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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.

International guidelines define as paroxysmal supraventricular tachycardia (PSVT) all supraventricular tachyarrhythmias other than atrial flutter and atrial fibrillation. Associate symptoms, such as chest pain and dyspnea, and possible ECG changes during arrhythmia, such as ST depression, may suggest to the emergency physician a diagnosis of acute coronary syndrome (ACS), and thus lead to a request for troponin (cTn) level. Here we provide a comprehensive synthesis covering published literature on the diagnostic and prognostic role of cTn in patients admitted to Emergency Department (ED) for an episode of PSVT. We performed an extensive evaluation article written in English and available in PubMed and Web of Science by using the following Medical Subject Headings (MeSH): "paroxysmal supraventricular tachycardia" AND/OR "supraventricular tachycardia" AND "Troponin" AND "Emergency Department" AND/OR "coronary artery disease". We also performed hand searching of reference lists of selected articles. A total of 17 articles were finally included. There was great variability about study design, setting and criteria for the definition of PSVT and/or type of troponin. Troponin levels were measured frequently (up to 79%) in patients admitted to ED for PSVT. About 30% of them showed cTn elevation. This elevation appears not to be associated with the presence of CAD. However, c-Tn measurements could retain utility in stratifying those with poorer prognosis among PSVT patients with an elevated cardiovascular risk profile.

Introduction Multiple Myeloma (MM) is a hematological neoplasia originating from plasma cells, which accounts almost 1% of all oncologic malignancies. The median age of patients at diagnosis is about 65 years old and over. In this age group, cardiovascular (CV) diseases often co-exist, increasing the risk of adverse events related to MM treatment. A comprehensive search on the main educational platforms was performed and high-quality original articles and reviews were included. Areas covered Patients affected by MM are at risk for heart failure, uncontrolled systemic hypertension, accelerated ischemic heart disease, arterial/venous thromboembolism and arrhythmias. These complications may be due to the effects of chemotherapy on the CV system, which may play on pre-existing risk factors, and amyloid deposition at cardiac level. Expert opinion This review provides an updated overview of the spectrum of CV diseases which may affect MM patients, highlighting possible treatment strategies according to the latest recommendations. Cooperation between onco-hematologist and cardiologist is crucial in managing this population, in particular for adequate risk assessment, early diagnosis of CV complications and proper treatment.

Endothelial dysfunction is an early abnormality in the process of atherosclerosis and cardiovascular disease and has been associated with worse clinical outcome. Cardiac rehabilitation (CR) has been reported to be helpful to reduce cardiovascular events in various types of cardiac disease, but the mechanisms of its beneficial effects remain only partially known. In this article, we review the studies that assessed the effect of CR on endothelial function in patients with various cardiac conditions. Available data show that CR significantly improves impaired endothelial function in these patients, which may contribute to the beneficial effects of CR on clinical outcome.

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.

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.

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 …

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.

We report the case of a 41-year-old, 7-weeks-pregnant patient, presenting with headache and generalized seizure due to cerebral venous thrombosis complicated by jugular thrombosis and thrombus dislocation into right cardiac cavities. The patient was treated with intravenous heparin, and underwent embolectomy in extracorporeal circulation. This case illustrates the variability of cerebral venous thrombosis progression and a potentially life-threatening condition even during anticoagulant therapy.

Patients with microvascular angina (MVA) often have persistence of symptoms despite full classical anti-ischemic therapy. In this study, we assessed the effect of ivabradine and ranolazine in MVA patients. We randomized 46 patients with stable MVA (effort angina, positive exercise stress test [EST], normal coronary angiography, coronary flow reserve2.5), who had symptoms inadequately controlled by standard anti-ischemic therapy, to ivabradine (5 mg twice daily), ranolazine (375 mg twice daily), or placebo for 4 weeks. The Seattle Angina Questionnaire (SAQ), EuroQoL scale, and EST were assessed at baseline and after treatment. Coronary microvascular dilation in response to adenosine and to cold pressor test and peripheral endothelial function (by flow-mediated dilation) were also assessed. Both drugs improved SAQ items and EuroQoL scale compared with placebo (p0.01 for all), with ranolazine showing some more significant effects compared with ivabradine, on some SAQ items and EuroQoL scale (p0.05). Time to 1-mm ST-segment depression and EST duration were improved by ranolazine compared with placebo. No effects on coronary microvascular function and on flow-mediated dilation were observed with drugs or placebo. In conclusion, ranolazine and ivabradine may have a therapeutic role in MVA patients with inadequate control of symptoms in combination with usual anti-ischemic therapy.

To assess the effects of short-acting nitrates on exercise stress test (EST) results and the relation between EST results and coronary blood flow (CBF) response to nitrates in patients with microvascular angina (MVA). We completed 2 symptom/sign limited ESTs on 2 separate days, in a random sequence and in pharmacological washout, in 29 MVA patients and in 24 patients with obstructive coronary artery disease (CAD): one EST was performed without any intervention (control EST, C-EST), and the other after sublingual isosorbide dinitrate, 5 mg (nitrate EST, N-EST). CBF response to nitroglycerin (25 μg) was assessed in the left anterior descending coronary artery by transthoracic Doppler-echocardiography. At C-EST. ST-segment depression ≥1 mm (STD) was induced in 26 (90 %) and 23 (96 %) MVA and CAD patients, respectively (p = 0.42), whereas at N-EST, STD was induced in 25 (86 %) and 14 (56 %) MVA and CAD patients, respectively (p = 0.01). Time and rate pressure product at 1 mm STD increased during N-EST, compared to C-EST, in CAD patients (475 ± 115 vs. 365 ± 146 s, 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.

Primary prevention is addressed to forestall the outbreak of cardiovascular disease by facing its natural causes and risk factors. At a different level, secondary prevention involves strategies and therapies targeting preclinical or clinical verification of cardiovascular disease development.

To assess whether abnormalities in cardiac uptake of (123)I-metaiodobenzylguanidine (MIBG) correlate with coronary microvascular dysfunction in patients with cardiac syndrome X (CSX).University hospital.29 patients (aged 59 (SD 7) years, 11 men) with typical CSX and a matched group of 20 healthy subjects (aged 56 (7) years, 8 men) were studied.Planar and single photon emission computed tomography (SPECT) MIBG myocardial scintigraphy was performed in all subjects. Coronary flow response (CFR) to adenosine and to cold pressor test (CPT) in the left anterior descending (LAD) coronary artery was assessed in all CSX patients and in 12 controls by transthoracic Doppler echocardiography.Abnormalities in cardiac MIBG scintigraphy were observed in 25 CSX patients (86.2%), but in no healthy control (p0.001). Compared to controls, CSX patients showed a lower heart/mediastinum (H/M) ratio of MIBG uptake (1.69 (0.24) vs 2.2 (0.3), p0.001) and a higher cardiac MIBG defect score (25 (22) vs 4 (2), p = 0.002). Both CFR to adenosine (3.31 (1.1) vs 1.94 (0.6), p0.001) and CFR to CPT (2.35 (0.5) vs 1.63 (0.4), p0.001) were lower in CSX patients than in controls. In CSX patients, however, no correlation was found between MIBG H/M ratio and CFR to adenosine (r = 0.17; p = 0.38) and to CPT (r = -0.28; p = 0.13), as well as between MIBG uptake score in the LAD territory and CFR to adenosine (r = 0.14; p = 0.47) and to CPT (r = 0.06; p = 0.73).Our data show striking abnormalities in cardiac adrenergic nerve function and in coronary microvascular function in CSX patients. However, no significant relation between the two abnormalities was found. Further studies are needed to clarify the mechanisms and the role of MIBG defects in CSX patients.

In patients with cardiac syndrome X (CSX) who present with refractory angina episodes, spinal cord stimulation (SCS) has beneficial effects. The mechanisms of SCS, however, remain speculative. We assessed the effects of SCS on cardiac sympathetic function in these patients.We studied 11 CSX patients treated by SCS for refractory angina (mean age, 60 +/- 9 years; 5 men and 6 women), both during SCS therapy (SCS-ON) and after withdrawal of SCS therapy (SCS-OFF), using a randomized crossover design. Planar and single photon emission computed tomography iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and technetium 99m sestamibi (MIBI) bicycle exercise stress testing were performed at the end of each period. Compared with 10 healthy control subjects, CSX patients showed a lower heart-mediastinum ratio for MIBG uptake (2.19 +/- 0.3 vs 1.69 +/- 0.3, P = .001) and a higher cardiac MIBG uptake score (4.0 +/- 2.5 vs 19.7 +/- 27, P = .08). There were no differences in CSX patients during the SCS-ON and SCS-OFF phases of the study in heart-mediastinum ratio (1.74 +/- 0.3 vs 1.69 +/- 0.3, P = .13), cardiac washout rate of MIBG (42.9% +/- 14% vs 43.3% +/- 14%, P = .08), or MIBG defect score (18.7 +/- 25 vs 19.7 +/- 27, P = .22). Reversible perfusion defects during the SCS-OFF phase were detected in 8 patients; an improvement in perfusion defects was observed in 2 patients (25%) during the SCS-ON phase.Our data confirm the presence of abnormal cardiac adrenergic nerve function in CSX patients. SCS was unable to result in significant improvement of cardiac MIBG uptake abnormalities, suggesting that its therapeutic effects are unlikely to be mediated by modulation of cardiac adrenergic nerve activity.

Experimental studies suggest that alcohol may have protective effects similar to that of ischemic preconditioning (IPC). The acute effects of alcohol on IPC in humans, however, are poorly known. In this study, we assessed the effect of alcohol administration on the warm-up phenomenon, as an expression of IPC, in patients with stable coronary artery disease (CAD). We randomized 45 stable CAD patients with positive (ST-segment depressionor =1 mm) exercise stress test to 1 of 3 groups of 15 patients each: (1) group 1 = 60 cc of gin (18.5 g of ethanol); (2) group 2 = 180 cc of red wine (18.9 g of ethanol); and (3) group 3 = placebo (120 cc of water). A first exercise test was performed 15 minutes after beverage administration. In those with a positive exercise test (13, 14, and 14 patients in the gin, wine, and placebo groups, respectively), a second exercise test was performed 15 minutes after the end of the first one. On the first test, there were no differences among groups in rate pressure product and time of exercise at 1-mm ST-segment depression, as well as in maximal ST segment depression. Furthermore, an improvement of the ischemic exercise variables was observed in each group, without any statistically significant differences among them. In conclusion, our data show that, in stable CAD patients, the acute intake of low doses of alcohol does not significantly influence IPC, as expressed by the warm-up phenomenon on exercise stress testing.

To investigate the determinants and prognostic value of heart rate variability (HRV) in acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention (PCI).We studied 64 patients with AMI (58.4 +/- 10 years, 56 men), treated by PCI within 12 h of symptom onset. Patients underwent 24-h electrocardiographic Holter recording before discharge. HRV was measured in the time- and frequency-domain. Cardiac events were assessed at 6 months.At univariate analysis, Thrombolysis in Myocardial Infarction (TIMI) flow grade3 was significantly predictive of reduced frequency-domain variables. On multivariate analysis, diabetes and pre-PCI time6 h were the strongest predictors of depressed HRV, with peak creatine kinase myocardial-type and lower left ventricular ejection fraction being also variably correlated with impaired HRV. At 6-month follow-up, seven patients (10.1%) had cardiac events (one AMI, six revascularization procedures). A low standard deviation of RR intervals was a significant predictor of events (P = 0.009), although only age was associated with the endpoint (P = 0.05) on multivariate analysis.Our study shows that, in AMI patients treated by primary PCI, a delay in coronary revascularization and AMI extension are key factors for determining depressed HRV.

Smoking induces an impairment of endothelium-dependent vasodilatation. In this study we assessed whether smoking also causes an impairment of endothelium-independent vasodilatation.We studied 2 groups of young healthy subjects: 1) 12 medical students (24.5 ± 0.9 years; 6 male) without cardiovascular risk factors (CVRFs), except smoking (≥10 cigarettes/day); 2) 12 matched controls (24.5 ± 1.1 years; 6 male) without any CVRF. Nitrate-mediated dilatation (NMD) of the brachial artery was assessed in response to the random administration of 4 different doses (10, 20, 30 and 40 μg) of sublingual nitroglycerin (NTG). Flow-mediated dilatation (FMD) was also assessed.The increasing doses of NTG determined a progressive increase of NMD in both groups, but the dose-response curve was significantly lower in smokers compared to controls (p 0.001). FMD was also lower in smokers, compared to controls (6.12 + 0.6 vs. 8.06 + 0.9%, p 0.001).Our data show that smoking induces an early impairment of endothelium-independent arterial dilatation.

To assess the effect of ranolazine on systemic vascular function in patients with type II diabetes mellitus (T2DM).We randomized 30 consecutive T2DM patients with no evidence of cardiovascular disease and no insulin therapy to receive one of the following 3 forms of treatment in a blinded fashion: ranolazine, 375 mg bid for 3 weeks (group 1); ranolazine, 375 mg bid for 2 weeks, followed by placebo bid for 1 week (group 2); placebo bid for 3 weeks (group 3). Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were assessed at baseline and after 48 h, and 2 and 3 weeks.FMD and NMD were similar among groups at baseline. Compared to the basal value, FMD significantly improved after 2 weeks in group 1 and in group 2 (p 0.01 for both), but not in group 3. At 3 weeks, FMD remained improved, compared to baseline, in group 1 (p 0.05), whereas returned to basal values in group 2 (p = 0.89 vs. baseline). No changes in NMD were observed in any group.In this controlled study, ranolazine was able to improve endothelial function in T2DM patients.

ST-segment depression during exercise stress testing in asymptomatic subjects showing normal coronary arteries is considered a "false-positive" result. Coronary microvascular dysfunction, however, might be a possible cause of ST-segment depression in these cases. We assessed the coronary blood flow response to adenosine and to cold pressor test in the left anterior descending artery, using transthoracic Doppler echocardiography in 14 asymptomatic subjects with exercise-induced ST-segment depression and normal coronary arteries (group 1), 14 patients with microvascular angina (group 2), and 14 healthy subjects (group 3). Flow-mediated dilation was assessed in the brachial artery. Central pain processing was assessed using cortical laser evoked potentials during chest and right hand stimulation with 3 sequences of painful stimuli. The coronary blood flow response to adenosine was 1.8 ± 0.4, 1.9 ± 0.5, and 3.1 ± 0.9 in groups 1, 2, and 3, respectively (p0.001). The corresponding coronary blood flow responses to the cold pressor test were 1.74 ± 0.4, 1.53 ± 0.3, and 2.3 ± 0.6 (p0.001). The flow-mediated dilation was 5.5 ± 2.3%, 4.6 ± 2.4%, and 9.8 ± 1.2% in the 3 groups, respectively (p0.001). The laser evoked potential N2/P2 wave amplitude decreased throughout the 3 sequences of stimulation in groups 1 and 3 but not in group 2 (chest, -19 ± 22%, +11 ± 42% and -36 ± 12%, p0.001; right hand, -22 ± 25%, +12 ± 43% and -30 ± 20%, p = 0.009; in groups 1, 2, and 3). In conclusion, exercise stress test-induced ST-segment depression in asymptomatic subjects with normal coronary arteries cannot be considered as a simple false-positive result, because it can be related to coronary microvascular dysfunction. The different symptomatic state compared to patients with microvascular angina can, at least in part, be explained by differences in cortical processing of neural pain stimuli.

The causes of coronary microvascular dysfunction (CMVD) in patients with cardiac syndrome X (CSX) are largely unknown. Common cardiovascular risk factors (CVRFs) and increased markers of inflammation have been associated with CMVD in some studies, but their role in determining CMVD in CSX patients remains poorly known.We studied 71 CSX patients (56 ± 9 years, 23 men) and 20 healthy volunteers (52 ± 7 years, nine men). Using transthoracic Doppler echocardiography, coronary microvascular vasodilator function was assessed in the left anterior descending coronary artery as the ratio of diastolic coronary blood flow (CBF) velocity at peak intravenous adenosine administration and during cold pressor test (CPT) to the respective basal CBF velocity values. Common CVRFs tended to be more frequent and C-reactive protein (CRP) levels were higher (P0.001) in CSX patients than in controls. Both CBF responses to adenosine (2.05 ± 0.6 vs. 2.92 ± 0.9, P0.001) and to CPT (1.71 ± 0.6 vs. 2.42 ± 0.7, P0.001) were lower in CSX patients than in controls. The differences between the two groups in CBF response to adenosine and in CBF response to CPT remained highly significant (P0.01 for both) after adjustment for all CVRFs, including serum CRP levels.In CSX patients, both endothelium-dependent and endothelium-independent CMVD cannot be reliably predicted by CVRFs (including serum CRP levels), alone or in combination.

Flow-mediated dilation (FMD) is a widely used tool to investigate endothelial function. However, FMD assessment may cause mechanical damage to the arterial endothelium. In this study we investigated the effect of FMD assessment on endothelial function. We studied 20 healthy subjects (26 ± 6 years; 12 males). FMD was assessed by measuring brachial artery dilation in response to hyperemia after 5 min of forearm cuff inflation. Subjects were studied on 2 subsequent days. On day 1 they underwent two consecutive FMD measures, with the second test (FMD2) performed 15 min after the first test (FMD1). On day 2, the subjects were randomized to receive either placebo (saline) or intravenous L: -arginine (10 g in 20 min). At the end of the infusion, patients underwent two consecutive FMD measures following the same protocol as on day 1. Asymmetric dimethyl-arginine (ADMA) serum levels were assessed on day 2 before FMD1 and FMD2. On day 1, FMD2 was lower than FMD1 in both groups (placebo 6.47 ± 2.1 vs. 7.86 ± 1.8%, P 0.01; arginine 6.13 ± 2.6 vs. 7.76 ± 2.7%, P 0.01). On day 2, a significant reduction of FMD was observed during FMD2 compared to FMD1 in the placebo group (5.82 ± 1.7 vs. 7.44 ± 2.2%, P 0.001), but not in the arginine group (7.19 ± 1.5 vs. 7.27 ± 1.5, P = 0.67). ADMA levels significantly increased compared to baseline after FMD1 (0.59 ± 0.12-0.91 ± 0.64 μmol/l, P = 0.036), with similar changes in the two groups. FMD assessment induces a significant impairment of endothelial function. An increase of endogenous NO synthesis inhibitors seems responsible for the phenomenon that is reversed by L: -arginine administration.

Background Previous follow-up studies of patients with cardiac syndrome X (CSX) reported good prognosis. However, some recent reports challenged this finding by showing appreciable mortality rates in patients with angina and normal coronary arteries admitted for acute coronary syndromes. Methods We performed clinical follow-up of 155 patients (mean age 58.9±10 years, 40 men) with typical CSX. The occurrence of major cardiac events (cardiac death, acute myocardial infarction), readmission for chest pain, revascularization procedures, angina status, and non cardiac events during follow-up were collected for each patient. Results At a mean follow-up time of 137±78 months (range 24–372) from the onset of symptoms, 4 patients died, 3 for cancers and 1 for acute pancreatitis. No patient died from cardiovascular causes or had any major cardiovascular event. Hospital readmission for recurrent chest pain was reported by 89 patients (58%), and 33 (22%) underwent at least one more coronary angiography. During follow-up, chest pain had remained unchanged in 33% of patients and had worsened in 14% of patients. Conclusion Our data show that patients with CSX have excellent long-term clinical prognosis. A significant number of patients, however, shows persistence or worsening of symptoms, as well as further recurrence to medical evaluation.

BACKGROUND We previously found a severe impairment of cardiac uptake of I-metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, on myocardial scintigraphy in a small group of patients with cardiac syndrome X (CSX), suggesting a dysfunction of cardiac adrenergic nerve fibres. In this study, we assessed the consistency of these previous findings in a larger group of these patients. METHODS Planar and single-photon emission computed tomography MIBG myocardial scintigraphy was performed in 40 CSX patients (58 +/- 7 years, 17 men). Cardiac MIBG uptake was measured by the heart/mediastinum ratio and by a single-photon emission computed tomography regional cardiac MIBG uptake defect score (higher values = lower uptake). As a control group, we studied 20 healthy individuals (56 +/- 6 years, nine men). An exercise stress Tc-SestaMIBI myocardial scintigraphy was performed in 34 CSX patients (85%). RESULTS Cardiac MIBG defects were observed in 30 patients (75%), with nine (22.5%) showing no cardiac MIBG uptake at all. Compared with controls, CSX patients showed a significantly lower heart/mediastinum ratio (1.70 +/- 0.35 vs. 2.1 +/- 0.22, P < 0.001) and a higher cardiac MIBG defect score (27 +/- 25 vs. 4.4 +/- 2.5, P < 0.001). No differences were found in lung MIBG uptake between the two groups. Reversible perfusion defects on stress myocardial scintigraphy were found in 17 out of 34 CSX patients (50%), all of whom also had abnormal cardiac MIBG uptake; cardiac MIBG uptake abnormalities were also present in nine of 17 patients with normal perfusion scintigraphic images. Cardiac MIBG uptake findings were similar in our first 12 patients and in the 28 patients studied subsequently. CONCLUSION Our data show a relevant impairment of cardiac MIBG uptake in patients with CSX, suggesting that functional abnormalities in cardiac adrenergic nerve function may play a significant role in the mechanisms responsible for the syndrome.

Myocardial cell damage caused by myocardial ischemia results from several factors that include the duration of ischemia, oxygen demand by cardiomyocytes at the time of ischemia, and the presence and entity of collateral blood flow to the ischemic area. Importantly, myocardial cell injury may derive not only from ischemia itself but also from detrimental phenomena occurring during the restoration of myocardial blood flow after the ischemic episode (reperfusion damage). In the last decades a lot of studies have demonstrated that cardiomyocytes have several mechanisms that provide them protection against the damage deriving from ischemia-reperfusion, also allowing a prolongation of survival in the most severe cases. In this article we review some of these mechanisms, also discussing their present and/or potential therapeutic applications in the clinical setting. The topics include the interventions aimed at reducing cardiac work through a reduction of oxygen demand by myocardial cells or at optimizing the utilization of energetic resources by myocardial cells in situations of ischemia, the importance of phenomena such as ischemic preconditioning (early and delayed) and postconditioning of myocardial cells, and, finally, the theoretic possibility of interventions aimed at preventing cell death consequent to apoptosis.

Objectives: To get insight in the mechanism of exercise-induced ST-segment elevation (STE) in patients with Q/QS waves at the electrocardiogram (ECG). Methods: We performed exercise stress test in 13 patients with anterior acute myocardial infarction treated by successful primary percutaneous coronary intervention (PCI). Results: Compared to rest, an additional STE >1 mm in one or more precordial ECG leads during exercise occurred in nine patients (69%), in the absence of symptoms. Conclusions: In acute myocardial infarction (MI) patients, treated by primary PCI and showing optimal coronary blood flow restoration at angiography, STE can still be induced by exercise in Q/QS wave ECG leads. This finding lends further support to the theory that exercise-induced STE in this clinical context is unlikely to represent by itself transient myocardial ischemia or viability.

Background. In ≈ 40% of patients with acute ischemic stroke, the cause remains undefined (cryptogenic stroke). Previous studies, using contrast echocardiography, showed a significant prevalence of a patent foramen ovale (PFO) in patients with cryptogenic stroke < 55 years of age, suggesting a causal role through paradoxical embolism. Contrast transesophageal echocardiography (TEE) is considered the gold standard for PFO detection. Recently, however, cardiac magnetic resonance (CMR) was also shown to reliably detect PFO. In this study we compared the accuracy of CMR and TEE in detecting PFO in a group of patients with cryptogenic stroke. Methods and Results . Sixteen patients (age 50 ± 13 years, 9 males) with cryptogenic ischemic stroke underwent contrast-enhanced TEE and contrast CMR for detection of possible PFO. Both imaging studies were performed during Valsalva maneuver. PFO grading results were assessed visually both for TEE and CMR, according to the entity of contrast passage in the left atrium (grade 0 = no PFO; grades 1, 2 and 3 = mild, medium and wide PFO, respectively). Nine patients (56%) were identified to have a PFO by contrast TEE. Contrast-enhanced CMR identified a PFO in only 5 (56%) of these patients. None of the 7 patients without PFO at TEE was shown to have a PFO at CMR. TEE showed a grade 1 PFO in 4 patients, a grade 2 PFO in 3 and a grade 3 PFO in 2 patients. Of these patients, CMR failed to identify PFO in all patients with a grade 1 PFO at TEE and underestimated the degree of the shunt in the other patients. Conclusions. Our data suggest that TEE should be considered the non-invasive diagnostic reference test to detect and characterize PFO in patients with ischemic cryptogenic stroke.

We assessed heart rate variability (HRV) and high-sensitivity C-reactive protein (CRP) serum levels in 77 patients with chronic stable angina (CSA), 47 of whom had obstructive coronary artery disease (CAD) and 30 normal or near-normal coronary arteries (NCA). The effect of percutaneous coronary interventions (PCI) and bypass surgery (CABG) on HRV and CRP was assessed in 36 patients (18 PCI, 18 CABG) 6 months after the intervention. A significant inverse correlation was found between CRP levels and HRV variables in CAD patients (best r value=−0.31, p =0.036 for very low frequency amplitude), but not in NCA patients. At follow-up, however, no significant correlation was found between CRP and HRV in PCI and CABG treated patients. Thus, while confirming the presence of a relation between cardiac autonomic dysfunction and inflammation in CAD patients, our data show that the association is lost after revascularization procedures.

showed a lower FMD (median [interquartile range] 8.5 % [7.3–9.3] vs. 4.7 % [2.7–7.2], p