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During the sixth World Symposium on Pulmonary Hypertension, the threshold of mean pulmonary arterial pressure (mPAP) for the definition of pulmonary hypertension (PH) has been lowered to a value of greater than 20 mmHg, measured by means of right heart catheterization at rest. In this review, we aim at describing the impact of the new definition of PH, analyzing the available data from the latest scientific literature concerning subjects with mPAP between 21 and 24 mmHg (defined as "mildly elevated PH"), discussing the impact of the new threshold for mPAP in the clinical practice, and highlighting the new perspectives in this field.

Purpose of ReviewOncological treatments are known to induce cardiac toxicity, but the impact of new-onset cancer in patients with pre-existing HF remains unknown. This review focuses on the epidemiology, pathophysiological mechanisms, and clinical implications of HF patients who develop malignancies.Recent FindingsNovel findings suggest that HF and cancer, beside common risk factors, are deeply linked by shared pathophysiological mechanisms. In particular, HF itself may enhance carcinogenesis by producing pro-inflammatory cytokines, and it has been suggested that neurohormonal activation, commonly associated with the failing heart, might play a pivotal role in promoting neoplastic transformation.SummaryThe risk of malignancies seems to be higher in HF patients compared to the general population, probably due to shared risk factors and common pathophysiological pathways. Additionally, management of these patients represents a challenge for clinicians, considering that the co-existence of these diseases significantly worsens patients’ prognosis and negatively affects therapeutic options for both diseases.

Background: Given the morbidity and mortality associated with pulmonary arterial hypertension (PAH), risk stratification approaches that guide therapeutic management have been previously employed. However, most patients remain in the intermediate-risk category despite initial therapy. Herein, we sought to determine whether echocardiographic parameters could improve the risk stratification of intermediate-risk patients. Methods: Prevalent PAH patients previously enrolled in observational studies at 3 pulmonary hypertension centers were included in this study. A validated PAH risk stratification approach was used to stratify patients into low-, intermediate-, and high-risk groups. Right ventricular echocardiographic parameters were used to further stratify intermediate-risk patients into intermediate-low- and intermediate-high-risk groups based on transplant-free survival. Results: From a total of 146 patients included in our study, 38 patients died over a median follow-up of 2.5 years. Patients with intermediate-/high-risk had worse echocardiographic parameters. Tricuspid annular plane systolic excursion (TAPSE) and the degree of tricuspid regurgitation (TR) were highly associated with survival (p < 0.01, p = 0.04, respectively) and were subsequently used to further stratify intermediate-risk patients. Among intermediate-risk patients, survival was worse for patients with TAPSE < 19 mm compared to those with TAPSE ≥ 19 mm (estimated one-year survival 74% vs. 96%, p < 0.01) and for patients with moderate/severe TR compared to those with no/trace/mild TR (estimated one-year survival 70% vs. 93%, p < 0.01). Furthermore, among intermediate-risk patients, those with both TAPSE < 19 mm and moderate/severe TR had an estimated one-year survival (56%) similar to that of high-risk patients (56%), and those with both TAPSE ≥ 19 mm and no/trace/mild TR had an estimated one-year survival (97%) similar to that of low-risk patients (95%). Conclusions: Echocardiography, a routinely performed, non-invasive imaging modality, plays a pivotal role in discriminating distinct survival phenotypes among prevalent intermediate-risk PAH patients using TAPSE and degree of TR. This can potentially help guide subsequent therapy.

Anthracyclines are widely used in anticancer protocols, but can induce cardiotoxicity by mechanisms that mainly involve oxidative damage and mitochondrial dysfunction. Radiotherapy can also impair cardiac function by promoting myocardial fibrosis, microvascular damage and decreased density of myocardial capillaries. Hence, we aim at investigating prospectively whether radiotherapy impacts heart function in lymphoma patients who had been already treated with anthracyclines. Twenty-nine consecutive patients with Hodgkin or non-Hodgkin lymphomas underwent echocardiography at baseline (before antineoplastic treatments), and then every two months, until 6 months after treatments completion. Echo evaluation included standard 2D and Speckle Tracking. Twenty-two patients treated with anthracycline-based regimens were eligible. Out of the 22 patients, 8 received chemotherapy only (subgroup 1), while 14 underwent radiotherapy after chemotherapy (subgroup 2). At the end of chemotherapy, ejection fraction was significantly reduced in the whole population. At 6 months after completion of therapies, E/E' increased and Global Longitudinal Strain was compromised in subgroup 2, suggesting additional damage induced by radiotherapy after chemotherapy. On the basis of the data from our small prospective study we can hypothesize that in lymphoma patients anthracyclines can worsen cardiac function, and radiotherapy may have an additional unfavorable myocardial impact.

Despite recent advances in Pulmonary Arterial Hypertension (PAH) treatment, this condition is still characterized by an extremely poor prognosis. In this review, we discuss the use of newly-approved drugs for PAH treatment with already known mechanisms of action (macitentan), innovative targets (riociguat and selexipag), and novel therapeutic approaches with initial up-front combination therapy. Secondly, we describe new potential signaling pathways and investigational drugs with promising role in the treatment of PAH.

Although there have been many improvements in prognosis for patients with cancer, anticancer therapies are burdened by the risk of cardiovascular toxicity. Heart failure is one of the most dramatic clinical expressions of cardiotoxicity, and it may occur acutely or appear years after treatment. This article reviews the main mechanisms and clinical presentations of left ventricular dysfunction induced by some old and new cardiotoxic drugs in cancer patients, referring to the most recent advances in the field. The authors describe the mechanisms of cardiotoxicity induced by anthracyclines, which can lead to cardiovascular problems in up to 48% of patients who take them. The authors also describe mechanisms of cardiotoxicity induced by biological drugs that produce left ventricular dysfunction through secondary mechanisms. They outline the recent advances in immunotherapies, which have revolutionised anticancer therapies.

Introduction: Cancer immunotherapies with monoclonal antibodies (mAbs) against immune checkpoints (i.e. CTLA-4 and PD-1/PD-L1) have revolutionized antineoplastic treatments. Immune checkpoint inhibitors (ICIs) approved for cancer immunotherapy are mAbs anti-CTLA-4 (ipilimumab), anti-PD-1 (nivolumab, pembrolizumab, and cemiplimab), and anti-PD-L1 (atezolizumab, avelumab, and durvalumab). Treatment with ICIs can be associated with immune-related adverse events (irAEs), including an increased risk of developing myocarditis. These findings are compatible with the observation that, CTLA-4, PD-1, and PD-L1 pathways play a central role in the modulation of autoimmunity.Areas covered: In this paper, we start from examining the pathogenesis of cardiovascular adverse events from ICIs, and then we focus on risk factors and strategies to prevent and manage this cardiotoxicity.Expert opinion: There is a growing need for a multidisciplinary approach of ICI-associated cardiotoxicity, involving oncologists, cardiologists, and immunologists. Prevention and effective management of ICIs cardiotoxicity starts with an in-depth screening and surveillance strategies of high-risk patients, in order to improve early detection and appropriate management in a personalized approach

Purpose of Review: Immune checkpoint inhibitors, such as monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1, have improved the outcome of many malignancies, but serious immune-related cardiovascular adverse events have been observed. Patients’ risk factors for these toxicities are currently being investigated. Recent Findings: Interfering with the CTLA-4 and PD-1 axes can bring to several immune-related adverse events, including cardiotoxic events such as autoimmune myocarditis, pericarditis, and vasculitis, suggesting that these molecules play an important role in preventing autoimmunity. Summary: Risk factors (such as pre-existing cardiovascular conditions, previous and concomitant cardiotoxic treatments, underlying autoimmune diseases, tumor-related factors, simultaneous immune-related toxic effects, and genetic factors) should be always recognized for the correct management of these toxicities.

Background: the European Society of Cardiology Heart Failure Association (HFA) together with the International Cardio-Oncology Society (ICOS) proposed charts for baseline CV risk assessment of cancer patients scheduled to receive anthracyclines and anti-human epidermal growth factor receptor-2 (HER2) agents. Methods: We investigated HFA/ICOS risk stratification, prescriptions of cardioactive drugs, and occurrence of CV events in a multicentric breast cancer (BC) cohort from 3 Italian Outpatient Cardio-Oncology Clinics. Results: 373 BCE patients who underwent a baseline Cardio-Oncologic evaluation were included, of whom 202 scheduled to receive anthracyclines and 171 anti-HER2. Mean age was 60 ± 12 years and 49% of BC patients had ≥2 CV risk factors. In the anthracyclines group, 51% were at low-risk, 43% at medium-risk and 6% at high-risk; while in the anti-HER2 group, 27% patients were at low-risk, 58% at medium-risk and 15% at high-risk. In both groups, a medium-to-high risk was associated with use of cardioactive therapies (p

Purpose of Review Along with population aging, the incidence of both heart failure (HF) and cancer is increasing. However, little is known about new-onset cancer in HF patients. This review aims at showing recent discoveries concerning this subset of patients. Recent Findings Not only cancer and HF share similar risk factors but also HF itself can stimulate cancer development. Some cytokines produced by the failing heart induce mild inflammation promoting carcinogenesis, as it has been recently suggested by an experimental model of HF in mice. Summary The incidence of new-onset cancer is higher in HF patients compared to the general population, and it significantly worsens their prognosis. Moreover, the management of HF patients developing new-onset cancer is challenging, especially due to the limited therapeutic options for patients affected by both cancer and HF and the higher risk of cardiotoxicity from anticancer drugs.

Systemic sclerosis is an auto-immune disease characterized by skin involvement that often affects multiple organ systems. Pulmonary hypertension is a common finding that can significantly impact prognosis. Molecular pathophysiological mechanisms underlying pulmonary hypertension in systemic sclerosis can be extremely heterogeneous, leading to distinct clinical phenotypes. In addition, different causes of pulmonary hypertension may overlap within the same patient. Since pulmonary hypertension treatment is very different for each phenotype, it is fundamental to perform an adequate diagnostic work-up to properly and promptly identify the prevalent mechanism underlying pulmonary hypertension in order to start the right therapies. When pulmonary hypertension is caused by a primary vasculopathy of the small pulmonary arteries, treatment with pulmonary vasodilators, often in an initial double-combination regimen, is indicated, aimed at reducing the mortality risk profile. In this review, we describe the different clinical phenotypes of pulmonary hypertension in the scleroderma population and discuss the utility of clinical tools to identify the presence of pulmonary vascular disease. Furthermore, we focus on systemic sclerosis-associated pulmonary arterial hypertension, highlighting the advances in the knowledge of right ventricular dysfunction in this setting and the latest updates in terms of treatment with pulmonary vasodilator drugs.

Metabolic syndrome (MetS) is a well established risk factor for cardiovascular (CV) diseases. In addition, several studies indicate that MetS correlates with the increased risk of cancer in adults. The mechanisms linking MetS and cancer are not fully understood. Several risk factors involved in MetS are also cancer risk factors, such as the consumption of high calorie-food or high fat intake, low fibre intake, and sedentary lifestyle. Other common aspects of both cancer and MetS are oxidative stress and inflammation. In addition, some anticancer treatments can induce cardiotoxicity, including, for instance, left ventricular (LV) dysfunction and heart failure (HF), endothelial dysfunction and hypertension. In this review, we analyse several aspects of MetS, cancer and cardiotoxicity from anticancer drugs. In particular, we focus on oxidative stress in ageing, cancer and CV diseases, and we analyse the connections among CV risk factors, cancer and cardiotoxicity from anticancer drugs.

Rationale: Dyspnea and exercise limitation are common symptoms in Systemic Sclerosis (SSc) patients. Multiorgan involvement and disease activity could lead patients to different clinical complications and affect prognosis. Aim of this study was to explore the role of cardiopulmonary exercise test (CPET) in the evaluation of exercise limitation and in the characterization of specific phenotypes of organ involvement in SSc patients. Methods: 24 consecutive patients (23 women, 51.3 ± 2.0 mean age) diagnosed with clinically stable SSc (EULAR 2013) underwent resting echocardiography and maximal symptom-limited incremental CPET. Patients were categorized into three groups: A (interstitial lung disease on CT scan), B (pulmonary vascular diesase), C (left ventricular dysfunction). Results were compared with those of 23 healthy controls and among SSc groups. Results: Compared to controls, SSc patients exhibited a significant reduction in functional capacity, ventilatory limitation and a higher estimated pulmonary pressure at echocardiography. Group A (3 patients) exhibited reduced ventilation, lower VO2max, higher PetCO2, and a worse oxygen uptake efficiency slope. Group B (6 patients) was charaterized by higher VE/VCO2 slope, reduced exercise capacity and a peculiar breathing pattern with the presence of exercise oscillatory ventilation. Group C (15 patients) showed lower ventilation, VO2max and VO2/work slope. Conclusion: CPET can unmask early exercise limitation and can be useful in the identification of different clinical phenotypes in SSc patients.

Despite advances in supportive and protective therapy for myocardial function, cardiovascular diseases due to antineoplastic therapy—primarily cardiomyopathy associated with contractile dysfunction—remain a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators are searching for alternative strategies that can timely recognise cardiovascular damage—thus permitting a quick therapeutic approach—or prevent the development of the disease. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as tyrosine kinase inhibitors. In recent years, metabolomics has proved to be a practical tool to highlight fundamental changes in the metabolic state in several pathological conditions. In this article, we present the state-of-the-art technology with regard to the metabolic mechanisms underlying cardiotoxicity and cardioprotection.

Rationale: A reduction in heart rate recovery (HRR) has been considered a marker of parasympathetic dysfunction, and it has been shown to be predictive of mortality in different clinical settings. It is unclear whether HRR is impaired in patients with pulmonary arterial hypertension (PAH) and whether it correlates with exercise impairment. Aim of this study was to evaluate the parasympathetic nervous activity by means of HRR after cardiopulmonary exercise testing (CPET) in patients with PAH and to explore its possible correlation with parameters of exercise capacity. Methods: 24 consecutive patients with Group 1 PAH (24 women, mean age 51.0 ± 6.6 years, 15 with idiopathic PAH, 7 with connective tissue-associated PAH, 2 PAH due to congenital heart disease) underwent maximal symptom-limited incremental CPET. HRR was calculated as the difference in heart rate between maximum tolerated exercise and 1 minute later. The results were compared with those of 15 healthy controls, and 15 patients with heart failure due to reduced left ventricular ejection fraction (HFrEF). Results: HRR was significantly lower in PAH compared to controls (11.83 ± 8.0 versus 25.67 ± 13.1, p Conclusions: A significant impairment in parasympathetic nervous activity was observed in our cohort of PAH patients, similar to that of HFrEF, and it was correlated with indices of exercise performance. Parasympathetic function imbalance may be a contributing factor to the reduced exercise tolerance in PAH patients.

A total of 169 faecal samples were collected from migrating birds, belonging to the Order of Passeriformes, in Campania region in order to isolate Campylobacter spp. Campylobacter spp. were isolated from 39 of the 169 birds examined (23.1%). Among these 36 were identified as C. jejuni and the remaining strains were identified as Campylobacter coli. Given the high isolation rates wild birds could be considered natural reservoir of infection.

This study was conducted with the aim to evaluate the prevalence of thermotolerant Campylobacter spp. in pheasant (Phasianus colchicus) in Southern Italy. To achieve this goal, 60 cloacal swabs were collected. Campylobacter spp. were isolated from 52 out of 60 cloacal swabs tested. As proved by PCR, 100% of the strains were identified as C. coli (52/52), and 10 out of the 52 (19.2%) positive samples were also positive to C. jejuni. The pheasant, can be considered, at least theoretically, as potential Campylobacter carriers.

Pet rabbits (n = 125) from Southern Italy were submitted to a serological screening for Encephalitozoon cuniculi, using an enzyme-linked immunosorbent assay (ELISA) and a carbon immunoassay (CIA). Seventy-eight examined rabbits showed clinical signs suggestive of encephalitozoonosis (head tilt, ataxia, paralysis, cataracts, uveitis, polyuria and polydipsia), whereas 47 were healthy rabbits. Antibodies anti-E. cuniculi were found in 84/125 (67.2%) sera analysed. The results of the chi-squared test showed that sex and health status had no significant effect (P > 0.05) on E. cuniculi seropositivity; however, rabbits older than 4 months had a seropositivity for E. cuniculi significantly (P < 0.05) higher than that of rabbits aged up to 4 months. The results of the present survey reinforce the assumption that rabbit may be indicated as the main reservoir of E. cuniculi; therefore, routine screening examinations in pet rabbits are strongly advised considering the zoonotic potential of this parasite.

Rectal swab samples were collected from 60 red squirrels (Sciurus vulgaris) from July 2006 to April 2007 in Southern Italy. Samples were tested for Campylobacter jejuni and C. coli by culture methods and suspected colonies were then confirmed by polymerase chain reaction. C. jejuni was detected in 5/60 (8.3%) samples examined but infection status was not related to age or sex and C. coli was not isolated. This is believed to be the first report of C. jejuni infection in the red squirrel.

During the period January 2004 to December 2005 four different ostrich farms were investigated to evaluate the presence of thermotolerant Campylobacter. A total of 150 ostriches were examined and all were found to be clinically healthy. Campylobacter spp. were isolated from 60/150 cloacal swabs. Among the isolates, 48 were identified as Campylobacter jejuni whereas the remainder were identified as Campylobacter coli. Campylobacter lari was not isolated. The ostriches, although apparently in a healthy body condition, can be considered, theoretically, as potential Campylobacter carriers.