Precision Cardiology: Phenotype-targeted Therapies for HFmrEF and HFpEF.

Heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) represent over half of heart failure cases but lack proven effective therapies beyond sodium-glucose cotransporter 2 inhibitor and diuretics. HFmrEF and HFpEF are heterogeneous conditions requiring precision phenotyping to enable tailored therapies. This review covers concepts on precision medicine approaches for HFmrEF and HFpEF. Areas discussed include HFmrEF mechanisms, anti-inflammatory and antifibrotic treatments for obesity-related HFpEF, If inhibition for HFpEF with atrial fibrillation, and mineralocorticoid receptor antagonism for chronic kidney disease-HFpEF. Incorporating precision phenotyping and matched interventions in HFmrEF and HFpEF trials will further advance therapy compared to blanket approaches.

Heterotypic and homotypic continuity in psychopathology: a narrative review.

Psychopathology is a process: it unfolds over time and involves several different factors. To extend our knowledge of such process, it is vital to understand the trajectories that lead to developing and maintaining a specific disorder. The construct of continuity appears very useful to this aim. It refers to the consistency, similarity, and predictability of behaviors or internal states across different developmental phases. This paper aims to present a narrative review of the literature on homotypic and heterotypic continuity of psychopathology across the lifespan. A detailed search of the published literature was conducted using the PsycINFO Record and Medline (PubMed) databases. Articles were included in the review based on the following criteria: (1) publication dates ranging from January 1970 to October 2022; and (2) articles being written in the English language. To ensure a thorough investigation, multiple combinations of keywords such as "continuity," "psychopathology," "infancy," "childhood," "adolescence," "adulthood," "homotypic," and "heterotypic" were used. Articles were excluded if exclusively focused on epidemiologic data and if not specifically addressing the topic of psychopathology continuity. The literature yielded a total of 36 longitudinal studies and an additional 190 articles, spanning the research published between 1970 and 2022. Studies on continuity focus on the etiology of different forms of mental disorders and may represent a fundamental resource from both a theoretical and clinical perspective. Enhancing our understanding of the different trajectories beneath psychopathology may allow clinicians to implement more effective strategies, focusing both on prevention and intervention. Since literature highlights the importance of early detection of clinical signs of psychopathology, future research should focus more on infancy and pre-scholar age.

Obesity and contraceptive use: impact on cardiovascular risk.

Obesity and oestrogen containing contraceptive products are well-known independent cardiovascular risk factors. However, a significant number of obese women continue to receive prescriptions of hormonal products that contain oestrogens for their contraception. We have conducted a narrative review to discuss the latest evidence, ongoing research, and controversial issues on the synergistic effect of obesity and contraceptive use, in terms of cardiovascular risk. There is compelling evidence of an interplay between obesity and contraception in increasing cardiovascular risk. Women who present both obesity and use of combined oral contraceptives (COCs) have a greater risk (between 12 and 24 times) to develop venous thromboembolism than non-obese non-COC users. Data here discussed offer new insights to increase clinicians' awareness on the cardiovascular risk in the clinical management of obese women. The synergistic effect of obesity and COCs on deep venous thrombosis risk must be considered when prescribing hormonal contraception. Progestin-only products are a safer alternative to COCs in patients with overweight or obesity. Obese women taking contraceptives should be viewed as an 'at risk' population, and as such, they should receive advice to change their lifestyle, avoiding other cardiovascular risk factors, as a form of primary prevention. This indication should be extended to young women, as data show that COCs should be avoided in obese women of any age.

Impact analysis of heart failure across European countries: an ESC-HFA position paper.

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs-in terms of quality of life-in European countries.

Post-percutaneous coronary intervention angina: From physiopathological mechanisms to individualized treatment.

Chronic ischemic heart disease (IHD) is a multifactorial disease with different underlying pathogenetic mechanisms. Percutaneous coronary intervention (PCI) is widely used in patients with IHD in order to reduce angina recurrence. However, after complete or incomplete revascularization procedures, patients may still present anginal symptoms, with a detrimental impact on quality of life and prognosis. This review summarizes the pathogenic mechanisms and the main challenges encountered in the diagnosis and management of post-PCI angina.

Living with stable angina: patients' pathway and needs in angina.

AIMS: There is evidence that stable angina patients may suffer from emotional disorders that further impair their quality of life. However, the emotional experience of living with stable angina from the patient's perspective still has to be explored. Thus, the main aim of this study was to explore patients' emotional experience of having stable angina and their reported needs during the pathway from the first symptoms, through the process of diagnosis, to management and related lifestyle changes. METHODS: A survey was conducted in 75 chronic ischemic heart disease patients with angina (Brazil, China, Romania, Russia, and Turkey) using a 75-min, face-to-face in-depth interview. RESULTS AND CONCLUSION: Patients' responses highlighted the need to increase individuals' awareness on the first signs and symptoms of the disease. The survey also showed that chronic stable angina patients need constant emotional support to overcome stress, anxiety, and depression. Finally, this study suggests the need to offer greater space for dialogue with healthcare professionals to get more comprehensive and 'patient-friendly' information.

An expert opinion paper on statin adherence and implementation of new lipid-lowering medications by the ESC Working Group on Cardiovascular Pharmacotherapy: Barriers to be overcome.

Benefits and safety on statins have been well-established over 20 years of research. Despite this, the vast majority of patients are not adequately treated and do not achieve the low-density lipoprotein cholesterol target levels. This is mainly due to poor adherence, which is associated with dangerous and sometimes fatal outcomes. To increase adherence and prevent worse outcomes, a combination therapy with lower dosage of statins and new lipid-lowering drugs may be used. However, the implementation of new lipid-lowering drugs in European countries is still at the beginning. For these reasons, the aim of this position paper is to give an up-to-date indication from the ESC Working Group on Cardiovascular Pharmacotherapy in order to discuss the barriers towards statins adherence and new lipid-lowering drugs implementation in Europe.

Hyperkalemia and Renin-Angiotensin-Aldosterone System Inhibitors Dose Therapy in Heart Failure With Reduced Ejection Fraction.

Renin-angiotensin-aldosterone system inhibitors (RAASi) are known to improve outcomes in patients who have heart failure with reduced ejection fraction (HFrEF). To reduce mortality in these patients, RAASi should be uptitrated to the maximally tolerated dose. However, RAASi may also cause hyperkalemia. As a result of this side-effect, doses of RAASi are reduced, discontinued and seldom reinstated. Thus, the therapeutic target needed in these patients is often not reached because of hyperkalemia. Also, submaximal dosing of RAASi may be a result of symptomatic hypotension, syncope, hypoperfusion, reduced kidney function and other factors. The reduction of RAASi dose leads to adverse outcomes, such as an increased risk of mortality. Management of these side-effects is pivotal to maximise the use of RAASi in HFrEF, particularly in high-risk patients.

Pharmacology of new treatments for hyperkalaemia: patiromer and sodium zirconium cyclosilicate.

Hyperkalaemia is a life-threatening condition, resulting from decreased renal function or dysfunctional homoeostatic mechanisms, often affecting patients with cardiovascular (CV) disease. Drugs such as renin-angiotensin-aldosterone system inhibitors (RAASi) are known to improve outcomes in CV patients but can also cause drug-induced hyperkalaemia. New therapeutic options exist to enhance potassium excretion in these patients. To this aim, we reviewed pharmacological properties and available data on patiromer and sodium zirconium cyclosilicate for the treatment of hyperkalaemia. These agents have been shown in randomized trials to significantly reduce serum potassium in patients with hyperkalaemia on renin-angiotensin-aldosterone system inhibitors. Additional research should focus on their long-term effects/safety profiles and drug-drug interactions.

Monitoring of biomarkers in heart failure.

The role of biomarkers is increasingly recognized in heart failure (HF) management, for diagnosis, prognostication, and screening of high-risk patients. Beyond natriuretic peptides and troponins, the utility of novel, emerging biomarkers is less established. This document reflects the key points of a Heart Failure Association of the European Society of Cardiology (ESC) consensus meeting on biomarker monitoring in HF.

Monitoring functional capacity in heart failure.

This document reflects the key points of a consensus meeting of the Heart Failure Association of European Society of Cardiology (ESC) held to provide an overview the role of physiological monitoring in the complex multimorbid heart failure (HF) patient. This article reviews assessments of the functional ability of patients with HF. The gold standard measurement of cardiovascular functional capacity is peak oxygen consumption obtained from a cardiopulmonary exercise test. The 6-min walk test provides an indirect measure of cardiovascular functional capacity. Muscular functional capacity is assessed using either a 1-repetition maximum test of the upper and lower body or other methods, such as handgrip measurement. The short physical performance battery may provide a helpful, indirect indication of muscular functional capacity.

Heart rate and blood pressure monitoring in heart failure.

It has been long known that incessant tachycardia and severe hypertension can cause heart failure (HF). In recent years, it has also been recognized that more modest elevations in either heart rate (HR) or blood pressure (BP), if sustained, can be a risk factor both for the development of HF and for mortality in patients with established HF. Heart rate and BP are thus both modifiable risk factors in the setting of HF. What is less clear is the question whether routine systematic monitoring of these simple physiological parameters to a target value can offer clinical benefits. Measuring these parameters clinically during patient review is recommended in HF management in most HF guidelines, both in the acute and chronic phases of the disease. More sophisticated systems now allow long-term automatic or remote monitoring of HR and BP and whether this more detailed patient information can improve clinical outcomes will require prospective RCTs to evaluate. In addition, analysis of patterns of both HR and BP variability can give insights into autonomic function, which is also frequently abnormal in HF. This window into autonomic dysfunction in our HF patients can also provide further independent prognostic information and may in itself be target for future interventional therapies. This article, developed during a consensus meeting of the Heart Failure Association of the ESC concerning the role of physiological monitoring in the complex multi-morbid HF patient, highlights the importance of repeated assessment of HR and BP in HF, and reviews gaps in our knowledge and potential future directions.

Left ventricular function monitoring in heart failure.

Imaging modalities are used for screening, risk stratification and monitoring of heart failure (HF). In particular, echocardiography represents the cornerstone in the assessment of left ventricular (LV) dysfunction. Despite the well-known limitations of LV ejection fraction, this parameter, repeated assessment of LV function is recommended for the diagnosis and care of patients with HF and provides prognostic information. Left ventricular ejection fraction (LVEF) has an essential role in phenotyping and appropriate guiding of the therapy of patients with chronic HF. This document reflects the key points concerning monitoring LV function discussed at a consensus meeting on physiological monitoring in the complex multi-morbid HF patient under the auspices of the Heart Failure Association of the ESC.

Renal function, electrolytes, and congestion monitoring in heart failure.

Congestion, renal function, and electrolyte imbalance (particularly potassium) are common problems in the management of the complex multi-morbid patient with heart failure (HF). Poor control of these fundamental clinical features is associated with adverse outcomes. Close monitoring of serum potassium and renal function is recommended by most current guidelines during the management of an episode of acute decompensated HF, yet the recommendations remain poorly implemented. Physicians are advised to treat a state of euvolaemia after an admission with decompensated HF and residual congestion is a marker of worse outcome, yet control of congestion is poorly assessed and managed in real-world practice. This document reflects the key points discussed by a panel of experts during a Heart Failure Association meeting on physiological monitoring of the complex multi-morbid HF patient, and here, we present to aspects related to renal function, electrolyte, and congestion monitoring.

Implantable devices for heart failure monitoring: the CardioMEMS™ system.

Several devices have been developed for heart failure (HF) treatment and monitoring. Among device-based monitoring tools, CardioMEMS™ has received growing research attention. This document reflects the key points of an ESC consensus meeting on implantable devices for monitoring in HF, with a particular focus on CardioMEMS™.

Physiological monitoring in the complex multimorbid heart failure patient - Conclusions.

Comorbidities are increasingly recognized as crucial components of the heart failure syndrome. Main specific challenges are polypharmacy, poor adherence to treatments, psychological aspects, and the need of monitoring after discharge. The chronic multimorbid patient therefore represents a specific heart failure phenotype that needs an appropriate and continuous management over time. This supplement issue covers the key points of a series of meeting coordinated by the Heart Failure Association of the European Society of Cardiology (ESC), that have discussed the issues surrounding the effective monitoring of our ever more complex and multimorbid heart failure patients. Here, we present an overview of the complex issues from a healthcare delivery perspective.

Who approves/pays for additional monitoring?

Major considerations in the provision of healthcare are availability, affordability, accessibility, and appropriateness, especially in the setting of heart failure where disease burden is growing, developments have been rapid and newer biomarkers, diagnostic and imaging techniques, monitoring systems, devices, procedures, and drugs have all been developed in a relatively short period of time. Many monitoring and diagnostic systems have been developed but the disproportionate cost of conducting trials of their effectiveness has limited their uptake. There are added complexities, in that the utilization of doctors for the supervision of the monitoring results may be optimal in one setting and not in another because of differences in the characteristics of organization of healthcare provision, making even interpretation of the trials we have had, still difficult to interpret. New technologies are continuously changing the approach to healthcare and will reshape the structure of the healthcare systems in the future. Mobile technologies can empower patients and carers by giving them more control over their health and social care needs and reducing their dependence on healthcare professionals for monitoring their health, but a significant problem is the integration of the multitude of monitored parameters with clinical data and the recognition of intervention thresholds. Digital technology can help, but we need to prove its cost/efficacy and how it will be paid for. Governments in many European countries and worldwide are trying to establish frameworks that promote the convergence of standards and regulations for telemedicine solutions and yet simultaneously health authorities are closely scrutinizing healthcare spending, with the objective of reducing and optimizing expenditure in the provision of health services. There are multiple factors to be considered for the reimbursement models associated with the implementation of physiological monitoring yet it remains a challenge in cash-strapped health systems.

Frailty in Heart Failure: Implications for Management.

Frailty is a complex clinical syndrome associated with ageing and chronic illness, resulting from multiple organ impairment; physiological reserves decrease and vulnerability to stressors increase. The role of frailty in cardiovascular disease has become increasingly recognised. Up to 79% of patients with heart failure are frail. Moreover, frailty is associated with a worse quality of life and poor prognosis. This review summarises the available literature on frailty in HF and highlights indications for its management.

New Advances in Atrial Fibrillation Management: The Role of Apixaban.

BACKGROUND: Prevention of stroke is a pivotal intervention in the management of patients with atrial fibrillation (AF). Because of the difficulties of safely implementing Vitamin K Antagonists in all patients, there has been a growing interest in improving the pharmacological management of AF with newer antithrombotic agents. The new oral anticoagulants (NOACs) have been developed to overcome the limitations and improve the efficacy of the conventional oral anticoagulant drugs. Among the NOACs, apixaban - a very specific antagonist of activated factor Xa - has pharmacokinetic and pharmacodynamic properties that allow significant efficacy in AF management. OBJECTIVE: The aim of this review is to summarise the available data on the efficacy of apixaban in patients with AF, with a particular focus on the implications for its clinical management. RESULTS AND CONCLUSION: Clinical application of apixaban in subgroups of patients with AF is still under investigation and some contraindications should be taken into account. Despite these limitations, apixaban is an effective alternative to warfarin and aspirin for stroke prevention in AF, with encouraging evidence also in terms of adherence to treatment.

Under-representation of elderly and women in clinical trials.

BACKGROUND: Elderly and women have been often under-represented in randomised clinical trials (RCTs) testing the effect of treatments on cardiovascular diseases (CVDs) even though these diseases highly affect both of them. AIMS: Taking into account these issues, the aim of this review is to critically analyse the topic of under-representation of elderly and women in cardiovascular RCTs. CONCLUSIONS: Compared to their younger counterparts, elderly have a higher incidence of disease-related morbidities, take more medicines and account for more adverse drug related events. Similarly, women present several differences in CVD pathophysiology, clinical manifestations and outcomes in comparison to their male counterparts. For these reasons, the results of RCTs obtained in younger men cannot be simply translated in elderly and women. Unfortunately, although international guidelines have been published to increase the enrolment of elderly and women, their recruitment is still insufficient. Thus, the inclusion of these subgroups in cardiovascular RCTs is a key aspect to acquire evidence-based knowledge in the understanding and management of CVDs in elderly and women.