Left ventricular ejection fraction digit bias and reclassification of heart failure with mildly reduced vs reduced ejection fraction based on the 2021 definition and classification of heart failure.

AIMS: Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF = 40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry. METHODS AND RESULTS: Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF = 40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF = 41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF. CONCLUSIONS: Many patients had reported EF = 40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes.

Prevention and Rehabilitation After Heart Transplantation: A Clinical Consensus Statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a Section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

Chronic heart failure: the role of di vericiguat.

The introduction of multiple new pharmacological agents over the past three decades in the field of heart failure with reduced ejection fraction (HFrEF) has led to reduced rates of mortality and hospitalizations, and consequently, the prevalence of HFrEF has increased, and up to 10% of patients progress to more advanced stages, characterized by high rates of mortality and hospitalizations and poor quality of life. Vericiguat, a novel oral soluble guanylate cyclase stimulator, has proved effective in patients with HFrEF who had recently been hospitalized or had received intravenous diuretic therapy. In these patients, vericiguat reduced the primary outcome of death from cardiovascular causes or first hospitalization for heart failure in comparison with placebo. By reducing hospital admissions in a population at a very high risk of re-hospitalization, vericiguat might have a positive impact on healthcare costs for the management of HFrEF.

The role of iron deficiency in heart failure.

Iron is an essential micronutrient for several physiological processes in the body beyond erythropoiesis. Iron deficiency (ID) is a common comorbidity observed in about 50% of patients with stable heart failure (HF) irrespective of the left ventricular function. The presence of ID is often as a multi-factorial condition, and it is associated with exercise intolerance, reduced quality of life, increased hospitalization rate, and mortality risk regardless of anaemia. The intravenous administration of iron to correct ID has emerged as a promising treatment in HF with reduced ejection fraction as it has been shown to alleviate symptoms, improve quality of life and exercise capacity, and reduce hospitalizations.

Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry.

BACKGROUND: Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance-IR or diabetes mellitus-T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF. METHODS: Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D. RESULTS: Compared with EU and IR, T2D was associated with increased filling pressures (E/e'ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO2 in the T2D group (+ 13% increase in RV dimension, - 21% decline in TAPSE/PAPS ratio and - 20% decrease in peak VO2). CONCLUSION: The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis. Trial registration ClinicalTrials.gov identifier: NCT023358017.

Concurrent Aerobic Plus Resistance Training Elicits Different Effects on Short-Term Blood Pressure Variability of Hypertensive Patients in Relation to Their Nocturnal Blood Pressure Pattern.

Background and Objectives: The purpose of this study was to investigate the effects of a 12-week concurrent training (CT) (i.e., aerobic plus resistance exercise) on short-term blood pressure variability (BPV) and BP values in hypertensive patients with non-dippper BP nocturnal pattern and underlying coronary artery disease. Material and Methods: The study included 72 consecutive patients who were divided into two groups according to the nocturnal BP pattern: dipping pattern (33 pts) and non-dipping (39 pts). Before starting CT and at 12 weeks, patients underwent the six minute walk test, ergometric test, assessment of 1-repetiton maximum (1 RM), and 24/h BP monitoring (24-h ABPM). Results: After CT, exercise capacity increased in both groups in a similar fashion. Twenty-four/h systolic BPV and daytime systolic BPV decreased significantly in the dipping group while they were unchanged in the non-dipping group (between groups changes: -1.0 ± 0.4 mmHg and -1.3 ± 0.9 mmHg; p = 0.02 and p = 0.006, respectively). Twenty-four/h systolic BP and daytime systolic BP decreased significantly in the dipping group while they were unchanged in the non-dipping group (between groups changes: -7.1 ± 2.6 mmHg and -7.8 ± 2.4 mmHg; p = 0.004 and p = 0.002, respectively). Nighttime systolic BP and BPV was unchanged in both groups. Twenty-four/h diastolic BP presented small but not significant changes in both groups. Conclusions: The effects of CT on BPV and BP were blunted in hypertensive subjects with a non-dipping BP pattern.

Implications of atrial fibrillation on the clinical course and outcomes of hospitalized COVID-19 patients: results of the Cardio-COVID-Italy multicentre study.

AIMS: To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9-24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P < 0.001). History of AF was associated with an increased risk of death after adjustment for clinical confounders related to COVID-19 severity and cardiovascular comorbidities, including history of heart failure (HF) and increased plasma troponin [adjusted hazard ratio (HR): 1.73; 95% confidence interval (CI) 1.06-2.84; P = 0.029]. Patients with a history of AF also had more in-hospital clinical events including new-onset AF (36.8% vs. 7.9%; P < 0.001), acute HF (25.3% vs. 6.3%; P < 0.001), and multiorgan failure (13.9% vs. 5.8%; P = 0.010). The association between AF and worse outcome was not modified by previous or concomitant use of anticoagulants or steroid therapy (P for interaction >0.05 for both) and was not related to stroke or bleeding events. CONCLUSION: Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities.

Remote monitoring and telemedicine.

Telemedicine and remote monitoring represent more than the communication of health data via a 'remote connection'. Modern systems can be stand-alone and can be equipped with the ability to acquire and summarize data in order to inform the patient, carer or health care giver. The information can be held locally or be shared with a health care centre. Contemporary telemedicine and telemonitoring solutions have shifted their focus, trying to work on a system which is ubiquitous, efficient and sustainable. Along with devices that collect and elaborate data, a new generation of plug and play sensors has also come to life, which with standardization can lower management costs and make introduction into practice more feasible. Multiple trials (TIM-HF, TEN-HMS and BEAT.HF) have reported varying outcomes, depending on the monitoring system and the background health care process. A special mention is necessary for home tele-rehabilitation programmes for patients with heart failure. Despite the progress obstacles remain, including adequate training, data ownership and handling and applicability to larger populations. This article will review contemporary advances in this area.

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™.

Home-based telerehabilitation in older patients with chronic obstructive pulmonary disease and heart failure: a randomised controlled trial.

Background: chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) frequently coexist in older people, reducing patients' quality of life (QoL) and increasing morbidity and mortality. Objective: we studied the feasibility and efficacy of an integrated telerehabilitation home-based programme (Telereab-HBP), 4 months long, in patients with combined COPD and CHF. The primary outcome was exercise tolerance evaluated at the 6-min walk test (6MWT). Secondary outcomes were time-to-event (hospitalisation and death), dyspnoea (MRC), physical activity profile (PASE), disability (Barthel) and QoL (MLHFQ and CAT). Study design: randomised, open, controlled, multicenter trial. Methods: the Telereab-HBP included remote monitoring of cardiorespiratory parameters, weekly phone-calls by the nurse, and exercise programme, monitored weekly by the physiotherapist. All outcomes were studied again after 2 months of a no-intervention period. Results: in total, 112 patients were randomised, 56 per group. Their mean (SD) age was 70 (9) years, and 92 (82.1%) were male. After 4 months, the IG were able to walk further than at baseline: mean (95% CI) Δ6MWT was 60 (22.2,97.8) m; the CG showed no significant improvement: -15 (-40.3,9.8) m; P = 0.0040 between groups. In IG, the media time to hospitalisation/death was 113.4 days compared with 104.7 in the CG (P = 0.0484, log-rank test). Other secondary outcomes: MRC (P = 0.0500), PASE (P = 0.0015), Barthel (P = 0.0006), MLHFQ (P = 0.0007) and CAT (P = 0.0000) were significantly improved in the IG compared with the CG at 4 months. IG maintained the benefits acquired at 6 months for outcomes. Conclusions: this 4-month Telereab-HBP was feasible and effective in older patients with combined COPD and CHF.

Diabetes Mellitus and Ischemic Heart Disease: The Role of Ion Channels.

Diabetes mellitus is one the strongest risk factors for cardiovascular disease and, in particular, for ischemic heart disease (IHD). The pathophysiology of myocardial ischemia in diabetic patients is complex and not fully understood: some diabetic patients have mainly coronary stenosis obstructing blood flow to the myocardium; others present with coronary microvascular disease with an absence of plaques in the epicardial vessels. Ion channels acting in the cross-talk between the myocardial energy state and coronary blood flow may play a role in the pathophysiology of IHD in diabetic patients. In particular, some genetic variants for ATP-dependent potassium channels seem to be involved in the determinism of IHD.

The Effect of Exercise Training on Autonomic Cardiovascular Regulation: From Cardiac Patients to Athletes.

Exercise training is increasingly promoted for physical and mental health and represents a major factor in both primary and secondary prevention of cardiovascular (CV) diseases. The beneficial effects of exercise, in part, can be ascribed to adaptations of neural CV regulation through several mechanisms. In this article, we summarize how exercise training affects neural CV regulation and outline the plasticity of neural network in the continuum from cardiac patients to elite athletes.

Pharmacological Management of Chronic Stable Angina: Focus on Ranolazine.

Percutaneous coronary intervention and anti-anginal medications have similar prognostic effectiveness in patients with chronic stable angina. The choice of optimal medical therapy for the management of chronic angina is of pivotal importance in patients with stable ischemic heart disease. The most commonly used anti-anginal agents have demonstrated equivalent efficacy in improving patient reported ischemic symptoms and quantitative exercise parameters. With regards to mortality, beta-blockers are beneficial only in the setting of depressed left ventricular systolic function after a recent myocardial infarction. Recent evidence suggests the lack of any benefit of beta-blockers in patients with preserved systolic function, even in the setting of prior myocardial infarction.Ranolazine is a non-haemodynamic anti-anginal agent. It is effective as adjunctive therapy in patients with chronic stable angina whose symptoms are un-adequately controlled by conventional treatment. The clinical development program of ranolazine has shown that the drug improves exercise performance, decreases angina and use of sublingual nitrates, compared to placebo. Ranolazine is well tolerated with neutral effect on haemodynamics. Besides its role in chronic stable angina, ranolazine has the potential for development in a number of other cardiovascular and non-cardiovascular conditions in the future.

A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial).

AIMS: AUGMENT-HF was an international, multi-centre, prospective, randomized, controlled trial to evaluate the benefits and safety of a novel method of left ventricular (LV) modification with alginate-hydrogel. METHODS: Alginate-hydrogel is an inert permanent implant that is directly injected into LV heart muscle and serves as a prosthetic scaffold to modify the shape and size of the dilated LV. Patients with advanced chronic heart failure (HF) were randomized (1 : 1) to alginate-hydrogel (n = 40) in combination with standard medical therapy or standard medical therapy alone (Control, n = 38). The primary endpoint of AUGMENT-HF was the change in peak VO2 from baseline to 6 months. Secondary endpoints included changes in 6-min walk test (6MWT) distance and New York Heart Association (NYHA) functional class, as well as assessments of procedural safety. RESULTS: Enrolled patients were 63 ± 10 years old, 74% in NYHA functional class III, had a LV ejection fraction of 26 ± 5% and a mean peak VO2 of 12.2 ± 1.8 mL/kg/min. Thirty-five patients were successfully treated with alginate-hydrogel injections through a limited left thoracotomy approach without device-related complications; the 30-day surgical mortality was 8.6% (3 deaths). Alginate-hydrogel treatment was associated with improved peak VO2 at 6 months-treatment effect vs. CONTROL: +1.24 mL/kg/min (95% confidence interval 0.26-2.23, P = 0.014). Also 6MWT distance and NYHA functional class improved in alginate-hydrogel-treated patients vs. Control (both P < 0.001). CONCLUSION: Alginate-hydrogel in addition to standard medical therapy for patients with advanced chronic HF was more effective than standard medical therapy alone for improving exercise capacity and symptoms. The results of AUGMENT-HF provide proof of concept for a pivotal trial. TRIAL REGISTRATION NUMBER: NCT01311791.

Changes in left atrial function following two regimens of combined exercise training in patients with ischemic cardiomyopathy: a pilot study.

Purpose: Left atrial dysfunction has shown to play a prognostic role in patients with ischemic cardiomyopathy (ICM) and is becoming a therapeutic target for pharmacological and non-pharmacological interventions. The effects of exercise training on the atrial function in patients with ICM have been poorly investigated. In the present study, we assessed the effects of a 12-week combined training (CT) program on the left atrial function in patients with ICM. Methods: We enlisted a total of 45 clinically stable patients and randomly assigned them to one of the following three groups: 15 to a supervised CT with low-frequency sessions (twice per week) (CTLF); 15 to a supervised CT with high-frequency sessions (thrice per week) (CTHF); and 15 to a control group following contemporary preventive exercise guidelines at home. At baseline and 12 weeks, all patients underwent a symptom-limited exercise test and echocardiography. The training included aerobic continuous exercise and resistance exercise. The analysis of variance (ANOVA) was used to compare within- and inter-group changes. Results: At 12 weeks, the CTLF and CTHF groups showed a similar increase in the duration of the ergometric test compared with the control (ANOVA p < 0.001). The peak atrial longitudinal strain significantly increased in the CTHF group, while it was unchanged in the CTLF and control groups (ANOVA p = 0.003). The peak atrial contraction strain presented a significant improvement in the CTHF group compared with the CTLF and control groups. The left ventricular global longitudinal strain significantly increased in both the CTHF and the CTLF groups compared with the control group (ANOVA p = 0.017). The systolic blood pressure decreased in the CTHF and CTLF groups, while it was unchanged in the control group. There were no side effects causing the discontinuation of the training. Conclusions: We demonstrated that a CT program effectively improved atrial function in patients with ICM in a dose-effect manner. This result can help with programming exercise training in this population.

The protective effect of Bergamot Polyphenolic Fraction on reno-cardiac damage induced by DOCA-salt and unilateral renal artery ligation in rats.

To date, the complex pathological interactions between renal and cardiovascular systems represent a real global epidemic in both developed and developing countries. In this context, renovascular hypertension (RVH) remains among the most prevalent, but also potentially reversible, risk factor for numerous reno-cardiac diseases in humans and pets. Here, we investigated the anti-inflammatory and reno-cardiac protective effects of a polyphenol-rich fraction of bergamot (BPF) in an experimental model of hypertension induced by unilateral renal artery ligation. Adult male Wistar rats underwent unilateral renal artery ligation and treatment with deoxycorticosterone acetate (DOCA) (20 mg/kg, s.c.), twice a week for a period of 4 weeks, and 1% sodium chloride (NaCl) water (n = 10). A subgroup of hypertensive rats received BPF (100 mg/kg/day for 28 consecutive days, n = 10) by gavage. Another group of animals was treated with a sub-cutaneous injection of vehicle (that served as control, n = 8). Unilateral renal artery ligation followed by treatment with DOCA and 1% NaCl water resulted in a significant increase in mean arterial blood pressure (MAP; p< 0.05. vs CTRL) which strongly increased the resistive index (RI; p<0.05 vs CTRL) of contralateral renal artery flow and kidney volume after 4 weeks (p<0.001 vs CTRL). Renal dysfunction also led to a dysfunction of cardiac tissue strain associated with overt dyssynchrony in cardiac wall motion when compared to CTRL group, as shown by the increased time-to-peak (T2P; p<0.05) and the decreased whole peak capacity (Pk; p<0.01) in displacement and strain rate (p<0.05, respectively) in longitudinal motion. Consequently, the hearts of RAL DOCA-Salt rats showed a larger time delay between the fastest and the lowest region (Maximum Opposite Wall Delay-MOWD) when compared to CTRL group (p<0.05 in displacement and p <0.01 in strain rate). Furthermore, a significant increase in the levels of the circulating pro-inflammatory cytokines and chemokines (p< 0.05 for IL-12(40), p< 0.01 for GM-CSF, KC, IL-13, and TNF- α) and in the NGAL expression of the ligated kidney (p< 0.001) was observed compared to CTRL group. Interestingly, this pathological condition is prevented by BPF treatment. In particular, BPF treatment prevents the increase of blood pressure in RAL DOCA-Salt rats (p< 0.05) and exerts a protective effect on the volume of the contralateral kidney (p <0.01). Moreover, BPF ameliorates cardiac tissue strain dysfunction by increasing Pk in displacement (p <0.01) and reducing the T2P in strain rate motion (p<0.05). These latter effects significantly improve MOWD (p <0.05) preventing the overt dyssynchrony in cardiac wall motion. Finally, the reno-cardiac protective effect of BPF was associated with a significant reduction in serum level of some pro-inflammatory cytokines and chemokines (p<0.05 for KC and IL-12(40), p<0.01 for GM-CSF, IL-13, and TNF- α) restoring physiological levels of renal neutrophil gelatinase-associated lipocalin (NGAL, p<0.05) protein of the tethered kidney. In conclusion, the present results show, for the first time, that BPF promotes an efficient renovascular protection preventing the progression of inflammation and reno-cardiac damage. Overall, these data point to a potential clinical and veterinary role of dietary supplementation with the polyphenol-rich fraction of citrus bergamot in counteracting hypertension-induced reno-cardiac syndrome.

The potential effect of natural antioxidants on endothelial dysfunction associated with arterial hypertension.

Arterial hypertension represents a leading cause of cardiovascular morbidity and mortality worldwide, and the identification of effective solutions for treating the early stages of elevated blood pressure (BP) is still a relevant issue for cardiovascular risk prevention. The pathophysiological basis for the occurrence of elevated BP and the onset of arterial hypertension have been widely studied in recent years. In addition, consistent progress in the development of novel, powerful, antihypertensive drugs and their appropriate applications in controlling BP have increased our potential for successfully managing disease states characterized by abnormal blood pressure. However, the mechanisms responsible for the disruption of endogenous mechanisms contributing to the maintenance of BP within a normal range are yet to be fully clarified. Recently, evidence has shown that several natural antioxidants containing active ingredients originating from natural plant extracts, used alone or in combination, may represent a valid solution for counteracting the development of arterial hypertension. In particular, there is evidence to show that natural antioxidants may enhance the viability of endothelial cells undergoing oxidative damage, an effect that could play a crucial role in the pathophysiological events accompanying the early stages of arterial hypertension. The present review aims to reassess the role of oxidative stress on endothelial dysfunction in the onset and progression of arterial hypertension and that of natural antioxidants in covering several unmet needs in the treatment of such diseases.

How to tackle therapeutic inertia in heart failure with reduced ejection fraction. A scientific statement of the Heart Failure Association of the ESC.

Guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF) reduces morbidity and mortality, but its implementation is often poor in daily clinical practice. Barriers to implementation include clinical and organizational factors that might contribute to clinical inertia, i.e. avoidance/delay of recommended treatment initiation/optimization. The spectrum of strategies that might be applied to foster GDMT implementation is wide, and involves the organizational set-up of heart failure care pathways, tailored drug initiation/optimization strategies increasing the chance of successful implementation, digital tools/telehealth interventions, educational activities and strategies targeting patient/physician awareness, and use of quality registries. This scientific statement by the Heart Failure Association of the ESC provides an overview of the current state of GDMT implementation in HFrEF, clinical and organizational barriers to implementation, and aims at suggesting a comprehensive framework on how to overcome clinical inertia and ultimately improve implementation of GDMT in HFrEF based on up-to-date evidence.