Vanetti M, Visca D, Ardesi F
… +5 more, Zappa M, Pessano S, Pignatti P, Fabbri LM, Spanevello A
Eur J Intern Med
· 2026 Jun · PMID 42342518
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BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a biomarker of systemic inflammation that has been investigated in different chronic diseases. However, its role as biomarker of severity in patients with stable ch...BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a biomarker of systemic inflammation that has been investigated in different chronic diseases. However, its role as biomarker of severity in patients with stable chronic obstructive pulmonary disease (COPD), and particularly its association with cardiovascular risk, remains unclear. This retrospective study aimed to evaluate whether a higher NLR (HNLR) is associated with worse disease control and increased cardiovascular risk compared to a lower NLR (LNLR) in stable COPD. METHODS: Data from inpatients admitted to a pulmonary rehabilitation center between 2021 and 2024 were analyzed. Patients were divided in two groups (HNLR ≥ 2.26 and LNLR < 2.26) based on the NLR threshold best associated with severe exacerbations according to ROC analysis. Comparison between groups and multivariate logistic regression analysis were performed. Cardiovascular risk was assessed using the European Society of Cardiology-recommended algorithm. RESULTS: A total of 247 patients were included. The HNLR group included a significantly (p < 0.05) higher number of patients with severe exacerbations in the previous year, lower forced expiratory volume in 1 second, higher residual volume, and increased partial pressure of carbon dioxide in arterial blood than the LNLR group. Chronic respiratory failure, atrial fibrillation and lung cancer were significantly more frequent in the HNLR group, and these patients had a significantly higher 10-year cardiovascular risk. CONCLUSION: Our data suggest that NLR used together with other clinical and functional parameters could represent a useful biomarker in stable COPD, associated with increased disease severity and higher estimated 10-year cardiovascular risk.
Nashtar MA, Salemdawod M, Sehovic H
… +9 more, Garipoglu G, Ödemis B, Tzalavras A, Steinmetz M, Canbay A, Özçürümez M, Varnavas V, Patsalis PC, Katsounas A
Eur J Intern Med
· 2026 Jun · PMID 42342517
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BACKGROUND/OBJECTIVES: Patients with heart failure (HF) are particularly vulnerable to systemic infection; however, the combined impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral bur...BACKGROUND/OBJECTIVES: Patients with heart failure (HF) are particularly vulnerable to systemic infection; however, the combined impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral burden, and emerging viral variants on outcomes in established HF remains incompletely defined. We investigated the independent association between SARS-CoV-2 infection and adverse in-hospital outcomes and evaluated the prognostic relevance of viral load and variant-specific patterns. METHODS: 2826 consecutive patients hospitalized with documented HF between March 2020 and October 2024 were analyzed. SARS-CoV-2 infection was confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) from nasopharyngeal swabs. Primary outcomes were cardiac decompensation, intensive care unit (ICU) admission, invasive mechanical ventilation, and in-hospital mortality. Secondary outcomes included total and ICU length of stay. Univariable and multivariable regression models were applied to assess associations with clinical outcomes. Viral burden was approximated using median and lowest cycle threshold (Ct) values. RESULTS: SARS-CoV-2 infection (n = 324, 11.5%) was independently associated with cardiac decompensation (adjusted OR 1.66), ICU admission (adjusted OR 1.95), invasive ventilation (adjusted OR 2.76), and in-hospital mortality (adjusted OR 2.60; all p < 0.01). Infection was further associated with prolonged hospitalization (+9.4 days) and ICU stay (+9.1 days; both p < 0.001). Among infected patients, lower median Ct values were independently associated with mortality (adjusted OR per unit increase 0.90; p = 0.0388). Earlier variants demonstrated substantially higher mortality and ICU utilization compared with Omicron sublineages. CONCLUSIONS: In hospitalized HF patients, SARS-CoV-2 infection independently increased mortality and healthcare resource utilization. Persistent viral burden and variant-specific heterogeneity further refined risk stratification, underscoring the sustained vulnerability of this high-risk population.
Eur J Intern Med
· 2026 Jun · PMID 42342516
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Epicardial adipose tissue (EAT) is gaining visibility as an imaging biomarker, yet its clinical maturity remains limited. The recent exchange between Angeli et al. and Momot et al. highlights persistent gaps in measureme...Epicardial adipose tissue (EAT) is gaining visibility as an imaging biomarker, yet its clinical maturity remains limited. The recent exchange between Angeli et al. and Momot et al. highlights persistent gaps in measurement standardisation, methodological transparency, and reproducibility-prerequisites for any translational advance. Mechanistic plausibility alone is insufficient: the key question is whether EAT adds meaningful prognostic value beyond established metabolic and imaging markers, and whether such gains are calibrated and clinically actionable. Phenotype‑specific signals, such as in atrial fibrillation, are intriguing but not definitive. Emerging indices of tissue "quality", including density and perivascular fat attenuation, require validated thresholds and outcome‑based evidence. The field now needs pragmatic trials testing EAT‑ or FAI‑guided strategies to determine whether adipose tissue imaging can genuinely improve patient outcomes.
Inotai A, Nagy D, Kovács G
… +7 more, Kovács S, Dóczi T, Nagy B, Tikhonoff V, Esposti LD, Kaló Z, Borghi C
Eur J Intern Med
· 2026 Jun · PMID 42323218
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BACKGROUND: Increasing evidence links elevated serum uric acid levels to adverse cardiorenal outcomes. To date, limited data exist on whether the benefits of urate-lowering therapies (ULTs) depend on timely treatment ini...BACKGROUND: Increasing evidence links elevated serum uric acid levels to adverse cardiorenal outcomes. To date, limited data exist on whether the benefits of urate-lowering therapies (ULTs) depend on timely treatment initiation and sustained adherence in patients at high cardiovascular risk. METHODS: An economic evaluation was conducted, based on a simulation model populated by Italian real-world patient-level data from the Uric Acid Right for Heart Health (URRAH) cohort to evaluate long-term cardiovascular, renal, and economic outcomes associated with timely allopurinol use. 10,000 patients with hyperuricemia (serum uric acid >5.6 mg/dL) and elevated cardiovascular risk were simulated over a 20-year time horizon. Timely initiation of allopurinol (before the first gout flare) was compared with treatment initiated only after symptomatic disease onset. Scenarios reflecting current and improved adherence to ULTs were assessed. Outcomes included major adverse cardiovascular events, end-stage renal disease onset, and economic outcomes from the payer's perspective. RESULTS: According to our model, timely initiation of allopurinol was associated with modest but consistent health gain (0.04 quality adjusted life years) including reductions in gout flares, cardiovascular- and renal endpoints. Timely allopurinol initiation was cost-saving and, from a health economic perspective, dominant over current practice. Improved ULT adherence amplified these benefits. CONCLUSION: Our hypothesis-generating research suggests that, in hyperuricemic patients at high cardiovascular risk, the potential benefits of allopurinol also depend on timely initiation and sustained adherence. While these findings do not constitute evidence of causal clinical benefit, they support a broader cardiorenal clinical approach to hyperuricemia management that extends beyond gout prevention.
Eur J Intern Med
· 2026 Jun · PMID 42323217
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For more than five decades, patients with the same condition have received markedly different care depending on which clinician they happen to see. This unwarranted clinical variation has been documented in nearly every...For more than five decades, patients with the same condition have received markedly different care depending on which clinician they happen to see. This unwarranted clinical variation has been documented in nearly every field of medicine, and decades of standardization efforts have not eliminated it. Artificial intelligence (AI) seemed to promise a fix: an algorithm would give the same answer every time, and randomized trials showed that, on average, AI assistance improved clinician performance. Yet clinicians use these tools far less than expected. The main barrier is now recognized as behavioral, not technical: different clinicians respond to the same AI recommendation in very different ways, and the algorithm's performance does little to predict who will follow it. This narrative review synthesizes the evidence on this obstacle through the perspective of human behavior and attitudes in decision-making. We show that the current challenges of AI deployment are essentially the same challenge of variation in clinical decision-making, now carried over into variation in how clinicians use AI. This produces two opposing errors: accepting an AI recommendation when it is wrong and ignoring it when it is correct. We then describe how these behavioral signals can be fed back into the AI deployment architecture to guide clinicians toward more appropriate use. Every day, across thousands of hospital wards and outpatient clinics, a quiet battle is fought between clinicians and the AI systems deployed to assist them. It is not a battle anyone declared, and neither side fully understands the other. Clinicians of varying age, experience, and psychological disposition encounter algorithmic recommendations with varying feelings, resulting in accepting them, overriding them, or simply ignoring them. The algorithms, on their part, maintain the provision of alerts and recommendations, oblivious to the wishes and needs of the clinicians they serve. The casualties are the patients, who expect consistent, evidence-based care but instead receive whatever combination of random human-algorithm interaction happened to prevail on that particular day, with that particular physician.
Sainaghi PP, Rizzi M, Tonello S
… +14 more, Vincenzi F, Primatesta M, Dianzani U, Rolla R, Tillio PA, Pirisi M, Lupia E, Franceschi F, Somma SD, Muiesan ML, Biolo G, Avanzi GC, Castello L, Delivida-NeedSpeed Study Group
Eur J Intern Med
· 2026 Jun · PMID 42321134
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BACKGROUND: Early prognostic stratification of septic patients at hospital admission is challenging, especially in the elderly. Considering the well-known immunomodulatory effects of vitamin D and its common deficiency a...BACKGROUND: Early prognostic stratification of septic patients at hospital admission is challenging, especially in the elderly. Considering the well-known immunomodulatory effects of vitamin D and its common deficiency among elderly, we aimed to evaluate if vitamin D plasma levels (25(OH)D) at hospital admission could be a prognostic biomarker in septic patients. METHODS: Secondary analysis of data and samples from the multicenter Need-Speed trial, a multicenter study involving the emergency and internal medicine wards of five Italian hospitals. 1132 consecutive patients admitted to hospital with suspected sepsis were enrolled. 859 were confirmed to have sepsis at the end of the diagnostic work-up and 829 patients were included in the analysis. 25(OH)D at admission was measured using an automated chemiluminescence assay. RESULTS: Among the 829 patients included (median age 81 years [IQR: 72-87]), severe hypovitaminosis D was observed (median 11.2 ng/mL [IQR: 8.0-19.4]). At univariate analysis, baseline 25(OH)D levels were significantly lower in patients who died at 30 and 90 days and higher among patients discharged alive within 15 days (p < 0.05). Multivariate models confirmed 25(OH)D as an independent predictor of 90-day mortality and of discharge alive at 15 days (p < 0.05). Moreover, a 25(OH)D threshold of 12 ng/mL independently predicted both survival at 90 days (OR: 0.5961 [0.4068-0.8735]) and discharge alive at 15 days (OR: 1.6055 [1.1738-2.1960]). CONCLUSIONS: Lower 25(OH)D levels were independently associated with poorer clinical outcomes in older patients with sepsis. Therefore, hypovitaminosis D assessment may provide prognostic value beyond validated risk stratification tools, warranting prospective validation.
Carlucci P, Marozzi MS, Corvasce F
… +7 more, Noviello S, Spataro F, Desantis V, Montagnani M, Ria R, Cicco S, Vacca A
Eur J Intern Med
· 2026 Jun · PMID 42321133
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BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by eosinophilic inflammation and potential cardiovascular involvement. The relationship between eosinophil burd...BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by eosinophilic inflammation and potential cardiovascular involvement. The relationship between eosinophil burden and subclinical cardiopulmonary vascular dysfunction remains unclear. METHODS: 27 EGPA patients were evaluated. Peripheral eosinophil counts (PEC) at diagnosis were analysed in relation to echocardiographic markers of pulmonary vascular load and right ventricular-pulmonary artery (RV-PA) coupling. Patients initiating anti-IL-5/R therapy (mepolizumab or benralizumab) underwent echocardiography assessing pulmonary artery systolic pressure (PAPs), tricuspid annular plane systolic excursion (TAPSE), TAPSE/PAPs ratio, and tricuspid regurgitation velocity (TRV) at diagnosis, treatment initiation (Baseline), and 24-month follow-up (T24) to assess temporal changes. Patients were stratified by median PEC. Multivariable regression and ROC analyses were performed. RESULTS: At Baseline, 33% of patients exhibited elevated PAPs (>25 mmHg) despite absence of clinical pulmonary hypertension. Higher PEC were associated with increased PAPs (p = 0.04) and reduced TAPSE/PAPs ratio (p = 0.03). Pulmonary vascular load worsened from diagnosis to T0 and improved after anti-IL-5/R therapy, with PAPs decreasing from 27.5 [18.0-30.0] mmHg to 18.0 [11.75-20.0] mmHg (p = 0.002) and TRV from 2.30 [1.65-2.48] to 1.80 [1.28-1.92] m/s (p = 0.005). Baseline PEC moderately discriminated patients with intermediate/high echocardiographic probability of pulmonary hypertension (AUC 0.751). CONCLUSION: Elevated PEC may signal early pulmonary vascular dysfunction and RV-PA uncoupling EGPA, which may be partially reverted with anti-IL-5/R therapy. These findings support the importance of early cardiovascular surveillance in eosinophil-rich EGPA.
Gragnano F, Artana C, Carrara G
… +18 more, Sacco A, Montalto C, Mennuni M, Zuin M, D'Ascenzo F, Nevo FD, De Sio V, De Luca L, Spoto G, Musumeci G, Oliva F, De Ferrari GM, Grosseto D, Calabrò P, Patti G, Campo G, Leonardi S, ATBV Quality Matters Investigators
Eur J Intern Med
· 2026 Jun · PMID 42321132
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BACKGROUND: Actionable quality gaps persist in low-density lipoprotein cholesterol (LDL-C) management after acute myocardial infarction (AMI). We aimed to quantify diagnostic and therapeutic inertia in LDL-C management a...BACKGROUND: Actionable quality gaps persist in low-density lipoprotein cholesterol (LDL-C) management after acute myocardial infarction (AMI). We aimed to quantify diagnostic and therapeutic inertia in LDL-C management after discharge in a real-world AMI population with verified and quantified consecutive inclusion. METHODS: We conducted a quality improvement audit of patients discharged alive with a primary diagnosis of AMI. Consecutiveness was quantified using the consecutive index (e.g., the ratio of included patients with available 6-month follow-up information to the total AMI discharges). Diagnostic inertia was defined as no evidence of LDL-C measurement post-discharge. Therapeutic inertia was defined as LDL-C ≥ 55 mg/dL in the absence of optimal lipid-lowering therapy among patients with at least one post-discharge LDL-C measurement. A multivariable model was developed to identify risk-adjusted probability of LDL-C target achievement at follow-up. RESULTS: Among 3490 AMI patients, 3130 had at least a follow-up assessment after discharge. At six months, 2603 patients had available information on vital status, follow-up assessment, and post-discharge LDL-C assessment status (consecutive index: 74.6% [95% CI: 73.1-76.0%]). Diagnostic inertia occurred in 19.3% (95% CI: 17.8-20.9%) and therapeutic inertia in 38.1% (95% CI: 35.7-40.6%). In a multivariable model, the explained variance was modest (R=14.4%; 95% CI: 12.0-18.2%). CONCLUSIONS: In a contemporary cohort including approximately 75% of patients surviving hospitalization for AMI, one in five patients did not undergo LDL-C testing during follow-up and two in five did not receive adequate lipid-lowering therapy despite failing to reach guideline-recommended targets. These findings highlight a substantial opportunity for structured quality improvement initiatives targeting LDL-C management after AMI.
Fumagalli S, Biagioli M, Niccolini M
… +13 more, Tariello A, Berni E, Davino D, De Angelis V, Santamaria E, Mengozzi A, Di Serio C, Spanalatte G, Da Silva Nakano DM, Cagnoni C, De Grazia D, Diemberger I, Virdis A
Eur J Intern Med
· 2026 Jun · PMID 42321131
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INTRODUCTION: Atrial fibrillation (AF) is frequently diagnosed in older subjects, being often associated with frailty. In AF patients, depression is important, increasing mortality when heart failure is present, reducing...INTRODUCTION: Atrial fibrillation (AF) is frequently diagnosed in older subjects, being often associated with frailty. In AF patients, depression is important, increasing mortality when heart failure is present, reducing adherence to therapy, and contributing to dementia development. Aim of this study was to identify the variables associated with depressive symptoms in older subjects with persistent AF. METHODS: All consecutive patients undergoing electrical cardioversion of the arrhythmia were enrolled and evaluated with the Comprehensive Geriatric Assessment (CGA). In particular, the Mini-Mental State Examination (MMSE) explored neurocognitive profile, the Geriatric Depression Scale (15-item version; GDS) depressive symptoms, and the Short Physical Performance Battery (SPPB) physical performance. Interleukine-6 (IL-6) levels were determined with ELISA kits. RESULTS: Overall, 258 patients were enrolled (age: 78±8 years; women: 41.1%; CHADS-VA: 3.5±1.4). Hypertension was highly prevalent (81.8%); left ventricular ejection fraction was normal (58±12%), and heart rate adequately controlled (80±17 bpm). MMSE, GDS and SPPB were, respectively, 27.9±2.5, 3.3±2.9 and 8.7±2.7. IL-6 concentration, available in 59.3% of patients, was 4.3±3.5 pg/mL. A multivariate analysis model showed that depressive symptoms were directly associated with CHADS-VA (p=0.019), and negatively with SPPB (p<0.001). When IL-6 was available, the correlation with SPPB persisted (p<0.001), the link with CHADS-VA disappeared (p=0.147), and was replaced by that with cytokine levels (p=0.011). CONCLUSIONS: Depressive symptoms in older AF patients are related to clinical complexity and to physical performance. IL-6, expression of chronic inflammation, has a significant association with GDS. These findings confirm that AF is a marker of cardiovascular aging and frailty.
Eur J Intern Med
· 2026 Jun · PMID 42315459
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Severe acquired brain injury (sABI) requires coordinated management across the acute and post-acute phases to optimize recovery and long-term outcomes. We read with great interest the recent study by Grifoni and colleagu...Severe acquired brain injury (sABI) requires coordinated management across the acute and post-acute phases to optimize recovery and long-term outcomes. We read with great interest the recent study by Grifoni and colleagues, which demonstrated the benefits of an interdisciplinary co-management model between the Neuro-Intensive Care Unit and the Intensive Neurorehabilitation Unit, resulting in reduced length of stay, fewer emergency transfers, lower mortality, and improved rehabilitation allocation. Building upon these findings, we highlight the potential importance of systematically considering Critical Illness Polyneuropathy and Myopathy (CIPNM), a common but frequently underrecognized complication of critical illness. CIPNM is a major cause of intensive care unit-acquired weakness and has been associated with prolonged mechanical ventilation, impaired functional recovery, increased morbidity, and higher mortality. Previous studies have reported a high prevalence of CIPNM among patients with sABI, particularly in those with disorders of consciousness admitted to rehabilitation settings. Because no specific pharmacological treatment is currently available, early recognition remains crucial to guide patient management, optimize rehabilitation strategies, and improve functional outcomes. Greater awareness of CIPNM within integrated neurocritical and neurorehabilitation pathways may contribute to more accurate prognostic assessment and ultimately enhance the quality of care delivered to this vulnerable patient population.
Eur J Intern Med
· 2026 Jun · PMID 42309944
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Coronary artery disease includes obstructive epicardial stenosis and ischemia with non-obstructive coronary arteries driven by microvascular dysfunction. Population screening is limited by the invasiveness and cost of cu...Coronary artery disease includes obstructive epicardial stenosis and ischemia with non-obstructive coronary arteries driven by microvascular dysfunction. Population screening is limited by the invasiveness and cost of current coronary tests. Retinal imaging provides accessible biomarkers that reflect both epicardial atherosclerosis and coronary microvascular dysfunction, thereby supporting risk stratification and endotype differentiation in coronary artery disease. The aim was to summarize links between retinal measures and coronary anatomy, physiology, and clinical phenotypes to inform risk assessment in cardiology. Narrative synthesis of studies linking retinal structure and perfusion (fundus metrics, OCT/OCTA vessel density in superficial/deep plexuses, foveal avascular zone, choroidal indices) with angiographic burden, functional indices of ischemia (CFR, IMR, PET-derived myocardial flow reserve), and clinical endotypes (obstructive CAD, INOCA, slow coronary flow). Retinal microvascular alterations-narrower arterioles, wider venules, and lower arteriovenous ratio-predict CAD, myocardial infarction, stroke, and cardiovascular mortality; OCT angiography frequently demonstrates reduced vessel density and enlarged FAZ correlating with stenosis burden, multivessel disease, and systemic risk profiles. In CMD/INOCA, patterns consistent with generalized microvascular dysfunction are observed, including sex-specific differences (e.g., venular calibre changes in women with microvascular angina) and associations between retinal metrics and myocardial flow abnormalities such as slow coronary flow. Retinal imaging yields accessible biomarkers reflecting systemic vascular alterations associated with both epicardial coronary atherosclerosis and coronary microvascular dysfunction and may assist risk stratification and endotype differentiation in CAD; however, clinical translation is constrained by device/segmentation heterogeneity, comorbidity confounding, small cross-sectional designs, and limited integration with quantitative coronary physiology. Standardized, multicentre longitudinal studies and AI-enhanced analytics are needed to establish prognostic value and clinical utility.
Santacroce G, Lenti MV, Lo Bello A
… +1 more, Di Sabatino A
Eur J Intern Med
· 2026 Jun · PMID 42309943
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Immune-mediated gastrointestinal disorders, including eosinophilic oesophagitis, coeliac disease, and inflammatory bowel disease, are increasingly managed with therapeutic goals that extend beyond symptom control. Among...Immune-mediated gastrointestinal disorders, including eosinophilic oesophagitis, coeliac disease, and inflammatory bowel disease, are increasingly managed with therapeutic goals that extend beyond symptom control. Among these, the concept of disease clearance - defined as remission across multiple domains of disease activity - is gaining attention and may be applicable across these disorders. However, important challenges remain, including lack of standardisation, uncertain long-term clinical relevance, and limited evidence regarding feasibility and cost-effectiveness in routine practice. Moreover, the term clearance may itself be misleading in chronic immune-mediated diseases, where current therapies suppress inflammation rather than eradicate the underlying pathogenic process. Future therapeutic strategies will likely move beyond inflammation control towards immune reprogramming, incorporating additional dimensions such as barrier and molecular healing. In this evolving scenario, what currently represents an aspirational construct may progressively approach a clinically meaningful therapeutic reality.
Boriani G, Imberti JF, Valenti A
… +3 more, Vitolo M, Lopez-Fernandez T, Mei DA
Eur J Intern Med
· 2026 Jun · PMID 42297696
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BACKGROUND: Atrial fibrillation (AF) is a frequent complication of Bruton's tyrosine kinase inhibitor (BTKi) therapy, yet the proportion of asymptomatic AF events in this setting remains poorly defined. OBJECTIVES: We ai...BACKGROUND: Atrial fibrillation (AF) is a frequent complication of Bruton's tyrosine kinase inhibitor (BTKi) therapy, yet the proportion of asymptomatic AF events in this setting remains poorly defined. OBJECTIVES: We aimed to estimate the proportion of asymptomatic AF among patients who develop AF during BTKi treatment and to explore factors influencing its detection. METHODS: We conducted a systematic literature review and meta-analysis following international guidelines. Studies reporting AF occurrence and symptom status according to the Common Terminology Criteria for Adverse Events (CTCAE) in BTKi-treated patients with hematologic malignancies were included. Asymptomatic AF was defined as CTCAE grade 1. RESULTS: Twenty-three studies including 2839 patients were analyzed. Overall, 292 AF events were reported, yielding a pooled AF prevalence of 9% (95% CI: 6-13%; I² = 77%). Among these, 49 events were asymptomatic, corresponding to a pooled proportion of 14% (95% CI: 8-24%) with low heterogeneity (I² = 23%). Subgroup analyses demonstrated a significantly higher proportion of asymptomatic AF in the study employing extended rhythm monitoring with a 7-day patch (64%; 95% CI: 38-84%), compared with health care record-based ascertainment or scheduled electrocardiographic evaluation (p for subgroup differences = 0.001). Age, sex, duration of follow-up, BTKi type, and study design were not significantly associated with the proportion of asymptomatic AF. CONCLUSIONS: Approximately one in seven AF episodes occurring during BTKi therapy are asymptomatic. This proportion is influenced by the method of rhythm monitoring and may be higher when prolonged monitoring strategies are employed.