Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30 months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5 mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis.

Clinical complexity of an Italian cardiovascular intensive care unit: the role of mortality and severity risk scores.

AIMS: The identification of patients at greater mortality risk of death at admission into an intensive cardiovascular care unit (ICCU) has relevant consequences for clinical decision-making. We described patient characteristics at admission into an ICCU by predicted mortality risk assessed with noncardiac intensive care unit (ICU) and evaluated their performance in predicting patient outcomes. METHODS: A total of 202 consecutive patients (130 men, 75 ±â€Š12 years) were admitted into our tertiary-care ICCU in a 20-week period. We evaluated, on the first 24 h data, in-hospital mortality risk according to Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score 3 (SAPS 3); Sepsis related Organ Failure Assessment (SOFA) Score and the Mayo Cardiac intensive care unit Admission Risk Score (M-CARS) were also calculated. RESULTS: Predicted mortality was significantly lower than observed (5% during ICCU and 7% at discharge) for APACHE II and SAPS 3 (17% for both scores). Mortality risk was associated with older age, more frequent comorbidities, severe clinical presentation and complications. The APACHE II, SAPS 3, SOFA and M-CARS had good discriminative ability in distinguishing deaths and survivors with poor calibration of risk scores predicting mortality. CONCLUSION: In a recent contemporary cohort of patients admitted into the ICCU for a variety of acute and critical cardiovascular conditions, scoring systems used in general ICU had good discrimination for patients' clinical severity and mortality. Available scores preserve powerful discrimination but the overestimation of mortality suggests the importance of specific tailored scores to improve risk assessment of patients admitted into ICCUs.

Effects of sacubitril/valsartan on the functional capacity of real-world patients in Italy: the REAL.IT study on heart failure with reduced ejection fraction.

Background: Heart failure (HF) significantly affects the morbidity, mortality, and quality of life of patients. New therapeutic strategies aim to improve the functional capacity and quality of life of patients while controlling HF-related risks. Real-world data on both the functional and cardiopulmonary exercise capacities of patients with HF with reduced ejection fraction upon sacubitril/valsartan use are lacking. Methods: A multicenter, retrospective, cohort study, called REAL.IT, was performed based on the data collected from the electronic medical records of nine specialized HF centers in Italy. Cardiopulmonary exercise testing was performed at baseline and after 12 months of sacubitril/valsartan therapy, monitoring carbon dioxide production (VCO2) and oxygen consumption (VO2). Results: The functional capacities of 170 patients were evaluated. The most common comorbidities were hypertension and diabetes (i.e., 53.5 and 32.4%, respectively). At follow-up, both the VO2 peak (from 15.1 ± 3.7 ml/kg/min at baseline to 17.6 ± 4.7 ml/kg/min at follow-up, p < 0.0001) and the predicted % VO2 peak (from 55.5 ± 14.1 to 65.5 ± 16.9, p < 0.0001) significantly increased from baseline. The VO2 at the anaerobic threshold (AT-VO2) increased from 11.5 ± 2.6 to 12.5 ± 3.3 ml/kg/min (p = 0.021), and the rate ratio between the oxygen uptake and the change in work (ΔVO2/Δwork slope) improved from 9.1 ± 1.5 to 9.9 ± 1.6 ml/min/W (p < 0.0001). Conclusions: Sacubitril/valsartan improves the cardiopulmonary capacity of patients with HFrEF in daily clinical practice in Italy.

A Novel Framework Based on Deep Learning Architecture for Continuous Human Activity Recognition with Inertial Sensors.

Frameworks for human activity recognition (HAR) can be applied in the clinical environment for monitoring patients' motor and functional abilities either remotely or within a rehabilitation program. Deep Learning (DL) models can be exploited to perform HAR by means of raw data, thus avoiding time-demanding feature engineering operations. Most works targeting HAR with DL-based architectures have tested the workflow performance on data related to a separate execution of the tasks. Hence, a paucity in the literature has been found with regard to frameworks aimed at recognizing continuously executed motor actions. In this article, the authors present the design, development, and testing of a DL-based workflow targeting continuous human activity recognition (CHAR). The model was trained on the data recorded from ten healthy subjects and tested on eight different subjects. Despite the limited sample size, the authors claim the capability of the proposed framework to accurately classify motor actions within a feasible time, thus making it potentially useful in a clinical scenario.

Implementation of the Care Bundle for the Management of Chronic Obstructive Pulmonary Disease with/without Heart Failure.

Chronic obstructive pulmonary disease (COPD) is often part of a more complex cardiopulmonary disease, especially in older patients. The differential diagnosis of the acute exacerbation of COPD and/or heart failure (HF) in emergency settings is challenging due to their frequent coexistence and symptom overlap. Both conditions have a detrimental impact on each other's prognosis, leading to increased mortality rates. The timely diagnosis and treatment of COPD and coexisting factors like left ventricular overload or HF in inpatient and outpatient care can improve prognosis, quality of life, and long-term outcomes, helping to avoid exacerbations and hospitalization, which increase future exacerbation risk. This work aims to address existing gaps, providing management recommendations for COPD with/without HF, particularly when both conditions coexist. During virtual meetings, a panel of experts (the authors) discussed and reached a consensus on the differential and paired diagnosis of COPD and HF, providing suggestions for risk stratification, accurate diagnosis, and appropriate therapy for inpatients and outpatients. They emphasize that when COPD and HF are concomitant, both conditions should receive adequate treatment and that recommended HF treatments are not contraindicated in COPD and have favorable effects. Accurate diagnosis and therapy is crucial for effective treatment, reducing hospital readmissions and associated costs. The management considerations discussed in this study can potentially be extended to address other cardiopulmonary challenges frequently encountered by COPD patients.

Incremental prognostic value of functional impairment assessed by 6-min walking test for the prediction of mortality in heart failure.

Natriuretic peptides (NP) are recognized as the most powerful predictors of adverse outcomes in heart failure (HF). We hypothesized that a measure of functional limitation, as assessed by 6-min walking test (6MWT), would improve the accuracy of a prognostic model incorporating a NP. This was a multicenter observational retrospective study. We studied the prognostic value of severe functional impairment (SFI), defined as the inability to perform a 6MWT or a distance walked during a 6MWT < 300 m, in 1696 patients with HF admitted to cardiac rehabilitation. The primary outcome was 1-year all-cause mortality. After adjusting for the baseline multivariable risk model-including age, sex, systolic blood pressure, anemia, renal dysfunction, sodium level, and NT-proBNP-or for the MAGGIC score, SFI had an odds ratio of 2.58 (95% CI 1.72-3.88; p < 0.001) and 3.12 (95% CI 2.16-4.52; p < 0.001), respectively. Adding SFI to the baseline risk model or the MAGGIC score yielded a significant improvement in discrimination and risk classification. Our data suggest that a simple, 6MWT-derived measure of SFI is a strong predictor of death and provide incremental prognostic information over well-established risk markers in HF, including NP, and the MAGGIC score.

Pharmacoutilization and adherence to sacubitril/valsartan in real world: the REAL.IT study in HFrEF.

AIMS: The current European Society of Cardiology (ESC) guidelines provide clear indications for the treatment of acute and chronic heart failure (HF). Nevertheless, there is a constant need for real-world evidence regarding the effectiveness, adherence, and persistence of drug therapy. We investigated the use of sacubitril/valsartan for the treatment of HF with reduced ejection fraction in real-world clinical practice in Italy. METHODS AND RESULTS: An observational, retrospective, non-interventional cohort study based on electronic medical records from nine specialized hospital HF centres in Italy was carried out on patients with prescription of sacubitril/valsartan. Overall, 948 patients had a prescription of sacubitril/valsartan, with 924 characterized over 6 months and followed up for 12 months. Pharmacoutilization data at 1 year of follow-up were available for 225 patients {mean age 69.7 years [standard deviation (SD) = 10.8], 81.8% male}. Of those, 398 (45.2%) reached the target dose of sacubitril/valsartan of 97/103 mg in a mean time of 6.9 (SD = 6.2) weeks. Blood pressure and hypotension in 61 patients (65%) and worsening of chronic kidney disease in 10 patients (10.6%) were the main reasons for not reaching the target dose. Approximatively 50% of patients had a change in sacubitril/valsartan dose during follow-up, and 158 (70.2%) were persistent with the treatment during the last 3 months of follow-up. A sensitivity analysis (persistence during the last 4 months of follow-up) showed persistence for 162 patients (72.0%). Adherence data, available for 387 patients, showed full adherence for 205 (53%). Discontinuation (102/717 patients, 14.2%) was mainly due to hypotension and occurred after a mean time of 34.3 (SD = 28.7) weeks. During follow-up, out of 606 patients with available data, 434 patients (71.6%) had an HF add-on drug or drugs concomitant with sacubitril/valsartan. HF-related hospitalization during follow-up was numerically higher in non-persistent (16/67 patients, 23.9%) vs. patients persistent to sacubitril/valsartan (30/158, 19%) (P = 0.405). CONCLUSIONS: Real-world data on the use of sacubitril/valsartan in clinical practice in Italy show a rapid titration to the target dose, high therapeutic adherence enabling a good level of therapeutic management in line with ESC guidelines for patients with reduced ejection fraction.

Heart failure patients with improved ejection fraction: Insights from the MECKI score database.

AIMS: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). METHODS AND RESULTS: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis. CONCLUSIONS: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Prognostic Value of 6-Minute Walk Test in Advanced Heart Failure With Reduced Ejection Fraction.

There is limited evidence regarding the prognostic value of the 6-minute walk test for patients with advanced heart failure (HF). Accordingly, we studied 260 patients presenting to inpatient cardiac rehabilitation (CR) with advanced HF. The primary outcome was 3-year all-cause mortality after discharge from CR. The association between 6-minute walk distance (6MWD) and the primary outcome was determined using the multivariable Cox regression analysis. To avoid collinearity, 6MWD at admission (6MWDadm) to CR and 6MWD at discharge (6MWDdisch) from CR were analyzed separately. At multivariable analysis, 4 baseline characteristics (age, ejection fraction, systolic blood pressure, and blood urea nitrogen) were identified as prognostic of the primary outcome (baseline risk model). After adjusting for the baseline risk model, the hazard ratios of 6MWDadm and 6MWDdisch modeled as per 50-m increase for the primary outcome were 0.92 (95% confidence interval [CI] 0.85 to 0.99, p = 0.035) and 0.93 (95% CI 0.88 to 0.99, p = -017), respectively. After adjusting for the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score, the corresponding hazard ratios were 0.91 (95% CI 0.84 to 0.98, p = 0.017) and 0.93 (95% CI 0.88 to 0.99, p = 0.016). The addition of either 6MWDadm or 6MWDdisch to the baseline risk model or the MAGGIC score yielded a statistically significant increase in global chi-square and in the net proportion of survivors reclassified downward. In conclusion, our data suggest that the distance covered during a 6-minute walk test predicts survival and provides incremental prognostic information on the top of well-established prognostic factors and the MAGGIC risk score in advanced HF.

Functional outcome after cardiac rehabilitation and its association with survival in heart failure across the spectrum of ejection fraction.

BACKGROUND: There is limited evidence regarding the effects of cardiac rehabilitation (CR) in patients with heart failure and preserved ejection fraction (HFpEF). METHODS: We studied 1784 patients admitted to inpatient CR. The patients were grouped into HFpEF (EF≥0.50), HF with mildly reduced EF (HFmrEF; EF 41-49), and HF with reduced EF (HFrEF; EF≤0.40). A standardized 6-min walking test was performed at admission and discharge. Measures of functional outcome were: (1) absolute increase in 6-min walking distance (6MWD) from admission to discharge >50 m and (2) increase in 6MWD to ≥300 among the patients who walked <300 m at admission. RESULTS: After adjustment, the patients with HFpEF or HFmrEF were as likely as those with HFrEF to achieve an increase in 6MWD >50 m (odds ratio 0.95 [95%CI 0.71-1.24; p=0.648] and 1.04 [95%CI 0.77-1.41; p=0.769], respectively) or an increase in 6MWD to ≥300 m (odds ratio 0.79 [95%CI 0.51-1.23; p=0.299] and 0.65 [95%CI 0.38-1.12; p=0.118], respectively). The adjusted hazard ratio of 5-year mortality for patients who achieved an increase in 6MWD >50 m was 0.60 (95%CI 0.51-0.71; p<0.001) and that for patients who achieved an increase in 6MWD at discharge to ≥300 m 0.61 (95%CI 0.48-0.79; p<0.001). In each EF group, both outcomes remained independently associated with improved survival. CONCLUSIONS: Our data suggest that patients with HFpEF or HFmrEF are as likely as those with HFrEF to benefit from CR in terms of functional improvement. Functional improvement was independently associated with improved long-term survival, regardless of EF.

Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction: Real-World Experience from Italy (the REAL.IT Study).

Sacubitril/valsartan reduces heart failure (HF)-related hospitalizations and cardiovascular mortality in PARADIGM-HF and has become a foundational treatment for HF with reduced ejection fraction (HFrEF). However, data of its routine real-world use are limited, and evidence from Italian settings is lacking. The REAL.IT study aimed to characterize the demographics, pharmacotherapy, clinical characteristics and outcomes of sacubitril/valsartan-treated Italian patients with HFrEF. Electronic medical records of patients initiating sacubitril/valsartan from October 2016 to June 2019 at nine specialized hospital outpatient HF centers across Italy were reviewed. Overall, 924 adults (mean age 64.5 years, 84.6% male) were included. At baseline, 38.7% had an ischemic HF etiology, 45.9% hypertension, 23.2% atrial fibrillation, 25.4% diabetes mellitus, 26.1% an implantable cardioverter-defibrillator and 31.9% coronary artery bypass grafting. There were no clear patterns of patient selection over time. During follow-up, NYHA class improved in 37.5% of patients after a mean of 5.3 ± 3.8 months; 36.1% and 16.7% of patients were in NYHA class III during characterization and after one year of follow-up, respectively. Left ventricular ejection fraction (LVEF) improved ≥5% in 56.3% of patients at one year; 39.7% had ≥30% reduction of N-terminal pro-B-type natriuretic peptide; 2.2% had hyperkalemia during characterization and 2.6% during follow-up; and 3.8% had hypotension during characterization and 12% during follow-up. A total of 50 (5.8%) of patients had device implantation (ICD/CRT) during follow-up. HF-related hospitalization was recorded in 19.6% of patients during follow-up; 3.8% of patients died, approximately 1.3% from cardiovascular causes. Our real-world data confirm the favorable effectiveness and tolerability of sacubitril/valsartan observed in pivotal randomized controlled trials.

Diabetes and SGLT2-iss inhibitors in patients with heart failure with preserved or mid-range left ventricular ejection fractions.

Diabetic patients frequently develop heart failure with preserved (HFpEF) or mid-range (HFmEF) cardiac ejection fractions. This condition may be secondary to diabetic cardiomyopathy or one of several relevant comorbidities, mainly hypertension. Several mechanisms link diabetes to HFpEF or HFmEF. Among these, non-enzymatic glycation of interstitial proteins, lipotoxicity, and endothelial dysfunction may promote structural damage and ultimate lead to heart failure. Findings from several large-scale trials indicated that treatment with sodium/glucose cotransporter 2 inhibitors (SGLT2-iss) resulted in significant improvements in cardiovascular outcomes in diabetic patients with high cardiovascular risk. However, there is currently some evidence that suggests a clinical advantage of using SGLT2-iss specifically in cases of HFpEF or HFmEF. Preclinical and clinical studies revealed that SGLT2-iss treatment results in a reduction in left ventricular mass and improved diastolic function. While some of the beneficial effects of SGLT2-iss have already been characterized (e.g., increased natriuresis and diuresis as well as reduced blood pressure, plasma volume, and arterial stiffness, and nephron-protective activities), there is increasing evidence suggesting that SGLT2-iss may have direct actions on the heart. These findings include SGLT2-iss-mediated reductions in the expression of hypertrophic foetal genes and diastolic myofilaments stiffness, increases in global phosphorylation of myofilament regulatory proteins (in HFpEF), inhibition of cardiac late sodium channel current and Na+/H+ exchanger activity, metabolic shifts, and effects on calcium cycling. Preliminary data from previously published studies suggest that SGLT2-iss could be useful for the treatment of HFpEF and HFmEF. Several large ongoing trials, including DELIVER AND EMPEROR -preserved have been designed to evalute the efficacy of SGLT2-iss in improving clinical outcomes in patients diagnosed with HFpEF. The goal of this manuscript is to review the use of SGLT2-iss inhibitors for HFpEF or HFmEF associated with diabetes.

Does moderate hyperkalemia influence survival in HF? Insights from the MECKI score data base.

BACKGROUND: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin-angiotensin-aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. OBJECTIVES: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. METHODS AND RESULTS: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9-7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1-14.1%] and 7.3% [IQR 3.4-15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. CONCLUSIONS: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

Testosterone deficiency independently predicts mortality in women with HFrEF: insights from the T.O.S.CA. registry.

AIMS: Testosterone deficiency (TD) is associated with increased morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). However, data in women are scanty. The aim of this study was to investigate the prognostic impact of TD on women with HFrEF. METHODS: Among 480 patients prospectively enrolled in the T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, a prospective, multicentre, nationwide, observational study, 94 women were included in the current analysis. The TD was defined as serum testosterone levels lower than 25 ng/dl. Data regarding clinical status, echocardiography, exercise performance, cardiovascular hospitalization, and survival after an average follow-up of 36 months were analysed. RESULTS: Thirty patients (31.9%) displayed TD. TD was associated with lower tricuspid annular plane excursion (TAPSE) to pulmonary arterial systolic pressure PASP ratio (TAPSE/PASP) (P = 0.008), peak oxygen consumption (VO2 peak) (P = 0.03) and estimated glomerular filtration rate (P < 0.001). TD was an independent predictor of the combined endpoint of all-cause mortality/cardiovascular hospitalization (HR: 10.45; 95% CI: 3.54-17.01; P = 0.001), all-cause mortality (HR: 8.33; 95%: 5.36-15.11; P = 0.039), and cardiovascular hospitalization (HR: 2.41; 95% CI: 1.13-4.50; P = 0.02). CONCLUSIONS: One-third of women with HFrEF displays TD that impacts remarkably on their morbidity and mortality. TD is associated with a worse clinical profile including exercise capacity, right ventricular-pulmonary arterial coupling, and renal function. These findings lend support to an accurate profiling of women with HF, a problem often overlooked in clinical trials.

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban.

INTRODUCTION: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. MATERIALS AND METHODS: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. RESULTS: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up. CONCLUSIONS: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.

Cardiac Rehabilitation for Older Women with Heart Failure.

Background: the role that sex plays in impacting cardiac rehabilitation (CR) outcomes remains an important gap in knowledge. Methods: we assessed sex differences in clinical and functional outcomes in 2345 older patients with heart failure (HF) admitted to inpatient CR. Three outcomes were considered: (1) the composite outcome of death during the index admission to CR or transfer to acute care; (2) three-year mortality; (3) change in six-minute walking distance (6MWD) from admission to discharge. Sex differences in outcomes were assessed using multivariable Cox or logistic regression models. Results: the hazard ratios of the composite outcome and of three-year mortality for females vs. males were 0.71 (95%CI:0.50−1.00; p = 0.049) and 0.68 (95%CI:0.59−0.79; p < 0.001), respectively. The standardized mean difference in 6MWD increase from admission to discharge between males and females was 0.10. The odds ratio of achieving an increase in 6MWD at discharge to values higher than the optimal sex-specific thresholds for predicting mortality for females vs. males was 2.21 (95%CI:1.53−3.20; p < 0.001). Conclusion: our findings suggest that older females with HF undergoing CR have better prognosis and garner similar improvement in 6MWD compared with their male counterparts. Nonetheless, females were more likely to achieve levels of functional capacity predictive of improved survival.

Plasma Levels of Intact Parathyroid Hormone and Congestion Burden in Heart Failure: Clinical Correlations and Prognostic Role.

Circulating parathyroid hormone (PTH) concentrations increase in heart failure (HF) and are related to disease severity. The relationship between PTH and congestion is still a matter of debate. The objective of this analysis was to evaluate the role of PTH as a marker of congestion and prognosis in HF. We enrolled 228 patients with HF. Intact PTH concentrations and HYDRA score (constituted by: B-type natriuretic peptide, blood urea nitrogen−creatinine ratio, estimated plasma volume status, and hydration status) were evaluated. The study endpoint was all-cause mortality. PTH levels were higher in acute compared with chronic HF and in patients with clinical signs of congestion (i.e., peripheral oedema and orthopnea). PTH concentrations significantly correlated with NYHA class and HYDRA score. At multivariate analysis of HYDRA score, estimated glomerular filtration rate (eGFR), and corrected serum calcium were independently determinants of PTH variability. Fifty patients (22%) died after a median follow-up of 408 days (interquartile range: 283−573). Using univariate Cox regression analysis, PTH concentrations were associated with mortality (hazard ratio [HR]: 1.003, optimal cut-off: >249 pg/mL­area under-the-curve = 0.64). Using multivariate Cox regression analysis, PTH was no longer associated with death, whereas HYDRA score, left ventricular ejection fraction, and eGFR acted as independent predictors for mortality (HR: 1.96, 0.97, and 0.98, respectively). Our study demonstrated that intact PTH was related to clinical and subclinical markers of congestion. However, intact PTH did not act as an independent determinant of all-cause death in HF patients.

Optimizing Therapies in Heart Failure: The Role of Potassium Binders.

Heart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3-18% of HF patients from randomized controlled trials and over 25% of HF patients in the "real world" setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K+ and to promote correct upgrades of therapies. In addition to the well-established use of sodium polystyrene sulfonate (SPS), two novel drugs have been recently introduced: sodium zirconium cyclosilicate (SZC) and patiromer. SZC and patiromer are gaining a central role for the treatment of chronic HK. SZC has been shown to reduce K+ levels within 48 h, with guaranteed maintenance of normokalemia for up to12 months. Patiromer has resulted in a statistically significant decrease in serum potassium for up to 52 weeks. Therefore, long-term results seemed to positively promote the implementation of these compounds in clinical practice due to their low rate side effects. The aim of this narrative review is to delineate the impact of new potassium binders in the treatment of patients with HF by providing a critical reappraisal for daily application of novel therapies for hyperkalemia in the HF setting.