The Therapy and Management of Heart Failure with Preserved Ejection Fraction: New Insights on Treatment.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterised by the presence of diastolic dysfunction and elevated left ventricular filling pressure, in the setting of a left ventricular ejection fraction of at least 50%. Despite the epidemiological prevalence of HFpEF, a prompt diagnosis is challenging and many uncertainties exist. HFpEF is characterised by different phenotypes driven by various cardiac and non-cardiac comorbidities. This is probably the reason why several HFpEF clinical trials in the past did not reach strong outcomes to recommend a single therapy for this syndrome; however, this paradigm has recently changed, and the unmet clinical need for HFpEF treatment found a proper response as a result of a new class of drug, the sodium-glucose cotransporter 2 inhibitors, which beneficially act through the whole spectrum of left ventricular ejection fraction. The aim of this review was to focus on the therapeutic target of HFpEF, the role of new drugs and the potential role of new devices to manage the syndrome.

Navigating Pubertal Goldilocks: The Optimal Pace for Hierarchical Brain Organization.

Adolescence is a timed process with an onset, tempo, and duration. Nevertheless, the temporal dimension, especially the pace of maturation, remains an insufficiently studied aspect of developmental progression. The primary objective is to estimate the precise influence of pubertal maturational tempo on the configuration of associative brain regions. To this end, the connection between maturational stages and the level of hierarchical organization of large-scale brain networks in 12-13-year-old females is analyzed. Skeletal maturity is used as a proxy for pubertal progress. The degree of maturity is defined by the difference between bone age and chronological age. To assess the level of hierarchical organization in the brain, the temporal dynamic of closed eye resting state high-density electroencephalography (EEG) in the alpha frequency range is analyzed. Different levels of hierarchical order are captured by the measured asymmetry in the directionality of information flow between different regions. The calculated EEG-based entropy production of participant groups is then compared with accelerated, average, and decelerated maturity. Results indicate that an average maturational trajectory optimally aligns with cerebral hierarchical order, and both accelerated and decelerated timelines result in diminished cortical organization. This suggests that a "Goldilocks rule" of brain development is favoring a particular maturational tempo.

Clonal hematopoiesis of indeterminate potential: implications for the cardiologists.

Myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and myelofibrosis, are characterized by somatic gene mutations in bone marrow stem cells, which trigger an inflammatory response influencing the development of associated cardiovascular complications. In recent years, the same mutations were found in individuals with cardiovascular diseases even in the absence of hematological alterations. These genetic events allow the identification of a new entity called 'clonal hematopoiesis of indeterminate potential' (CHIP), as it was uncertain whether it could evolve toward hematological malignancies. CHIP is age-related and, remarkably, myocardial infarction, stroke, and heart failure were frequently reported in these individuals and attributed to systemic chronic inflammation driven by the genetic mutation. We reviewed the connection between clonal hematopoiesis, inflammation, and cardiovascular diseases, with a practical approach to improve clinical practice and highlight the current unmet needs in this area of knowledge.

Heart Failure Preserved Ejection Fraction in Women: Insights Learned from Imaging.

While the prevalence of heart failure, in general, is similar in men and women, women experience a higher rate of HFpEF compared to HFrEF. Cardiovascular risk factors, parity, estrogen levels, cardiac physiology, and altered response to the immune system may be at the root of this difference. Studies have found that in response to increasing age and hypertension, women experience more concentric left ventricle remodeling, more ventricular and arterial stiffness, and less ventricular dilation compared to men, which predisposes women to developing more diastolic dysfunction. A multi-modality imaging approach is recommended to identify patients with HFpEF. Particularly, appreciation of sex-based differences as described in this review is important in optimizing the evaluation and care of women with HFpEF.

Corrigendum to: In pursuit of balance: RAASi and hyperkalemia treatment.

[This corrects the article DOI: 10.1093/eurheartjsupp/suad053.].

In pursuit of balance: renin-angiotensin-aldosterone system inhibitors and hyperkalaemia treatment.

Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure (HF) patients due to the disease itself, which often co-exists with chronic kidney disease and diabetes mellitus, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. In particular, hyperkalaemia opposes to their administration or up-titration, thus impacting on mortality. New K+ binders, namely, patiromer and sodium zirconium cyclosilicate, are an intriguing option to manage hyperkalaemia in HF patients, both to reduce its fatal effects and to let clinicians up-titrate RAAS inhibitors. Even if their real impact on strong outcomes is still to be determined, we hereby provide an overview of hyperkalaemia in HF and its current management. New trials are welcome to fill the gap in knowledge.

Heart failure therapy: the fifth card.

The 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) have abandoned the sequential approach for optimal drug therapy and propose four drug classes (enzyme inhibitors conversion agents, angiotensin receptor antagonists, beta-blockers, and sodium-glucose cotransporter inhibitors 2) to be initiated and titrated in all patients with an ejection fraction <35%. This new approach offers advantages such as rapid introduction and titration, better tolerability, and early instrumental re-evaluation. In the VICTORIA study, the molecule vericiguat, a soluble guanylate cyclase activator, was shown to reduce the composite outcome of death from cardiovascular causes and first hospitalization for HF in a high-risk population. An additional randomized clinical trial (VICTOR) is ongoing to evaluate the efficacy and safety of vericiguat in a population with HF on optimized therapy and with no recent episodes of stabilization.

Antecedent use of renin-angiotensin system inhibitors is associated with reduced mortality in elderly hypertensive Covid-19 patients.

OBJECTIVES: The effect of renin-angiotensin system inhibitors (RASIs) on mortality in patients with coronavirus disease (Covid-19) is debated. From a cohort of 1352 consecutive patients admitted with Covid-19 to Papa Giovanni XXIII Hospital in Bergamo, Italy, between February and April 2020, we selected and studied hypertensive patients to assess whether antecedent (prior to hospitalization) use of RASIs might affect mortality from Covid-19 according to age. METHODS AND RESULTS: Arterial hypertension was present in 688 patients. Overall mortality (in-hospital or shortly after discharge) was 35% (N = 240). After adjusting for 26 medical history variables via propensity score matching, antecedent use of RASIs (N = 459, 67%) was associated with a lower mortality in older hypertensive patients (age above the median of 68 years in the whole series), whereas no evidence of a significant effect was found in the younger group of the same population (P interaction = 0.001). In an analysis of the subgroup of 432 hypertensive patients older than 68 years, we considered two RASI drug subclasses, angiotensin-converting enzyme inhibitors (ACEIs, N = 156) and angiotensin receptor blockers (ARBs, N = 140), and assessed their respective effects by taking no-antecedent-use of RASIs as reference. This analysis showed that both antecedent use of ACEIs and antecedent use of ARBs were associated with a lower Covid-19 mortality (odds ratioACEI = 0.57, 95% confidence interval 0.36--0.91, P = 0.018) (odds ratioARB = 0.49, 95% confidence interval 0.29--0.82, P = 0.006). CONCLUSION: In the population of over-68 hypertensive Covid-19 patients, antecedent use of ACEIs or ARBs was associated with a lower all-cause mortality, whether in-hospital or shortly after discharge, compared with no-antecedent-use of RASIs.

Haemodynamic characteristics of COVID-19 patients with acute respiratory distress syndrome requiring mechanical ventilation. An invasive assessment using right heart catheterization.

AIMS: Interstitial pneumonia due to coronavirus disease 2019 (COVID-19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID-19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID-19 patients has been reported so far. METHODS AND RESULTS: Twenty-one mechanically-ventilated COVID-19 patients underwent right heart catheterization. Their data were compared both with those obtained from non-mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with 'typical' acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID-19 patients than in controls [3.8 (2.7-4.5) vs. 2.4 (2.1-2.8) L/min/m2 , P < 0.001], but slightly lower than in ARDS patients (P = 0.024). Intrapulmonary shunt and lung compliance were inversely related in COVID-19 patients (r = -0.57, P = 0.011) and did not differ from ARDS patients. Despite this, pulmonary vascular resistance of COVID-19 patients was normal, similar to that of control subjects [1.6 (1.1-2.5) vs. 1.6 (0.9-2.0) WU, P = 0.343], and lower than reported in ARDS patients (P < 0.01). Pulmonary hypertension was present in 76% of COVID-19 patients and in 19% of control subjects (P < 0.001), and it was always post-capillary. Pulmonary artery wedge pressure was higher in COVID-19 than in ARDS patients, and inversely related to lung compliance (r = -0.46, P = 0.038). CONCLUSIONS: The haemodynamic profile of COVID-19 patients needing mechanical ventilation is characterized by combined cardiopulmonary alterations. Low pulmonary vascular resistance, coherent with a blunted hypoxic vasoconstriction, is associated with high cardiac output and post-capillary pulmonary hypertension, that could eventually contribute to lung stiffness and promote a vicious circle between the lung and the heart.

Role of rehabilitation in the elderly after an acute event: insights from a real-life prospective study in the subacute care setting.

BACKGROUND: Any acute event, either primary or secondary to a chronic disease, is generally followed by some degree of physical impairment. Subacute care (SAC) represents one of the inpatient intermediate care settings aimed at completing recovery and restoring functional capacity. Debate exists on the role of the rehabilitation treatment in the SAC setting. AIM: The aim of this study was to compare the outcomes of patients managed in two different SAC Units where A) patients undergo an individualized rehabilitation program on top of optimal medical therapy (OMT) B) patients receive OMT only. DESIGN: Real-life prospective study. SETTING: SAC units. POPULATION: Seventy-five chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) patients transferred after an acute hospitalization. METHODS: Upon SAC admission, the following scales were obtained: cumulative illness rating scale comorbidity and severity (CIRSC and CIRSS), mini mental state examination (MMSE), Performance-Oriented Mobility Assessment (POMA), Barthel Index (BI), the 10-meter walking test (10MWT). Pre-admission BI was also collected based on history. Upon SAC discharge, BI, POMA, and 10MWT were repeated. RESULTS: Patients (44 in Group A, 31 in Group B) were similar with regard to age, gender, MMSE, clinical complexity, pre-admission BI, admission 10MWT, POMA, and bedrest conditions. Admission BI was lower in Group A. In both groups BI was lower when compared to the respective pre-admission score. Upon discharge, Group A patients were characterized by a higher BI and POMA compared to Group B. Indeed, BI and POMA improved at discharge only in Group A patients. Only this latter group reached the pre-morbid BI. Upon discharge the number of bedrest patients decreased only in Group A. The percentage of patients discharged home was also much higher in Group A, while a greater number of Group B patients were transferred to a rehabilitation ward or were enrolled in an integrated home care assistance program. CONCLUSIONS: In a real-life prospective experience, a better outcome is demonstrated in elderly CHF and COPD patients undergoing a rehabilitative approach during their in-hospital SAC stay. CLINICAL REHABILITATION IMPACT: An individualized rehabilitation program should integrate medical treatment of CHF and BPCO patients in the SAC setting. This approach demonstrates a better cost-effectiveness management of these patients.