Depression in Heart Failure with Reduced Ejection Fraction, an Undervalued Comorbidity: An Up-To-Date Review.

Introduction: Depression is a common and severe comorbidity among individuals with heart failure (HF). Up to a third of all HF patients are depressed, and an even higher proportion have symptoms of depression. Aim: In this review, we evaluate the relationship between HF and depression, explain the pathophysiology and epidemiology of both diseases and their relationship, and highlight novel diagnostic and therapeutic options for HF patients with depression. Materials and Methods: This narrative review involved keyword searches of PubMed and Web of Science. Review search terms included ["Depression" OR "Depres*" OR "major depr*"] AND ["Heart Failure" OR "HF" OR "HFrEF" OR "HFmrEF" OR "HFpEF" OR "HFimpEF"] in all fields. Studies included in the review met the following criteria: (A) published in a peer-reviewed journal; (B) described the impact of depression on HF and vice versa; and (C) were opinion papers, guidelines, case studies, descriptive studies, randomized control trials, prospective studies, retrospective studies, narrative reviews, and systematic reviews. Results: Depression is an emergent HF risk factor and strongly relates with worse clinical outcomes. HF and depression share multiple pathways, including platelet dis-reactivity, neuroendocrine malfunction, inappropriate inflammation, tachi-arrhythmias, and frailty in the social and community setting. Existing HF guidelines urge evaluation of depression in all HF patients, and numerous screening tools are available. Depression is ultimately diagnosed based on DSM-5 criteria. There are both non-pharmaceutical and pharmaceutical treatments for depression. Regarding depressed symptoms, non-pharmaceutical treatments, such as cognitive-behavioral therapy and physical exercise, have shown therapeutic results, under medical supervision and with an effort level adapted to the patient's physical resources, together with optimal HF treatment. In randomized clinical studies, selective serotonin reuptake inhibitors, the backbone of antidepressant treatment, did not demonstrate advantage over the placebo in patients with HF. New antidepressant medications are currently being studied and could provide a chance to enhance management, treatment, and control of depression in patients with HF. Conclusions: Despite the substantial link between depression and HF, their combination is underdiagnosed and undertreated. Considering the hopeful yet unclear findings of antidepressant trials, further research is required to identify people who may benefit from antidepressant medication. The goal of future research should be a complete approach to the care of these patients, who are anticipated to become a significant medical burden in the future.

Cardiorenal syndrome: Pathophysiology as a key to the therapeutic approach in an under-diagnosed disease.

Cardiorenal syndrome is a clinical condition that impacts both the heart and the kidneys. One organ's chronic or acute impairment can lead to the other's chronic or acute dysregulation. The cardiorenal syndrome has been grouped into five subcategories that describe the etiology, pathophysiology, duration, and pattern of cardiac and renal dysfunction. This classification reflects the large spectrum of interrelated dysfunctions and underlines the bidirectional nature of heart-kidney interactions. However, more evidence is needed to apply these early findings in medical practice. Understanding the relationship between these two organs during each organ's impairment has significant clinical implications that are relevant for therapy in both chronic and acute conditions. The epidemiology, definition, classification, pathophysiology, therapy, and outcome of each form of cardiorenal syndrome are all examined in this review.

Diabetic Cardiomyopathy: Definition, Diagnosis, and Therapeutic Implications.

A strict bidirectional relationship exists between diabetes mellitus and heart failure. Diabetic cardiomyopathy is a specific cardiac manifestation of patients with diabetes characterized by left ventricular hypertrophy and diastolic dysfunction in the early phase up to overt heart failure with reduced systolic function in the advanced stages. The pathogenesis of this condition is multifactorial and recognizes as main promoting factors the presence of insulin resistance and hyperglycemia. Diabetic cardiomyopathy exerts a negative prognostic impact in affected patients and no target treatments are currently available. More efforts are needed to better define the diagnostic and therapeutic approach in this specific setting.

Prognostic Value of Hormonal Abnormalities in Heart Failure Patients.

The model used to explain the pathophysiologic substrate and progressive worsening in chronic heart failure (CHF) is based on the hyperactivity of renin-angiotensin-aldosterone system and adrenergic pathway. Although the neurohormonal medical approach has many advantages, it has several pitfalls, as demonstrated by high rates of CHF mortality and hospitalization. A growing body of evidence has led to the hypothesis that CHF is a multiple hormone deficiency syndrome, characterized by a reduced anabolic drive that has relevant functional and prognostic implications. The aim of this review is to summarize the evidence of reduced drive of main anabolic axes in CHF.

Prognostic role of transthoracic echocardiography in patients affected by heart failure and reduced ejection fraction.

Heart failure with reduced ejection fraction is a common and malignant condition, which recognizes a lot of causes and that carries a poor long-term prognosis. All patients with reduced left ventricular ejection fraction, both asymptomatic and symptomatic, should be evaluated with transthoracic echocardiography as a depth analysis of first level, due to its characteristics of accuracy, availability, safety and low costs. In fact, echocardiography is an essential tool to establish not only the diagnosis, but also the aetiology and the understanding pathophysiology of heart failure. Moreover, by the new more sensitive and more specific echocardiographic technologies, such as tissue Doppler imaging or strain rate or speckle tracking or three-dimensional echocardiography, it is possible to identify other recognized high-risk parameters associated with adverse outcome, which are useful to guide therapy and follow-up management of heart failure patients. Therefore, this review would underline the prognostic role of some echocardiographic parameters in the evaluation and management of patients with heart failure and reduced ejection fraction.

Alterations of left ventricular deformation and cardiac sympathetic derangement in patients with systolic heart failure: a 3D speckle tracking echocardiography and cardiac ¹²³I-MIBG study.

PURPOSE: Myocardial contractile function is under the control of cardiac sympathetic activity. Three-dimensional speckle tracking echocardiography (3D-STE) and cardiac imaging with (123)I-metaiodobenzylguanidine ((123)I-MIBG) are two sophisticated techniques for the assessment of left ventricular (LV) deformation and sympathetic innervation, respectively, which offer important prognostic information in patients with heart failure (HF). The purpose of this investigation was to explore, in patients with systolic HF, the relationship between LV deformation assessed by 3D-STE and cardiac sympathetic derangement evaluated by (123)I-MIBG imaging. METHODS: We prospectively studied 75 patients with systolic HF. All patients underwent a 3D-STE study (longitudinal, circumferential, area and radial) and (123)I-MIBG planar and SPECT cardiac imaging. RESULTS: 3D-STE longitudinal, circumferential and area strain values were correlated with (123)I-MIBG late heart to mediastinum (H/M) ratio and late SPECT total defect score. After stratification of the patients according to ischaemic or nonischaemic HF aetiology, we observed a good correlation of all 3D-STE measurements with late H/M ratio and SPECT data in the ischaemic group, but in patients with HF of nonischaemic aetiology, no correlation was found between LV deformation and cardiac sympathetic activity. At the regional level, the strongest correlation between LV deformation and adrenergic innervation was found for the left anterior descending coronary artery distribution territory for all four 3D-STE values. In multivariate linear regression analyses, including age, gender, LV ejection fraction, NYHA class, body mass index, heart rate and HF aetiology, only 3D-STE area and radial strain values significantly predicted cardiac sympathetic derangement on (123)I-MIBG late SPECT. CONCLUSION: This study indicated that 3D-STE measurements are correlated with (123)I-MIBG planar and SPECT data. Furthermore, 3D-STE area and radial strain values, but not LVEF, predict cardiac sympathetic derangement in human postischaemic HF.

Nuclear assessment of right ventricle.

For many years, the right ventricle (RV) has been considered a passive chamber with a relatively insignificant role in the overall functionality of the heart. More recently, the role of performance of RV in the clinical presentation and long-term prognosis of multiple pathological states, such as congenital heart diseases, chronic heart failure, pulmonary hypertension, and chronic obstructive pulmonary disease. Despite echocardiography and cardiac magnetic resonance are the 2 most commonly used imaging techniques for noninvasive assessment of RV, nuclear imaging provides new opportunities for comprehensive evaluation of RV from a single study, because it can assess right ventricular perfusion and metabolism as well as morphology and ejection fraction. In this review, we summarize the application of radionuclide techniques (nuclear cardiology) for evaluation of the RV, focusing on its emerging role in the assessment of right ventricular perfusion and metabolism.

Aortic and Mitral Calcification Is Marker of Significant Carotid and Limb Atherosclerosis in Patients with First Acute Coronary Syndrome.

PURPOSE: Atherosclerosis is a systemic disease and coronary artery disease is frequently associated with peripheral artery disease. As aortic and mitral valvular calcification (VC) share some etiopathogenetic mechanisms with atherosclerosis, we analyzed the risk profile and the echocardiographic characteristics of patients admitted for first acute coronary syndrome (ACS) to investigate whether the presence of VC could be a marker of asymptomatic hemodynamically significant peripheral atherosclerosis. METHODS: A total of 151 patients admitted for ACS without previous history of cardiovascular disease were consecutively enrolled. The presence of VC was identified by echocardiography; a carotid stenosis ≥50% by ultrasound identified carotid artery disease (CarAD); an ankle-brachial index ≤0.9 or ≥1.4 identified lower extremity artery disease (LEAD). Significant peripheral atherosclerosis was defined by the presence of CarAD and/or LEAD. RESULTS: Peripheral atherosclerosis was diagnosed in 82 (54.3%) patients; isolated CarAD in 24, isolated LEAD in 20, both diseases in 38 patients. VC was present in 103 (68.2%) patients. By multivariate analysis, age (OR = 1.059, 95% CI 1.007-1.113, P = 0.025), diabetes mellitus (OR = 5.068, 95% CI 1.480-17.351, P = 0.010), VC (OR = 7.422, 95% CI 2.421-22.880, P < 0.001), and multivessel CAD (OR = 3.317, 95% CI 1.281-8.586, P = 0.013) were the only independent predictors of having peripheral atherosclerosis. C-statistic for VC was not inferior to that obtained by age (0.728, 95% CI 0.649-0.797 vs. 0.800, 95% CI 0.727-0.861, P = 0.101) and to that obtained by the combination of multivessel CAD with diabetes (0.750; 95% CI 0.673-0.817, P = 0.635), and, furthermore, it was higher than that obtained by diabetes alone (0.620, 95% CI 0.538-0.698, P = 0.036). CONCLUSION: Ruling out the presence of significant peripheral atherosclerosis should be routinely considered in patients with ACS showing VC at echocardiography.

Crosslink between atrial fibrillation and cancer: a therapeutic conundrum.

Atrial fibrillation (AF) is more common in patients with malignancies than in general population. The pathophysiological processes include the pro-inflammatory condition and the exaggerated inflammatory reaction to chemotherapy, radiotherapy, and surgery interventions. Thus, it is pivotal to decrease morbidity and mortality in this group by providing appropriate care and prevention. In this subset, the risk of thromboembolic and bleeding events is high and the common risk score such as CHA2DS2-VASc and HAS-BLED employed in non-oncologic patients have limited evidence in cancer patients. A paucity of evidence in the setting in individuals having both malignancies and atrial fibrillation entangle the clinician when it comes to therapeutic management. Tailored management is recommended of anticoagulation treatment could be difficult, and there is. In this review, we try to explain the mechanism of AF in cancer patients as well as its management in this setting.

Cardiovascular disease and psychiatric disorders: An-up-to date review.

Cardiovascular diseases (CVD) and mental health disorders (MHD) are respectively the first and second most prevalent diseases in high-income countries and the two most relevant causes of disability worldwide. The close association between the two conditions has been known for a long time and research has been able to document how the co-morbidity between cardiovascular disorders and mental health disorders is a negative prognostic factor for both conditions. This strong connection and the relevance of the impact of the association have led to define a new branch of cardiology, known as behavioral cardiology. The aim of the new branch is just to study the nexus CVD-MHD in order to prevent or decrease the burden of MHD on CVD and vice versa. This review describes the epidemiological evidence of the relationship between MHD on CVD at the state of the art among clinical research.

Strike early-strike strong lipid-lowering strategy with PCSK9i in ACS patients. Real-world evidence from AT-TARGET-IT registry.

AIMS: No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in real-world. This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. METHODS: The lipid control outcome was the percentage of patients reaching the LDL-C target of < 55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all cause death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization) during follow-up in relation to quartiles of LDL-C at first lipid control. RESULTS: We included 771 patients with ACS from AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischemia-driven revascularization in lower quartile of LDL-C values at first lipid control (<23 mg/dL) and in patients reaching LDL-C <55 mg/dL. CONCLUSIONS: Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk.

This study, from AT-TARGET-IT registry, investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. Intensive and early PCSK9i therapy reduce composite major cardiovascular (CV) events in patients in reaching LDL-C target values. A strike early-strike strong strategy is safe and effective.

Percutaneous treatment of patients with heart diseases: selection, guidance and follow-up. A review.

Aortic stenosis and mitral regurgitation, patent foramen ovale, interatrial septal defect, atrial fibrillation and perivalvular leak, are now amenable to percutaneous treatment. These percutaneous procedures require the use of Transthoracic (TTE), Transesophageal (TEE) and/or Intracardiac echocardiography (ICE). This paper provides an overview of the different percutaneous interventions, trying to provide a systematic and comprehensive approach for selection, guidance and follow-up of patients undergoing these procedures, illustrating the key role of 2D echocardiography.

Impact of Age and Heart Rate on Strain-Derived Myocardial Work in a Population of Healthy Subjects.

Background: The influence of age and gender on strain-imaging-derived myocardial work (MW) was recently investigated in healthy subjects. No information is available on the impact of heart rate (HR) on MW. Methods: 177 healthy subjects (47% men, mean age 42 years) underwent an echo-Doppler exam, including quantification of global longitudinal strain (GLS). Cuff blood pressure was used as a surrogate of left ventricular peak pressure to estimate global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). Statistical analyses were performed according to age and HR tertiles. Results: GWW was higher in the third HR tertile, i.e., ≥74 bpm (74.7 ± 33.6 mmHg %) than in the first HR tertile (<66 bpm) (61.0 ± 32.5 mmHg %) (p < 0.02). In the pooled population, by adjusting for systolic blood pressure, GLS, E/e' ratio and left atrial volume index, age was independently associated with GCW (ß = 0.748) and GWI (ß = 0.685) (both p < 0.0001) and HR with GWW (ß = 0.212, p = 0.006) and GWE (ß = −0.204, p = 0.007). Conclusions: In healthy subjects age shows a mild influence on GCW. HR exerts an independent negative impact on GWW and GWE: the higher HR the greater wasted work and lower myocardial efficiency.

Venous Thromboembolism and Cancer: A Comprehensive Review from Pathophysiology to Novel Treatment.

Acute thrombotic events can unveil occult cancer, as they are its first manifestation in about 20 to 30% of all cases. Malignancy interacts in an intricate way with the hemostatic system, promoting both thrombosis and bleeding. The main pathway involved in these reactions involves the activation of tumor-associated procoagulant factors, which eventually results in clot formation. The clinical manifestation of cancer-related thrombotic events mainly involves the venous side, and manifests in a broad spectrum of conditions, including unusual sites of venous thrombosis. The selection of patients who have a balanced risk-benefit profile for management of anticoagulation is complex, given individual patient goals and preferences, different prognosis of specific cancers, common comorbidities, potential drug-drug interactions, underweight states, and the competing risks of morbidity and mortality. Anticoagulant treatment in cancer settings is broadly debated, considering the potential application of direct oral anticoagulants in both thromboprophylaxis and secondary prevention, having demonstrated its efficacy and safety compared to conventional treatment. This review aims to provide a brief overview of the pathophysiology and management of cancer-related thrombosis, summarizing the results obtained in recent clinical trials.

Myocardial perfusion scintigraphy and echocardiography for detecting coronary artery disease in hypertensive patients: a meta-analysis.

PURPOSE: This meta-analysis summarized the accuracy of stress myocardial perfusion scintigraphy (MPS) and stress echocardiography for the diagnosis of coronary artery disease (CAD) in patients with arterial hypertension. METHODS: We searched for studies in which stress MPS or stress echocardiography were performed to detect CAD in hypertensive patients, with coronary angiography used as the reference test, published from January 1980 to December 2010. Studies performed in patients with known CAD, acute coronary syndrome and previous revascularization procedures were excluded. RESULTS: Of 1,263 studies, 13 met the inclusion criteria. Pooled summary estimates showed that stress MPS had a sensitivity of 0.90 [95% confidence interval (CI) 0.82-0.95] and a specificity of 0.63 (95% CI 0.53-0.72). For stress MPS, the area under the curve (AUC) at the summary receiver-operating characteristic (SROC) graph was 0.83 (95% CI 0.80-0.86). At meta-regression analysis, the presence of positive stress electrocardiography as inclusion criterion was the only significant effect modifier (p < 0.01). Pooled summary estimates showed that stress echocardiography had a sensitivity of 0.77 (95% CI 0.69-0.83) and a specificity of 0.89 (95% CI 0.83-0.93). For stress echocardiography, the AUC at SROC was 0.91 (95% CI 0.88-0.93). At the meta-regression analysis no significant effect modifier was detected. CONCLUSION: MPS has high sensitivity for detecting CAD in hypertensive patients, with specificity comparable to that reported in the general population, whereas stress echocardiography shows higher specificity but substantially reduced sensitivity compared to MPS.

N-terminal pro-b-type natriuretic peptide and left atrial function in patients with congestive heart failure and severely reduced ejection fraction.

AIMS: Amino-terminal portion of pro-B-type natriuretic peptide (NT-pro-BNP) is a valuable diagnostic and prognostic marker in congestive heart failure (CHF). In CHF patients, elevation of natriuretic peptide levels correlate with decreased left ventricular (LV) ejection fraction (EF) and increased left atrial (LA) volumes, but a correlation with LA function that is a determinant of haemodynamic and clinical status in CHF with independent prognostic value has never been investigated. Aim of this study was to evaluate the relationship between cardiac neurohormonal activation and LA function in patients with CHF due to dilated cardiomyopathy. METHODS AND RESULTS: One hundred and one patients (86% males; mean age, 64 ± 11 years) with dilated ischaemic or non-ischaemic cardiomyopathy, LV EF ≤45% (mean LV EF, 33 ± 8%), and New York Heart Association class II-IV underwent transthoracic echocardiography to evaluate LA fractional active and total emptying from M- and B-Mode images, and, on the same day, venous blood sample collection to dose NT-pro-BNP. By univariate analyses, NT-pro-BNP significantly correlated to age, LA dimensions, LA function indexes, EF, and functional class. At multivariate analysis, LV EF and M- or B-Mode indexes of LA function were the only independent predictors of NT-pro-BNP values. A NT-pro-BNP cut-off of 1480 pg/mL identified LA dysfunction with 89% specificity and 54% sensitivity. CONCLUSION: In CHF patients with severely impaired systolic function, NT-pro-BNP levels reflect LA and LV dysfunction. These data should prompt studies to investigate the relationship between changes of LA function and NT-pro-BNP levels and their clinical value as prognostic and therapeutic targets in CHF.

An Emergent Form of Cardiotoxicity: Acute Myocarditis Induced by Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. ICIs have shown great promise in the treatment of several advanced malignancies. However, therapy with these immunomodulatory antibodies may lead to a wide spectrum of immune-related adverse events in any organ and any tissue. Cardiologic immune-related events include pericarditis, pericardial effusion, various types of arrhythmias including the occurrence of complete atrioventricular block, myocardial infarction, heart failure, and myocarditis. Although relatively rare, myocarditis is associated with a very high reported mortality in comparison to other adverse events. Myocarditis often presents significant diagnostic complexity and may be under-recognized. When confronted with an unexpected change in the clinical picture, the physician must differentiate between immune-related adverse events, cancer worsening, or other causes unrelated to the cancer or its therapy. However, this is not always easy. Therefore, with the increasing use of checkpoint inhibitors in cancer, all providers who care for patients with cancer should be made aware of this rare, but potentially fatal, cardiologic immune-related adverse event, and able to recognize when prompt consultation with a cardiologist specialist is indicated. In this review, we evaluate currently available scientific evidence and discuss clinical manifestations and new potential approaches to the diagnosis and therapy of acute myocarditis induced by ICIs. Temporary or permanent discontinuation of the ICIs and high-dose steroids have been administered to treat myocarditis, but symptoms may worsen in some patients despite therapy.

Epidemiology, prognosis, and clinical manifestation of cardiovascular disease in COVID-19.

INTRODUCTION: At the end of 2019, a novel coronavirus was identified as the cause of a pneumonia cluster in Wuhan, China. Since then, the contagion has rapidly spread all over the world resulting in a global pandemic. Since frequent cardiovascular (CV) system involvement has soon been detected in patients occurring coronavirus disease 2019 (COVID-19), we would provide a simple review available to cardiologists who are going to be involved in the management of COVID-19 patients from several levels: from diagnosis to prevention and management of CV complications. AREAS COVERED: We investigate the role of CV diseases in COVID-19: from the incidence of CV comorbidities to their negative impact on prognosis. We also search Literature in order to identify the main CV manifestations in patients occurring virus infection and their management by cardiologists. EXPERT OPINION: Specific treatments for CV involvement associated with COVID-19 are still debated. Results from ongoing trials are needed to further clarify issues about the therapeutic approach, which is constantly changing according to the continuous flow of published evidence. Finally, it seems necessary to sensitize all population to raise awareness on CV diseases in the COVID era, to hinder the underestimation of both new-onset acute CV diseases and the consequences of chronic mistreated CV diseases.

Differences in echocardiographic assessment with standard Doppler and tissue Doppler imaging of left ventricular filling pressure in idiopathic and ischemic dilated cardiomyopathy.

BACKGROUND: In idiopathic and ischemic dilated cardiomyopathy (DCM) there are differences in left atrial and ventricular relaxation. We assessed the hypothesis of an influence of these dissimilarities in assessing left ventricular filling pressure (LVFP) in these two DCMs by standard Doppler and tissue Doppler imaging. In particular, we focused on early transmitral flow to early diastolic motion velocity of mitral annulus ratio (E/Ea), useful to estimate normal or elevated LVFP. However, when found in intermediate range (8-15), its role is unclear. METHODS AND RESULTS: We evaluated 26 patients with ischemic and 21 patients with idiopathic DCM. To validate the echocardiographic estimation of LVFP, a sample (12 patients) underwent LVFP assessment by catheterization. In idiopathic DCM, E/Ea directly related to duration of retrograde pulmonary venous flow (ARd) (r = 0.66 P = 0001). In ischemic DCM E/Ea inversely related only to systolic to diastolic velocity ratio of pulmonary venous flow (S/D) (r =-0.56 P = 0002). After a mean follow up of 6 months, by a second echocardiogram we observed a direct relation between E/Ea and ARd percentage variation (r = 0.52 P = 0.02) in idiopathic DCM group, whereas in the ischemic DCM group there was an inverse relation between E/Ea and S/D percentage variation (r =-0.59 P = 0.02). CONCLUSIONS: In conclusion, ARd in idiopathic and S/D in ischemic DCM might be used as specific additional information to estimate LVFP when E/Ea falls within intermediate range.