Evidence on clinical relevance of cardiovascular risk evaluation in the general population using cardio-specific biomarkers.

In recent years, the formulation of some immunoassays with high-sensitivity analytical performance allowed the accurate measurement of cardiac troponin I (cTnI) and T (cTnT) levels in reference subjects. Several studies have demonstrated the association between the risk of major cardiovascular events and cardiac troponin concentrations even for biomarker values within the reference intervals. High-sensitivity cTnI and cTnT methods (hs-cTn) enable to monitor myocardial renewal and remodelling, and to promptly identify patients at highest risk ofheart failure. An early and effective treatment of individuals at higher cardiovascular risk may revert the initial myocardial remodelling and slow down heart failure progression. Specific clinical trials should be carried out to demonstrate the efficacy and efficiency of the general population screening by means of cost-benefit analysis, in order to better identify individuals at higher risk for heart failure (HF) progression with hs-cTn methods.

"Interstitial fibrosis is associated with left atrial remodeling and adverse clinical outcomes in selected low-risk patients with hypertrophic cardiomyopathy".

BACKGROUND: Cardiovascular magnetic resonance (CMR) extracellular volume (ECV) allows non-invasive detection of myocardial interstitial fibrosis, which may be related to diastolic dysfunction and left atrial (LA) remodeling in hypertrophic cardiomyopathy (HCM). While the prognostic role of LGE is well-established, interstitial fibrosis and LA dysfunction are emerging novel markers in HCM. This study aimed to explore the interaction between interstitial fibrosis by ECV, LA morpho-functional parameters and adverse clinical outcomes in selected low-risk patients with HCM. METHODS: 115 HCM patients and 61 matched controls underwent CMR to identify: i) interstitial fibrosis by ECV in hypertrophied left ventricular LGE-negative remote myocardium (r-ECV); ii) LA indexed maximum (LAVi max) and minimum (LAVi min) volumes, ejection fraction (LA-EF) and strain (reservoir εs, conduit εe and booster εa), by CMR feature-tracking. 2D-echocardiographic assessment of diastolic function was also performed within 6 months from CMR. A composite endpoint including worsening NYHA class, heart failure hospitalization, atrial fibrillation and all-cause death was evaluated at 2.3 years follow-up. HCM patients were divided into two groups, according to r-ECV values of controls. RESULTS: Patients with r-ECV ≥29% (n = 45) showed larger LA volumes (LAVimax 63 vs. 54 ml/m2, p < 0.001; LAVimin 43 vs. 28 ml/m2, p ã€ˆ0001), worse LA function (εs 16 vs. 28%, εe 8 vs. 15%, εa 8 vs. 14%, LA-EF 33 vs. 49%, all p < 0.001) and elevated Nt-proBNP (1115 vs. 382 pg/ml, p = 0.002). LA functional parameters inversely correlated with r-ECV (εs r = -0.54; LA-EF r = -0.46; all p < 0.001) and E/e' (εs r = -0.52, LA-EF r = -0.46; all p < 0.006). r-ECV ≥29% and LAVi min >30 ml/m2 have been identified as possible independent factors associated with the endpoint. CONCLUSIONS: In HCM diffuse interstitial fibrosis detected by increased r-ECV is associated with LA remodeling and emerged as a potential independent predictor of adverse clinical outcomes, on top of the well-known prognostic impact of LGE.

A patient with heart failure, who is frail: How does this affect therapeutic decisions?

Patients with heart failure (HF) are heterogeneous, not only related to comorbidities but also in the presentation of frailty syndrome. Frailty syndrome also affects patients with HF across the lifespan. Frailty in patients with HF has a significant impact on clinical features, diagnosis, management, adverse medical outcomes and costs. In everyday clinical practice, frail patients with HF require an individualized approach, often imposing the need to modify therapeutic decisions. The aim of this review is to illustrate how frailty and multimorbidity in HF can affect therapeutic decisions. The scientific evidence underlying this publication was obtained from an analysis of papers indexed in the PubMed database. The search was limited to articles published between 1990 and July 2022. The search was limited to full-text papers published in English. The database was searched for relevant MeSH phrases and their combinations and keywords including: "elderly, frail"; "frailty, elderly"; "frail older adults"; "frailty, older adults"; "adult, frail older"; "frailty, heart failure"; "frailty, multimorbidity"; "multimorbidity, heart failure"; "multimorbidity, elderly"; "older adults, cardiovascular diseases". In therapeutic decisions regarding patients with HF, additionally burdened with multimorbidity and frailty, it becomes necessary to individualize the approach in relation to optimization and treatment of coexisting diseases, frailty assessment, pharmacological and non-pharmacological treatment and in the implementation of invasive procedures in the form of implantable devices or cardiac surgery.

European Society of Cardiology Quality Indicators for Cardiovascular Disease Prevention: developed by the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with the European Association for Preventive Cardiology of the European Society of Cardiology.

AIMS: To develop a set of quality indicators (QIs) for the evaluation of the care and outcomes for atherosclerotic cardiovascular disease (ASCVD) prevention. METHODS AND RESULTS: The Quality Indicator Committee of the European Society of Cardiology (ESC) formed the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with Task Force members of the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice and the European Association of Preventive Cardiology (EAPC). We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care for ASCVD prevention by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. In total, 17 main and 14 secondary QIs were selected across six domains of care for ASCVD prevention: (i) structural framework, (ii) risk assessment, (iii) care for people at risk for ASCVD, (iv) care for patients with established ASCVD, (v) patient education and experience, and (vi) outcomes. CONCLUSION: We present the 2021 ESC QIs for Cardiovascular Disease Prevention, which have been co-constructed with EAPC using the ESC methodology for QI development. These indicators are supported by evidence from the literature, underpinned by expert consensus and aligned with the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice to offer a mechanism for the evaluation of ASCVD prevention care and outcomes.

Revisiting a Prognosticating Algorithm from Cardiopulmonary Exercise Testing in Chronic Heart Failure (from the MECKI Score Population).

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with ß blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3 years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without ß blockers, whereas those with ß-blockers had 11% (p <0.0001). In patients without ß blockers, 36%, 24%, and 7% CV events were observed in those with peak VO2 ≤10, with peak VO2 >10 <18, and with peak VO2 ≥18 ml/kg/min (p = 0.0001), respectively; in MECKI patients with peak VO2 ≤10 and patients with intermediate exercise capacity, a peak respiratory exchange ratio (≥1.15) and VE/VCO2 slope (≥35) were diriment, respectively (p = 0.0001). EOV, when occurred, increased risk. In MECKI patients on ß blockers, 29%, 17%, and 8% CV events were noticed in those with a peak VO2 ≤8, with peak VO2 = 8 to 12, and patients with peak VO2 ≥12 ml/kg/min, respectively (p = 0.0000); when EOV was monitored an increment of risk was witnessed. In conclusion, the outcome of this algorithm was confirmed with the MECKI cohort.

A simple lung ultrasound protocol for the screening of COVID-19 pneumonia in the emergency department.

The most relevant manifestation of coronavirus disease 2019 (COVID-19) is interstitial pneumonia. Several lung ultrasound (US) protocols for pneumonia diagnosis are used in clinical practice, but none has been proposed for COVID-19 patients' screening in the emergency department. We adopted a simplified 6-scan lung US protocol for COVID-19 pneumonia diagnosis (LUSCOP) and compared its sensitivity with high resolution computed tomography (HRCT) in patients suspected for COVID-19, presenting to one Emergency Department from February 21st to March 15th, 2020, during the outbreak burst in northern Italy. Patients were retrospectively enrolled if both LUSCOP protocol and HRCT were performed in the Emergency Department. The sensitivity of LUSCOP protocol and HRCT were compared. COVID-19 pneumonia's final diagnosis was based on real-time reverse-transcription polymerase chain reaction from nasal-pharyngeal swab and on clinical data. Out of 150 suspected COVID-19 patients, 131 were included in the study, and 130 had a final diagnosis of COVID-19 pneumonia. The most frequent lung ultrasonographic features were: bilateral B-pattern in 101 patients (77%), B-pattern with subpleural consolidations in 26 (19.8%) and lung consolidations in 2 (1.5%). LUSCOP Protocol was consistent with HRCT in correctly screening 130 out of the 131 COVID-19 pneumonia cases (99.2%). In one case COVID-19 pneumonia was excluded by both HRCT and lung US. LUSCOP protocol showed optimal sensitivity and can be proposed as a simple screening tool for COVID-19 pneumonia diagnosis in the context of outbreak burst areas where prompt isolation of suspected patients is crucial for patients' and operators' safety.

The ergoreflex: how the skeletal muscle modulates ventilation and cardiovascular function in health and disease.

The control of ventilation and cardiovascular function during physical activity is partially regulated by the ergoreflex, a cardiorespiratory reflex activated by physical activity. Two components of the ergoreflex have been identified: the mechanoreflex, which is activated early by muscle contraction and tendon stretch, and the metaboreflex, which responds to the accumulation of metabolites in the exercising muscles. Patients with heart failure (HF) often develop a skeletal myopathy with varying degrees of severity, from a subclinical disease to cardiac cachexia. HF-related myopathy has been associated with increased ergoreflex sensitivity, which is believed to contribute to dyspnoea on effort, fatigue and sympatho-vagal imbalance, which are hallmarks of HF. Ergoreflex sensitivity increases significantly also in patients with neuromuscular disorders. Exercise training is a valuable therapeutic option for both HF and neuromuscular disorders to blunt ergoreflex sensitivity, restore the sympatho-vagal balance, and increase tolerance to physical exercise. A deeper knowledge of the mechanisms mediating ergoreflex sensitivity might enable a drug or device modulation of this reflex when patients cannot exercise because of advanced skeletal myopathy.

Delphi consensus recommendations on how to provide cardiovascular rehabilitation in the COVID-19 era.

This Delphi consensus by 28 experts from the European Association of Preventive Cardiology (EAPC) provides initial recommendations on how cardiovascular rehabilitation (CR) facilities should modulate their activities in view of the ongoing coronavirus disease 2019 (COVID-19) pandemic. A total number of 150 statements were selected and graded by Likert scale [from -5 (strongly disagree) to +5 (strongly agree)], starting from six open-ended questions on (i) referral criteria, (ii) optimal timing and setting, (iii) core components, (iv) structure-based metrics, (v) process-based metrics, and (vi) quality indicators. Consensus was reached on 58 (39%) statements, 48 'for' and 10 'against' respectively, mainly in the field of referral, core components, and structure of CR activities, in a comprehensive way suitable for managing cardiac COVID-19 patients. Panelists oriented consensus towards maintaining usual activities on traditional patient groups referred to CR, without significant downgrading of intervention in case of COVID-19 as a comorbidity. Moreover, it has been suggested to consider COVID-19 patients as a referral group to CR per se when the viral disease is complicated by acute cardiovascular (CV) events; in these patients, the potential development of COVID-related CV sequelae, as well as of pulmonary arterial hypertension, needs to be focused. This framework might be used to orient organization and operational of CR programmes during the COVID-19 crisis.

HFA of the ESC position paper on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider Part 3: at the hospital and discharge.

The growing population of left ventricular assist device (LVAD)-supported patients increases the probability of an LVAD- supported patient hospitalized in the internal or surgical wards with certain expected device related, and patient-device interaction complication as well as with any other comorbidities requiring hospitalization. In this third part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the hospitalized LVAD-supported patient are presented including blood pressure assessment, medical therapy of the LVAD supported patient, and challenges related to anaesthesia and non-cardiac surgical interventions. Finally, important aspects to consider when discharging an LVAD patient home and palliative and end-of-life approaches are described.

Heart Failure Association of the European Society of Cardiology position paper on the management of left ventricular assist device-supported patients for the non-left ventricular assist device specialist healthcare provider: Part 2: at the emergency department.

The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD-supported patients and the probability of those patients to present to the emergency department with expected and non-expected device-related and patient-device interaction complications. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to suffer from other co-morbidities common in the older population. In this second part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the LVAD-supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD-supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail.

Secondary prevention through cardiac rehabilitation: from knowledge to implementation. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation.

Increasing awareness of the importance of cardiovascular prevention is not yet matched by the resources and actions within health care systems. Recent publication of the European Commission's European Heart Health Charter in 2008 prompts a review of the role of cardiac rehabilitation (CR) to cardiovascular health outcomes. Secondary prevention through exercise-based CR is the intervention with the best scientific evidence to contribute to decrease morbidity and mortality in coronary artery disease, in particular after myocardial infarction but also incorporating cardiac interventions and chronic stable heart failure. The present position paper aims to provide the practical recommendations on the core components and goals of CR intervention in different cardiovascular conditions, to assist in the design and development of the programmes, and to support healthcare providers, insurers, policy makers and consumers in the recognition of the comprehensive nature of CR. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, national or individual centre level, need to consider where and how structured programmes of CR can be delivered to all patients eligible. Thus a novel, disease-oriented document has been generated, where all components of CR for cardiovascular conditions have been revised, presenting both well-established and controversial aspects. A general table applicable to all cardiovascular conditions and specific tables for each clinical disease have been created and commented.

[Takotsubo syndrome during SARS-CoV-2 pneumonia: a possible cardiovascular complication]. / Sindrome Takotsubo in corso di polmonite da SARS-CoV-2: una possibile complicanza cardiovascolare.

Takotsubo syndrome (TTS) is one of the causes of myocardial infarction with non-obstructive coronary arteries, and is often triggered by physical events (e.g. acute respiratory failure), or emotional events (e.g. loss of a family member, cardiac stress induced by an acute illness). SARS-CoV-2 pneumonia currently represents a worldwide health problem; the correlations between cardiovascular disease, myocardial injury and SARS-CoV-2 infection are still unclear, but initial data show that myocardial damage represents a negative prognostic factor. Myocardial injury during SARS-CoV-2, as defined by a pathological rise in circulating troponin levels, is not an uncommon complication in hospitalized patients, and is significantly more frequent in intensive care unit patients and among those who died. In this setting, myocardial injury is mainly secondary to type 2 myocardial infarction (mismatch in myocardial oxygen supply and demand during respiratory failure); other causes include myocarditis, coronary thrombosis, sepsis or septic shock. At present, only few cases of TTS have been described during SARS-CoV-2. Here we report the case of a patient hospitalized for pneumonia and respiratory failure due to SARS-CoV-2 with subsequent onset of TTS triggered by both physical and emotional events.

Increased serum uric acid level predicts poor prognosis in mildly severe chronic heart failure with reduced ejection fraction. An analysis from the MECKI score research group.

BACKGROUND: Hyperuricemia prognostic impact on clinical outcomes in chronic heart failure (HF) patients has been investigated with inconclusive results. OBJECTIVES: Aim of the study was to evaluate the prognostic impact of serum uric acid (SUA) on long-term clinical outcomes in HF. METHODS: An analysis of MECKI (Metabolic Exercise Cardiac Kidney Index) database, with median follow-up of 3.4 years. RESULTS: Relation between SUA and all-cause/ cardiovascular (CV) deaths have been analysed in 4,577 patients (3,688 males, age 62.7 ±â€¯12.9 years), with reduced ejection fraction HF (35 ± 11%), peakVO2 1151 ± 440 ml/min; NYHA class I-II (72.6%), III-IV (27.4%). SUA was associated with increased total and CV mortality (HR 1.120 and HR 1.128, respectively p < 0.0001), also after adjustment for peakVO2, VE/VCO2 slope, diuretic use and MECKI score. SUA was significantly associated with CV mortality only in NYHA class I-II (HR 1.17, p < 0.0001) while there was no association in class III-IV (HR 1.03, p = NS). No prognostic added values of SUA with respect to the MECKI score was observed at the ROC analysis. CONCLUSIONS: SUA is confirmed to be associated with increased mortality, but in less severe HF only. However SUA did not show additional prognostic power to the MECKI score.

Integration of a palliative approach into heart failure care: a European Society of Cardiology Heart Failure Association position paper.

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence-based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a 'good death'. This new position paper aims to provide day-to-day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline-directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure.

Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.

Left Atrial Function Predicts Cardiovascular Events in Patients With Chronic Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure (HF) is known to be the most widespread epidemic of cardiovascular disease. Among several factors with prognostic value for the clinical course of HF, left atrial (LA) function has not yet been fully examined. The aim of this prospective study was to evaluate LA function for the prediction of major cardiovascular outcomes in stable patients with chronic HF with reduced ejection fraction. Additionally, as secondary end points, cardiovascular mortality and atrial fibrillation were analyzed separately. METHODS: The predictive value of LA function evaluated by speckle-tracking echocardiography was assessed in a population of 286 outpatients referred to the authors' institution for routine evaluation of chronic HF. Global peak atrial longitudinal strain was measured at the end of the reservoir phase and calculated by averaging in all LA segments. RESULTS: During a median follow-up period of 48 ± 11 months, major adverse cardiac events occurred in 98 patients (34%). In a multivariate model, global peak atrial longitudinal strain (hazard ratio, 0.95; 95% CI, 0.94-0.96; P = .02), left ventricular ejection fraction (hazard ratio, 0.95; 95% CI, 0.93-0.97; P = .01), and renal failure (hazard ratio, 0.98; 95% CI, 0.97-0.99; P = .01) were independent predictors of an adverse outcome. Sixty-six patients (23%) died of cardiac causes. Fifty-four patients (19%) developed atrial fibrillation. Patients with lower global peak atrial longitudinal strain showed worse event-free survival and developed atrial fibrillation more frequently than those with higher levels. CONCLUSIONS: LA function assessed by speckle-tracking echocardiography is an independent prognostic marker in patients with HF with reduced ejection fraction.