Asymptomatic hyperuricemia: to treat or not a threat? A clinical and evidence-based approach to the management of hyperuricemia in the context of cardiovascular diseases.

Asymptomatic hyperuricemia is defined by serum uric acid levels above 6.2 mg/dl in women and 7 mg/dl in men. In the presence of monosodium urate crystal formation and articular inflammation, hyperuricemia may become symptomatic (namely nephrolithiasis and gout). Uric acid results from purine catabolism and is at the centre of a complex metabolic interplay that involves oxidative stress, inflammation, renin-angiotensin-aldosterone system (RAAS) activation and insulin resistance. Uric acid levels present a continuous relation with conditions like hypertension and chronic kidney disease (CKD) and are reported to have an impact on risk of cardiovascular events. However, whether elevated uric acid is a causal agent and thus a possible therapeutic target is still uncertain and matter of further investigation. Treating symptomatic hyperuricemia involves lowering uric acid drugs and controlling inflammation. Urate-lowering agents are well tolerated but show minimal impact on cardiovascular events in patients with gout. Use of direct-acting urate-lowering agents in asymptomatic hyperuricemia associated with cardiovascular diseases does not warrant a clear benefit, whereas addressing cardiovascular issues with guideline-recommended therapies lowers uric acid and reduces the occurrence of cardiovascular events. Regular assessment of uric acid and clinical symptoms is advised before starting and renewing a urate-lowering treatment.

Guideline-Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Incident Cancer.

BACKGROUND: It has been postulated that cancer hampers the delivery of guideline-directed medical therapy (GDMT) for heart failure (HF). However, few data are available in this regard. METHODS: We performed a retrospective analysis from the HF Outpatient Clinic of the IRCCS Ospedale Policlinico San Martino in Genova, Italy. All HF patients evaluated between 2010 and 2019, with a left ventricular ejection fraction <50% and at least two visits ≥3 months apart with complete information about GDMT were included in the study. We assessed the prescription of GDMT-in particular, beta-blockers (BB), renin-angiotensin system inhibitors (RASi), and mineralocorticoid antagonists (MRA)-at the time of the last HF evaluation and compared it between patients with and without incidental cancer. For those with incidental cancer, we also evaluated modifications of GDMT comparing the HF evaluations before and after cancer diagnosis. RESULTS: Of 464 HF patients, 39 (8%) had incidental cancer. There were no statistical differences in GDMT between patients with and without incidental cancer at last evaluation. In the year following cancer diagnosis, of 33 patients with incidental cancer on BB, none stopped therapy, but two had a down-titration to a dosage <50%; of 27 patients on RASi, two patients stopped therapy and three had a down-titration to a dosage <50%; of 19 patients on MRA, four stopped therapy. CONCLUSIONS: Although HF patients with incidental cancer may need to have GDMT down-titrated at the time of cancer diagnosis, this does not appear to significantly hinder the delivery of HF therapies during follow-up.

Persistent increase of cardiovascular and cerebrovascular events in COVID-19 patients: a 3-year population-based analysis.

AIMS: We evaluated the incidence and relative risk of major post-acute cardiovascular consequences of SARS-CoV-2 infection in a large real-world population from a primary care database in a region at moderate cardiovascular risk followed up in the period 2020-22. METHODS AND RESULTS: This is a retrospective cohort analysis using data from a cooperative of general practitioners in Italy. Individuals aged >18 affected by COVID-19 starting from January 2020 have been followed up for 3 years. Anonymized data from 228 266 patients in the period 2020-22 were considered for statistical analysis and included 31 764 subjects with a diagnosis of COVID-19. An equal group of subjects recorded in the same database in the period 2017-19 was used as propensity score-matched comparison as an unquestionable COVID-19-free population. Out of the 228 266 individuals included in the COMEGEN database during 2020-22, 31 764 (13.9%) were ascertained positive with SARS-CoV-2 infection by a molecular test reported to general practitioners. The proportion of individuals with a new diagnosis of major adverse cardiovascular and cerebrovascular events was higher in the 2020-22 COVID-19 group than in the 2017-19 COMEGEN propensity score-matched comparator, with an odds ratio of 1.73 (95% confidence interval: 1.53-1.94; P < 0.001). All major adverse cardiovascular and cerebrovascular events considered showed a significantly higher risk in COVID-19 individuals. Incidence calculated for each 6-month period after the diagnosis of COVID-19 in our population was the highest in the first year (1.39% and 1.45%, respectively), although it remained significantly higher than in the COVID-19-free patients throughout the 3 years. CONCLUSION: The increase of cardiovascular risk associated with COVID-19 might be extended for years and not limited to the acute phase of the infection. This should promote the planning of longer follow-up for COVID-19 patients to prevent and promptly manage the potential occurrence of major adverse cardiovascular and cerebrovascular events.

Association between Immune Checkpoint Inhibitors and Atherosclerotic Cardiovascular Disease Risk: Another Brick in the Wall.

In recent years, immune checkpoint inhibitors have significantly changed the field of oncology, emerging as first-line treatment, either alone or in combination with other regimens, for numerous malignancies, improving overall survival and progression-free survival in these patients. However, immune checkpoint inhibitors might also cause severe or fatal immune-related adverse events, including adverse cardiovascular events. Initially, myocarditis was recognized as the main immune checkpoint inhibitor-related cardiac event, but our knowledge of other potential immune-related cardiovascular adverse events continues to broaden. Recently, preclinical and clinical data seem to support an association between immune checkpoint inhibitors and accelerated atherosclerosis as well as atherosclerotic cardiovascular events such as cardiac ischemic disease, stroke, and peripheral artery disease. In this review, by offering a comprehensive overview of the pivotal role of inflammation in atherosclerosis, we focus on the potential molecular pathways underlying the effects of immune checkpoint inhibitors on cardiovascular diseases. Moreover, we provide an overview of therapeutic strategies for cancer patients undergoing immunotherapy to prevent the development of cardiovascular diseases.

A Mobile App-based Approach in Cardiovascular Disease Prevention: A Prospective Randomized Study.

Cardiovascular risk factors are prevalent in the Italian population, and cardiovascular diseases remain a leading cause of mortality in the Western world. As the incidence of risk factors and cardiovascular diseases increases with age, effective and early prevention and management strategies are crucial. This study aims to evaluate the feasibility and potential benefits of using the Heartaway® mobile application as an additional intervention to standard clinical care for patients with hypertension. The study will explore improvements in blood pressure control, medication adherence, cardiovascular risk factors, lifestyle habits, and cardiovascular outcomes. The results of this study may contribute to a broader integration of telemedicine into cardiovascular disease prevention in the clinical practice.

Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy and Cardiac Amyloidosis: From Clinical Management to Catheter Ablation Indication.

Atrial fibrillation (AF) is the most common arrhythmia in patients affected by cardiomyopathies. Reports estimate a prevalence of 27% in patients with hypertrophic cardiomyopathy (HCM) and 40% in patients with cardiac amyloidosis (CA). The presence of AF typically results in progressive functional decline, an increased frequency of hospitalizations for heart failure, and a higher thromboembolic risk. Medical management using mainly beta-blockers or amiodarone has produced variable outcomes and a high rate of recurrence. Catheter ablation reduces symptom burden and complications despite a moderate rate of recurrence. Recent evidence suggests that an early rhythm control strategy may lead to more favorable short- and long-term outcomes. In this review, we summarize contemporary data on the management of AF in patients with cardiomyopathy (HCM and CA) with particular reference to the timing and outcomes of ablation procedures.

SARS-CoV-2 Related Myocarditis: What We Know So Far.

A minority of patients with severe acute respiratory syndrome coronavirus 2 (COVID-19) develop cardiovascular complications, such as acute cardiac lesions with elevated troponins, de novo systolic heart failure, pericardial effusion and, rarely, acute myocarditis. The prevalence of COVID-19-related myocarditis ranges from 10 to 105 cases per 100,000 COVID-19-infected individuals, with a male predominance (58%) and a median age of 50 years. The etiopathogenetic mechanism is currently unclear, but may involve direct virus-mediated damage or an exaggerated immune response to the virus. Mortality is high, as fulminant myocarditis (FM) develops very often in the form of cardiogenic shock and ventricular arrhythmias. Hence, medical therapy with ACE inhibitors and beta-blockers may not always be sufficient, in which case inotropic and immunosuppressive drugs, most commonly corticosteroids, may be necessary. In this review we analyze the current data on COVID-19 myocarditis, management strategies and therapy, with a brief description of COVID-19 vaccine-associated myocarditis to help clinicians dealing with this peculiar form of myocarditis.

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.

Role of Arterial Hypertension and Hypertension-Mediated Organ Damage in Cardiotoxicity of Anticancer Therapies.

PURPOSE OF THE REVIEW: Arterial hypertension (AH) is the most common cardiovascular (CV) risk factor in the community and in oncologic patients. It also represents the most important CV condition predisposing to anticancer treatment-related cardiotoxicity. This risk is heightened in the presence of cardiac AH-mediated organ damage (HMOD). Influence of AH and HMOD on the development of cardiotoxicity will be reviewed, with a focus on specific scenarios and implications for management of oncologic patients. RECENT FINDINGS: Not adequately controlled AH before or during anticancer treatments and/or development of AH during or after completion of such therapies have detrimental effects on the clinical course of oncologic patients, particularly if HMOD is present. As overlooking CV health can jeopardize the success of anticancer treatments, the goal for clinicians caring for the oncologic patient should include the treatment of AH and HMOD.

A contemporary update on cancer and takotsubo syndrome.

Takotsubo syndrome (TTS) is characterized by a transient left ventricular systolic dysfunction, burdened by significant acute and long-term mortality and morbidity. The prognosis of TTS, especially in the long-term, is influenced by both non-cardiovascular (non-CV) and CV comorbidities, among which cancer is one of the most common. The presence of a malignancy is proven to be associated with higher mortality in TTS. Moreover, a number of anticancer treatments has been reported to possibly cause TTS as a form of cardiotoxicity, even though clearcut associations are lacking. The aim of this narrative review is to sum up contemporary knowledge on the association of cancer and TTS, addressing unmet needs and practical implications. The importance of a close collaboration between cardiologists and oncologists is herein highlighted, both to allow an adequate management of the acute TTS phase, and to actively and safely return to the oncologic management once the acute setting is resolved.

Exploring the influence of takotsubo syndrome on oncologic patients' mortality.

It has been reported that patients affected by takotsubo syndrome (TTS) with a concurrent diagnosis of cancer suffer from greater mortality as compared to their non-cancer counterpart. It remains unclear whether TTS worsens the prognosis of cancer patients as well. Aim of this study was to compare outcomes of cancer patients with and without TTS. We combined data from two independent cohorts: one consisted of a prospective multicentre TTS registry; the second cohort consisted of all oncologic patients from two Cardio-Oncology Outpatient Clinics, who did not have cardiovascular conditions at the time of the cardio-oncologic visit. From the TTS registry, we selected patients with cancer (cancer-TTS patients). Next, we matched these patients with those from the cardio-oncologic cohort (cancer non-TTS patients) in a 1:2 fashion by age, sex, and type and cancer staging. Study endpoint was all-cause mortality. Among 318 TTS patients, 42 (13%) had a concurrent diagnosis of cancer. Characteristics of cancer-TTS patients and of the 84 matched cancer non-TTS subjects were comparable with the exception of diabetes mellitus, which was more common in cancer non-TTS patients. All-cause mortality was similar between cancer-TTS and cancer non-TTS patients. At Cox regression analysis TTS was not associated with mortality (OR 1.4, 95% CI 0.6-3.3, p = 0.43). Our findings show that even in the presence of acute heart failure due to TTS, the prognosis of oncologic patients is driven by the malignancy itself. Our results may prove useful for integrated management of cardio-oncologic patients.

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.

Baseline cardio-oncologic risk assessment in breast cancer women and occurrence of cardiovascular events: The HFA/ICOS risk tool in real-world practice.

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 BC 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 < 0.0001). There were no LVD events in anthracycline recipients, and 16 LVD among anti-HER2 patients. A medium-to-high risk was not associated with LVD occurrence (p = 0.17). CONCLUSIONS: Patients with medium-to-high HFA/ICOS risk were more likely to receive cardioactive therapies, possibly explaining the lack of association of risk categories with LVD occurrence.