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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.

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.

BackgroundIn childhood cancer survivors (CCSs) anthracycline-related cardiotoxicity is an important cause of morbidity and late mortality, but the optimal modality of cardiac surveillance still remains to be defined. The aim of this study was to assess whether non-invasive echocardiography-based functional cardiac measures can detect early subclinical myocardial changes in long-term pediatric cancer survivors who received anthracycline therapy.MethodsTwenty anthracycline-treated long-term CCSs and 20 age, sex, and body surface area matched healthy controls were enrolled in this study. Among cancer survivors, mean age at diagnosis was 6.5 ± 4.4 years, and the mean cumulative anthracycline dose was 234.5 ± 87.4 mg/m2. All subjects underwent a comprehensive functional echocardiographic protocol study including two-dimensional echocardiography (2D Echo), tissue Doppler imaging (TDI), speckle tracking (STE) and three-dimensional echocardiography (3D Echo). Patients were studied at a mean follow-up time of 6.5 ± 2.8 years from the end of therapy.ResultsNo significant differences in two-dimensional left ventricle ejection fraction (LVEF), diastolic parameters and speckle tracking (STE)-derived myocardial strain were observed between patients treated with anthracyclines and controls. Myocardial performance index was significantly prolonged (p = 0.005) and three-dimensional LVEF was significantly reduced (p = 0.002) in CCSs compared to controls, even though most values were within the normal range. There were no significant correlations between 2D, STE, and 3D echocardiographic parameters and age at diagnosis or duration of follow-up. No significant differences in echocardiographic parameters were found when stratifying cancer patients according to established risk factors for anthracycline cardiomyopathy.ConclusionsThis study found significantly reduced three-dimensional LVEF in CCSs compared with controls, despite no significant differences in two-dimensional LVEF and longitudinal strain values. These findings suggest that long-term CCSs who had received anthracycline therapy may be found to have subclinical features of myocardial dysfunction. However, further studies are needed to demonstrate the validity of new imaging techniques, including STE and 3D Echo, to identify patients at risk for cardiomyopathy in the long-term follow-up of CCSs.

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

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.

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.

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

Treatment of patients with chronic stable angina has two main objectives: to improve clinical outcome and to reduce angina symptoms. Prognosis is mainly improved by a reduction in cardiovascular risk factor burden, which may be achieved by appropriate lifestyle changes and, for some risk factors (e.g. hypercholesterolaemia, hypertension, diabetes), appropriate pharmacological therapy (including, in particular, statins and renin–angiotensin–aldosterone system inhibitors) and use of antithrombotic agents. Symptoms can be improved by a variable combination of traditional (beta-blockers, calcium channel blockers, nitrates) and novel (e.g. ivabradine, ranolazine) anti-ischaemic drugs, which may act through reduction in myocardial oxygen consumption and/or improvement of myocardial perfusion.

BACKGROUND Although some previous studies assessed characteristics and outcome of patients with suspected no-ST-segment elevation acute myocardial infarction (NSTEMI), but no obstructive coronary artery disease (NOCAD) at angiography, most were performed before high-sensitivity troponin assays were available. METHODS AND RESULTS We reviewed data of patients admitted to our hospital with a suspicion of NSTEMI between 2013 and 2016. Patients with previous evidence of CAD (except those with fully percutaneous coronary revascularization) were excluded. Patients were divided into those with obstructive CAD and those with NOCAD (no coronary stenosis ≥50% in any vessel). The final population included 430 patients - 317 (73.7%) with CAD and 113 (26.3%) with NOCAD. Compared with CAD, NOCAD patients were younger, more frequently women, and had a lower prevalence of cardiovascular risk factors and peak troponin level. In-hospital death or myocardial infarction occurred in eight (2.5%) and two (1.8%) patients in CAD and NOCAD patients, respectively (P = 1.00). A lower left ventricular ejection fraction (LVEF) and left main CAD were the only independent predictors of in-hospital death and death or myocardial infarction. CONCLUSIONS Among patients with suspect NSTEMI, about one-fourth showed NOCAD at angiography in the era of elevated sensitivity troponin assays and when excluding patients with largely predictable obstructive CAD. Higher troponin levels were associated with obstructive CAD, but a lower LVEF and left main disease only predicted in-hospital outcome in this population.

Previous studies of patients with primary stable microvascular angina showed excellent prognosis despite frequent recurrence of symptoms.1,2 Recent large studies challenged this view, however, reporting a sizeable rate of major adverse cardiovascular events (MACE) in patients with stable angina and no obstructive coronary artery disease.3,4 To get further insight into this clinical controversy, we performed long-term follow-up of a rather large population of patients with microvascular angina. We included in this study all patients with primary stable microvascular angina who participated in clinical investigations performed at our institute between 1991 and 2011. All patients had exercise-induced angina, positive exercise stress test, angiographically normal coronary arteries, and no other relevant cardiac or systemic disease.5 In suspected cases, coronary spasm was excluded by ergonovine test. Patients were carefully characterized for cardiovascular risk factors and symptoms. All patients gave their informed consent to participate in the study, which was approved by our institutional review board. Follow-up was done by clinical visits or structured telephone interview. In the case of death, its cause …

Microvascular angina (MVA), i.e. angina caused by abnormalities of the coronary microcirculation, is increasingly recognised in clinical practice. The pathogenetic mechanisms of MVA are heterogeneous and may involve both structural and functional alterations of coronary microcirculation, and functional abnormalities may variably involve an impairment of coronary microvascular dilatation and an increased microvascular constrictor activity. Both invasive and non-invasive diagnostic tools exist to identify patients with MVA in clinical practice. Prognosis has been reported to be good in primary MVA patients, although the prognostic implications of coronary microvascular dysfunction (CMVD) in more heterogeneous populations of angina patients need further assessment. Management of primary MVA can be challenging, but pharmacological and non-pharmacological treatments exist that allow satisfactory control of symptoms in most patients

Background A sizeable proportion of patients with primary stable microvascular angina (MVA; exercise-induced angina, positive exercise stress test [EST], normal coronary arteries) have recurrent symptoms during follow-up. There have been no previous studies, however, on the long-term results of EST and their correlation with symptom outcome.Methods and Results:Follow-up EST was performed in 71 MVA patients at an average of 16.2 years (range, 5-25 years) from the first EST. Angina status was assessed on weekly frequency of angina episodes and nitroglycerin consumption and by whether symptoms had worsened, improved, or remained unchanged over time. At follow-up EST, 41 patients (group 1) had exercise-induced ischemia, whereas 30 patients (group 2) had negative EST. Compared to group 2, group 1 patients more frequently had exercise-induced dyspnea, and had a greater maximum ST-segment depression and a lower coronary blood flow response to adenosine and cold pressor test, but group 2 patients had a more frequent history of rest angina. No differences between the 2 groups were found at follow-up in angina status or change in symptom status during follow-up. Conclusions Electrocardiogram results improve significantly in a sizeable proportion of patients with MVA. Changes in EST results, however, were not associated with clinical outcome.

Background The role of exercise stress test (EST)-induced ST-segment elevation (STE) in electrocardiographic lead aVR in predicting severe coronary artery disease (CAD) is controversial. Hypothesis Assessment of lead aVR during EST can be helpful to identify patients with severe CAD. Methods We performed maximal EST in 200 patients undergoing coronary angiography for suspect of CAD. Four angiographic findings of severe CAD were considered: (1) left main (LM) disease; (2) LM or equivalent LM (LM/EQLM) disease; (3) LM or proximal left anterior descending (LAD) artery (LM/proxLAD) disease; and (4) LM or 3-vessel (LM/3V) disease. Results LM, LM/EQLM, LM/proxLAD, and LM/3V disease were shown in 6 (3%), 13 (6.5%), 33 (16.5%), and 27 (13.5%) patients, respectively. EST-induced STE in aVR occurred in 41 patients (20.5%). ST-segment depression (STD) in ≥5 leads was the only predictor of LM stenosis (odds ratio [OR]: 6.18, 95% confidence interval [CI]: 1.19-32.2, P = 0.03) and the most significant variable associated with LM/proxLAD stenosis (OR: 4.73, 95% CI: 2.0-11.2, P = 0.0001); maximal STD ≥3 mm was the most significant variable associated with LM/EQLM (OR: 7.58, 95% CI: 2.31-24.9, P = 0.001) and LM/3V (OR: 3.86, 95% CI: 1.47-10.1, P = 0.006) CAD. EST-induced STE in aVR was associated with LM/proxLAD disease only (OR: 3.23, 95% CI: 1.44-7.24, P = 0.004). At multivariate analysis, STD in ≥5 leads was the only independent predictor of LM/proxLAD disease (OR: 3.99, 95% CI: 1.58-10.1, P = 0.003). Conclusions EST-induced STE in lead aVR does not significantly increase the prediction of severe CAD compared with severity and extension of STD as assessed in the other electrocardiographic leads.

Remote ischemic preconditioning (RIPC) reduces myocardial damage caused by prolonged ischemia [(1)][1]. Recent studies, however, showed that RIPC has other favorable effects, including a reduction of platelet reactivity during invasive cardiac interventions [(2,3)][2]. In this study we assessed

BACKGROUND Because approximately 10% of patients with no-ST-segment elevation acute coronary syndrome (NSTE-ACS) show no obstructive coronary artery disease (NOCAD) on angiography, we assessed the spectrum of diagnoses and the predictors of outcome of these patients. METHODS AND RESULTS We studied 178 patients admitted to a coronary care unit with an initial diagnosis of NSTE-ACS, based on clinical, ECG and laboratory data, but found to have NOCAD. The final diagnosis in these patients was heterogeneous; true NSTE-ACS (ie, coronary thrombosis on an unstable plaque) was ascertained in 1 patient (0.6%), whereas diagnosis at discharge was microvascular NSTE-ACS in 56.2% of patients, variant angina in 10.1%, myocarditis in 8.9%, takotsubo disease in 7.9%, tachyarrhythmia-related chest pain in 6.7%, and non-cardiac pain in 9.6%. At 24.5-month follow-up, 21 deaths (11.8%) had occurred, 9 (5.1%) from cardiovascular causes, including 2 (1.12%) coronary deaths. By multivariable Cox analysis, age only predicted global (hazard ratio [HR] 1.07 [1.02-1.12]; P=0.006) and cardiovascular (HR 1.08 [1.01-1.16]; P=0.04) mortality; non-coronary vascular disease was the main predictor of cardiovascular death or readmission for cardiovascular disease (HR 3.28 [1.75-6.14]; P

Background Several patients with successful percutaneous coronary interventions (PCIs) show evidence of coronary microvascular dysfunction (CMVD), which can be responsible for persistent positivity of electrocardiographic exercise stress test (EST). In this study, we assessed whether post-PCI CMVD may predict clinical outcome in patients undergoing successful elective PCI of an isolated stenosis of the left anterior descending (LAD) coronary artery. Methods We studied 29 patients (age 64±6, 23 M) with stable coronary artery disease and isolated stenosis (>75%) of the LAD coronary artery who underwent successful PCI with stent implantation. Coronary blood flow (CBF) velocity response to adenosine and to cold-pressor test (CPT) was assessed in the LAD coronary artery by transthoracic Doppler echocardiography 24h and 3months after PCI. The primary end-point was a combination of death, admission for acute coronary syndromes (ACS) or target vessel revascularization (TVR). Results No death or ACS occurred during 36months of follow-up, but TVR was performed in 5 patients (17.2%). CBF response to CPT at 3months after PCI was 1.31±0.2 vs. 1.71±0.4 in patients with or without TVR, respectively (p=0.03), whereas CBF response to adenosine at 3months in these two groups was 1.70±0.3 vs. 2.05±0.4 (p=0.059). Conclusions Our data suggest that, in patients with successful PCI of LAD coronary artery stenosis, lower CBF response to the endothelium-dependent vasodilator stimulus CPT is associated with long-term recurrence of restenosis.