Inflammation scores based on C-reactive protein and albumin predict mortality in hospitalized older patients independent of the admission diagnosis.

Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.

Effect of SAcubitril/Valsartan on left vEntricular ejection fraction and on the potential indication for Implantable Cardioverter Defibrillator in primary prevention: the SAVE-ICD study.

PURPOSE: Sacubitril/valsartan has been associated with a positive reverse left ventricular remodelling in patients with heart failure with reduced ejection fraction (HFrEF). These patients may also benefit from an ICD implant. We aimed to assess EF improvement after 6 months of treatment with sacubitril/valsartan, evaluating when ICD as primary prevention was no longer indicated. METHODS: Multicentre, observational, prospective study enrolling all consecutive patients with HFrEF and EF ≤ 35% with an ICD as primary prevention and starting treatment with sacubitril/valsartan (NCT03935087). Resynchronization therapy and patients experiencing appropriate ICD therapies before sacubitril/valsartan were excluded. RESULTS: Two-hundred-and-thirty patients were enrolled (73.9% males, mean age 64.3 ± 12.1 years) After 6 months of treatment, a reduction in left ventricular end-diastolic and end-systolic volumes was noted and LVEF increased from 28.3 ± 5.6% to 32.2 ± 6.5% (p < 0.001). At 6 months, a non-ischemic aetiology of cardiomyopathy and a final dose of sacubitril/valsartan > 24/26 mg twice daily were associated with a higher probability of an absolute increase of > 5% in LVEF. A total of 5.3% of primary prevention patients still had an arrhythmic event in the first 6 months after treatment with sacubitril/valsartan started. CONCLUSIONS: Sacubitril/valsartan improves systolic function in HFrEF, mainly due to reverse left ventricular remodelling. Improvement in EF after 6 months of treatment could help prevent ICD implantation in nearly one out of four patients, with important clinical and economic implications. However, the risk of sudden cardiac death in this recovered HFrEF population has not been thoroughly studied, and the present data should be interpreted only as hypothesis-generating.

Risk of syncopal recurrences in patients treated with permanent pacing for bradyarrhythmic syncope: role of correlation between symptoms and electrocardiogram findings.

AIMS: To evaluate the risk of syncopal recurrences after pacemaker implantation in a population of patients with syncope of suspected bradyarrhythmic aetiology. METHODS AND RESULTS: Prospective, multicentre, observational registry enrolling 1364 consecutive patients undergoing pacemaker implantation for syncope of bradyarrhythmic aetiology (proven or presumed). Before pacemaker implantation, all patients underwent a cardiac work-up in order to establish the bradyarrhythmic aetiology of syncope. According to the results of the diagnostic work-up, patients were divided into three groups: Group A, patients in whom a syncope-electrocardiogram (ECG) correlation was established (n = 329, 24.1%); Group B, those in whom clinically significant bradyarrhythmias were detected without a documented syncope-ECG correlation (n = 877, 64.3%); and Group C, those in whom bradyarrhythmias were not detected and the bradyarrhythmic origin of syncope remained presumptive (n = 158, 11.6%). During a median follow-up of 50 months, 213 patients (15.6%) reported at least one syncopal recurrence. Patients in Groups B and C showed a significantly higher risk of syncopal recurrences than those in Group A [hazard ratios (HRs): 1.60 and 2.66, respectively, P < 0.05]. Failure to establish a syncope-ECG correlation during diagnostic work-up before pacemaker implantation was an independent predictor of syncopal recurrence on multivariate analysis (HR: 1.90; P = 0.002). CONCLUSION: In selecting patients with syncope of suspected bradyarrhythmic aetiology for pacemaker implantation, establishing a correlation between syncope and bradyarrhythmias maximizes the efficacy of pacing and reduces the risk of syncopal recurrences.

Atrial High-Rate Episodes in Elderly Patients: The Anticoagulation Therapy Dilemma.

Atrial fibrillation (AF) has been associated with higher morbidity and mortality rates, especially in older patients. Subclinical atrial fibrillation (SCAF) is defined as the presence of atrial high-rate episodes (AHREs) > 190 bpm for 10 consecutive beats > 6 min and <24 h, as detected by cardiac implanted electronic devices (CIEDs). The selection of eligible patients for anticoagulation therapy among elderly individuals with AHREs detected through CIEDs remains a contentious issue. The meta-analysis of ARTESiA and NOAH-AFNET 6 clinical trials revealed that taking Edoxaban or Apixaban as oral anticoagulation therapy can reduce the risk of stroke by approximately 32% while increasing the risk of major bleeding by approximately 62%. However, it is still unclear which are, among patients with SCAF, those who can take the highest net clinical benefit from anticoagulant therapy. The present review summarizes the current evidence on this intriguing issue and suggests strategies to try to better stratify the risk of stroke and systemic embolism in patients with AHREs. We propose incorporating some parameters including chronic kidney disease (CKD), obesity, enlarged left atrial volume, the efficacy in blood pressure management, and frailty into the traditional CHA2DS2-VASc score. Future trials will be needed to verify the clinical usefulness of the proposed prognostic score mainly in the view of a personalized therapeutic approach in patients with SCAF.

Heart rate variability and autonomic nervous system imbalance: Potential biomarkers and detectable hallmarks of aging and inflammaging.

The most cutting-edge issue in the research on aging is the quest for biomarkers that transcend molecular and cellular domains to encompass organismal-level implications. We recently hypothesized the role of Autonomic Nervous System (ANS) imbalance in this context. Studies on ANS functions during aging highlighted an imbalance towards heightened sympathetic nervous system (SNS) activity, instigating a proinflammatory milieu, and attenuated parasympathetic nervous system (PNS) function, which exerts anti-inflammatory effects via the cholinergic anti-inflammatory pathway (CAP) and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. This scenario strongly suggests that ANS imbalance can fuel inflammaging, now recognized as one of the most relevant risk factors for age-related disease development. Recent recommendations have increasingly highlighted the need for actionable strategies to improve the quality of life for older adults by identifying biomarkers that can be easily measured, even in asymptomatic individuals. We advocate for considering ANS imbalance as a biomarker of aging and inflammaging. Measures of ANS imbalance, such as heart rate variability (HRV), are relatively affordable, non-invasive, and cost-effective, making this hallmark easily diagnosable. HRV gains renewed significance within the aging research landscape, offering a tangible link between pathophysiological perturbations and age-related health outcomes.

Prevalence and predictors of subclinical atrial fibrillation in hospitalized older adults.

Subclinical atrial fibrillation (SCAF) is associated with an increased risk of clinical AF, major cardiovascular events and death. Short-term evidence on SCAF in older populations is scarce, especially in the hospital setting. We performed a cross-sectional study on 60 multimorbid older consecutive patients (aged 80+) admitted to an Internal Medicine and Geriatrics Unit for acute medical diseases with no history of AF, in order to investigate prevalence and predictors of SCAF. Portable ECG monitoring was placed on admission and ECG recording lasted for 5 days. Mean age: 85.7±4.9 years. Female prevalence: 58.3%. High burden of comorbidities: 87.9%. All enrolled patients had CHA2DS2-VASc score ≥3. SCAF was detected in 16 patients (26.7%) and 11 patients (18.4%) had at least a SCAF episode lasting 6 minutes or longer. No clinical, laboratory and echocardiographic parameters predicted SCAF. Patients with ≥2004 supraventricular ectopic beats/24h (SVEBs/24h) had a 6-fold higher prevalence of SCAF than patients with <411 SVEBs/24h (p=0.038). Time to first SCAF episode was within 3 days of ECG recording in all enrolled patients. SCAF is highly prevalent in older adults hospitalized for acute diseases. This finding may affect clinical management and prognosis. Our study could foster larger multicenter studies in similar settings.

Causes of syncopal recurrences in patients treated with permanent pacing for bradyarrhythmic syncope: Findings from the SYNCOPACED registry.

BACKGROUND: Few studies have examined the causes of syncope/collapse recurrences in patients with a previously implanted pacemaker for bradyarrhythmic syncope. OBJECTIVE: The purpose of this study was to assess the causes of syncope/collapse recurrences after pacemaker implantation for bradyarrhythmic syncope in a large patient population. METHODS: The SYNCOpal recurrences in patients treated with permanent PACing for bradyarrhythmic syncope (SYNCOPACED) registry was a prospective multicenter observational registry enrolling 1364 consecutive patients undergoing pacemaker implantation for bradyarrhythmic syncope. During follow-up, the time to the first syncope/collapse recurrence was recorded. Patients with syncope/collapse recurrences underwent a predefined diagnostic workup aimed at establishing the mechanism of syncope/collapse. RESULTS: During a median follow-up of 50 months, 213 patients (15.6%) reported at least 1 syncope/collapse recurrence. The risk of syncope/collapse recurrence was highest in patients who underwent implantation for cardioinhibitory vasovagal syncope (26.4%), followed by unexplained syncope and chronic bifascicular block (21.5%), cardioinhibitory carotid sinus syndrome (17.2%), atrial fibrillation needing pacing (15.5%), atrioventricular block (13.6%), and sinus node disease (12.5%) (P = .017). The most frequent cause of syncope/collapse recurrence was reflex syncope (27.7%), followed by orthostatic hypotension (26.3%), pacemaker or lead malfunction (5.6%), structural cardiac disease (5.2%), and atrial and ventricular tachyarrhythmias (4.7% and 3.8%, respectively). In 26.8% of cases, the mechanism of syncope/collapse remained unexplained. CONCLUSION: In patients receiving a pacemaker for bradyarrhythmic syncope, reflex syncope and orthostatic hypotension are the most frequent mechanisms of syncope/collapse recurrence after implantation. Pacing system malfunction, structural cardiac diseases, and tachyarrhythmias are rare mechanisms. The mechanism remains unexplained in >25% of patients.