scores. This narrative review tries to find the best evidence by analysing subgroups and risk scores of patients from meta-analysis and RCTs in order to try to apply PM and to provide good practice points (GPP) on grey aspects and open questions not fully covered by current guidelines on carotid endarterectomy (CEA) and stenting for stroke prevention.

Association between neutrophil to lymphocyte ratio and carotid artery wall thickness in healthy pregnant women.

OBJECTIVE: Pregnancy may elicit a state of mild inflammation that might affect, either directly or indirectly, haematological parameters associated with systemic inflammation. In particular, both Neutrophil-to-lymphocyte ratio (NLR) and Red blood cells Distribution Width (RDW) have been found to be elevated in complicated pregnancy. However, data regarding the association of these haematological parameters with common carotid artery (CCA) intima-media thickness (IMT) in healthy pregnancy are scanty. Aim of this study was to evaluate possible changes in CCA-IMT during normal pregnancy and in the postpartum period, and to correlate these changes with NLR and RDW. STUDY DESIGN: Between October 2019 and February 2020, a prospective study was carried out on 73 consecutive healthy pregnant women (32.8 ± 4.9 yrs/old). Women underwent obstetric assessment, complete blood cell counts with calculation of NLR and RDW, two-dimensional transthoracic echocardiography and carotid Doppler ultrasonography. RESULTS: During normal pregnancy, both NLR and RDW progressively increased (p < 0.0001); likewise, parameters of carotid dimensions also significantly increased (p < 0.0001). Hematological and morphological changes all decreased in postpartum period. By univariable logistic regression, the variables which showed the greatest independent association with CCA-IMT (defined as CCA-IMT ≥0.55 mm) were: age (HR 1.33, 95% CI 1.15-1.53, p < 0.0001), pre-pregnant BMI (HR 2.75, 95% CI 1.72-4.41, p < 0.0001), third trimester E/e' ratio (HR 1.64, 95% CI 1.34-2.02, p < 0.0001), and third trimester NLR (HR 3.00, 95% CI 1.64-5.50, p < 0.0001). Multivariable logistic regression analysis demonstrated that third trimester NLR was the only variable that retained statistical significance (HR 2.49, 95% CI 1.35-4.59, p = 0.003). An NLR ≥ 2 reached 83% of sensitivity and 99% of specificity in identifying a CCA-IMT ≥0.55 mm (AUC = 0.95). A strong linear correlation of both third trimester NLR and RDW with CCA-IMT was observed (r = 0.89 and 0.83, respectively). CONCLUSIONS: Pregnancy is a state of chronic mild inflammation and the progressive increase in NLR and RDW during normal pregnancy is significantly associated with CCA intimal-medial thickening.

[HCF-ANMCO/AICPR/GIEC/ITAHFA/SICOA/SICP/SIMG/SIT Cardiological Societies Council Consensus document: Anticoagulant therapy in venous thromboembolism and atrial fibrillation of the patient with cancer. Current knowledge and new evidence]. / Documento di consenso della Consulta delle Società Cardiologiche HCF-ANMCO/AICPR/GIEC/ITAHFA/SICOA/SICP/SIMG/SIT: La terapia anticoagulante nel tromboembolismo venoso e nella fibrillazione atriale del paziente con cancro. Le attuali conoscenze e le nuove evidenze.

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, either symptomatic or incidental, is a common complication in the history of cancer disease. The risk of VTE is 4-7-fold higher in oncology patients, and it represents the second leading cause of death, after cancer itself. In cancer patients, compared with the general population, VTE therapy is associated with higher rates of recurrent thrombosis and/or major bleeding. The need for treatment of VTE in patients with cancer is a challenge for the clinician because of the multiplicity of types of cancer, the disease stage and the imbricated cancer treatment. Historically, in cancer patients, low molecular weight heparins have been preferred for treatment of VTE. More recently, in large randomized clinical trials, direct oral anticoagulants (DOACs) demonstrated to reduce the risk of VTE. However, in the "real life", uncertainties remain on the use of DOACs, especially for the bleeding risk in patients with gastrointestinal cancers and the potential drug-to-drug interactions with specific anticancer therapies.In cancer patients, atrial fibrillation can arise as a perioperative complication or for the side effect of some chemotherapy agents, as well as a consequence of some associated risk factors, including cancer itself. The current clinical scores for predicting thrombotic events (CHA2DS2-VASc) or for predicting bleeding (HAS-BLED), used to guide antithrombotic therapy in the general population, have not yet been validated in cancer patients. Encouraging data for DOAC prescription in patients with atrial fibrillation and cancer are emerging: recent post-hoc analysis showed safety and efficacy of DOACs for the prevention of embolic events compared to warfarin in cancer patients. Currently, anticoagulant therapy of cancer patients should be individualized with multidisciplinary follow-up and frequent reassessment. This consensus document represents an advanced state of the art on the subject and provides useful notes on clinical practice.

Genomewide Association Study of Platelet Reactivity and Cardiovascular Response in Patients Treated With Clopidogrel: A Study by the International Clopidogrel Pharmacogenomics Consortium.

Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss-of-function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals, using adenosine diphosphate-induced platelet reactivity and major cardiovascular and cerebrovascular events as outcome parameters. GWAS for platelet reactivity revealed a strong signal for CYP2C19*2 (P value = 1.67e-33). After correction for CYP2C19*2 no other single-nucleotide polymorphism reached genomewide significance. GWAS for a combined clinical end point of cardiovascular death, myocardial infarction, or stroke (5.0% event rate), or a combined end point of cardiovascular death or myocardial infarction (4.7% event rate) showed no significant results, although in coronary artery disease, percutaneous coronary intervention, and acute coronary syndrome subgroups, mutations in SCOS5P1, CDC42BPA, and CTRAC1 showed genomewide significance (lowest P values: 1.07e-09, 4.53e-08, and 2.60e-10, respectively). CYP2C19*2 is the strongest genetic determinant of on-clopidogrel platelet reactivity. We identified three novel associations in clinical outcome subgroups, suggestive for each of these outcomes.

[New insights into the seriousness of acute myocardial injury during COVID-19]. / Nuove acquisizioni sulla gravità del danno cardiaco acuto in corso di COVID-19.

Retrospective data from Chinese cohorts published in the last few days have placed a strong emphasis on the possibility that acute myocardial injury represents a critical component in the development of serious complications in patients hospitalized with COVID-19. These analyses showed that 19-27% of hospitalized patients with moderate/severe COVID-19 developed acute myocardial injury, defined as an increase in troponin levels. Fifty-sixty percent of these patients died. The highest mortality rate was detected among patients with both progressively incremental troponin levels and a history of cardiovascular disease. Some pathophysiological reasons have been hypothesized regarding the frequently observed increase in troponin levels in patients hospitalized with COVID-19, but, at the moment, these data could already suggest some clinical management implications, also with the aim of prospectively collecting research data: a troponin dosage should be considered, as a prognostic indicator, in all patients with moderate/severe COVID-19 at hospital admission, periodically during hospitalization, and in the case of clinical deterioration. In those patients with increased troponin levels, serial determinations should be carried out to define the enzymatic trajectory and therefore also the degree of clinical attention that must necessarily be closer in those who turn out to have persistently high or increasing troponin levels. In order to reduce the overdiagnosis risk of acute myocardial injury in critically ill patients, detection of increased troponin levels should always be contextualized into a multi-parametric evaluation.