Mechanisms, prevalence and management of cardiac arrhythmias in cancer patients: a comprehensive review.

Recently, prognosis and survival of cancer patients has improved due to progression and refinement of cancer therapies; however, cardiovascular sequelae in this population augmented and now represent the second cause of death in oncological patients. Initially, the main issue was represented by heart failure and coronary artery disease, but a growing body of evidence has now shed light on the increased arrhythmic risk of this population, atrial fibrillation being the most frequently encountered. Awareness of arrhythmic complications of cancer and its treatments may help oncologists and cardiologists to develop targeted approaches for the management of arrhythmias in this population. In this review, we provide an updated overview of the mechanisms triggering cardiac arrhythmias in cancer patients, their prevalence and management.

Prognostic Assessment of Early Repolarization/J Wave Electrocardiographic Pattern in Patients With Stable Ischemic Heart Disease.

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.

Management of Patients with Asymptomatic Carotid Stenosis May Need to Be Individualized: A Multidisciplinary Call for Action.

The optimal management of patients with asymptomatic carotid stenosis (ACS) is the subject of extensive debate. According to the 2017 European Society for Vascular Surgery guidelines, carotid endarterectomy should (Class IIa; Level of Evidence: B) or carotid artery stenting may be considered (Class IIb; Level of Evidence: B) in the presence of one or more clinical/imaging characteristics that may be associated with an increased risk of late ipsilateral stroke (e.g., silent embolic infarcts on brain computed tomography/magnetic resonance imaging, progression in the severity of ACS, a history of contralateral transient ischemic attack/stroke, microemboli detection on transcranial Doppler, etc.), provided documented perioperative stroke/death rates are <3% and the patient's life expectancy is >5 years. Besides these clinical/imaging characteristics, there are additional individual, ethnic/racial or social factors that should probably be evaluated in the decision process regarding the optimal management of these patients, such as individual patient needs/patient choice, patient compliance with best medical treatment, patient sex, culture, race/ethnicity, age and comorbidities, as well as improvements in imaging/operative techniques/outcomes. The present multispecialty position paper will present the rationale why the management of patients with ACS may need to be individualized.

Assessment and pathophysiology of microvascular disease: recent progress and clinical implications.

The development of novel, non-invasive techniques and standardization of protocols to assess microvascular dysfunction have elucidated the key role of microvascular changes in the evolution of cardiovascular (CV) damage, and their capacity to predict an increased risk of adverse events. These technical advances parallel with the development of novel biological assays that enabled the ex vivo identification of pathways promoting microvascular dysfunction, providing novel potential treatment targets for preventing cerebral-CV disease. In this article, we provide an update of diagnostic testing strategies to detect and characterize microvascular dysfunction and suggestions on how to standardize and maximize the information obtained from each microvascular assay. We examine emerging data highlighting the significance of microvascular dysfunction in the development CV disease manifestations. Finally, we summarize the pathophysiology of microvascular dysfunction emphasizing the role of oxidative stress and its regulation by epigenetic mechanisms, which might represent potential targets for novel interventions beyond conventional approaches, representing a new frontier in CV disease reduction.

The central role of conventional 12-lead ECG for the assessment of microvascular obstruction after percutaneous myocardial revascularization.

Guidelines report that the optimal treatment for ST-elevation myocardial infarction (STEMI) is a primary percutaneous coronary intervention (PPCI) when performed timely by trained operators. Yet, the reopening of the infarct-related artery (IRA) is not always followed by myocardial reperfusion. This phenomenon is most commonly called "no-reflow", is caused by microvascular obstruction (MVO) and is associated to a worse outcome. Electrocardiogram (ECG) is crucial for the diagnosis of STEMI, but is also useful for the assessment of MVO. In this review we summarize ECG-derived parameters associated to MVO and their prognostic relevance.

Assessment of flow-mediated dilation reproducibility: a nationwide multicenter study.

OBJECTIVE: Impaired flow-mediated dilation (FMD) is associated with cardiovascular risk factors and provides prognostic information. Despite the noninvasive nature of this technique, a major limitation to its widespread use is low reproducibility. The aim of this study was to evaluate impact of methodological standardization among different investigation sites on brachial artery FMD reproducibility. METHODS: Seven Italian centers recruited 135 healthy volunteers, aged 20-60 years. FMD was assessed by high-resolution ultrasound equipped with a stereotactic probe-holding device. Certified sonographers recorded brachial artery scans at baseline (day 1a), 1 h after (day 1b), and 1 month later (day 30). Endothelium-independent vasodilation (EIVD) to sublingual glyceril-trinitrate was recorded at day 1 and day 30. FMD and EIVD were blindly evaluated at the coordinating center by an automated edge detection system. The intra-session (day 1a versus 1b) and inter-session (day 1a versus 30) coefficients of variation were calculated. RESULTS: FMD was not significantly (P = 0.91) different at day 1a, day 1b and day 30 (6.52 ± 2.9, 6.42 ± 3.1, 6.57 ± 2.8%, respectively). The FMD intra-session coefficient of variation was 9.9 ± 8.4% (from 7.6 to 11.9% across centers). The FMD inter-session coefficient of variation was 12.9 ± 11.6% (from 11.6 to 16.1% across centers). Inter-session coefficient of variation for EIDV was 19.7 ± 16.8%. CONCLUSIONS: This study shows a homogeneous coefficient of variation for FMD among different centers. The inter-session coefficient of variation was similar to the intra-session coefficient of variation, representing the intrinsic FMD variability. We demonstrate for the first time that rigorous and standardized procedure may provide reproducible FMD assessment to study endothelial function in multicenter clinical trials.

Transient endothelial dysfunction following flow-mediated dilation assessment.

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.

Current clinical features, diagnostic assessment and prognostic determinants of patients with variant angina.

BACKGROUND: Clinical characteristics and outcome of patients with variant angina were assessed in the 1970-1980s of the past Century. The recent progress in prevention, diagnosis and treatment of coronary artery disease may have significantly modified clinical characteristics and prognosis of these patients. METHODS: From January 1991 to December 2002, 202 patients (57.1+/-12 years; 166 men) were diagnosed to have variant angina at our Institute. Detailed clinical findings and clinical events were prospectively collected for each patient. RESULTS: The median time from the first angina attack to diagnosis was 2 months (range 1-276), with diagnosis requiring >6 months in 31.7% of patients. Coronary angiography (n=183) showed normal coronary arteries in 42.1% of patients and significant coronary stenoses (>50%) in 44.3%, with multi-vessel disease in 8.7%. Diagnosis of variant angina was done during coronary angiography in 3% of cases during the first half of the study period, but in 42% of patients in the second half of the study period. Major cardiac events (MCE, i.e., death, resuscitation from cardiac arrest, myocardial infarction) occurred in 41 patients (20.3%), with 43.9% of events occurring within 1 month of symptom onset. The only variable significantly associated with MCE was the detection during angina of ST segment elevation in both anterior and inferior ECG leads (odds ratio 3.24; 95% confidence interval 1.43-7.36; P=0.005). CONCLUSION: Our data suggest that variant angina is still a frequently overlooked diagnosis, and a timely diagnosis would be crucial to prevent early life-threatening events. Patients with diffuse ST segment elevation on ECG are those at the highest risk of MCE, independently of angiographic findings.

Assessment of systemic inflammation and infective pathogen burden in patients with cardiac syndrome X.

Inflammation plays a key role in coronary artery disease (CAD), but whether it is involved in the pathogenesis of syndrome X (SX) is not known. Thus, we assessed the presence of systemic inflammation in patients with SX and its possible relation to infections from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus. We studied 55 patients with SX (57 +/- 8 years old; 27 women), 49 with stable angina and obstructive CAD (56 +/- 8 years old; 24 women), and 60 healthy controls (57 +/- 11 years old; 24 women). Plasma levels of high-sensitivity C-reactive protein and interleukin-1 receptor antagonist were measured in all patients. Infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus was assessed in 43 patients with SX, 40 patients with CAD, and in 39 controls. Patients with SX had lower serum levels of C-reactive protein than did patients with CAD (4.06 +/- 6.8 vs 5.99 +/- 7.8 mg/L, p = 0.013) but higher levels of C-reactive protein than did controls (1.75 +/- 1.98 mg/L; p = 0.008). Plasma levels of interleukin-1 receptor antagonist were higher in patients with CAD (570 +/- 738 pg/ml) and patients with SX (494 +/- 677 pg/ml) than in controls (254 +/- 174, pg/ml; p = 0.0003 vs CAD and p = 0.013 vs SX) but did not differ significantly between patients with CAD or SX (p = 0.20). There were no differences across groups in the prevalence of infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus and in the prevalence of 1, 2, 3, and 4 infections (p = 0.99). Among patients with SX, no correlation was found between markers of inflammation and indexes of disease activity (angina episodes, exercise test results). Our data show evidence of increased low-grade systemic inflammation in patients with cardiac SX, which was unrelated to an increased infectious pathogen burden.