Cine-cardiac magnetic resonance to distinguish between ischemic and non-ischemic cardiomyopathies: a machine learning approach.

OBJECTIVE: This work aimed to derive a machine learning (ML) model for the differentiation between ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) on non-contrast cardiovascular magnetic resonance (CMR). METHODS: This retrospective study evaluated CMR scans of 107 consecutive patients (49 ICM, 58 NICM), including atrial and ventricular strain parameters. We used these data to compare an explainable tree-based gradient boosting additive model with four traditional ML models for the differentiation of ICM and NICM. The models were trained and internally validated with repeated cross-validation according to discrimination and calibration. Furthermore, we examined important variables for distinguishing between ICM and NICM. RESULTS: A total of 107 patients and 38 variables were available for the analysis. Of those, 49 were ICM (34 males, mean age 60 ± 9 years) and 58 patients were NICM (38 males, mean age 56 ± 19 years). After 10 repetitions of the tenfold cross-validation, the proposed model achieved the highest area under curve (0.82, 95% CI [0.47-1.00]) and lowest Brier score (0.19, 95% CI [0.13-0.27]), showing competitive diagnostic accuracy and calibration. At the Youden's index, sensitivity was 0.72 (95% CI [0.68-0.76]), the highest of all. Analysis of predictions revealed that both atrial and ventricular strain CMR parameters were important for the identification of ICM patients. CONCLUSION: The current study demonstrated that using a ML model, multi chamber myocardial strain, and function on non-contrast CMR parameters enables the discrimination between ICM and NICM with competitive diagnostic accuracy. CLINICAL RELEVANCE STATEMENT: A machine learning model based on non-contrast cardiovascular magnetic resonance parameters may discriminate between ischemic and non-ischemic cardiomyopathy enabling wider access to cardiovascular magnetic resonance examinations with lower costs and faster imaging acquisition. KEY POINTS: • The exponential growth in cardiovascular magnetic resonance examinations may require faster and more cost-effective protocols. • Artificial intelligence models can be utilized to distinguish between ischemic and non-ischemic etiologies. • Machine learning using non-contrast CMR parameters can effectively distinguish between ischemic and non-ischemic cardiomyopathies.

Syncope and Cannabis: hypervagotonia from chronic abuse? A case report and literature review.

BACKGROUND: Cannabis is the most consumed drug worldwide and number of users is increasing, particularly among youth. Moreover, cannabis potential therapeutic properties have renewed interest to make it available as a treatment for a variety of conditions. Albeit rarely, cannabis consumption has been associated with cardiovascular diseases such as arrhythmias, myocardial infarction (MI) and potentially sudden death. CASE PRESENTATION: A 24-year-old woman presented to the emergency department sent by her cardiologist because of a recent finding of a 16 seconds asystole on the implantable loop recorder (ILR) she implanted 7 months before for recurrent syncopes. She declared that she is a heavy cannabis user (at least 5 cannabis-cigarette per day, not mixed up with tobacco, for no less than 12 years) and all syncopes occurred shortly after cannabis consumption. After a collective discussion with the heart team, syncope unit, electrophysiologists and toxicologist, we decided to implant a dual chamber pacemaker with a rate response algorithm due to the high risk of trauma of the syncopal episodes. 24 months follow-up period was uneventful. CONCLUSIONS: Cannabis cardiovascular effects are not well known and, although rare, among these we find ischemic episodes, tachyarrhythmias, symptomatic sinus bradycardia, sinus arrest, ventricular asystole and possibly death. Because of cannabis growing consumption both for medical and recreational purpose, cardiovascular diseases associated with cannabis use may become more and more frequent. In the light of the poor literature, we believe that cannabis may produce opposite adverse effects depending on the duration of the habit. Acute administration increases sympathetic tone and reduces parasympathetic tone; conversely, with chronic intake an opposite effect is observed: repetitive dosing decreases sympathetic activity and increases parasympathetic activity. Clinicians should be aware of the increased risk of cardiovascular complications associated with cannabis use and should investigate its consumption especially in young patients presenting with cardiac dysrhythmias.

Why is it Important to Assess and Treat Alexithymia in the Cardiologic Field? An Overview of the Literature.

Background: Alexithymia has been found to be associated with several somatic illnesses, such as cardiovascular, indicating that it might be a risk factor for early death in the long-term course of post-myocardial infarction. From the cardiology perspective, the aim was to collect current evidence about the relationship between alexithymia and somatic illness. Methods: The literature was synthesized and summarized in a narrative format. The literature search was carried out in PubMed. Pertinent studies published in the last 50 years written in English were included and organized by three main topics ("The relation between alexithymia and somatic illness from the cardiology perspective"; "How do assess alexithymia?"; "Treating alexithymia") to be discussed. Results: High alexithymia is a dimensional trait that affects around 10% of the general population and up to 55% of people with essential hypertension. Also, the link between alexithymia and cardiovascular activity has been pointed out. There are several validated tools to assess alexithymia, as well as treatment options. Conclusion: Knowledge about the main features of alexithymia, as well as its assessment and treatment, can promote a multifactorial approach to the primary, secondary, and tertiary prevention of cardiac diseases.

Depression in Heart Failure with Reduced Ejection Fraction, an Undervalued Comorbidity: An Up-To-Date Review.

Introduction: Depression is a common and severe comorbidity among individuals with heart failure (HF). Up to a third of all HF patients are depressed, and an even higher proportion have symptoms of depression. Aim: In this review, we evaluate the relationship between HF and depression, explain the pathophysiology and epidemiology of both diseases and their relationship, and highlight novel diagnostic and therapeutic options for HF patients with depression. Materials and Methods: This narrative review involved keyword searches of PubMed and Web of Science. Review search terms included ["Depression" OR "Depres*" OR "major depr*"] AND ["Heart Failure" OR "HF" OR "HFrEF" OR "HFmrEF" OR "HFpEF" OR "HFimpEF"] in all fields. Studies included in the review met the following criteria: (A) published in a peer-reviewed journal; (B) described the impact of depression on HF and vice versa; and (C) were opinion papers, guidelines, case studies, descriptive studies, randomized control trials, prospective studies, retrospective studies, narrative reviews, and systematic reviews. Results: Depression is an emergent HF risk factor and strongly relates with worse clinical outcomes. HF and depression share multiple pathways, including platelet dis-reactivity, neuroendocrine malfunction, inappropriate inflammation, tachi-arrhythmias, and frailty in the social and community setting. Existing HF guidelines urge evaluation of depression in all HF patients, and numerous screening tools are available. Depression is ultimately diagnosed based on DSM-5 criteria. There are both non-pharmaceutical and pharmaceutical treatments for depression. Regarding depressed symptoms, non-pharmaceutical treatments, such as cognitive-behavioral therapy and physical exercise, have shown therapeutic results, under medical supervision and with an effort level adapted to the patient's physical resources, together with optimal HF treatment. In randomized clinical studies, selective serotonin reuptake inhibitors, the backbone of antidepressant treatment, did not demonstrate advantage over the placebo in patients with HF. New antidepressant medications are currently being studied and could provide a chance to enhance management, treatment, and control of depression in patients with HF. Conclusions: Despite the substantial link between depression and HF, their combination is underdiagnosed and undertreated. Considering the hopeful yet unclear findings of antidepressant trials, further research is required to identify people who may benefit from antidepressant medication. The goal of future research should be a complete approach to the care of these patients, who are anticipated to become a significant medical burden in the future.

Role of cardiac MRI in the diagnosis of immune checkpoint inhibitor-associated myocarditis.

Immune checkpoint inhibitor (ICI)-induced cardiotoxicity is a rare immune-related adverse event (irAE) characterized by a high mortality rate. From a pathological point of view, this condition can result from a series of causes, including binding of ICIs to target molecules on nonlymphocytic cells, cross-reaction of T lymphocytes against tumor antigens with off-target tissues, generation of autoantibodies and production of proinflammatory cytokines. The diagnosis of ICI-induced cardiotoxicity can be challenging, and cardiac magnetic resonance (CMR) represents the diagnostic tool of choice in clinically stable patients with suspected myocarditis. CMR is gaining a central role in diagnosis and monitoring of cardiovascular damage in cancer patients, and it is entering international cardiology and oncology guidelines. In this narrative review, we summarized the clinical aspects of ICI-associated myocarditis, highlighting its radiological aspects and proposing a novel algorithm for the use of CMR.

Multiparametric analysis of coronary flow in psoriasis using a coronary flow reserve companion.

BACKGROUND: Coronary microvascular dysfunction (CMD) is usually evaluated measuring coronary flow velocity reserve (CFVR). A more comprehensive analysis of CFVR including additional consideration of the associated logical companion-CFVR, where hyperemic diastolic coronary flow velocity may act as surrogate, was applied in this study to elucidate the mechanism of CMD in psoriasis. METHODS AND RESULTS: Coronary flow velocity reserve was analysed using transthoracic echocardiographs of 127 psoriasis patients (age 36 ± 8 years; 104 males) and of 52 sex- and age-matched healthy controls. CFVR determination was repeated in the patient subgroup (n = 78) receiving anti-inflammatory therapy. Baseline and hyperemic microvascular resistance (MR) were calculated. CMD was defined as CFVR ≤ 2.5. Four endotypes of CMD were identified referring to concordant or discordant impairments of hyperemic flow or CFVR. We evaluated the companion-CFVR, as derived from the quadratic mean of hyperemic and diastolic flow velocity at rest. Coronary flow parameters, including CFVR (p = 0.01), were different among the two endotypes having CFVR > 2.5. Specifically, all 11 (14%) patients with CFVR deterioration despite therapy, belonged to endotype 1, and had higher baseline and hyperemic MR (p < 0.0001, both). Interestingly, while CFVR was comparable in patients with worsened versus those with improved CFVR, the companion-CFVR could discriminate by being lower in patients with worsened CFVR (p = 0.01). CONCLUSIONS: The reduced CFVR in psoriasis is driven by decreased companion-CFVR, combined with increased hyperemic MR. Adoption of the mandatory companion-CFVR enables a personalized characterization superior to that achieved by exclusive consideration of CFVR.

Efficacy and safety of N-acetyl-GED-0507-34-LEVO gel in patients with moderate-to severe facial acne vulgaris: a phase IIb randomized double-blind, vehicle-controlled trial.

BACKGROUND: Preliminary in vitro and in vivo studies have supported the efficacy of the peroxisome proliferator-activated receptor-γ (PPARγ) modulator N-acetyl-GED-0507-34-LEVO (NAC-GED) for the treatment of acne-inducing sebocyte differentiation, improving sebum composition and controlling the inflammatory process. OBJECTIVES: To evaluate the efficacy and safety of NAC-GED (5% and 2%) in patients with moderate-to-severe facial acne vulgaris. METHODS: This double-blind phase II randomized controlled clinical trial was conducted at 36 sites in Germany, Italy and Poland. Patients aged 12-30 years with facial acne, an Investigator Global Assessment (IGA) score of 3-4, and an inflammatory and noninflammatory lesion count of 20-100 were randomized to topical application of the study drug (2% or 5%) or placebo (vehicle), once daily for 12 weeks. The co-primary efficacy endpoints were percentage change from baseline in total lesion count (TLC) and IGA success at week 12; the safety endpoints were adverse events (AEs) and serious AEs. This study was registered with EudraCT (2018-003307-19). RESULTS: Between Q1 in 2019 and Q1 in 2020 450 patients [n = 418 (92·9%) IGA 3; n = 32 (7·1%) IGA 4] were randomly assigned to NAC-GED 5% (n = 150), NAC-GED 2% (n = 150) or vehicle (n = 150). The percentage change in TLC reduction was statistically significantly higher in both the NAC-GED 5% [-57·1%, 95% confidence interval (CI) -60·8 to -53·4; P < 0·001] and NAC-GED 2% (-44·7%, 95% CI -49·1 to -40·1; P < 0·001) groups compared with vehicle (-33·9%, 95% CI -37·6 to -30·2). A higher proportion of patients treated with NAC-GED 5% experienced IGA success (45%, 95% CI 38-53) vs. the vehicle group (24%, 95% CI 18-31; P < 0·001). The IGA success rate was 33% in the NAC-GED 2% group (P = not significant vs. vehicle). The percentage of patients who had one or more AEs was 19%, 16% and 19% in the NAC-GED 5%, NAC-GED 2% and vehicle groups, respectively. CONCLUSIONS: The topical application of NAC-GED 5% reduced TLC, increased the IGA success rate and was safe for use in patients with acne vulgaris. Thus, NAC-GED, a new PPARγ modulator, showed an effective clinical response. What is already known about this topic? Acne vulgaris, one of the most common dermatological diseases, affects more than 85% of adolescents. There is a medical need for innovative and safe treatment of acne vulgaris. The peroxisome proliferator-activated receptor-γ (PPARγ) is involved in lipid metabolism and specifically in cell differentiation, sebum production and the inflammatory reaction. What does this study add? N-acetyl-GED-0507-34-LEVO (NAC-GED 5%), a PPARγ modulator, significantly improves acne manifestations in patients with moderate-to-severe acne and is safe and well tolerated. The results suggest that the PPARγ receptor is a novel therapeutic target for acne. The results provide a basis for a large phase III trial to assess the effectiveness and safety profile of NAC-GED in combating a disease that afflicts 80-90% of adolescents.

Role of coronary microvascular dysfunction in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is one of the greatest unmet needs in modern medicine. The lack of an appropriate therapy may reflect the lack of an accurate comprehension of its pathophysiology. Coronary microvascular rarefaction in HFpEF was first hypothesized in an autopsy study that showed how HFpEF patients had lower microvascular density and more myocardial fibrosis than control subjects. This was later confirmed in vivo when it was noted that HFpEF is associated with reduced myocardial flow reserve (MFR) at single photon emission computed tomography (SPECT) and that coronary microvascular dysfunction may play a role in HFpEF disease processes. HFpEF patients were found to have lower coronary flow reserve (CFR) and a higher index of microvascular resistance (IMR). What is the cause of microvascular dysfunction? In 2013, a new paradigm for the pathogenesis of HFpEF has been proposed. It has been postulated that the presence of a proinflammatory state leads to coronary microvascular endothelial inflammation and reduced nitric oxide bioavailability, which ultimately results in heart failure. Recently, it has also been noted that inflammation is the main driver of HFpEF, but via an increase in inducible nitric oxide synthase (iNOS) resulting in a decrease in unfolded protein response. This review summarizes the current evidence on the etiology of coronary microvascular dysfunction in HFpEF, focusing on the role of inflammation and its possible prevention and therapy.

New insights to the potential mechanisms driving coronary flow reserve impairment in Cushing's syndrome: A pilot noninvasive study by transthoracic Doppler echocardiography.

BACKGROUND: The contribution of functional and/or structural remodeling to reduced coronary flow velocity reserve (CFVR), reflecting impaired coronary microcirculation in Cushing's syndrome (CS), has not been clearly elucidated. We aimed to identify the potential mechanisms of coronary microvascular impairment in CS. METHODS: We studied 15 CS patients (11 female, age 50 ±â€¯9 years) without clinical evidence of cardiovascular disease. Coronary flow velocity in the left anterior descending coronary artery was measured by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. Average peak flow velocities, CFVR, and microvascular resistance in baseline (BMR) and hyperemic conditions (HMR) were assessed. CFVR ≤2.5 was considered a marker of microvascular disease (CMD). Diastolic function (E/e'), global longitudinal strain (GLS) and fractional pulse pressure (fPP), an index of arterial stiffness, were also assessed. RESULTS: CMD was present in 5 patients (33.3%). CMD was primarily driven by increased baseline peak flow velocity (29 ±â€¯12 versus 19.6 ±â€¯4.2 cm/s, p = .03) in the presence of decreased BMR (3.62 ±â€¯0.6 versus 5.46 ±â€¯1.4 mm Hg·s/cm, p = .03). Moreover, urinary cortisol and E/e' were higher (p = .001 and p = .001, respectively) and GLS was lower (p = .009) in patients with CMD. fPP was higher in patients with CMD (p = .01). Urinary cortisol correlated to CFVR (p = .008), E/e' (p < .0001) and GLS (p < .0001). fPP directly correlated to average peak flow velocities at rest (p = .01) and inversely to BMR (p = .03). CONCLUSIONS: Functional microvascular regulatory impairment seems to be the potential mechanism of CMD in CS. CMD seems to be related to decreased myocardial contractility and diastolic dysfunction associated with cortisol excess.

Coronary flow reserve is related to the extension and transmurality of myocardial necrosis and predicts functional recovery after acute myocardial infarction.

BACKGROUND: Few studies have examined the effect of transmurality of myocardial necrosis on coronary microcirculation. The aim of this study was to examine the influence of cardiac magnetic resonance-derived (GE-MRI) structural determinants of coronary flow reserve (CFR) after anterior myocardial infarction (STEMI), and their predictive value on regional functional recovery. METHODS: Noninvasive CFR and GE-MRI were studied in 37 anterior STEMI patients after primary coronary angioplasty. The wall motion score index in the left descending anterior coronary artery territory (A-WMSI) was calculated at admission and follow-up (FU). Recovery of regional left ventricular (LV) function was defined as the difference in A-WMSI at admission and FU. The necrosis score index (NSI) and transmurality score index (TSI) by GE-MRI were calculated in the risk area. Baseline (BMR) and hyperemic (HMR) microvascular resistance, arteriolar resistance index (ARI), and coronary resistance reserve (CRR) were calculated at the Doppler echocardiography. RESULTS: Bivariate analysis indicated that the CPK and troponin I peak, heart rate, NSI, TSI, BMR, the ARI, and CRR were related to CFR. Multivariable analysis revealed that TSI was the only independent determinant of CFR. The CFR value of >2.27, identified as optimal by ROC analysis, was 77% specific and 73% sensitive with accuracy of 76% in identifying patients with functional recovery. CONCLUSIONS: Preservation of microvascular function after AMI is related to the extent of transmurality of myocardial necrosis, is an important factor influencing regional LV recovery, and can be monitored by noninvasive CFR.

Prognosis and first diagnostic ECG in STEMI patients referred to the emergency medical system for primary PCI.

BACKGROUND: Pathological Q waves (QWs) in the first ECG recorded at hospital admission has been found to correlate with myocardial damage and mortality in STEMI patients. We investigated the association between new QWs recorded in the pre-hospital setting and adverse outcome during the hospital stay. METHODS: A pre-hospital ECG was recorded in 248 patients with STEMI who underwent primary PCI. Patients were divided into two groups based on the presence (n = 44, QWs) or absence (n = 204, non-QWs) of new QWs. RESULTS: Patients with new QWs had a higher prevalence of anterior infarct, cardiogenic shock and a lower LV ejection fraction. In-hospital mortality was higher in patients with new QWs. The percentage of patients with new QWs increased progressively with increasing pain to ECG time. CONCLUSIONS: New QWs provide rapid prognostic information in the pre-hospital phase of STEMI by identifying patients at risk of adverse outcome during the hospital stay.

Takotsubo Syndrome is Associated with Mood Disorders and Antidepressants Use, not with Anxiety and Impairment of Quality of Life Due to the Psychiatric Disorder.

BACKGROUND: The aim was to study the association between mood and anxiety disorders and the Tako-Tsubo Syndrome (TTS) and to determine the role of antidepressants and the impairment of quality of life due the comorbid psychiatric disorder. METHODS: Case-control study: 19 consecutive patients (17 female) with TTS compared to 76 controls without TTS, were randomly selected from the database of a nationwide epidemiological study after matching (gender, age and residence) by controls. Psychiatric diagnoses were carried out according to the ICD-10 using semi-structured interview tools (ANTAS-SCID) administered by clinical staff. Quality of Life (Qol) was assessed by means of SF-12. RESULTS: Only Major Depressive Disorders (MDD) showed higher frequencies in cases with statistical significance difference (p=0.014) as well as at least one Mood Disorder Diagnosis [MDD or BD] (p=0.002). The lifetime prevalence of at least one anxiety disorder with no comorbid mood disorder did not show a higher frequency in cases (p=0.57).The score at SF-12 in the TTS group was similar to those of controls (p=0.71)In the TTS group, the score at SF-12 in people with one mood or anxiety diagnosis (N=7) was similar to those without mood or anxiety diagnosis (p=0.75). The use of antidepressants was higher in TTS group (15.79% vs 1.31%; p=0.030). CONCLUSION: The study shows an association between TTS with depressive disorders and antidepressants use and does not confirm the association with anxiety syndromes. The study suggests the need to investigate the possible interactions between antidepressants use and mood disorders in studies with appropriate design and sample size.

Feasibility, symptoms, adverse effects, and complications associated with noninvasive assessment of coronary flow velocity reserve in women with suspected or known coronary artery disease.

BACKGROUND: Microvascular coronary impairment, defined as reduced coronary flow reserve, represents the predominant etiologic mechanism of ischemia in women with chest pain and no obstructive coronary artery disease. Transthoracic echocardiography (TTE) is a noninvasive method for assessing coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD). The purpose of this investigation was to define the safety profile, feasibility, adverse events, and rate of complications of the test in women with suspected CAD. METHODS: We evaluated CFVR in LAD with TTE during adenosine infusion in 1455 women aged 66.4±11.9 years. RESULTS: A complete CFVR study was achieved in 1429 pts (feasibility 98.2%), the test being performed also in the early phase of acute coronary syndrome and on obese patients. Minor symptoms or adverse effects occurred in 43.7% of patients not requiring test termination: hyperpnea (16.7%), flushing (9.4%), atypical chest pain (9.9%), headache (6.6%), minor arrhythmias (2.9%), chest pain with EKG changes (1.5%) were the symptoms reported. No major complications were observed. CONCLUSIONS: Noninvasive assessment of CFVR in LAD by TTE is a very feasible method with very low incidence of adverse events and complications in women with suspected or known CAD. It is safe and can be used when evaluating female patients with atherosclerotic LAD disease or with coronary microvascular impairment.

Left ventricular hypertrophy or storage disease? the incremental value of speckle tracking strain bull's-eye.

Left ventricular hypertrophy (LVH) develops in response to a variety of physical, genetic, and biochemical stimuli and represents the early stage of ventricular remodeling. In patients with LVH, subclinical left ventricular (LV) dysfunction despite normal ejection fraction (EF) may be present before the onset of symptoms, which portends a dismal prognosis. Strain measurement with two-dimensional speckle tracking echocardiography (STE) represents a highly reproducible and accurate alternative to LVEF determination. The present review focuses on current available evidence that supports the incremental value of STE in the diagnostic and prognostic workup of LVH. When assessing the components of LV contraction, STE has an incremental value in differentiating between primary and secondary LVH and in the differential diagnosis with storage diseases. In addition, STE provides unique information for the stratification of patients with LVH, enabling to detect intrinsic myocardial dysfunction before LVEF reduction.

Echocardiographic assessment of left ventricular systolic function: from ejection fraction to torsion.

Assessment of left ventricular (LV) systolic function is the cornerstone of the echocardiographic examination. There are many echocardiographic parameters that can be used for clinical and research purposes, each one with its pros and cons. The LV ejection fraction is the most used one due to its feasibility and predictability, but it also has many limits, related to both the imaging technique used for calculation and to the definition itself. LV longitudinal function is expression of subendocardial fibers contraction. Because the subendocardium is often involved early in many pathological processes, its analysis has been a fertile field for the development of sensitive parameters. Longitudinal function can be evaluated in many ways, such as M-mode echocardiography, tissue Doppler imaging, and speckle tracking echocardiography. This latter is a relatively new tool to assess LV function through measurement of myocardial strain, with a high temporal and spatial resolution and a better inter- and intra-observer reproducibility compared to Doppler strain. It is angle independent, not affected by translation cardiac movements, and can assess simultaneously the entire myocardium along all the three-dimensional geometrical (longitudinal, circumferential, and radial) axes. Speckle tracking echocardiography also allows the analysis of LV torsion. The aim of this paper was to review the main echocardiographic parameters of LV systolic function and to describe its pros and cons.

Artificial Intelligence in the Differential Diagnosis of Cardiomyopathy Phenotypes.

Artificial intelligence (AI) is rapidly being applied to the medical field, especially in the cardiovascular domain. AI approaches have demonstrated their applicability in the detection, diagnosis, and management of several cardiovascular diseases, enhancing disease stratification and typing. Cardiomyopathies are a leading cause of heart failure and life-threatening ventricular arrhythmias. Identifying the etiologies is fundamental for the management and diagnostic pathway of these heart muscle diseases, requiring the integration of various data, including personal and family history, clinical examination, electrocardiography, and laboratory investigations, as well as multimodality imaging, making the clinical diagnosis challenging. In this scenario, AI has demonstrated its capability to capture subtle connections from a multitude of multiparametric datasets, enabling the discovery of hidden relationships in data and handling more complex tasks than traditional methods. This review aims to present a comprehensive overview of the main concepts related to AI and its subset. Additionally, we review the existing literature on AI-based models in the differential diagnosis of cardiomyopathy phenotypes, and we finally examine the advantages and limitations of these AI approaches.

A case series of the twiddler syndrome.

Background: Twiddler syndrome (TS) is a complication of cardiac implantable electronic device (CIED) implantation, caused by the deliberate or unconscious manipulation of the device by the patient himself, which results in dislocation of the leads by retraction towards the subcutaneous pocket. Case summary: This report describes two clinical cases that occurred in our centre, for which two different solutions were successfully implemented. In the first case, a complete removal of the stimulation system was performed, and a leadless pacemaker (PM; Medtronic Micra VR) was implanted. In the second case, the patient underwent a revision procedure. The PM was disconnected, and the electrodes were debrided, a submuscular pocket for the PM was created, and at the end of the procedure, the PM was anchored to the pectoralis major. Discussion: Twiddler syndrome is a not so rare and serious complication of CIED implantation, leading to device malfunctioning and higher risk of infection of the pocket due to multiple re-interventions. In these two cases, different surgical solutions were performed, both resulting to be effective to solve the effects of TS.

Indirect Calorimetry-Based Novel Approach for Evaluating Metabolic Flexibility and Its Association with Circulating Metabolic Markers in Middle-Aged Subjects.

We propose a novel method for assessing metabolic flexibility (MF) through indirect calorimetry. A total of twenty healthy volunteers (10 females; 10 males) aged 45-65 were categorized into a Low-Intensity activity group (LI, 0-1 session of 1 h per week) and a High-Intensity activity group (HI, 5-6 sessions of 2 h per week). Volunteers underwent a stepwise exercise test on a cycle ergometer, connected to a calorimeter, to examine respiratory gas exchange to evaluate peak fatty acid Oxidation (PFO) and peak carbohydrate oxidation (PCO). Circulating peroxisome proliferator-activated receptor α (PPARα) biomarkers, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio and N-oleoylethanolamine (OEA), and the endocannabinoid- 2-arachidonoylglycerol (2-AG), were evaluated. We developed two MF parameters: the MF index (MFI), calculated by the product of PFO normalized per kg of fat-free mass (FFM) and the percentage of VO2max at PFO, and the peak energy substrates' oxidation (PESO), computed by summing the kilocalories from the PFO and PCO, normalized per kg FFM. The MFI and PESO were significantly different between the HI and LI groups, showing strong correlations with the circulating bioactive substances. Higher DHA/EPA ratio (p ≤ 0.05) and OEA (p ≤ 0.01), but lower 2-AG levels (p ≤ 0.01) were found in the HI group. These new parameters successfully established a functional link between MF and the balance of PPARα/endocannabinoid systems.

Maternal-fetal dyad beyond the phenomenology of pregnancy: from primordial cardiovascular prevention on out, do not miss this boat!

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention.