Paget Disease of Bone Harboring Bone Metastatic Neuroendocrine Cancer: A Case Report.

In this case report, we describe an uncommon case of neuroendocrine cancer of unknown origin began with cauda equina syndrome in a patient affected by Paget disease of bone (PDB). A 76-year-old man with diagnosis of PDB, without history of pain or bone deformity, developed sudden severe low back pain. Bone alkaline phosphatase was increased and MRI and whole-body scintigraphy confirmed the localization of the disease at the third vertebra of the lumbar spine. Treatment with Neridronic Acid was started, but after only 2 weeks of therapy anuria and bowel occlusion occurred together with lower limb weakness and walking impairment. Cauda equina syndrome consequent to spinal stenosis at the level of L2-L3 was diagnosed after admission to Emergency Department and the patient underwent neurosurgery for spinal medulla decompression. The histologic results showed a complete subversion of bone structure in neoplastic tissue, consistent with metastatic neuroendocrine carcinoma of unknown origin. In conclusion, low back pain in the elderly may require deep investigation to individuate rare diseases. In asymptomatic patients with apparently stable PDB, the sudden appearance of pain or neurologic symptoms may alert the clinician for the possibility of other superimposing diseases, like bone metastases.

Multi-modality imaging for pre-procedural planning of transcatheter mitral valve interventions.

Transcatheter mitral valve interventions (TMVI), either repair or replacement, are established alternative options for patients with mitral regurgitation (MR) deemed not suitable for conventional open-heart surgery. Multi-modality imaging plays a pivotal role in the selection of patients, gaining insights into the anatomy of the mitral valve the mechanism and the severity of MR, which are essential to predict the success of these procedures. The aim of this review is to provide an overview on the role of multi-modality imaging in the patient selection and pre-procedural planning of TMVI.

The implantable cardiac monitor in heart failure patient: a possible new indication?

Implantable cardiac monitors (ICMs) have found increasing use in clinical practice over the years, proving, when used in high-risk populations, to facilitate the diagnosis of bradyarrhythmias and tachyarrhythmias requiring treatment. Experience with heart failure patients undergoing pacemaker (PMK) or implantable defibrillator (ICD) implantation, which allow for continuous electrocardiographic monitoring and transthoracic impedance assessment, has made it possible to identify predictors of heart failure flare-ups. In this context, the use of telemonitoring has been shown to ensure better management of patients with heart failure. These benefits cannot be assessed to date in patients with heart failure and left ventricular ejection fraction (LVEF) > 35% who have no indication for PMK or ICD implantation. This population has been shown to have a significant incidence of ventricular arrhythmias and bradyarrhythmias. In addition, a significant number of cerebrovascular events are observed in this population, largely attributable to the high incidence of atrial fibrillation (AF). In this population, the occurrence of AF has also been shown to have a negative impact on patients' prognosis; at the same time, a rhythm control strategy has been shown to be more beneficial in this area than a rate control strategy. Studies also suggest arrhythmias have a negative impact on the cognitive status and quality of life of heart failure patients. These reasons could justify the implantation of ICMs equipped with telemonitoring systems in heart failure patients. The information provided by the monitoring system, if properly managed, could bring benefits in terms of prognosis and quality of life along with a reduction in economic costs. We will try here, by answering a few questions, to assess whether there is an indication for ICM in heart failure, which patients should be candidates and how these patients should be managed.

The value of the 12-lead electrocardiogram in the prediction of sudden cardiac death.

Sudden cardiac death (SCD) can be caused by several clinical conditions, overt or misconceived, which recognize different pathophysiologies determining the development of fatal arrhythmic events. In the various forms of structural heart disease such as ischaemic heart disease, cardiomyopathies (e.g. hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy), channelopathies (e.g. long-QT syndrome, congenital short QT, Brugada syndrome, early repolarization (ER) syndrome, and idiopathic ventricular fibrillation) but also in the apparently healthy subject, the 12-lead electrocardiogram (ECG) has proved, over the years, to be a reliable and readily available method for stratifying the risk of adverse arrhythmic events and consequently SCD. Several electrocardiographic markers have been shown to be associated with adverse outcomes in different types of patients. Although with different sensitivity and specificity in each clinical condition, depolarization abnormalities, such as QRS fragmentation, Q waves, QRS duration, left posterior fascicular block, low QRS voltage, and left ventricular hypertrophy and similarly repolarization abnormalities as ER pattern, T wave alternans, QT interval, and QT dispersion, have shown significant efficacy in predicting SCD. Despite the advancement of techniques especially in the field of imaging, the correct interpretation of the 12-lead ECG remains, therefore, an effective tool for assessing the possible prognostic outcome in terms of arrhythmic risk and SCD in different types of patients.

The electrocardiogram in non-ischaemic-dilated cardiomyopathy.

This article summarizes the main electrocardiogram (ECG) findings in dilated cardiomyopathy (DCM) patients. Recent reports are described in the great 'pot' of DCM peculiar ECG patterns that are typical of specific forms of DCM. Patients with late gadolinium enhancement on CMR, who are at greatest arrhythmic risk, have also distinctive ECG features. Future studies in large DCM populations should evaluate the diagnostic and prognostic value of the ECG.

New Insight in Cardiorenal Syndrome: From Biomarkers to Therapy.

Cardiorenal syndrome consists in the coexistence of acute or chronic dysfunction of heart and kidneys resulting in a cascade of feedback mechanisms and causing damage to both organs associated with high morbidity and mortality. In the last few years, different biomarkers have been investigated with the aim to achieve an early and accurate diagnosis of cardiorenal syndrome, to provide a prognostic role and to guide the development of targeted pharmacological and non-pharmacological therapies. In such a context, sodium-glucose cotransporter 2 (SGLT2) inhibitors, recommended as the first-line choice in the management of heart failure, might represent a promising strategy in the management of cardiorenal syndrome due to their efficacy in reducing both cardiac and renal outcomes. In this review, we will discuss the current knowledge on the pathophysiology of cardiorenal syndrome in adults, as well as the utility of biomarkers in cardiac and kidney dysfunction and potential insights into novel therapeutics.

Low Perception of Obesity as a Pathological Condition Among Italian Cardiologists.

INTRODUCTION: Obesity is not only an important modifiable cardiovascular risk factor but also a chronic disease with relevant consequences on morbidity and mortality in the general population. According to European guidelines, cardiologists must recognize and treat it properly. AIMS: To assess perception of obesity as a modifiable pathological condition and the importance to treat it in a real-world sample of cardiologists and residents in cardiology. METHODS: A nationwide, web-based, epidemiological survey on the perception of obesity as a disease and as a modifiable cardiovascular risk factors was conducted in 137 medical doctors (cardiologists and residents in cardiology). Participants filled with their answers a questionnaire of 31 questions about perception of obesity and strategies on cardiovascular disease prevention in clinical practice. RESULTS: Of 137 individuals enrolled in our survey only 5 (3.6%) reported to measure waist circumference in their clinical practice and only 3 (2.2%) reported to measure waist-to-hip ratio. One-hundred-twenty participants (87.6%) would not prescribe an anti-obesity drug to a patient with grade II obesity. Sixty-eight (49.6%) participants have never read or heard of a clinical trial on obesity. On the other hand, 134 (97.8%) routinely measured blood pressure in their clinical practice, 129 (94.2%) would prescribe a statin for a hypercholesterolemic patient and 132 (96.4%) subjects have read/heard a clinical trial on type 2 diabetes in their life. CONCLUSIONS: Although obesity is a chronic disease and an important modifiable cardiovascular risk factor such as arterial hypertension, hypercholesterolemia, cigarette smoke and diabetes, cardiologists and residents in cardiology substantially underestimate it ignoring that it should be treated as a proper disease.

The pivotal role of ECG in cardiomyopathies.

Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Recent technological advances in cardiovascular imaging offer an opportunity for deep phenotypic and etiological definition. Electrocardiogram (ECG) is the first-line diagnostic tool in the evaluation of both asymptomatic and symptomatic individuals. Some electrocardiographic signs are pathognomonic or fall within validated diagnostic criteria of individual cardiomyopathy such as the inverted T waves in right precordial leads (V1-V3) or beyond in individuals with complete pubertal development in the absence of complete right bundle branch block for the diagnosis of arrhythmogenic cardiomyopathy of the right ventricle (ARVC) or the presence of low voltages typically seen in more than 60% of patients with amyloidosis. Most other electrocardiographic findings such as the presence of depolarization changes including QRS fragmentation, the presence of epsilon wave, the presence of reduced or increased voltages as well as alterations in the repolarization phase including the negative T waves in the lateral leads, or the profound inversion of the T waves or downsloping of the ST tract are more non-specific signs which can however raise the clinical suspicion of cardiomyopathy in order to initiate a diagnostic procedure especially using imaging techniques for diagnostic confirmation. Such electrocardiographic alterations not only have a counterpart in imaging investigations such as evidence of late gadolinium enhancement on magnetic resonance imaging, but may also have an important prognostic value once a definite diagnosis has been made. In addition, the presence of electrical stimulus conduction disturbances or advanced atrioventricular blocks that can be seen especially in conditions such as cardiac amyloidosis or sarcoidosis, or the presence of left bundle branch block or posterior fascicular block in dilated or arrhythmogenic left ventricular cardiomyopathies are recognized as a possible expression of advanced pathology. Similarly, the presence of ventricular arrhythmias with typical patterns such as non-sustained or sustained ventricular tachycardia of LBBB morphology in ARVC or non-sustained or sustained ventricular tachycardia with an RBBB morphology (excluding the "fascicular pattern") in arrhythmogenic left ventricle cardiomyopathy could have a significant impact on the course of each disease. It is therefore clear that a learned and careful interpretation of ECG features can raise suspicion of the presence of a cardiomyopathy, identify diagnostic "red flags" useful for orienting the diagnosis toward specific forms, and provide useful tools for risk stratification. The purpose of this review is to emphasize the important role of the ECG in the diagnostic workup, describing the main ECG findings of different cardiomyopathies.

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.

The Complex but Fascinating Relationship between Sport and Atrial Fibrillation: From Pathophysiology to the Clinical Scenario.

Atrial fibrillation (AF) is the most common cause of hospital admission among all arrhythmias in the general population. Moreover, AF represents the most common arrhythmia in the athletic population as well. The complex but fascinating relationship between sport and atrial fibrillation has not yet been fully clarified. Although the benefits of moderate physical activity in controlling cardiovascular risk factors and in reducing the risk of atrial fibrillation have been widely demonstrated, some concerns have been raised about the potential adverse effects of physical activity. Endurance activity in middle-aged men athletes appears to increase the risk of AF. Several different physiopathological mechanisms may explain the increased risk of AF in endurance athletes, including the imbalance of the autonomic nervous system, changes in left atrial size and function and presence of atrial fibrosis. The goal of this article is to review the epidemiology, pathophysiology and clinical management for AF in athletes, including pharmacological and electrophysiological strategies.

New Insights on the Toxicity on Heart and Vessels of Breast Cancer Therapies.

Cardiovascular diseases are largely represented in patients with cancer and appear to be important side effects of cancer treatments, heavily affecting quality of life and leading to premature morbidity and death among cancer survivors. In particular, treatments for breast cancer have been shown to potentially play serious detrimental effects on cardiovascular health. This review aims to explore the available literature on breast cancer therapy-induced side effects on heart and vessels, illustrating the molecular mechanisms of cardiotoxicity known so far. Moreover, principles of cardiovascular risk assessment and management of cardiotoxicity in clinical practice will also be elucidated. Chemotherapy (anthracycline, taxanes, cyclophosphamide and 5-fluorouracil), hormonal therapy (estrogen receptor modulator and gonadotropin or luteinizing releasing hormone agonists) and targeted therapy (epidermal growth factor receptor 2 and Cyclin-dependent kinases 4 and 6 inhibitors) adverse events include arterial and pulmonary hypertension, supraventricular and ventricular arrhythmias, systolic and diastolic cardiac dysfunction and coronary artery diseases due to different and still not well-dissected molecular pathways. Therefore, cardiovascular prevention programs and treatment of cardiotoxicity appear to be crucial to improve morbidity and mortality of cancer survivors.

Coronary microvascular dysfunction and findings of heart failure with preserved ejection fraction in patients with microvascular angina.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of Prior Statin Therapy on In-Hospital Outcome of STEMI Patients Treated with Primary Percutaneous Coronary Intervention.

Background: Prior statin therapy has a cardioprotective effect in patients undergoing elective or urgent percutaneous coronary intervention (PCI). However, data on patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI are still controversial. We retrospectively evaluated the effect of prior statin therapy on in-hospital clinical outcomes in consecutive STEMI patients undergoing primary PCI. Methods: A total of 1790 patients (mean age 67 ± 11 years, 1354 men) were included. At admission, all patients were interrogated about prior (>6 months) statin therapy. The primary endpoint of the study was the composite of in-hospital mortality, acute pulmonary edema, and cardiogenic shock in patients with or without prior statin therapy. Results: A total of 427 patients (24%) were on prior statin therapy. The incidence of the primary endpoint was similar in patients with or without prior statin therapy (15% vs. 16%; p = 0.38). However, at multivariate analysis, prior statin therapy was associated with a lower risk of the primary endpoint, after adjustment for major prognostic predictors (odds ratio 0.61 [95% CI 0.39−0.96]; p = 0.03). Conclusions: This study demonstrated that prior statin therapy is associated with a better in-hospital clinical outcome in patients with STEMI undergoing primary PCI compared to those without prior statin therapy.

Cardiac Rehabilitation and Endothelial Function.

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.

Electrocardiographic Findings and Clinical Outcome in Patients with COVID-19 or Other Acute Infectious Respiratory Diseases.

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 ± 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 ≥ 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.