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Recent studies suggested that early repolarization (ER)/J wave at the electrocardiogram (ECG) is associated with increased risk of sudden death and ventricular arrhythmias in patients with acute myocardial infarction. In this study, we prospectively assessed whether ER/J wave has any long-term prognostic implications in patients with stable ischemic heart disease (IHD). We enrolled consecutive clinically stable patients with documented IHD, referred to undergo a routine ECG. ER (typical concave ST-segment elevation) and J wave were diagnosed according to prospectively defined criteria. The final population included 617 patients with documented IHD (455 men; age 68.1 ± 11 years). ER/J wave was found in 138 patients (22.4%), 13 of whom (2.1%) showed ER and 133 (21.6%) a J wave. At a follow-up of 8.1±2.9 years, 160 deaths occurred (25.9%), 60 (9.7%) attributed to cardiovascular causes. Total mortality was lower in patients with versus those without ER/J wave (18.8% vs 28.0%; hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.40 to 0.93, p = 0.02). The difference, however, was not significant after adjustment for confounding clinical variables (HR 0.78, 95% CI 0.51 to 1.19, p = 0.25). No significant difference was found in cardiovascular death between patients with (7.2%) and those without (10.4%) ER/J wave (adjusted HR 0.78, 95% CI 0.40 to 1.55, p = 0.48). Similar results were obtained for ER and J wave separately, and for ECG location of ER/J wave (inferior or lateral/precordial) and type of J wave (notched or slurred). The ER/J wave pattern at the ECG is not associated with increased risk of long-term mortality in clinically stable patients with a documented history of IHD.

Background Transcatheter aortic valve implantation (TAVI) in the treatment of severe aortic stenosis has considerably grown in the latest years. There are limited data, however, about predictors of long-term prognosis in this population. Particularly, whether arrhythmic burden is associated with clinical outcome has poorly been investigated. Methods We performed 24-hour 3-channel ECG Holter recording (HM) in 284 consecutive patients who underwent TAVI for severe aortic stenosis at our Center within 30 days from a successful procedure (average 10.2 days, range 2-30). For each patient we obtained the number of premature ventricular complexes (PVCs) and the presence of non-sustained ventricular tachycardia (NSVT, ≥3 PVCs with a rate ≥100 bpm). Assessment of clinical events at follow-up was performed by clinical visits or telephone interview of patients or relatives (in case of fatal events). The primary end-point of the study was a composite of cardiovascular death and resuscitation from cardiac arrest (CVE); total mortality was assessed as secondary end-point. Results Frequent PVCs (≥30/hour) and episodes of NSVT were found in 49 (20.2%) and 52 (21.4%) patients, respectively. Clinical outcome was obtained for 243 patients (85.6%). At an average follow-up of 3.5 year (range 1.0-8.6), CVE occurred in 25 patients (8.8%) and 64 died (22.5%). Frequent PVCs at HM were detected in 11/25 (44.0%) and 38/218 (17.4%) patients with and without CVE, respectively (p=0.006). Episodes of NSVT were detected in 9/25 (36.0%) and 43/218 (19.7%) patients with and without CVE, respectively (p=0.07). Furthermore, frequent PVCs were present in 18/64 (28.1%) and 31/179 (17.3%) patients dead and alive, respectively (p=0.07), whereas NSVT episodes were detected in 17/64 (26.6%) and 35/179 (19.6%) patients dead and alive, respectively (p=0.29). Frequent PVCs maintained independent association with CVE after correction for confounding variables at multivariable analysis (HR 2.63; 95 CI 1.05-6.62; p=0.04). Conclusions Our data indicate that assessment of ventricular arrhythmic burden after TAVI is helpful to identify patients at increased risk of cardiovascular death/cardiac arrest during medium follow-up.

Background Left main coronary artery disease (LMCAD) heavily affects prognosis of patients with suspected CAD. Thus, its identification/exclusion is an important step in the assessment of these patients. Although being the gold standard to identify LMCAD, invasive coronary angiography (ICA) is burdened by some risks, while coronary computed tomography angiography (CCTA) has still limited availability, quite high costs and associated radiologic risks. In the past decades, several studies demonstrated the utility of ECG exercise stress test (EST) for the identification of LM disease in patients with suspected CAD. However, the pre-test probability of CAD of subjects undergoing EST has significantly changed in the last decades. Accordingly, in this study we aimed to assess the predictive value of EST for the presence/absence of LMCAD in a contemporary population of patients with suspected CAD. Methods We retrospectively enrolled 495 consecutive patients, referred to our Center between years 2018 and 2021 because of suspected CAD, who underwent both an EST (standard treadmill Bruce protocol) and ICA (within 12 months of the EST). Patients with a history of coronary artery bypass surgery were excluded. Results Overall, 24 patients (4.8%) were found to have LMCAD at ICA. Among clinical variables, only male gender (p=0.025) and smoking (p=0.003) were associated with LMCAD. A number of ECG leads with EST-induced ST-segment depression (STD) ≥5 and a maximal STD ≥2 mm were more frequently found in patients with, compared to those without LMCAD (29.2 vs 9.8%, p=0.003; and 58.3 vs 24.8%, p Conclusions Our data indicate that EST continues to be a valuable tool for predicting the presence/absence of LMCAD in contemporary populations of patients with suspected coronary artery disease.

Background Although the detection of a rise and/or fall pattern of cardiac troponin (cTn) serum levels in presence of a clinical context of acute myocardial ischemia, represents the main criterion for the diagnosis of acute myocardial infarction (AMI), troponins may increase in various conditions of myocardial injury different from ischemic myocardial necrosis or simply following myocardial ischemia, in the absence of cell necrosis. Some studies found that troponins also increase after physical exertion and other types of stressful stimuli in the absence of obstructive CAD and myocardial ischemia. No previous study, however, investigated the relation between cTn serum levels and the extent of myocardial ischemia in patients with a suspect of CCS. Methods We prospectively enrolled consecutive patients undergoing an elective stress myocardial perfusion scintigraphy (MPS) because of a clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups based on the evidence and degree of stress-induced MI at MPS: 1) group 1, no MI (≤4%); 2) group 2, mild MI (5-10%); 3) group 3, moderate-to-severe MI (≥10%). High sensitivity (hs)-cTnI was measured immediately before (T0) and 1 hour (T1) and 4 hours (T2) after the stress test. A successive evaluation of patients was performed at 24 months. Results One-hundred consecutive patients (64 males; age 65.5±9.5 years) were enrolled in the study. Serum hs-cTnI concentrations significantly increased after MPS, compared to baseline, in the whole population, from (median, interquartile range) 3.9 (2.5-6.1) ng/L at T0, to 4.2 (2.8-7.3) ng/L at T1 (p Conclusions In patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and the extent of myocardial ischemia and is mainly related to myocardial work, as indicated by HR achieved during the test.

Background Myocardial bridging (MB) is a congenital epicardial coronary abnormality, in which a segment of the artery runs through the myocardium, determining dynamic stenosis during systole. Whether MB can be responsible by itself for myocardial ischemia remains unclear. Thus, we aimed to evaluate whether the dynamic stenosis related to MB can cause signs and symptoms of myocardial ischemia. Methods We enrolled 41 consecutive patients who underwent coronary angiography because of chest pain suspected for ischemic heart disease and were found to have MB in the absence of any significant flow-limiting coronary stenosis and any other cardiac disease. A group of 14 patients who also underwent coronary angiography because of chest pain suspected for ischemic heart disease, but found to be free of any coronary or cardiac abnormality (including MB) and also showed negative results at exercise stress test (EST) served as controls. All enrolled patients underwent a maximal treadmill EST according to standard Bruce protocol. A complete echocardiographic examination was performed at rest and at peak exercise. Results Baseline EST parameters were comparable between groups, whereas peak diastolic blood pressure (pDBP) was slightly higher in the MB group (p=0.044). No clinically significant differences were found in baseline echocardiographic parameters, although the E wave deceleration time (DcT) was longer (p=0.038) and global longitudinal strain (GLS) was higher (p=0.05) in the MB group. During exercise, left ventricular ejection fraction (LVEF) improved significantly in both groups (p Moreover, among MB patients, no differences were found in stress echocardiographic results between those with positive vs. those with negative EST. Conclusions We failed to demonstrate any significant ischemic impairment of LV systolic and diastolic function at maximal EST in patients with MB. Moreover, we also failed to demonstrate any LV dysfunction in MB patients that developed ECG signs of myocardial ischemia during EST, as compared to those without evidence of myocardial ischemia. Thus, our data question about the ability of MB itself to trigger significant myocardial ischemia in clinical practice.

Background A significant proportion of patients recovering from SARS-CoV-2 infection (Covid-19) complain a wide variety of bothersome symptoms, including symptoms potentially related to cardiac involvement, that may significantly impair their quality of life (post-Covid or long-Covid syndrome). However, full diagnostic investigation usually does not reveal significant structural or functional cardiac abnormalities. Whether cardiac autonomic dysfunction and/or endothelial dysfunction may play a role in post-COVID-19 symptoms, however, has poorly been investigated. Methods We prospectively enrolled 63 young adult patients (age 18-55 years) without any previous cardiovascular disease, referred to our “Post-COVID-19” Day Hospital ward for a clinical follow-up after 3 months from SARS-CoV-2 infection. In all patients endothelium-dependent vasodilator function was assessed non-invasively by measuring the change of brachial artery diameter in response to hyperaemia after 5 minutes of forearm ischemia (flow-mediated dilatation, FMD); furthermore, endothelium-independent vasodilator function was assessed by measuring the change of brachial artery diameter in response to sublingual nitro-glycerine (25 µg) (nitrate-mediated dilatation, NMD). A 24-hour ECG Holter monitoring (HM) was performed to assess cardiac autonomic function by obtaining time-domain and frequency-domain parameters of heart rate variability (HRV). Results Symptoms of potential cardiac origin (dyspnoea on exertion, chest pain, arrhythmic symptoms) were referred by 47 patients (74.6%, Group 1), whereas 16 (25.4%, Group 2) were free from any possible cardiac symptom. The two groups did not differ in age, sex and cardiovascular risk factors. FMD was 7.29±3.4% and 7.01±2.3% in Group 1 and 2, respectively (p=0.77), whereas NMD was 11.1±3.8% and 14.2±4.9 in the two groups, respectively (p=0.013). No significant differences were observed for HRV parameters between the two groups (see Table). Conclusions Our data do not support a role for both endothelial dysfunction and cardiac autonomic dysfunction in the persistence of symptoms of potential cardiac origin in patients with a recent SARS-CoV-2 infection. The lower endothelium-independent arterial vasodilator found in these patients, however, deserves further investigation.

Coronary microvascular dysfunction (CMD) may cause symptoms of myocardial ischemia (microvascular angina [MVA]), but recent studies suggested that it might also contribute to the syndrome of heart failure with preserved ejection fraction (HFpEF). In this study we assessed the relation of CMD with findings of HFpEF in MVA patients.We enrolled 36 consecutive patients with MVA, in whom we assessed: 1) coronary blood flow (CBF) response to adenosine and cold pressor test (CPT) by color-Doppler echocardiography of the left anterior descending coronary artery; 2) complete echocardiographic examination; 3) N-terminal-pro-B-natriuretic peptide (NT-proBNP); 4) grade of dyspnea by the modified Medical Research Scale.Among patients, 15 had definite HFpEF findings (group 1), 12 had equivocal HFpEF findings (group 2) and 9 had no evidence of HFpEF findings (group 3). Group 1 patients were older, had more cardiovascular risk factors and higher NT-proBNP levels (P=0.018), and showed a higher prevalence of diastolic dysfunction. Left ventricle dimensions and systolic function, however, did not differ among groups. Dyspnea was also not significantly different among groups (P=0.19). CBF to adenosine was 1.85±0.47, 1.78±0.40 1.49±0.32 in group 1, 2 and 3, respectively (P=0.13). Similarly, CBF response to CPT was 1.57±0.4, 1.49±0.2 and 1.45±0.3 in the 3 groups, respectively (P=0.74). Both CBF response to adenosine and CPT showed no relation with the severity of dyspnea symptoms.Our data suggest that in patients with MVA there is no relation between the grade of impairment of coronary microvascular dilatation and findings of HFpEF.

Type 2 diabetes mellitus (DM) represents, with its macro and microvascular complications, one of the most critical healthcare issues for the next decades. Remarkably, in the context of regulatory approval trials, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) proved a reduced incidence of major adverse cardiovascular events (MACEs), i.e., cardiovascular death and heart failure (HF) hospitalizations. The cardioprotective abilities of these new anti-diabetic drugs seem to run beyond mere glycemic control, and a growing body of evidence disclosed a wide range of pleiotropic effects. The connection between diabetes and meta-inflammation seems to be the key to understanding how to knock down residual cardiovascular risk, especially in this high-risk population. The aim of this review is to explore the link between meta-inflammation and diabetes, the role of newer glucose-lowering medications in this field, and the possible connection with their unexpected cardiovascular benefits.

The paradigm for the management of patients presenting with angina and/or myocardial ischemia has been historically centered on the detection and treatment of obstructive coronary artery disease (CAD). However, in a considerable proportion (30-50%) of patients undergoing coronary angiography, obstructive CAD is excluded. Thus, functional mechanisms may be involved in determining myocardial ischemia and should be investigated. In particular, coronary vasomotor disorders both at epicardial and at microvascular level may play a crucial role, but a definitive diagnosis of these disorders can at times be difficult, given the transience of symptoms, and often requires the use of coronary provocative tests. Of importance, these tests may provide relevant information on the pathogenic mechanism of myocardial ischemia, allowing physicians to tailor the therapies of their patients. Furthermore, several studies underscored the important prognostic information deriving from the use of coronary provocative tests. Nevertheless, their use in clinical practice is currently limited and mainly restricted to specialized centers, with only a minority of patients receiving a benefit from this diagnostic approach. In this review, we explain the pathophysiological bases for the use of provocative tests, along with their clinical, prognostic and therapeutic implications.

Aims The main severe complications of SARS-CoV-2 infection are pneumonia and respiratory distress syndrome. Recent studies, however, reported that cardiac injury, as assessed by troponin levels, is associated with a worse outcome in these patients. No study hitherto assessed whether the simple standard electrocardiogram (ECG) may be helpful for risk stratification in these patients. Methods and results We studied 324 consecutive patients admitted to our Emergency Department with a confirmed diagnosis of SARS-CoV-2 infection. Standard 12-lead ECG recorded on admission was assessed for cardiac rhythm and rate, atrioventricular and intraventricular conduction, abnormal Q/QS wave, ST segment and T wave changes, corrected QT interval, and tachyarrhythmias. At a mean follow-up of 31 ± 11 days, 44 deaths occurred (13.6%). Most ECG variables were significantly associated with mortality, including atrial fibrillation (P = 0.002), increasing heart rate (P = 0.002), presence of left bundle branch block (LBBB; P < 0.001), QRS duration (P, Graphical Abstract Graphical Abstract

Background A sizeable number of patients with a diagnosis of non-ST segment elevation acute coronary syndrome show non-obstructive coronary artery disease. In this study we assessed whether differences in vascular and cardiac autonomic function exist between non-ST segment elevation acute coronary syndrome patients with obstructive or non-obstructive coronary artery disease. Methods and results Systemic endothelium-dependent and independent vascular dilator function (assessed by flow-mediated dilation and nitrate-mediated dilation of the brachial artery, respectively) and cardiac autonomic function (assessed by time-domain and frequency-domain heart rate variability parameters) were assessed on admission in 120 patients with a diagnosis of non-ST segment elevation acute coronary syndrome. Patients were divided into two groups according to coronary angiography findings: (a) 59 (49.2%) with obstructive coronary artery disease (≥50% stenosis in any epicardial arteries); (b) 61 (50.8%) with non-obstructive coronary artery disease. No significant differences between the two groups were found in both flow-mediated dilation (5.03 ± 2.6 vs. 5.40 ± 2.5%, respectively; P = 0.37) and nitrate-mediated dilatation (6.79 ± 2.8 vs. 7.30 ± 3.4%, respectively; P = 0.37). No significant differences were also observed between the two groups both in time-domain and frequency-domain heart rate variability variables, although the triangular index tended to be lower in obstructive coronary artery disease patients (30.2 ± 9.5 vs. 33.9 ± 11.6, respectively; P = 0.058). Neither vascular nor heart rate variability variables predicted the recurrence of angina, requiring emergency room admission or re-hospitalisation, during 11.3 months of follow-up. Conclusions Among patients admitted with a diagnosis of non-ST segment elevation acute coronary syndrome we found no significant differences in systemic vascular dilator function and cardiac autonomic function between those with obstructive coronary artery disease and those with non-obstructive coronary artery disease.

Up to 50% of patients presenting with stable, mainly exercise-induced, chest pain and 10-20% of those admitted to hospital with chest pain suggesting an acute coronary syndrome show normal or near-normal coronary arteries at angiography. Coronary microvascular dysfunction (CMD) is a major cause of symptoms in these patients. However, controversial data exist about their prognosis. In this article, we critically review characteristics and results of the main studies that assessed clinical outcome of patients with angina chest pain and nonobstructive coronary artery disease presenting with either a stable angina pattern or an acute coronary syndrome. Published data indicate that the patients included in most studies are heterogeneous and a major determinant of clinical outcome is the presence of atherosclerotic, albeit not obstructive, coronary artery disease. Long-term prognosis seems instead excellent in patients with totally normal coronary arteries and a syndrome of CMD-related stable angina (microvascular angina). On the other hand, the prognostic impact of CMD in patients presenting with an acute coronary syndrome needs to be better assessed in future studies.

AimsThe “early repolarization” (ER) pattern and J wave are frequent findings on standard ECG. Controversial data have recently been reported about their prognostic implications in healthy subjects, but no longitudinal prospective study specifically designed to investigate their long-term prognostic value has hitherto been published.Methods and ResultsWe prospectively enrolled 4,176 consecutive subjects with no evidence of cardiovascular disease who were referred for standard ECG recording for routine check-ups or pre-operative assessments for non-cardiovascular surgery. ECGs were prospectively assessed for the presence of ER/J wave. A 10-year follow-up was available for 3,937 patients (94.3%), 660 of whom (16.8%) showed ER/J wave whereas 3,277 did not. A total of 644 deaths occurred (16.3%), 116 (2.95%) of which were attributed to cardiovascular causes. Both total and cardiovascular mortality adjusted for clinical and laboratory variables did not differ significantly between patients with vs. without ER/J wave (HR 0.94; 95% CI 0.75–1.19; p = 0.63 and HR 0.61; 95% CI 0.31–1.21; p = 0.16, respectively). No significant association with total and cardiovascular mortality was also found in pre-specified analyses for ER and J wave alone, ER/J wave detected in specific ECG regions (i.e., inferior, lateral, precordial), and type of J wave (notched or slurred).ConclusionIn this specifically designed prospective study of individuals without any evidence of cardiovascular disease, we found no significant association of ER/J wave with the risk of the total as well as cardiovascular mortality during long-term follow-up.

Aims Cardiac troponin I (cTnI) is considered a marker of myocardial necrosis. However, several studies have shown that cTnI increases also after short episodes of myocardial ischaemia. Nevertheless, it is unknown whether the changes in cTnI show differences according to the cause of myocardial ischaemia. Thus, our study aimed to evaluate cTnI response to ischaemia in patients with stable coronary artery disease (CAD), patients with microvascular angina (MVA), and transient ischaemia induced during percutaneous coronary intervention (PCI). Methods and results We studied four groups of patients: (1) patients with stable angina and obstructive CAD (coronary stenosis ≥50% and/or fractional flow reserve Conclusions Hs-cTnI serum levels increase after EST, both in patients with obstructive CAD and coronary microvascular dysfunction (CMD), but a similar increase is also observed in healthy subjects. More consistent hs-cTnI level increase with later peak-level is observed in patients with obstructive CAD after transient ischaemia induced during PCI.

Aims Transcatheter aortic valve implantation (TAVI) has become a first-line treatment for most patients with severe aortic stenosis (AS) at intermediate/high surgical risk, resulting in significant improvement of clinical outcome. However, whether ventricular arrhythmias (VAs) or cardiac autonomic dysfunction influence outcome and whether TAVI has any effects on VAs and cardiac autonomic function is unknown. Thus, this study was aimed to investigate: I1) whether VAs and autonomic dysfunction [as assessed by heart rate variability (HRV)] are associated with clinical outcome and (2) the effects of TAVI on VAs and HRV, in patients with severe AS. Methods and results We studied 71 consecutive patients with severe aortic stenosis, admitted to our department of Cardiovascular Medicine to undergo TAVI. Patients with previous cardiac surgery, percutaneous coronary revascularization, acute coronary syndrome, and other significant heart valve disease or relevant comorbidities were excluded. The day before TAVI all patients underwent transthoracic Doppler echocardiography (TTDE), including global longitudinal strain (GLS) assessment, and 24-h ECG Holter monitoring (HM), to assess VA burden and HRV. A clinical follow-up was performed at 6 months from discharge. Furthermore, TTDE and 24-h HM were performed at follow-up in 38 (54.5%) and 29 (40.8%) patients, respectively. The primary endpoint was the occurrence of major clinical events (MACE), that include death, hospitalization for cardiac causes, pacemaker implantation, myocardial infarction, or stroke. Of 71 patients (48 female, mean age 80.5 ± 6.5 years) enrolled in the study, a 6-month clinical follow-up could be performed in 54 (76%). MACE occurred in 21 patients (38.9%), 8 of whom (14.8%) had hospitalization for heart failure, 13 (24%) required pacemaker implantation, and 3 had stroke (5.6%). Compared to baseline, at follow-up the mean aortic valve gradient (50.6 ± 11.4 vs. 8.38 ± 3.23 mmHg, P 10 per hour were detected in a higher number of patients at 6-month follow-up, compared to baseline (23.8% vs. 45.2%; P = 0.022). No significant differences were detected in most time-domain and frequency-domain HRV parameters. Unexpectedly, SDNNi (62.8 ± 19.1 vs. 41.9 ± 16.5; P = 0.008), RMSSD (54.6 ± 36.6 vs. 30.1 ± 17.9; P = 0.024) and VLF (56.4 ± 49.6 vs. 29 ± 12.7; P = 0.028) were found to be significantly higher at follow-up compared to baseline. Conclusions Our data show that, in patients with severe AS, TAVI does not seem to have significant effects on VA burden, despite echocardiographic and clinical improvement. Similarly, our data failed to show significant improvement of sympatho-vagal balance at follow-up compared to baseline in these patients.

Background and aims Diabetes mellitus (DM) is a risk factor for left ventricle (LV) diastolic dysfunction. Aim of this study was to investigate whether endothelial and/or autonomic dysfunction are associated with LV diastolic dysfunction in DM patients. Methods We studied 84 non-insulin-dependent type II DM (T2DM) patients with no heart disease by assessing: 1) LV diastolic function by echocardiography; 2) peripheral vasodilator function, by measuring flow-mediated dilation (FMD) and nitrate-mediate dilation (NMD); 3) heart rate variability (HRV) on 24-hour Holter electrocardiographic monitoring. Results Twenty-five patients (29.8%) had normal LV diastolic function, while 47 (55.9%) and 12 (14.3%) showed a mild and moderate/severe diastolic dysfunction, respectively. FMD in these 3 groups was 5.25±2.0, 4.95±1.6 and 4.43±1.8% (p=0.42), wherease NMD was 10.8±2.3, 8.98±3.0 and 8.82±3.2%, respectively (p=0.02). HRV variables did not differ among groups. However, the triangular index tended to be lower in patients with moderate/severe (p=0.09) and a significant correlation was found between the E/e' ratio and both the triangular index (r=-0.26; p=0.022) and LF amplitude (r=-0.29; p=0.011). Conclusions In T2DM patients an impairment of endothelium-independent, but not endothelium-dependent, dilatation seems associated with LV diastolic dysfunction. The possible role of cardiac autonomic dysfunction in diastolic dysfunction deserves investigation in larger populations of patients. This article is protected by copyright. All rights reserved.

About 90% of patients with clinical presentation of acute myocardial infarction (AMI) undergoing coronary angiography have obstructive coronary artery disease (CAD) (i.e. ≥50% stenosis). These patients have well-established therapeutic management.1,2 However, 10% of patients with AMI have no-significant epicardial CAD on coronary angiography, that includes both patients with normal coronary arteries and patients with mild coronary atheromatosis (stenosis < 50%). The aetiology of the myocardial necrosis is not immediately apparent, and there are few data about therapeutic strategies.3,4 Importantly, identifying the pathophysiological mechanism of myocardial infarction with no obstructive coronary arteries (MINOCA) is key for prognostic assessment and therapeutic approach.5–7

A large number of studies has demonstrated that abnormalities of coronary microcirculation may be responsible for both acute and chronic cardiac ischemic syndromes. In clinical practice the microvascular origin of myocardial ischemia and angina is usually considered in patients who are found to have normal or near-normal coronary arteries at angiography. In this article, we review the diagnostic approach to patients with suspected coronary microvascular dysfunction as a cause of ischemic syndromes and also suggest a classification of chronic and acute microvascular coronary ischemic syndrome, including myocardial infarction with normal coronary arteries.

BACKGROUND AND AIMS Previous studies showed that troponin blood levels may increase after exercise. In this study, we assessed whether, among patients with suspected of having stable angina, the increase in troponin I (TnI) levels after exercise stress test (EST) might help identify those with obstructive coronary artery disease (CAD) and myocardial ischemia. METHODS We performed maximal treadmill EST in 50 patients (age 64 ± 9 years; 38 men) admitted to our Cardiology Department to undergo elective coronary angiography because of a suspicion of stable angina. TnI was measured before and 12 h after EST. RESULTS TnI increased after EST compared with baseline in the whole population (from 0.44 ± 0.76 to 0.84 ± 1.12 ng/dl, P

Differently to the common belief, the industry quest for ultra-low-power neural networks is just at the beginning. Examples are the efforts carried by open communities such as TinyML and TinyMLPerf currently focusing on deep learning frameworks for Machine Learning (ML) and associated applications targeting micro-controllers (MCUs). However little attention has been put on deep learning frameworks and applications to enable ultra-low precision ML. These are enabling technologies to target uW hardware implementations. This work aims to compare two Deep Learning frameworks with support to deep quantization, QKeras and Larq, that abstract Tensorflow and Keras frameworks. Currently, Tensorflow is one of the most used deep learning tools by the research and industry communities aimed at deploying ML on the field. Two applications are presented with associated deeply quantized neural networks: Human Activity Recognition (HAR) exploiting a Hybrid Binary Neural Network (HBN) and Anomaly Detection for Industry 4.0 based on a Hybrid Binary AutoEncoder (HBAE). The pros and cons of the frameworks will be discussed during their usage on those applications. Results show an accuracy of up to 98.6% for the HBN and a PSNR up to 111.2 for the HBAE. The inference time has also been measured on different ARM-based architecture.

The platypnea-orthodeoxia syndrome (POS) is a rare clinical entity characterized by the development of dyspnea...

Background. Cardiac involvement in coronavirus SARS-CoV-2 infection (COVID-19) has been reported in a sizeable proportion of patients and associated with a negative outcome, furthermore, a pre-existing heart disease is associated with increased mortality in these patients. In this prospective single-center case-control study we investigated whether COVID-19 patients present different rates and clinical implications of an abnormal electrocardiogram (ECG) compared to patients with an acute infectious respiratory disease (AIRD) caused by other pathogens. Methods. We studied 556 consecutive patients admitted to the emergency department of our hospital with symptoms of AIRD, 324 were diagnosed to have COVID-19 and 232 other causes of AIRD (no-COVID-19 group). Standard 12-lead ECG performed on admission was assessed for various kinds of abnormalities, including ST segment/T wave changes, atrial fibrillation, ventricular arrhythmias, and intraventricular conduction disorders. Results. ECG abnormalities were found in 120 (37.0%) and 101 (43.5%) COVID-19 and no-COVID-19 groups, respectively (p = 0.13). No differences in ECG abnormalities were found between the 2 groups after adjustment for clinical and laboratory variables. During a follow-up of 45 &plusmn, 16 days, 51 deaths (15.7%) occurred in the COVID-19 and 30 (12.9%) in the no-COVID-19 groups (p = 0.39). ST segment depression &ge, 0.5 mm (p = 0.016), QRS duration (p = 0.016) and presence of any ECG abnormality (p = 0.027) were independently associated with mortality at multivariable Cox regression analysis. Conclusion. Among patients hospitalized because of AIRD, we found no significant differences in abnormal ECG findings between COVID-19 vs. no-COVID-19 patients. The ECG on admission was helpful to identify patients with increased risk of death in both groups of patients.

In this work, a digital circuit is proposed to eliminate the dependence of measurements of tri-axial accelerometers from the spatial orientation of the sensor. It is suitable for a large number of applications, from wearable system to human activity recognition and prediction. The circuit implements a new, hardware friendly, vector rotation algorithm which contributes to reduce the occupied area and the power dissipation. The design has been targeted to FPGA and std_cells in 65 nm CMOS technology. In the second case, it returns a power dissipation of 1 μW and an area of about 0.024 mm2. The obtained results show the possibility to integrate the module with the embedded circuitry of inertial sensors.

In this paper, an energy efficient HW accelerator for AI edge-computing in Human Activity Recognition is proposed. The system processes samples from a tri-axial accelerometer and classifies the human activities by using a novel Hybrid Neural Network (HNN) topology, which has been designed to reduce the computational complexity of the system while preserving its accuracy. The HW design improves the characteristics of the HNN by means of an architecture that is aimed to reduce the allocated physical resources and the memory accesses. While accuracy measured on ad-hoc dataset is 97.5 %, measurements from synthesis with CMOS 65 nm standard cells report power consumption of 6.3 μW when the sensor output data rate is 25 Hz, normally used for HAR.

International audience; Human Activity Recognition requires very high accuracy to be effectively employed into practical applications, ranging from elderly care to microsurgical devices. The highest accuracies are achieved by Deep Learning models, but these are not easily deployable in handheld or wearable devices with very constrained resources. We therefore present a new HAR system suitable for a compact FPGA implementation. A new Binarized Neural Network (BNN) architecture achieves the classification based on data from a single tri-axial accelerometer. From our experiments, the effect of gravity and the unknown orientation of the sensor cause a degradation of the accuracy. In order to compensate for these issues, we propose a HW-friendly algorithm to pre-process the raw acceleration signal. Moreover, the very low power and hardware friendly BNN has been trained and validated on the PAMAP2 dataset, for which the pre-processing operations increase the accuracy from 51% to 99% in the best case. A iming for a low-power design, we designed both a custom circuit to perform the pre-processing operations and a hardware accelerator for the BNN. The design on FPGA features a power dissipation of 72 mW and occupies 6788 LUTs.

A custom Human Activity Recognition system is presented based on the resource-constrained Hardware (HW) implementation of a new partially binarized Hybrid Neural Network. The system processes data in real-time from a single tri-axial accelerometer, and is able to classify between 5 different human activities with an accuracy of 97.5% when the Output Data Rate of the sensor is set to 25 Hz. The new Hybrid Neural Network (HNN) has binary weights (i.e. constrained to +1 or −1) but uses non-binarized activations for some layers. This, in conjunction with a custom pre-processing module, achieves much higher accuracy than Binarized Neural Network. During pre-processing, the measurements are made independent from the spatial orientation of the sensor by exploiting a reference frame transformation. A prototype has been realized in a Xilinx Artix 7 FPGA, and synthesis results have been obtained with TSMC CMOS 65 nm LP HVT and 90 nm standard cells. Best result shows a power consumption of $6.3~\mu \text{W}$ and an area occupation of 0.2 mm $^{\mathbf {2}}$ when real-time operations are set, enabling in this way, the possibility to integrate the entire HW accelerator in the auxiliary circuitry that normally equips inertial Micro Electro-Mechanical Systems (MEMS).

In this brief, a new custom circuit is proposed to make the acquisitions of low-power tri-axial accelerometers independent from the spatial orientation of the sensors. For the purpose, a new vector rotation algorithm has been developed in order to reduce the overall computational effort and the complexity of the resulting circuit. The modularity of the computational scheme and the specific design choices have limited the area occupancy and the power dissipation of the circuit to negligible values with respect to the circuitry embedded in typical low-power accelerometers. The design has been prototyped with a Xilinx Artix-7 FPGA, where it achieves a maximum throughput of 81.2 kHz. Synthesis using a 65-nm CMOS standard cells library provides a maximum throughput of 223 kHz and an occupied area of 0.024 mm2. By setting the sample rate of the sensor to 25 Hz used as reference in many motion sensing applications, the standard cells power dissipation is about 1 $\mu \text{W}$ . Comparisons with the state-of-the-art in the literature show a maximum area and power reduction of 40% and 55%, respectively.

Background Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular events, but risk stratification of asymptomatic T2DM patients remains a challenging issue. We conducted a pilot study to assess whether endothelial dysfunction might help identify, among asymptomatic T2DM patients, those at increased risk of cardiovascular events. Methods We studied 61 consecutive T2DM patients with no evidence of cardiovascular disease and no insulin therapy. Endothelial function was assessed by flow-mediated dilation (FMD) of the right brachial artery. The primary endpoint was a combination of major cardiovascular events (MACE: cardiovascular death, acute coronary events, coronary interventions, and acute cerebrovascular accidents). FMD was repeated at follow-up in 48 patients (79%). Results A total of 10 MACE (16.4%) occurred during a mean follow-up of 48 months, including three acute myocardial infarctions, five coronary revascularizations for stable angina, and two acute ischaemic strokes. FMD at enrolment was lower in patients with compared with patients without MACE (3.78 ± 0.97% vs 4.70 ± 1.33%, respectively; P = .04). No other clinical or laboratory variables (age, diabetes duration, glycated haemoglobin, cardiovascular risk factors, drug therapy, and nitrate-mediated dilation) were associated with MACE. FMD at follow-up was also lower in patients with (n = 10) compared with those without (n = 38) MACE (3.66 ± 1.29 vs 4.85 ± 1.92; P = .006). Conclusions Our data suggest that assessment of FMD might be helpful to identify patients at increased risk of MACE among individuals with asymptomatic T2DM; accordingly, a large study is warranted to adequately define the clinical utility of FMD assessment in the management of T2DM patients.

"Early repolarization" (ER) is a frequent finding at standard electrocardiogram (ECG). In this study we assessed whether ER is associated with an increased risk of events, as recently suggested by some studies. We prospectively enrolled 4,176 consecutive subjects without any heart disease who underwent routine ECG recording. ER was diagnosed in case of typical concave ST-segment elevation ≥0.1 mV; a J wave was diagnosed when the QRS showed a notch or a slur in its terminal part. In this study we compared the 6-year outcome of all 687 subjects with ER/J wave and 687 matched subjects without ER/J wave (controls). Both groups included 335 males and 352 females, and age was 48.8 ± 18 years. Overall, 145 deaths occurred (11%), only 11 of which attributed to cardiac causes. No sudden death was reported. Cardiac deaths occurred in 5 (0.8%) and 6 (0.9%) ER/J wave subjects and controls, respectively (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.26 to 2.80, p = 0.79). Both ER (OR 1.68, 95% CI 0.21 to 13.3, p = 0.62) and J wave (OR 0.91, 95% CI 0.28 to 3.00, p = 0.88) showed no association with cardiac death. Total mortality was 11.5% in the ER/J wave group and 10.6% in the control group (OR 1.10, 95% CI 0.78 to 1.56, p = 0.58). Both ER (OR 0.44, 95% CI 0.16 to 1.24, p = 0.12) and J wave (OR 1.20, 95% CI 0.85 to 1.70, p = 0.30) showed also no association with all-cause death. In subjects without any evidence of heart disease, we found no significant association of ER/J wave with the risk of cardiac, as well as all-cause, death at medium-term follow-up.

An ultra low power hardware implementation of Human Activity Recognition systems imposes very tight constraints. Therefore it requires a very thoughtful balancing between highly accurate results and the reduction of the allocated physical resources. Deep Learning models provide the highest accuracies, however their typical computational complexity and memory requirements are not easily deployable in handheld or wearable devices which embody very constrained memory and computation capabilities. In this work, we introduce a new HAR system built with a new Hybrid Binarized Neural Network suitable for a very compact and ultra low-power hardware implementation. The system receives data from MEMS based inertial sensors and makes the acquisitions independent from the sensor spatial orientation and the gravity acceleration signal. The system has been trained and validated on the PAMAP2 and SHL dataset. In both cases, it achieves accuracies higher than 99% in the best case, with different input sensor configurations. A custom circuit has been implemented, which extensively shares circuitry between the different functional sub-modules of the system to minimize the amount of mapped physical resources. The FPGA implementation on a Xilinx Artix 7 achieves a total power dissipation of 72 mW and occupies 6788 LUTs.

We previously demonstrated that bariatric surgery (BS) leads to a short-term significant improvement of endothelial function and coronary microvascular function. In this study we assessed whether BS maintains its beneficial effect at long-term follow up.We studied 19 morbidly obese patients (age 43±9years, 12 women) without any evidence of cardiovascular disease who underwent BS. Patients were studied before BS, at 3 months and at 4.0±1.5years follow up.Peripheral vascular function was assessed by flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), i.e., brachial artery diameter changes in response to post-ischemic forearm hyperhaemia and to nitroglycerin administration, respectively. Coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to intravenous adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery.Together with improvement of anthropometric and metabolic profile, at long-term follow-up patients showed a significant improvement of FMD (6.43±2.88 vs. 8.21±1.73%, p=0.018), and CBF response to both adenosine (1.73±0.48 vs. 2.58±0.54; p0.01) and CPT (1.43±0.30 vs. 2.23±0.48; p0.01), compared to basal values. No differences in vascular end-points were shown at 3-month and 4-year follow-up after BS.Our data show that, in morbidly obese patients, BS exerts beneficial and long lasting effects on peripheral endothelial function and on coronary microvascular dilator function.

Background Previous studies showed that troponin blood levels may increase after exercise. In this study we assessed whether, among patients admitted with suspected unstable angina, the increase in high-sensitive troponin T (hs-TnT) levels after exercise stress test (EST) might help identify those with obstructive coronary artery disease (CAD) and predict symptom recurrence during short term follow-up. Methods Maximal treadmill EST was performed in 69 consecutive patients admitted to the emergency room with a suspicion of unstable angina (acute chest pain but confirmed normal serum levels of cardiac troponins) was measured before and 4 hours after EST. Coronary angiography was performed in 22 patients (32.8%). Results hs-TnT increased after EST compared to baseline in the whole population (from 0.84±0.65 to 1.17±0.87 ng/dL, p