Association Between Gut Microbiota and Delirium in Acutely Ill Older Adults.

Our aim was to investigate the association between gut microbiota and delirium occurrence in acutely ill older adults. We included 133 participants 65+ years consecutively admitted to the emergency department of a tertiary university hospital, between September 2019 and March 2020. We excluded candidates with ≥24-hour antibiotic utilization on admission, recent prebiotic or probiotic utilization, artificial nutrition, acute gastrointestinal disorders, severe traumatic brain injury, recent hospitalization, institutionalization, expected discharge ≤48 hours, or admission for end-of-life care. A trained research team followed a standardized interview protocol to collect sociodemographic, clinical, and laboratory data on admission and throughout the hospital stay. Our exposure measures were gut microbiota alpha and beta diversities, taxa relative abundance, and core microbiome. Our primary outcome was delirium, assessed twice daily using the Confusion Assessment Method. Delirium was detected in 38 participants (29%). We analyzed 257 swab samples. After adjusting for potential confounders, we observed that a greater alpha diversity (higher abundance and richness of microorganisms) was associated with a lower risk of delirium, as measured by the Shannon (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.60-0.99; p = .042) and Pielou indexes (OR = 0.69; 95% CI = 0.51-0.87; p = .005). Bacterial taxa associated with pro-inflammatory pathways (Enterobacteriaceae) and modulation of relevant neurotransmitters (Serratia: dopamine; Bacteroides, Parabacteroides: GABA) were more common in participants with delirium. Gut microbiota diversity and composition were significantly different in acutely ill hospitalized older adults who experienced delirium. Our work is an original proof-of-concept investigation that lays a foundation for future biomarker studies and potential therapeutic targets for delirium prevention and treatment.

Brain injury biomarkers do not predict delirium in acutely ill older patients: a prospective cohort study.

Delirium is a common, serious, and often preventable neuropsychiatric emergency mostly characterized by a disturbance in attention and awareness. Systemic insult and inflammation causing blood-brain-barrier (BBB) damage and glial and neuronal activation leading to more inflammation and cell death is the most accepted theory behind delirium's pathophysiology. This study aims to evaluate the relationship between brain injury biomarkers on admission and delirium in acutely ill older patients. We performed a prospective cohort study which analyzed plasma S100B levels at admission in elderly patients. Our primary outcome was delirium diagnosis. Secondary outcomes were association between S100B, NSE and Tau protein and delirium diagnosis and patients' outcomes (admissions to intensive care, length of hospital stay, and in-hospital mortality). We analyzed 194 patients, and 46 (24%) developed delirium, 25 on admission and 21 during hospital stay. Median of S100B at admission in patients who developed delirium was 0.16 and median was 0.16 in patients who didn't develop delirium (p: 0.69). Levels S100B on admission did not predict delirium in acutely ill elderly patients.Trial registration: The study was approved by the local institutional review board (CAPPESq, no. 77169716.2.0000.0068, October 11, 2017) and registered in Brazilian Clinical Trials Registry (ReBEC, no. RBR-233bct).

Accuracy of two prognostic indexes to predict mortality in older adults with advanced dementia.

Dementia is a cause of disability among older adults. Accessing advanced dementia prognosis is a challenge. Objective: The objective of this study was to evaluate the accuracy of the Charlson and Carey indexes in predicting 3-year survival of older adults with advanced dementia. Methods: This is a retrospective cohort study of 238 patients aged ≥60 years with advanced dementia from an outpatient clinic and classified as stage ≥6A by using the Functional Assessment Staging scale. We excluded patients with missing data. We reviewed the semi-structured interview (clinical, sociodemographic, and functional data) from the baseline visit. This information was used to calculate 3-year mortality risks according to the Charlson and Carey indexes. We used Cox proportional hazard models to evaluate the associations of all-cause mortality with both indexes, adjusted for sociodemographic variables. We used Harrell's C measure to determine the discrimination. We calculated the absolute differences between observed and predicted 3-year mortality risks for each index for calibration. Results: In 238 patients, the average age was 80.5±7.8 years, with 36% being men. The median follow-up time was 1.8 years (0.05-3.0). The 3-year all-cause mortality rate was 50% (119 deaths). The Carey index was associated with mortality, with one point increase related to a 15% increase in the mortality risk (hazard ratio [HR]=1.15, 95% confidence interval (95%CI) 1.06-1.25, p=0.001), even after adjustment. Accuracy for the Charlson index and Carey index was 0.55 (95%CI 0.49-0.60) and 0.60 (95%CI 0.52-0.62), respectively, with no difference between them (p=0.44). Conclusions: Both indexes had poor discrimination and calibration performances in predicting 3-year mortality in patients with advanced dementia.

Demência é uma causa de incapacidade e dependência em idosos. A avaliação prognóstica na fase avançada é desafiadora. Objetivo: Avaliar a acurácia dos índices de Charlson e Carey na predição de mortalidade em até três anos de idosos com demência avançada. Métodos: Estudo de coorte retrospectiva que incluiu 238 pacientes acompanhados em ambulatório especializado em um país de renda média, com idade ≥60 anos e demência avançada classificada como estágio ≥6A pela escala Functional Assessment Staging (FAST). Foram excluídos pacientes com dados incompletos para análise. Realizou-se revisão da primeira consulta, que consiste em entrevista com dados clínicos, sociodemográficos e funcionais utilizados para calcular a probabilidade de óbito em três anos, de acordo com os índices. Foram usados modelos de risco proporcional de Cox para avaliar as associações de mortalidade por todas as causas com os dois índices, ajustados para variáveis sociodemográficas. As discriminações dos dois modelos foram comparadas usando o cálculo C de Harrell. Para a calibração, foram calculadas as diferenças absolutas entre os riscos observados e preditos por cada um dos índices. Resultados: Foram avaliados 238 pacientes, com média de idade de 80,5±7,8 anos, 36% do sexo masculino. A mediana do tempo de acompanhamento foi de 1,8 anos (intervalo interquartil=0,05­3,0). A taxa de mortalidade por todas as causas em três anos foi de 50% (119 óbitos). O índice de Carey foi associado à mortalidade, mas o de Charlson não. Um aumento de 1 ponto no Carey foi relacionado a aumento de 15% no risco de morte (hazard ratio [HR]=1,15, intervalo de confiança [IC95%] 1,06­1,25, p=0,001), mesmo após ajuste para variáveis sociodemográficas. A acurácia do índice de Charlson foi de 0,55 (IC95% 0,49­0,60) e a do índice de Carey de 0,60 (IC95% 0,52­0,62), sem diferença significativa na discriminação (p=0,44). Ambos os índices tiveram performances insatisfatórias na discriminação e na calibração. Conclusões: O índice de Carey foi associado à mortalidade, porém esse resultado não foi encontrado para o índice de Charlson. Ambos os índices tiveram desempenho insatisfatório na discriminação e na calibração para predizer a mortalidade em três anos em pacientes com demência avançada, o que indica que esses escores não são recomendados para predizer a mortalidade nessa população.

Applicability of the GLIM criteria for the diagnosis of malnutrition in older adults in the emergency ward: A pilot validation study.

BACKGROUND & AIMS: Acutely ill older adults are at higher risk of malnutrition. This study aimed to explore the applicability and accuracy of the GLIM criteria to diagnose malnutrition in acutely ill older adults in the emergency ward (EW). METHODS: We performed a retrospective secondary analysis, of an ongoing cohort study, in 165 participants over 65 years of age admitted to the EW of a Brazilian university hospital. Nutrition assessment included anthropometry, the Simplified Nutritional Assessment Questionnaire (SNAQ), the Malnutrition Screening Tool (MST), and the Mini-Nutritional Assessment (MNA). We diagnosed malnutrition using GLIM criteria, defined by the parallel presence of at least one phenotypic [nonvolitional weight loss (WL), low BMI, low muscle mass (MM)] and one etiologic criterion [reduced food intake or assimilation (RFI), disease burden/inflammation]. We used the receiver operating characteristic (ROC) curves and Cox and logistic regression for data analyses. RESULTS: GLIM criteria, following the MNA-SF screening, classified 50.3% of participants as malnourished, 29.1% of them in a severe stage. Validation of the diagnosis using MNA-FF as a reference showed good accuracy (AUC = 0.84), and moderate sensitivity (76%) and specificity (75.1%). All phenotypic criteria combined with RFI showed the best metrics. Malnutrition showed a trend for an increased risk of transference to intensive care unit (OR = 2.08, 95% CI 0.99, 4.35), and severe malnutrition for in-hospital mortality (HR = 4.23, 95% CI 1.2, 14.9). CONCLUSION: GLIM criteria, following MNA-SF screening, appear to be a feasible approach to diagnose malnutrition in acutely ill older adults in the EW. Nonvolitional WL combined with RFI or acute inflammation were the best components identified and are easily accessible, allowing their potential use in clinical practice.

COVID-19 is not over and age is not enough: Using frailty for prognostication in hospitalized patients.

BACKGROUND: Frailty screening using the Clinical Frailty Scale (CFS) has been proposed to guide resource allocation in acute care settings during the pandemic. However, the association between frailty and coronavirus disease 2019 (COVID-19) prognosis remains unclear. OBJECTIVES: To investigate the association between frailty and mortality over 6 months in middle-aged and older patients hospitalized with COVID-19 and the association between acute morbidity severity and mortality across frailty strata. DESIGN: Observational cohort study. SETTING: Large academic medical center in Brazil. PARTICIPANTS: A total of 1830 patients aged ≥50 years hospitalized with COVID-19 (March-July 2020). MEASUREMENTS: We screened baseline frailty using the CFS (1-9) and classified patients as fit to managing well (1-3), vulnerable (4), mildly (5), moderately (6), or severely frail to terminally ill (7-9). We also computed a frailty index (0-1; frail >0.25), a well-known frailty measure. We used Cox proportional hazards models to estimate the association between frailty and time to death within 30 days and 6 months of admission. We also examined whether frailty identified different mortality risk levels within strata of similar age and acute morbidity as measured by the Sequential Organ Failure Assessment (SOFA) score. RESULTS: Median age was 66 years, 58% were male, and 27% were frail to some degree. Compared with fit-to-managing-well patients, the adjusted hazard ratios (95% confidence interval [CI]) for 30-day and 6-month mortality were, respectively, 1.4 (1.1-1.7) and 1.4 (1.1-1.7) for vulnerable patients; 1.5 (1.1-1.9) and 1.5 (1.1-1.8) for mild frailty; 1.8 (1.4-2.3) and 1.9 (1.5-2.4) for moderate frailty; and 2.1 (1.6-2.7) and 2.3 (1.8-2.9) for severe frailty to terminally ill. The CFS achieved outstanding accuracy to identify frailty compared with the Frailty Index (area under the curve = 0.94; 95% CI = 0.93-0.95) and predicted different mortality risks within age and acute morbidity groups. CONCLUSIONS: Our results encourage the use of frailty, alongside measures of acute morbidity, to guide clinicians in prognostication and resource allocation in hospitalized patients with COVID-19.

A fuller picture of COVID-19 prognosis: the added value of vulnerability measures to predict mortality in hospitalised older adults.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) disproportionally affects older adults, the use of conventional triage tools in acute care settings ignores the key aspects of vulnerability. OBJECTIVE: This study aimed to determine the usefulness of adding a rapid vulnerability screening to an illness acuity tool to predict mortality in hospitalised COVID-19 patients. DESIGN: Cohort study. SETTING: Large university hospital dedicated to providing COVID-19 care. PARTICIPANTS: Participants included are 1,428 consecutive inpatients aged ≥50 years. METHODS: Vulnerability was assessed using the modified version of PRO-AGE score (0-7; higher = worse), a validated and easy-to-administer tool that rates physical impairment, recent hospitalisation, acute mental change, weight loss and fatigue. The baseline covariates included age, sex, Charlson comorbidity score and the National Early Warning Score (NEWS), a well-known illness acuity tool. Our outcome was time-to-death within 60 days of admission. RESULTS: The patients had a median age of 66 years, and 58% were male. The incidence of 60-day mortality ranged from 22% to 69% across the quartiles of modified PRO-AGE. In adjusted analysis, compared with modified PRO-AGE scores 0-1 ('lowest quartile'), the hazard ratios (95% confidence interval) for 60-day mortality for modified PRO-AGE scores 2-3, 4 and 5-7 were 1.4 (1.1-1.9), 2.0 (1.5-2.7) and 2.8 (2.1-3.8), respectively. The modified PRO-AGE predicted different mortality risk levels within each stratum of NEWS and improved the discrimination of mortality prediction models. CONCLUSIONS: Adding vulnerability to illness acuity improved accuracy of predicting mortality in hospitalised COVID-19 patients. Combining tools such as PRO-AGE and NEWS may help stratify the risk of mortality from COVID-19.

Divergent: Age, Frailty, and Atypical Presentations of COVID-19 in Hospitalized Patients.

BACKGROUND: Although frailty has been associated with atypical manifestations of infections, little is known about COVID-19 presentations in hospitalized frail patients. We aimed to investigate the association between age, frailty, and clinical characteristics of COVID-19 in hospitalized middle-aged and older adults. METHOD: Longitudinal observational study comprising 711 patients aged ≥50 years consecutively admitted to a university hospital dedicated to COVID-19 severe cases, between March and May 2020. We reviewed electronic medical records to collect data on demographics, comorbidities, COVID-19 signs/symptoms, and laboratory findings on admission. We defined frailty using the Clinical Frailty Scale (CFS = 1-9; frail ≥5). We also documented in-hospital mortality. We used logistic regressions to explore associations between age, frailty, and COVID-19 signs/symptoms; and between typical symptoms (fever, cough, dyspnea) and mortality. RESULTS: Participants had a mean age of 66 ± 11 years, and 43% were female. Overall, 25% were frail, and 37% died. The most common COVID-19 presentations were dyspnea (79%), cough (74%), and fever (62%), but patients aged ≥65 years were less likely to have a co-occurrence of typical symptoms, both in the absence (OR = 0.56; 95% CI = 0.39-0.79) and in the presence of frailty (OR = 0.52; 95% CI = 0.34-0.81). In contrast, older age and frailty were associated with unspecific presentations, including functional decline, acute mental change, and hypotension. After adjusting for age, sex, and frailty, reporting fever was associated with lower odds of mortality (OR = 0.70; 95% CI = 0.50-0.97). CONCLUSIONS: Atypical COVID-19 presentations are common in frail and older hospitalized patients. Providers should be aware of unspecific disease manifestations during the management and follow-up of this population.

Delirium in older adults / Delirium em idosos

This narrative review provides a broad examination of the most current concepts on the etiopathogenesis, diagnosis, prevention, and treatment of delirium, an acute neuropsychiatric syndrome characterized by fluctuating changes in cognition and consciousness. With the interaction of underlying vulnerability and severity of acute insults, delirium can occur at any age but is particularly frequent in hospitalized older adults. Delirium is also associated with numerous adverse outcomes, including functional impairment, cognitive decline, increased healthcare costs, and death. Its diagnosis is based on clinical and cognitive assessments, preferably following systematized detection instruments, such as the Confusion Assessment Method (CAM). Delirium and its consequences are most effectively fought using multicomponent preventive interventions, like those proposed by the Hospital Elder Life Program (HELP). When prevention fails, delirium management is primarily based on the identification and reversal of precipitating factors and the non-pharmacological control of delirium symptoms. Pharmacological interventions in delirium should be restricted to cases of dangerous agitation or severe psychotic symptoms.

Esta revisão narrativa examina de maneira abrangente os conceitos mais atuais sobre etiopatogenia, diagnóstico, prevenção e tratamento do delirium, uma síndrome neuropsiquiátrica aguda caracterizada por mudanças flutuantes na cognição e na consciência. Com a interação entre a vulnerabilidade subjacente e a gravidade dos insultos agudos, delirium pode ocorrer em qualquer idade, mas afeta com notória frequência idosos hospitalizados. Delirium também está associado a diversos desfechos adversos, incluindo prejuízo funcional, declínio cognitivo, aumento dos custos de saúde e morte. O diagnóstico é baseado em avaliações clínicas e cognitivas, com preferência para o uso de instrumentos de detecção sistematizados, como o Confusion Assessment Method (CAM). Delirium e suas consequências são combatidos de forma mais eficaz por meio de intervenções preventivas com múltiplos componentes, como as propostas pelo Hospital Elder Life Program (HELP). Quando há falha na prevenção, o manejo do delirium se baseia principalmente na identificação e na reversão dos fatores precipitantes e no controle não farmacológico dos sintomas do delirium. As intervenções farmacológicas no delirium devem ser restritas aos casos de agitação perigosa ou sintomas psicóticos graves.

Association Between Level of Arousal and 30-Day Survival in Acutely Ill Older Adults.

OBJECTIVE: To investigate the association between impaired arousal on admission and 30-day mortality in acutely ill older adults. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients age +65 years admitted to the geriatric ward of a tertiary university hospital from 2010 to 2018 in Sao Paulo, Brazil. METHODS: Participants were evaluated on admission according to a standardized comprehensive geriatric assessment model. Delirium was detected using the short version of the Confusion Assessment Method (Short-CAM). We used 2 alternative criteria to define impaired arousal: lethargy, stupor, or coma according to the Short-CAM; and a Glasgow Coma Scale (GCS) score of ≤13. Our primary outcome was time-to-death in 30 days, and we used Cox proportional hazards models to explore the association between impaired arousal and decreased survival. RESULTS: We included 1554 admissions with a mean age of 81 years and of whom 61% were women. Overall, prevalent delirium was observed in 28% of the cases. We found that in 33% of admissions, patients were lethargic, stuporous, or comatose, and that in 23%, they had GCS scores of ≤13. General 30-day mortality was 19% but reached 32% in patients with GCS scores of ≤13. Impaired arousal was independently associated with lower survival in 30 days, both when defined using Short-CAM criteria [lethargy + stupor + coma: hazard ratio (HR) 2.33, 95% confidence interval (CI) 1.66‒3.27] and GCS scores (GCS 12‒13: HR 1.62, 95% CI 1.13‒2.33; GCS ≤ 11: HR 2.53, 95% CI 1.68‒3.80). In interaction analyses, we confirmed our results in patients who had impaired arousal but were neither delirious (lethargy + stupor + coma: HR 2.16, 95% CI 1.44‒3.24; GCS ≤ 11: HR 3.07; 95% CI 1.50‒6.29) nor demented (lethargy + stupor + coma: HR 1.95, 95% CI 1.15‒3.28). CONCLUSIONS AND IMPLICATIONS: Level of arousal on admission was an independent predictor of 30-day survival in acutely ill older adults, regardless of delirium or baseline dementia. Clinicians should be aware that even if unsure of whether a patient has delirium, arousal assessment can provide crucial clinical and prognostic insight.

Delirium and post-discharge dementia: results from a cohort of older adults without baseline cognitive impairment.

OBJECTIVES: to investigate the association between delirium occurrence in acutely ill older adults and incident dementia after hospital discharge. METHODS: retrospective cohort study examining acutely ill older adults aged +60 years and consecutively admitted to the geriatric ward of a tertiary university hospital from 2010 to 2016. Inclusion criteria were absence of baseline cognitive decline on admission and documented clinical follow-up of +12 months after discharge. Admission data were collected from our local database, including results from a standardized comprehensive geriatric assessment completed for every patient. Pre-existing cognitive decline was identified based on clinical history, CDR and IQCODE-16. Delirium was diagnosed using short-CAM criteria, while post-discharge dementia after 12 months was identified based on medical records' review. We used competing-risk proportional-hazard models to explore the association between delirium and post-discharge dementia. RESULTS: we included 309 patients. Mean age was 78 years, and 186 (60%) were women. Delirium was detected in 66 (21%) cases. After a median follow-up of 24 months, 21 (32%) patients who had experienced delirium progressed with dementia, while only 38 (16%) of those without delirium had the same outcome (P = 0.003). After adjusting for possible confounders, delirium was independently associated with post-discharge dementia with a sub-hazard ratio of 1.94 (95%CI = 1.10-3.44; P = 0.022). CONCLUSION: one in three acutely ill older adults who experienced delirium in the hospital developed post-discharge dementia during follow-up. Further understanding of delirium as an independent and potentially preventable risk factor for cognitive decline emphasizes the importance of systematic initiatives to fight it.

The influence of trait anxiety on the elevation of arterial pressure induced by L-NAME in rats.

Due to the high prevalence of anxiety disorders and hypertension comorbidity in the general population, the establishment of anxiety as a risk factor for elevated blood pressure, or the reverse, is of great relevance. In this context, animal models can be of great scientific value, as they permit the control of several variables. Bearing this in mind, the influence of anxiety, not as a state, but as a personality trait (trait anxiety), on blood pressure elevation and vice versa were investigated for the first time in rats, using the free-exploratory paradigm (FEP). Sixty adult male Wistar rats were evaluated on FEP and categorized according to their levels of anxiety. From this sample, 24 animals with high (n=12) and low (n=12) trait anxiety were allocated to two treatment groups: (1) l-NAME (N(G)-nitro-l-arginine methyl ester, 20mg/kg, p.o., for 7 days to increase blood pressure; n=6/anxiety category); (2) CTRL (tap water, p.o., for 7 days; n=6/anxiety category). During treatment, measurements of systolic blood pressure (SBP) were taken daily. After treatment, the animals were again tested on FEP. SBP and trait anxiety levels were compared pre- and post-treatment. Additionally, correlations between trait anxiety levels and SBP increases (l-NAME group) were analyzed. The results showed that l-NAME was able to induce significant SBP elevation, but only for the high-anxious animals, while SBP elevation did not significantly interfere with anxiety levels. A significant correlation between anxiety levels and SBP peaks in response to l-NAME was also shown. No differences were observed between the levels of anxiety before and after treatment. These findings suggest that individuals with high trait anxiety are more susceptible to increases in blood pressure, but that high blood pressure does not affect the levels of trait anxiety.

Ecocardiografia bidimensional convencional pode não detectar cardiomiopatia hipertrófica apical: relato de caso / Conventional bidimensional echocardiography may not detect apical hypertrophic cardiomyopathy: case report

A cardiomiopatia hipertrófica (CMH) é uma doença genética cardíaca, caracterizada por hipertrofia ventricular esquerda. É assimétrica na maioria das vezes. O método diagnóstico considerado padrão para detecção de CMH é o ecocardiograma bidimensional. Os casos de CMH que passam despercebidos por esse método são poucos, e para eles há a necessidade de um outro exame de imagem que melhor visualize o tipo morfológico da doença apresentada: a ressonância magnética cardíaca (RMC). Este relato descreve um paciente com alterações eletrocardiográficas de base e que foi diagnosticado com CMH apical unicamente pela RMC, sem apresentar anormalidade significativa à ecocardiografia convencional.

Isquemia miocárdica investigada com ecocardiografia sob estresse físico em pacientes com incompetência cronotrópica em uso de betabloqueador / Myocardial ischemia during exercise echocardiography in patients with chronotropic incompetence in use of beta blockers

Introdução: Objetivo: Avaliar a influência da utilização de betabloqueador em pacientes com incompetência cronotrópica, submetidos à Ecocardiografia sob Estresse. Método: Estudo observacional, transversal e retrospectivo, realizado entre janeiro/2001 e outubro/2008. Após exclusão de pacientes com precordialgia típica, com doença arterial coronariana estabelecida e que não usavam betabloqueador, foram avaliados 635 pacientes que faziam uso regular desta droga, suspensa 3 dias antes da execução do exame. A amostra foi dividida em 2 grupos: G1 e G2 (com e sem incompetência cronotrópica), que foram comparados quanto à características clínicas, hemodinâmicas, eletrocardiográficas e ecocardiográficas . Resultados: O G1 constituiu-se de 81 pacientes (13 por cento); o G2 de 554 pacientes (87 por cento). Quanto às características, os pacientes do G1 eram idosos (p=0,002), apresentavam mais precordialgia atípica (p=0,013, mais dispnéia durante o exame (p=0,001) e eram sintomáticos (p=0,009). Do ponto de vista ecocardiográfico, não foi possível diferenciar os dois grupos, quanto ao diagnóstico de isquemia miocárdica induzida pelo esforço (p=0,140) e, também quanto ao índice de escore de motilidade do ventrículo esquerdo durante o exercício (p=0,223). Todavia, G1 demonstrou maior índice de massa do ventrículo esquerdo (p=0,001). Conclusão: Isquemia miocárdica investigada com ecocardiografia sob estresse físico foi senelhante nos grupos estudados.

Chronotropic incompetence and coronary artery disease.

OBJECTIVE: Although chronotropic incompetence (CI) represents an independent predictor of mortality and incidence of coronary artery disease, its pathophysiological mechanisms remain unknown. The purpose of this investigation was to evaluate wall motion abnormalities of the left ventricle and location of coronary arterial lesions in patients with and without CI. METHODS: After exclusion of confounding factors, 610 patients (mean age of 58.4 +/- 11 years; 275 men) with ischaemia who underwent exercise echocardiography were studied. Based on heart rate (HR) reached in treadmill testing, patients were divided into two groups: Chl (97 patients who did not reach 85% of maximum HR recommended for age) and ChC (513 patients who achieved 85% of the maximum age-predicted HR). RESULTS: There was a higher frequency of dyspnoea (5.2% vs. 0.6%, P = 0.003), systemic hypertension (69.1% vs. 57.3%, P = 0.031) and obesity (38.1% vs. 22.6%, P = 0.001), and a lower tolerance to effort (dyspnoea as limitation of physical effort: 36.1% vs. 8.0%, P < 0.0001; duration of treadmill test: 4.4 +/- 2.2 vs. 7.2 +/- 2.8, P < 0.0001; METs: 6.0 +/- 2.6 vs. 8.4 +/- 2.9, P = 0.002) in Chl compared to ChC. The wall motion score index (WMSI) was higher in Chl than in ChC, both at rest (1.15 +/- 0.29 vs. 1.07 +/- 0.19, P = 0.011) and after exercise (1.24 +/- 0.29 vs. 1.15 +/- 0.19, P = 0.002). Systolic function, which was evaluated in peak exercise through WMSI, was significantly more altered in the Chl group. The presence of severe injuries in right coronary was independently associated with CI (adjusted OR = 3.57, CI 95%: 1.86-6.87). CONCLUSION: Chronotropic incompetence is associated with ventricular dysfunction in peak exercise and critical right coronary artery lesions.