The early safety profile of simultaneous vaccination against influenza and Respiratory Syncytial Virus (RSV) in patients with high-risk heart failure.

The safety of simultaneous vaccination for Respiratory Syncytial Virus (RSV) and influenza in vulnerable high-risk heart failure (HF) patients remains unclear. In an open-label, prospective study, 105 patients received concurrent influenza (Vaxigrip Tetra, season 2023/2024, Sanofi) and RSV (Arexvy, GSK) vaccinations from September 15th to November 17th, 2023. Adverse events were collected on the fourth-day post-vaccination. Overall, the vaccination was well tolerated, with the most common reaction being injection site pain (63 %). General symptoms occurred in 33 % of patients, predominantly fatigue (23 %), myalgia (12 %), and headache (9 %). Grade 3 reactions were observed in 6 % of patients, and a few experienced temperature elevation or flu-like symptoms, managing them with antipyretics. Notably, there were no exacerbations of HF, hospitalizations, or deaths within a week post-vaccination. This study indicates the safety of simultaneous influenza and RSV vaccination in high-risk HF patients, with a low incidence of mild adverse events.

Spot urine sodium as a marker of urine dilution and decongestive abilities in acute heart failure.

The decongestion ability in response to diuretic treatment plays a crucial role in the treatment of acute heart failure. This effectiveness is evaluated through the assessment of sodium concentration and urine volume, which are also treatment goals themselves. However, the bidirectional interconnection between these factors remains not fully understood. The objective of this study is to provide mechanistic insights into the correlation between spot urine sodium concentrations (UNa+) and urine dilution. This aims to better understand of the decongestive abilities in acute heart failure (AHF). The study was single-center, prospective, conducted on a group of 50 AHF patients. Each participant received a standardized furosemide dose of 1 mg per kg of body weight. Hourly diuresis was measured in the first 6 h of the study, and urine composition was assessed at predefined timepoints. The study group presented the exponential (rather than linear) pattern of relationship between UNa+ and 6-h urine volume, whereas relationship between eGFR and 6-h urine volume was linear (r = 0.61, p < 0.001). The relationship between UNa+ and all other analyzed indices of urine dilution, including the change from baseline in urine creatinine concentration, urine osmolarity, and urine osmolarity corrected for urine sodium, also exhibited an exponential relationship. Patients who were chronically exposed to furosemide demonstrated a significantly lower urine dilution (1.78 [1.18-3.54] vs 11.58 [3.9-17.88]; p < 0.001) in comparison to naïve individuals. In conclusion, it should be noted that in AHF higher UNa+ is associated with disproportionally higher urine dilution, and patients naïve to furosemide have significantly greater ability to dilute urine when compare to chronic furosemide users.

Prognostic significance and clinical determinants of residual dyspnoea at discharge in acute heart failure: a single-centre, prospective observational study.

OBJECTIVE: This study aimed to assess the prognostic significance of residual (discharge) dyspnoea in acute heart failure (AHF) patients. DESIGN: Single-centre, prospective observational study. SETTING: Patients hospitalised for decompensated AHF in a single cardiology centre, in Poland. PARTICIPANTS: All patients (n=202) who survived the hospitalisation with the primary diagnosis of AHF and were discharged from the hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: 1-year all-cause mortality; and the composite endpoint of 1-year all-cause mortality and rehospitalisation for the HF (whichever occurred first). RESULTS: On admission, 159 (78.7%) AHF patients presented dyspnoea at rest, while residual resting dyspnoea at discharge was present in 16 patients (7.9%). There were 48 (24%) patients with moderate/severe exertional dyspnoea at discharge. In the multivariable model, the resting dyspnoea at discharge was related to a higher risk of both 1-year mortality and composite outcome, with HR (95% CI) 8.0 (3.7 to 17.3) and 5.1 (2.6 to 10.2), respectively, both p<0.0001. Analogically, moderate or severe residual dyspnoea at discharge was related to the heightened risk of study both outcomes, with HR (95% CI) 3.1 (1.8 to 5.4) and 1.8 (1.1 to 2.9), respectively, p<0.01. CONCLUSIONS: Among AHF patients the residual dyspnoea at discharge was unexpectedly common and was associated with an unfavourable outcome during 1-year follow-up.

Sex-stratified patterns of emergency cardiovascular admissions prior and during the COVID-19 pandemic.

The COVID-19 pandemic has had a significant impact on global public health, with long-term consequences that are still largely unknown. This study aimed to assess the data regarding acute cardiovascular hospital admissions in five European centers before and during the pandemic. A multicenter, multinational observational registry was created, comparing admissions to the emergency departments during a 3-months period in 2020 (during the pandemic) with the corresponding period in 2019 (pre-pandemic). Data on patient demographics, COVID-19 test results, primary diagnosis, comorbidities, heart failure profile, medication use, and laboratory results were collected. A total of 8778 patients were included in the analysis, with 4447 patients in 2019 and 4331 patients in 2020. The results showed significant differences in the distribution of cardiovascular diseases between the two years. The frequency of pulmonary embolism (PE) increased in 2020 compared to 2019, while acute heart failure (AHF) and other cardiovascular diseases decreased. The odds of PE incidence among hospitalized patients in 2020 were 1.316-fold greater than in 2019. The incidence of AHF was 50.83% less likely to be observed in 2020, and the odds for other cardiovascular diseases increased by 17.42% between the 2 years. Regarding acute coronary syndrome (ACS), the distribution of its types differed between 2019 and 2020, with an increase in the odds of ST-segment elevation myocardial infarction (STEMI) in 2020. Stratification based on sex revealed further insights. Among men, the incidence of AHF decreased in 2020, while other cardiovascular diseases increased. In women, only the incidence of STEMI showed a significant increase. When analyzing the influence of SARS-CoV-2 infection, COVID-positive patients had a higher incidence of PE compared to COVID-negative patients. COVID-positive patients with ACS also exhibited symptoms of heart failure more frequently than COVID-negative patients. These findings provide valuable information on the impact of the COVID-19 pandemic on acute cardiovascular hospital admissions. The increased incidence of PE and changes in the distribution of other cardiovascular diseases highlight the importance of monitoring and managing cardiovascular health during and post pandemic period. The differences observed between sexes emphasize the need for further research to understand potential sex-specific effects of COVID-19 on cardiovascular outcomes.

Role of dietary sodium restriction in chronic heart failure: systematic review and meta-analysis.

BACKGROUND: Dietary sodium restriction remains a guidelines-approved lifestyle recommendation for chronic heart failure (CHF) patients. However, its efficacy in clinical outcome improvement is dubious. OBJECTIVE: The study evaluated whether dietary sodium restriction in CHF reduces clinical events. METHODS: We performed a systematic review of the following databases: Academic Search Ultimate, ERIC, Health Source Nursing/Academic Edition, MEDLINE, Embase, Clinicaltrials.gov and Cochrane Library (trials) to find studies analysing the impact of sodium restriction in the adult CHF population. Both observational and interventional studies were included. Exclusion criteria included i.e.: sodium consumption assessment based only on natriuresis, in-hospital interventions or mixed interventions-e.g. sodium and fluid restriction in one arm only. The review was conducted following PRISMA guidelines. Meta-analysis was performed for the endpoints reported in at least 3 papers. Analyses were conducted in Review Manager (RevMan) Version 5.4.1. RESULTS: Initially, we screened 9175 articles. Backward snowballing revealed 1050 additional articles. Eventually, 9 papers were evaluated in the meta-analysis. All-cause mortality, HF-related hospitalizations and the composite of mortality and hospitalisation were reported in 8, 6 and 3 articles, respectively. Sodium restriction was associated with a higher risk of the composite endpoint (OR 4.12 [95% CI 1.23-13.82]) and did not significantly affect the all-cause mortality (OR 1.38 [95% CI 0.76-2.49]) or HF hospitalisation (OR 1.63 [95% CI 0.69-3.88]). CONCLUSIONS: In a meta-analysis, sodium restriction in CHF patients worsened the prognosis in terms of a composite of mortality and hospitalizations and did not influence all-cause mortality and HF hospitalisation rate.

The blunted loop diuretic response in acute heart failure is driven by reduced tubular responsiveness rather than insufficient tubular delivery. The role of furosemide urine excretion on diuretic and natriuretic response in acute heart failure.

AIMS: Diuretic response in heart failure is blunted when compared to healthy individuals, but the pathophysiology underlying this phenomenon is unclear. We aimed to investigate whether the diuretic resistance mechanism is related to insufficient furosemide tubular delivery or low tubular responsiveness. METHODS AND RESULTS: We conducted a prospective, observational study of 50 patients with acute heart failure patients divided into two groups based on previous furosemide use (furosemide naïve: n = 28 [56%] and chronic furosemide users: n = 22 [44%]). Each patient received a protocol-derived, standardized furosemide dose based on body weight. We measured diuretic response and urine furosemide concentrations. The furosemide naïve group had significantly higher urine volumes and natriuresis when compared to chronic users at all timepoints (all p < 0.05). Urine furosemide delivery was similar in furosemide naïve versus chronic users after accounting for differences in estimated glomerular filtration rate (28.02 [21.03-35.89] vs. 29.70 [18.19-34.71] mg, p = 0.87). However, the tubular response to delivered diuretic was dramatically higher in naïve versus chronic users, that is the urine volume per 1 µg/ml of urine furosemide at 2 h was 148.6 ± 136.1 versus 50.6 ± 56.1 ml (p = 0.005). CONCLUSIONS: Patients naïve to furosemide have significantly better diuresis and natriuresis when compared to chronic furosemide users. The blunted diuretic response in patients with chronic loop diuretic exposure is driven by decreased tubular responsiveness rather than insufficient furosemide tubular delivery.

Relationship of Vascular Endothelial Growth Factor C, a Lymphangiogenesis Modulator, With Edema Formation, Congestion and Outcomes in Acute Heart Failure.

BACKGROUND: Although vascular endothelial growth factor C (VEGF-C) is a known lymphangiogenesis modulator, its relationship with congestion formation and outcomes in acute heart failure (AHF) is unknown. METHODS: Serum VEGF-C levels were measured in 237 patients hospitalized for AHF. The population was stratified by VEGF-C levels and linked with clinical signs of congestion and outcomes. RESULTS: The study's population was divided in VEGF-C tertiles: low (median [Q25-Q75]: 33 [15-175]), medium (606 [468-741]) and high (1141 [968-1442] pg/mL). The group with low VEGF-C on admission presented with the highest prevalence of severe lower-extremity edema (low VEGF-C vs medium VEGF-C vs high VEGF-C): 30% vs 13% vs 20%; P = 0.02); the highest percentage of patients with ascites: 22% vs 9% vs 6%; P = 0.006; and the lowest proportion of patients with pulmonary congestion: 22% vs 30% vs 46%; P = 0.004. The 1-year mortality rate was the highest in the low VEGF-C tertile: 35% vs 28% vs 18%, respectively; P = 0.049. The same pattern was observed for the composite endpoint (death and AHF rehospitalization): 45% vs 43% vs 26%; P = 0.029. The risks of death at 1-year follow-up and composite endpoint were significantly lower in the high VEGF-C group. CONCLUSIONS: Low VEGF-C was associated with more severe signs of congestion (signs of fluid accumulation) and adverse clinical outcomes.

A family case series of inherited thrombocytopenia.

Inherited thrombocytopenia (IT) is a heterogeneous group of diseases with a genetic origin. The primary symptom presented by patients is a reduced platelet count in the peripheral blood. Nevertheless, certain forms of IT are characterized by the occurrence of other congenital malformations or predisposition to acquire additional diseases. Five related subjects with lifelong thrombocytopenia were admitted to our clinic. A total of 16 cases of persistent thrombocytopenia were investigated in the family history. Molecular and cytogenetic analysis covered MECOM, MPL, RUNX1, ETV6, and GATA1 genes, whose mutations are known to cause predisposing forms of IT. The laboratory testing revealed thrombocytopenia ranging from 19 to 65 × 109/L in the subjects. Mild bleeding symptoms were present in each of the subjects, while two of five had a history of severe hemorrhage requiring transfusion of blood products. Establishing a diagnosis of IT protects the patient from unnecessary treatment and enables the appropriate surveillance.

A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials.

Augmented peripheral chemoreceptor sensitivity (PChS) is a common feature of many sympathetically mediated diseases, among others, and it is an important mechanism of the pathophysiology of heart failure (HF). It is related not only to the greater severity of symptoms, especially to dyspnea and lower exercise tolerance but also to a greater prevalence of complications and poor prognosis. The causes, mechanisms, and impact of the enhanced activity of peripheral chemoreceptors (PChR) in the HF population are subject to intense research. Several methodologies have been established and utilized to assess the PChR function. Each of them presents certain advantages and limitations. Furthermore, numerous factors could influence and modulate the response from PChR in studied subjects. Nevertheless, even with the impressive number of studies conducted in this field, there are still some gaps in knowledge that require further research. We performed a review of all clinical trials in HF human patients, in which the function of PChR was evaluated. This review provides an extensive synthesis of studies evaluating PChR function in the HF human population, including methods used, factors potentially influencing the results, and predictors of increased PChS.

Machine Learning Approach to Understand Worsening Renal Function in Acute Heart Failure.

Acute heart failure (AHF) is a common and severe condition with a poor prognosis. Its course is often complicated by worsening renal function (WRF), exacerbating the outcome. The population of AHF patients experiencing WRF is heterogenous, and some novel possibilities for its analysis have recently emerged. Clustering is a machine learning (ML) technique that divides the population into distinct subgroups based on the similarity of cases (patients). Given that, we decided to use clustering to find subgroups inside the AHF population that differ in terms of WRF occurrence. We evaluated data from the three hundred and twelve AHF patients hospitalized in our institution who had creatinine assessed four times during hospitalization. Eighty-six variables evaluated at admission were included in the analysis. The k-medoids algorithm was used for clustering, and the quality of the procedure was judged by the Davies-Bouldin index. Three clinically and prognostically different clusters were distinguished. The groups had significantly (p = 0.004) different incidences of WRF. Inside the AHF population, we successfully discovered that three groups varied in renal prognosis. Our results provide novel insight into the AHF and WRF interplay and can be valuable for future trial construction and more tailored treatment.

COVID-19 Related Myocarditis in Adults: A Systematic Review of Case Reports.

Despite the progress of its management, COVID-19 maintains an ominous condition which constitutes a threat, especially for the susceptible population. The cardiac injury occurs in approximately 30% of COVID-19 infections and is associated with a worse prognosis. The clinical presentation of cardiac involvement can be COVID-19-related myocarditis. Our review aims to summarise current evidence about that complication. The research was registered at PROSPERO (CRD42022338397). We performed a systematic analysis using five different databases, including i.a. MEDLINE. Further, the backward snowballing technique was applied to identify additional papers. Inclusion criteria were: full-text articles in English presenting cases of COVID-19-related myocarditis diagnosed by the ESC criteria and patients over 18 years old. The myocarditis had to occur after the COVID-19 infection, not vaccination. Initially, 1588 papers were screened from the database search, and 1037 papers were revealed in the backward snowballing process. Eventually, 59 articles were included. Data about patients' sex, age, ethnicity, COVID-19 confirmation technique and vaccination status, reported symptoms, physical condition, laboratory and radiological findings, applied treatment and patient outcome were investigated and summarised. COVID-19-related myocarditis is associated with the risk of sudden worsening of patients' clinical status, thus, knowledge about its clinical presentation is essential for healthcare workers.

Clinical determinants and prognostic significance of hypocapnia in acute heart failure.

The aim of this research was to examine the prevalence of hyperventilation (defined by pCO2 value) among acute heart failure (AHF) patients and to link it with potential triggers and prognosis. All patients underwent dyspnea severity assessment and capillary blood examination on hospital admission and during hospitalization. Out of 241 AHF patients, 57(24%) were assigned to low pCO2 group (pCO2 ≤ 30 mmHg) and 184 (76%) to normal pCO2 group (pCO2 > 30 mmHg). Low pCO2 group had significantly lower HCO3- (22.3 ± 3.4 vs 24.7 ± 2.9 mmol/L, p < 0.0001) and significantly higher lactate level (2.53 ± 1.6 vs 2.14 ± 0.97 mmol/L, p = 0.03). No differences between groups were observed in respect to the following potential triggers of hyperventilation: hypoxia (sO2 92.5 ± 5.2 vs 92 ± 5.6% p = 0.57), infection (CRP 10.5[4.9-26.4]vs 7.15[3.45-17.35] mg/L, p = 0.47), dyspnea severity (7.8 ± 2.3vs 8.0 ± 2.3 points, p = 0.59) and pulmonary congestion (82.5 vs 89.1%, p = 0.19), respectively. Low pCO2 value was related to an increased 4-year all-cause mortality hazard ratio (HR) (95% CI) 2.2 (1.3-3.6); p = 0.002 and risk of death and of rehospitalization for HF, HR (95% CI) 2.0 (1.3-3.0); p = 0.002. Hyperventilation is relatively frequent in AHF and is related to poor prognosis. Low pCO2 was not contingent on expected potential triggers of dyspnea but rather on tissue hypoperfusion.

An Artificial Intelligence Approach to Guiding the Management of Heart Failure Patients Using Predictive Models: A Systematic Review.

Heart failure (HF) is one of the leading causes of mortality and hospitalization worldwide. The accurate prediction of mortality and readmission risk provides crucial information for guiding decision making. Unfortunately, traditional predictive models reached modest accuracy in HF populations. We therefore aimed to present predictive models based on machine learning (ML) techniques in HF patients that were externally validated. We searched four databases and the reference lists of the included papers to identify studies in which HF patient data were used to create a predictive model. Literature screening was conducted in Academic Search Ultimate, ERIC, Health Source Nursing/Academic Edition and MEDLINE. The protocol of the current systematic review was registered in the PROSPERO database with the registration number CRD42022344855. We considered all types of outcomes: mortality, rehospitalization, response to treatment and medication adherence. The area under the receiver operating characteristic curve (AUC) was used as the comparator parameter. The literature search yielded 1649 studies, of which 9 were included in the final analysis. The AUCs for the machine learning models ranged from 0.6494 to 0.913 in independent datasets, whereas the AUCs for statistical predictive scores ranged from 0.622 to 0.806. Our study showed an increasing number of ML predictive models concerning HF populations, although external validation remains infrequent. However, our findings revealed that ML approaches can outperform conventional risk scores and may play important role in HF management.

Serum Osmolarity and Vasopressin Concentration in Acute Heart Failure-Influence on Clinical Course and Outcome.

Neurohormone activation plays an important role in Acute Heart Failure (AHF) pathophysiology. Serum osmolarity can affect this activation causing vasopressin excretion. The role of serum osmolarity and vasopressin concentration and its interaction remain still unexplored in AHF. The objective of our study was to evaluate the relationship of serum osmolarity with clinical parameters, vasopressin concentration, in-hospital course, and outcomes in AHF patients. The study group consisted of 338 AHF patients (male (76.3%), mean age of 68 ± 13 years) with serum osmolarity calculated by the equation: 1.86 × sodium [mmol/L] + (glucose [mg/dL]/18) + (urea [mg/dL]/2.8) + 9 and divided into osmolarity quartiles marked as: low: <287 mOsm/L, intermediate low: 287−294 mOsm/L, intermediate high: 295−304 mOsm/L, and high: >304 mOsm/L. There was an increasing age gradient in the groups and patients differed in the occurrence of comorbidities and baseline clinical and laboratory parameters. Importantly, analysis revealed that vasopressin presented a linear correlation with osmolarity (r = −0.221, p = 0.003) and its concentration decreased with quartiles (61.6 [44.0−81.0] vs. 57.8 [50.0−77.3] vs. 52.7 [43.1−69.2] vs. 45.0 [30.7−60.7] pg/mL, respectively, p = 0.034). This association across quartiles was observed among de novo AHF (63.6 [55.3−94.5] vs. 58.0 [50.7−78.6] vs. 52.0 [46.0−58.0] vs. 38.0 [27.0−57.0] pg/mL, respectively, p = 0.022) and was not statistically significant in patients with acute decompensated heart failure (ADHF) (59.5 [37.4−80.0] vs. 52.0 [38.0−74.5] vs. 57.0 [38.0−79.0] vs. 50.0 [33.0−84.0] pg/mL, respectively, p = 0.849). The worsening of renal function episodes were more frequent in quartiles with higher osmolarity (4 vs. 2 vs. 13 vs. 11%, respectively, p = 0.018) and patients that belonged to the quartiles with low and high osmolarity were characterized more often by incidence of worsening heart failure (20 vs. 9 vs. 10 vs. 22%, respectively, p = 0.032). There was also a U-shape distribution in relation to one-year mortality (31 vs. 19 vs. 23 vs. 37%, respectively, p = 0.022). In conclusion, there was an association of serum osmolarity with clinical status and both in-hospital and out-of-hospital outcomes. Moreover, the linear dependence between vasopressin concentration and serum osmolarity in the AHF population was identified and was driven mainly by patients with de novo AHF which suggests different pathophysiological paths in ADHF and AHF de novo.

Novel Phenotyping for Acute Heart Failure-Unsupervised Machine Learning-Based Approach.

Acute heart failure (AHF) is a life-threatening, heterogeneous disease requiring urgent diagnosis and treatment. The clinical severity and medical procedures differ according to a complex interplay between the deterioration cause, underlying cardiac substrate, and comorbidities. This study aimed to analyze the natural phenotypic heterogeneity of the AHF population and evaluate the possibilities offered by clustering (unsupervised machine-learning technique) in a medical data assessment. We evaluated data from 381 AHF patients. Sixty-three clinical and biochemical features were assessed at the admission of the patients and were included in the analysis after the preprocessing. The K-medoids algorithm was implemented to create the clusters, and optimization, based on the Davies-Bouldin index, was used. The clustering was performed while blinded to the outcome. The outcome associations were evaluated using the Kaplan-Meier curves and Cox proportional-hazards regressions. The algorithm distinguished six clusters that differed significantly in 58 variables concerning i.e., etiology, clinical status, comorbidities, laboratory parameters and lifestyle factors. The clusters differed in terms of the one-year mortality (p = 0.002). Using the clustering techniques, we extracted six phenotypes from AHF patients with distinct clinical characteristics and outcomes. Our results can be valuable for future trial constructions and customized treatment.

Novel Therapeutic Devices in Heart Failure.

Heart failure (HF) constitutes a significant clinical problem and is associated with a sizeable burden for the healthcare system. Numerous novel techniques, including device interventions, are investigated to improve clinical outcome. A review of the most notable currently studied devices targeting pathophysiological processes in HF was performed. Interventions regarding autonomic nervous system imbalance, i.e., baroreflex activation therapy; vagus, splanchnic and cardiopulmonary nerves modulation; respiratory disturbances, i.e., phrenic nerve stimulation and synchronized diaphragmatic therapy; decongestion management, i.e., the Reprieve system, transcatheter renal venous decongestion system, Doraya, preCardia, WhiteSwell and Aquapass, are presented. Each segment is divided into subsections: potential pathophysiological target, existing evidence and weaknesses or unexplained issues. Novel therapeutic devices represent great potential in HF therapy management; however, further evidence is necessary to fully evaluate their utility.

Novel Biomarkers of Renal Dysfunction and Congestion in Heart Failure.

Heart failure is a major public health problem and, despite the constantly emerging, new, effective treatments, it remains a leading cause of morbidity and mortality. Reliable tools for early diagnosis and risk stratification are crucial in the management of HF. This explains a growing interest in the development of new biomarkers related to various pathophysiological mechanisms of HF. In the course of this review, we focused on the markers of congestion and renal dysfunction in terms of their interference with cardiovascular homeostasis. Congestion is a hallmark feature of heart failure, contributing to symptoms, morbidity, and hospitalizations of patients with HF and has, therefore, become a therapeutic target in AHF. On the other hand, impaired renal function by altering the volume status contributes to the development and progression of HF and serves as a marker of an adverse clinical outcome. Early detection of congestion and an adequate assessment of renal status are essential for the prompt administration of patient-tailored therapy. This review provides an insight into recent advances in the field of HF biomarkers that could be potentially implemented in diagnosis and risk stratification of patients with HF.