The relation between vascular risk factors and flow in cerebral perforating arteries. A 7 Tesla MRI study.

INTRODUCTION: Cerebral perforating arteries provide blood supply to the deep regions of the brain. Recently, it became possible to measure blood flow velocity and pulsatility in these small arteries. It is unknown if vascular risk factors are related to these measures. METHODS: We measured perforating artery flow with 2D phase contrast 7 Tesla MRI at the level of the centrum semiovale (CSO) and the basal ganglia (BG) in seventy participants from the Heart Brain Connection study with carotid occlusive disease (COD), vascular cognitive impairment (VCI), or no actual cerebrovascular disease. Vascular risk factors included hypertension, diabetes, hyperlipidemia and smoking. RESULTS: No consistent relations were found between any of the vascular risk factors and either flow velocity or flow pulsatility, although there was a relation between lower diastolic blood pressure and higher pulse pressure and higher cerebral perforator pulsatility (p=0,045 and p=0,044, respectively) at the BG level. Results were similar in stratified analyses for patients with and without a history of cardiovascular disease, or only COD or VCI. CONCLUSION: We conclude that, cross-sectionally, cerebral perforating artery flow velocity and pulsatility are largely independent of the presence of common vascular risk factors in a population with a mixed vascular burden.

Lower cerebral blood flow predicts cognitive decline in patients with vascular cognitive impairment.

INTRODUCTION: Chronic cerebral hypoperfusion is one of the assumed pathophysiological mechanisms underlying vascular cognitive impairment (VCI). We investigated the association between baseline cerebral blood flow (CBF) and cognitive decline after 2 years in patients with VCI and reference participants. METHODS: One hundred eighty-one participants (mean age 66.3 ± 7.4 years, 43.6% women) underwent arterial spin labeling (ASL) magnetic resonance imaging (MRI) and neuropsychological assessment at baseline and at 2-year follow-up. We determined the association between baseline global and lobar CBF and cognitive decline with multivariable regression analysis. RESULTS: Lower global CBF at baseline was associated with more global cognitive decline in VCI and reference participants. This association was most profound in the domain of attention/psychomotor speed. Lower temporal and frontal CBF at baseline were associated with more cognitive decline in memory. DISCUSSION: Our study supports the role of hypoperfusion in the pathophysiological and clinical progression of VCI. HIGHLIGHTS: Impaired cerebral blood flow (CBF) at baseline is associated with faster cognitive decline in VCI and normal aging. Our results suggest that low CBF precedes and contributes to the development of vascular cognitive impairment. CBF determined by ASL might be used as a biomarker to monitor disease progression or treatment responses in VCI.

A cluster of blood-based protein biomarkers associated with decreased cerebral blood flow relates to future cardiovascular events in patients with cardiovascular disease.

Biological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters associated with lower CBF in patients with CVD may explain underlying processes. In 428 participants (74% cardiovascular diseases; 26% reference participants) from the Heart-Brain Connection Study, we assessed the relationship between 92 plasma proteins from the Olink® cardiovascular III panel and normal-appearing grey matter CBF, using affinity propagation and hierarchical clustering algorithms, and generated a Biomarker Compound Score (BCS). The BCS was related to cardiovascular risk and observed cardiovascular events within 2-year follow-up using Spearman correlation and logistic regression. Thirteen proteins were associated with CBF (ρSpearman range: -0.10 to -0.19, pFDR-corrected <0.05), and formed one cluster. The cluster primarily reflected extracellular matrix organization processes. The BCS was higher in patients with CVD compared to reference participants (pFDR-corrected <0.05) and was associated with cardiovascular risk (ρSpearman 0.42, p < 0.001) and cardiovascular events (OR 2.05, p < 0.01). In conclusion, we identified a cluster of plasma proteins related to CBF, reflecting extracellular matrix organization processes, that is also related to future cardiovascular events in patients with CVD, representing potential targets to preserve CBF and mitigate cardiovascular risk in patients with CVD.

Lower haemoglobin concentrations are associated with impaired cognition in patients with carotid artery occlusion.

Background: Patients with carotid artery occlusion (CAO) are vulnerable to cognitive impairment (CI). Anaemia is associated with CI in the general population. We hypothesized that lower haemoglobin is associated with cognitive impairment (CI) in patients with CAO and that this association is accentuated by cerebral blood flow (CBF). Methods: 104 patients (mean age 66±8 years, 77% men) with complete CAO from the Heart-Brain Connection study were included. Anaemia was defined as haemoglobin < 12 g/dL for women and < 13 g/dL for men. Cognitive test results were standardized into z-scores (using a reference group) in four cognitive domains. Patients were classified as cognitively impaired when ≥ one domain was impaired. The association between lower haemoglobin and both cognitive domain z-scores and the presence of CI was assessed with adjusted (age, sex, education and ischaemic stroke) regression models. Total CBF (measured with phase contrast MRI) and the interaction term haemoglobin*CBF were additionally added to the analyses. Results: Anaemia was present in 6 (6%) patients and was associated with CI (RR 2.54, 95% CI 1.36; 4.76). Lower haemoglobin was associated with the presence of CI (RR per minus 1 g/dL haemoglobin 1.15, 95% CI 1.02; 1.30). This association was strongest for the attention-psychomotor speed domain (RR for impaired attention-psychomotor speed functioning per minus 1 g/dL haemoglobin 1.27, 95% CI 1.09;1.47) and ß for attention-psychomotor speed z-scores per minus 1 g/dL haemoglobin -0.19, 95% CI -0.33; -0.05). Adjustment for CBF did not affect these results and we found no interaction between haemoglobin and CBF in relation to cognition. Conclusion: Lower haemoglobin concentrations are associated with CI in patients with complete CAO, particularly in the domain attention-psychomotor speed. CBF did not accentuate this association. If validated in longitudinal studies, haemoglobin might be a viable target to prevent cognitive deterioration in patients with CAO.

Risk evaluation of cognitive impairment in patients with heart failure: A call for action.

Background: Cognitive impairment (CI) is common in patients with heart failure (HF) and impacts treatment adherence and other aspects of patient life in HF. Recognition of CI in patients with HF is therefore important. We aimed to develop a risk model with easily available patient characteristics, to identify patients with HF who are at high risk to be cognitively impaired and in need for further cognitive investigation. Methods & results: The risk model was developed in 611 patients ≥ 60 years with HF from the TIME-CHF trial. Fifty-six (9 %) patients had CI (defined as Hodkinson Abbreviated Mental Test ≤ 7). We assessed the association between potential predictors and CI with least-absolute-shrinkage-and-selection-operator (LASSO) regression analysis. The selected predictors were: older age, female sex, NYHA class III or IV, Charlson comorbidity index ≥ 6, anemia, heart rate ≥ 70 bpm and systolic blood pressure ≥ 145 mmHg. A model that combined these variables had a c-statistic of 0.70 (0.63-0.78). The model was validated in 155 patients ≥ 60 years with HF from the ECHO study. In the validation cohort 51 (33 %) patients had CI (defined as a Mini Mental State Exam ≤ 24). External validation showed an AUC of 0.56 (0.46-0.66). Conclusions: This risk model with easily available patient characteristics has poor predictive performance in external validation, which may be due to case-mix variation. These findings underscore the need for active screening and standardized assessment for CI in patients with HF.

A cluster of blood-based protein biomarkers reflecting coagulation relates to the burden of cerebral small vessel disease.

Biological processes underlying cerebral small vessel disease (cSVD) are largely unknown. We hypothesized that identification of clusters of inter-related bood-based biomarkers that are associated with the burden of cSVD provides leads on underlying biological processes. In 494 participants (mean age 67.6 ± 8.7 years; 36% female; 75% cardiovascular diseases; 25% reference participants) we assessed the relation between 92 blood-based biomarkers from the OLINK cardiovascular III panel and cSVD, using cluster-based analyses. We focused particularly on white matter hyperintensities (WMH). Nineteen biomarkers individually correlated with WMH ratio (r range: 0.16-0.27, Bonferroni corrected p-values <0.05), of which sixteen biomarkers formed one biomarker cluster. Pathway analysis showed that this biomarker cluster predominantly reflected coagulation processes. This cluster related also significantly to other cSVD manifestations (lacunar infarcts, microbleeds, and enlarged perivascular spaces), which supports generalizability beyond WMHs. To study possible causal effects of biological processes reflected by the cluster we performed a mediation analysis that showed a mediation effect of the cluster on the relation between age and WMH ratio (proportion mediated 17%), and hypertension and WMH-volume (proportion mediated 21%). In conclusion, we identified a cluster of blood-based biomarkers reflecting coagulation, that is related to manifestations of cSVD, corroborating involvement of coagulation abnormalities in the etiology of cSVD.

Non-Invasive Assessment of Damping of Blood Flow Velocity Pulsatility in Cerebral Arteries With MRI.

BACKGROUND: Damping of heartbeat-induced pressure pulsations occurs in large arteries such as the aorta and extends to the small arteries and microcirculation. Since recently, 7 T MRI enables investigation of damping in the small cerebral arteries. PURPOSE: To investigate flow pulsatility damping between the first segment of the middle cerebral artery (M1) and the small perforating arteries using magnetic resonance imaging. STUDY TYPE: Retrospective. SUBJECTS: Thirty-eight participants (45% female) aged above 50 without history of heart failure, carotid occlusive disease, or cognitive impairment. FIELD STRENGTH/SEQUENCE: 3 T gradient echo (GE) T1-weighted images, spin-echo fluid-attenuated inversion recovery images, GE two-dimensional (2D) phase-contrast, and GE cine steady-state free precession images were acquired. At 7 T, T1-weighted images, GE quantitative-flow, and GE 2D phase-contrast images were acquired. ASSESSMENT: Velocity pulsatilities of the M1 and perforating arteries in the basal ganglia (BG) and semi-oval center (CSO) were measured. We used the damping index between the M1 and perforating arteries as a damping indicator (velocity pulsatilityM1 /velocity pulsatilityCSO/BG ). Left ventricular stroke volume (LVSV), mean arterial pressure (MAP), pulse pressure (PP), and aortic pulse wave velocity (PWV) were correlated with velocity pulsatility in the M1 and in perforating arteries, and with the damping index of the CSO and BG. STATISTICAL TESTS: Correlations of LVSV, MAP, PP, and PWV with velocity pulsatility in the M1 and small perforating arteries, and correlations with the damping indices were evaluated with linear regression analyses. RESULTS: PP and PWV were significantly positively correlated to M1 velocity pulsatility. PWV was significantly negatively correlated to CSO velocity pulsatility, and PP was unrelated to CSO velocity pulsatility (P = 0.28). PP and PWV were uncorrelated to BG velocity pulsatility (P = 0.25; P = 0.68). PWV and PP were significantly positively correlated with the CSO damping index. DATA CONCLUSION: Our study demonstrated a dynamic damping of velocity pulsatility between the M1 and small cerebral perforating arteries in relation to proximal stress. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

Sex and Cardiovascular Function in Relation to Vascular Brain Injury in Patients with Cognitive Complaints.

BACKGROUND: Emerging evidence shows sex differences in manifestations of vascular brain injury in memory clinic patients. We hypothesize that this is explained by sex differences in cardiovascular function. OBJECTIVE: To assess the relation between sex and manifestations of vascular brain injury in patients with cognitive complaints, in interaction with cardiovascular function. METHODS: 160 outpatient clinic patients (68.8±8.5 years, 38% female) with cognitive complaints and vascular brain injury from the Heart-Brain Connection study underwent a standardized work-up, including heart-brain MRI. We calculated sex differences in vascular brain injury (lacunar infarcts, non-lacunar infarcts, white matter hyperintensities [WMHs], and microbleeds) and cardiovascular function (arterial stiffness, cardiac index, left ventricular [LV] mass index, LV mass-to-volume ratio and cerebral blood flow). In separate regression models, we analyzed the interaction effect between sex and cardiovascular function markers on manifestations of vascular brain injury with interaction terms (sex*cardiovascular function marker). RESULTS: Males had more infarcts, whereas females tended to have larger WMH-volumes. Males had higher LV mass indexes and LV mass-to-volume ratios and lower CBF values compared to females. Yet, we found no interaction effect between sex and individual cardiovascular function markers in relation to the different manifestations of vascular brain injury (p-values interaction terms > 0.05). CONCLUSION: Manifestations of vascular brain injury in patients with cognitive complaints differed by sex. There was no interaction between sex and cardiovascular function, warranting further studies to explain the observed sex differences in injury patterns.

Easier Said Than Done: Healthcare Professionals' Barriers to the Provision of Patient-Centered Primary Care to Patients with Multimorbidity.

Patient-centered care (PCC) has the potential to entail tailored primary care delivery according to the needs of patients with multimorbidity (two or more co-existing chronic conditions). To make primary care for these patients more patient centered, insight on healthcare professionals' perceived PCC implementation barriers is needed. In this study, healthcare professionals' perceived barriers to primary PCC delivery to patients with multimorbidity were investigated using a constructivist qualitative design based on semi-structured interviews with nine general and nurse practitioners from seven general practices in the Netherlands. Purposive sampling was used, and the interview content was analyzed to generate themes representing experienced barriers. Barriers were identified in all eight PCC dimensions (patient preferences, information and education, access to care, physical comfort, emotional support, family and friends, continuity and transition, and coordination of care). They include difficulties achieving mutual understanding between patients and healthcare professionals, professionals' lack of training and education in new skills, data protection laws that impede adequate documentation and information sharing, time pressure, and conflicting financial incentives. These barriers pose true challenges to effective, sustainable PCC implementation at the patient, organizational, and national levels. Further improvement of primary care delivery to patients with multimorbidity is needed to overcome these barriers.

Making care more patient centered; experiences of healthcare professionals and patients with multimorbidity in the primary care setting.

BACKGROUND: The present study describes how primary care can be improved for patients with multimorbidity, based on the evaluation of a patient-centered care (PCC) improvement program designed to foster the eight PCC dimensions (patient preferences, information and education, access to care, physical comfort, coordination of care, continuity and transition, emotional support, and family and friends). This study characterizes the interventions implemented in practice as part of the PCC improvement program and describes the experiences of healthcare professionals and patients with the resulting PCC delivery. METHODS: This study employed a mixed-methods design. Semi-structured interviews were conducted with nine general practitioners and nurse practitioners from seven primary care practices in Noord-Brabant, the Netherlands, that participated in the program (which included interventions and workshops). The qualitative interview data were examined using thematic analysis. A longitudinal survey was conducted with 138 patients with multimorbidity from these practices to assess perceived improvements in PCC and its underlying dimensions. Paired sample t tests were performed to compare survey responses obtained at a 1-year interval corresponding to program implementation. RESULTS: The PCC improvement program is described, and themes necessary for PCC improvement according to healthcare professionals were generated [e.g. Aligning information to patients' needs and backgrounds, adapting a coaching role]. PCC experiences of patients with multimorbidity improved significantly during the year in which the PCC interventions were implemented (t = 2.66, p = 0.005). CONCLUSION: This study revealed how primary PCC can be improved for patients with multimorbidity. It emphasizes the importance of investing in PCC improvement programs to tailor care delivery to heterogenous patients with multimorbidity with diverse care needs. This study generates new perspectives on care delivery and highlights opportunities for its improvement according to the eight dimensions of PCC for patients with multimorbidity in a primary care setting.

Cerebral blood flow and cognitive functioning in patients with disorders along the heart-brain axis: Cerebral blood flow and the heart-brain axis.

INTRODUCTION: We examined the role of hemodynamic dysfunction in cognition by relating cerebral blood flow (CBF), measured with arterial spin labeling (ASL), to cognitive functioning, in patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (MRI; ie, possible vascular cognitive impairment [VCI]). METHODS: We included 439 participants (124 HF; 75 COD; 127 possible VCI; 113 reference participants) from the Dutch multi-center Heart-Brain Study. We used pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Neuropsychological tests covered global cognition and four cognitive domains. RESULTS: CBF values were lowest in COD, followed by VCI and HF, compared to reference participants. This did not explain cognitive impairment, as we did not find an association between CBF and cognitive functioning. DISCUSSION: We found that reduced CBF is not the major explanatory factor underlying cognitive impairment in patients with hemodynamic dysfunction along the heart-brain axis.

The Need for Co-Creation of Care with Multi-Morbidity Patients-A Longitudinal Perspective.

BACKGROUND: Primary care delivery for multimorbid patients is complex, due to single disease-oriented guidelines, complex care needs, time constraints and the involvement of multiple healthcare professionals. Co-creation of care, based on the quality of communication and relationships between healthcare professionals and patients, may therefore be valuable. This longitudinal study investigates the relationships of co-creation of care to physical and social well-being and satisfaction with care among multimorbid patients in primary care. METHODS: In 2017 and 2018, longitudinal surveys were conducted among multimorbid patients from seven primary care practices in Noord-Brabant, the Netherlands (n = 138, age = 73.50 ± 9.99). Paired sample t-tests and multivariate regression analyses were performed. (3) Results: Co-creation of care improved significantly over time (t = 2.25, p = 0.026), as did social well-being (t = 2.31, p = 0.022) and physical well-being (t = 2.72, p = 0.007) but not satisfaction with care (t = 0.18, p = 0.858). Improvements in co-creation of care from T0 to T1 were associated with social well-being (B = 0.157, p = 0.002), physical well-being (B = 0.216, p = 0.000) and satisfaction with care (B = 0.240, p = 0.000). (4) Conclusions: Thus, investment in co-creation of care by primary care practices may lead to better outcomes for multimorbid patients.

Views of patients with multi-morbidity on what is important for patient-centered care in the primary care setting.

BACKGROUND: Patient-centered care (PCC) has been proposed as the way forward in improving primary care for patients with multi-morbidity. However, it is not clear what PCC exactly looks like in practice for patients with multi-morbidity. A better understanding of multi-morbid patients' views on what PCC should look like and which elements are most important may help to improve care delivery for this vulnerable population. The present study thus aimed to identify views of patients with multi-morbidity on the relative importance of PCC aspects in a Dutch primary care setting. METHODS: Interviews were conducted with 16 patients with multi-morbidity using Q-methodology, which combines quantitative and qualitative analyses. The participants ranked 28 statements about the eight dimensions of PCC (patients' preferences, information and education, access to care, emotional support, family and friends, continuity and transition, physical comfort, and coordination of care) by relative importance. By-person factor analysis using centroid factor extraction and varimax rotation were used to reveal factors that represent viewpoints. Qualitative interview data were used to interpret the viewpoints. RESULTS: The analyses revealed three factors representing three distinct viewpoints of patients with multi-morbidity on what is important for patient-centered care in the primary care setting. Patients with viewpoint 1 are prepared proactive patients who seem to be well-off and want to be in charge of their own care. To do so, they seek medical information and prefer to be supported by a strongly coordinated multidisciplinary team of healthcare professionals. Patients with viewpoint 2 are everyday patients who visit GPs and require well-coordinated, respectful, and supportive care. Patients with viewpoint 3 are vulnerable patients who are less resourceful in terms of communication skills and finances, and thus require accessible care and professionals taking the lead while treating them with dignity and respect. CONCLUSION: The findings of this study suggest that not all patients with multi-morbidity require the same type of care delivery, and that not all aspects of PCC delivery are equally important to all patients.

The importance of patient-centered care and co-creation of care for satisfaction with care and physical and social well-being of patients with multi-morbidity in the primary care setting.

BACKGROUND: Patients with multi-morbidity have complex care needs that often make healthcare delivery difficult and costly to manage. Current healthcare delivery is not tailored to the needs of patients with multi-morbidity, although multi-morbidity poses a heavy burden on patients and is related to adverse outcomes. Patient-centered care and co-creation of care are expected to improve outcomes, but the relationships among patient-centered care, co-creation of care, physical well-being, social well-being, and satisfaction with care among patients with multi-morbidity are not known. METHODS: In 2017, a cross-sectional survey was conducted among 216 (of 394 eligible participants; 55% response rate) patients with multi-morbidity from eight primary care practices in Noord-Brabant, the Netherlands. Correlation and regression analyses were performed to identify relationships among patient-centered care, co-creation of care, physical well-being, social well-being, and satisfaction with care. RESULTS: The mean age of the patients was 74.46 ± 10.64 (range, 47-94) years. Less than half (40.8%) of the patients were male, 43.3% were single, and 39.3% were less educated. Patient-centered care and co-creation of care were correlated significantly with patients' physical well-being, social well-being, and satisfaction with care (all p ≤ 0.001). Patient-centered care was associated with social well-being (B = 0.387, p ≤ 0.001), physical well-being (B = 0.368, p ≤ 0.001) and satisfaction with care (B = 0.425, p ≤ 0.001). Co-creation of care was associated with social well-being (B = 0.112, p = 0.006) and satisfaction with care (B = 0.119, p = 0.007). CONCLUSIONS: Patient-centered care and co-creation of care were associated positively with satisfaction with care and the physical and social well-being of patients with multi-morbidity in the primary care setting. Making care more tailored to the needs of patients with multi-morbidity by paying attention to patient-centered care and co-creation of care may contribute to better outcomes.

Incidence, Predictors, and Outcomes of New-Onset Atrial Fibrillation in Critically Ill Patients with Sepsis. A Cohort Study.

RATIONALE: Patients admitted to intensive care units with sepsis are prone to developing cardiac dysrhythmias, most commonly atrial fibrillation. OBJECTIVES: To determine the incidence, risk factors, and outcomes of atrial fibrillation in a cohort of critically ill patients with sepsis. METHODS: We assessed the association between atrial fibrillation and mortality using time-dependent competing risks survival analysis. Subsequently, for development of a risk score estimating the probability of a first occurrence of atrial fibrillation within the following 24 hours, we performed logistic regression analysis. MEASUREMENTS AND MAIN RESULTS: Among 1,782 patients with sepsis admitted to two tertiary intensive care units in the Netherlands between January 2011 and June 2013, a total of 1,087 episodes of atrial fibrillation occurred in 418 (23%) individuals. The cumulative risk of new-onset atrial fibrillation was 10% (95% confidence interval [CI], 8-12), 22% (95% CI, 18-25), and 40% (95% CI, 36-44) in patients with sepsis, severe sepsis, and septic shock, respectively. New-onset atrial fibrillation was associated with a longer stay (hazard ratio [HR], 0.55; 95% CI, 0.48-0.64), an increased death rate (HR, 1.52; 95% CI, 1.16-2.00), and an overall increased mortality risk (subdistribution HR, 2.10; 95% CI, 1.61-2.73) when considering discharge as a competing event. A simple risk score for daily prediction of atrial fibrillation occurrence yielded good discrimination (C statistic, 0.81; 95% CI, 0.79-0.84) and calibration (chi-square, 9.38; P = 0.31), with similar performance in an independent validation cohort (C statistic, 0.80; 95% CI, 0.76-0.85). CONCLUSIONS: Atrial fibrillation is a common complication of sepsis and independently associated with excess mortality. A simple risk score may identify patients at high risk of this complication. Clinical trial registered with www.clinicaltrials.gov (NCT 01905033).

Incidence, risk factors and outcomes of new-onset atrial fibrillation in patients with sepsis: a systematic review.

INTRODUCTION: Critically ill patients with sepsis are prone to develop cardiac dysrhythmias, most commonly atrial fibrillation (AF). Systemic inflammation, circulating stress hormones, autonomic dysfunction, and volume shifts are all possible triggers for AF in this setting. We conducted a systematic review to describe the incidence, risk factors and outcomes of new-onset AF in patients with sepsis. METHODS: MEDLINE, EMBASE and Web Of Science were searched for studies reporting the incidence of new-onset AF, atrial flutter or supraventricular tachycardia in patients with sepsis admitted to an intensive care unit, excluding studies that primarily focused on postcardiotomy patients. Studies were assessed for methodological quality using the GRADE system. Risk factors were considered to have a high level of evidence if they were reported in ≥ 2 studies using multivariable analyses at a P value <0.05. Subsequently, the strength of association was classified as strong, moderate or weak, based on the reported odds ratios. RESULTS: Eleven studies were included. Overall quality was low to moderate. The weighted mean incidence of new-onset AF was 8% (range 0 to 14%), 10% (4 to 23%) and 23% (6 to 46%) in critically ill patients with sepsis, severe sepsis and septic shock, respectively. Independent risk factors with a high level of evidence included advanced age (weak strength of association), white race (moderate association), presence of a respiratory tract infection (weak association), organ failure (moderate association), and pulmonary artery catheter use (moderate association). Protective factors were a history of diabetes mellitus (weak association) and the presence of a urinary tract infection (weak association). New-onset AF was associated with increased short-term mortality in five studies (crude relative effect estimates ranging from 1.96 to 3.32; adjusted effects 1.07 to 3.28). Three studies reported a significantly increased length of stay in the ICU (weighted mean difference 9 days, range 5 to 13 days), whereas an increased risk of ischemic stroke was reported in the single study that looked at this outcome. CONCLUSIONS: New-onset AF is a common consequence of sepsis and is independently associated with poor outcome. Early risk stratification of patients may allow for pharmacological interventions to prevent this complication.