Impact of the withdrawal of renin-angiotensin-aldosterone inhibitors on mortality in COVID-19 patients.

Background: Chronic use of Angiotensin-converting enzyme (ACE) inhibitors (ACEi) and aldosterone-receptor blockers (ARB) is not associated with worse outcomes in patients with COVID-19. However, evidence on the impact of their discontinuation during hospital admission is scarce. Our aim was to determine whether withdrawal of ACEi, ARB and mineralocorticoid receptor antagonists (MRA) is associated with all-cause mortality in a real-life large cohort of patients with SARS-CoV-2 infection. Methods: Observational cohort study from a large referral center from 1 March 2020 to 20 April 2020. Withdrawal of renin-angiotensin-aldosterone system inhibitors was defined as the absence of any received dose during hospital admission in patients receiving chronic treatment. Prescriptions during admission were confirmed by data from the central pharmacy computerized system. Results: A total of 2042 patients (mean age 68.4±17.6, 57.1% male) with confirmed COVID-19 were included. During a median follow-up of 57 (21-55) days, 583 (28.6%) died. Prior to hospital admission 468 (22.9%), 343 (16.8%) and 83 (4.1%) patients were receiving ACEi, ARB and MRA respectively. During the study period, 216 (46.2%), 193 (56.3%) and 41 (49.4%) were withdrawn from the corresponding drug. After adjusting for age, cardiovascular risk factors, baseline comorbidities and in-hospital COVID-19 dedicated treatment, withdrawal of ACE inhibitors (hazard ration [HR] 1.48 [95% confidence interval -CI- 1.16-1.89]) and MRA (HR 2.01 [95% CI 1.30-3.10]) were shown to be independent predictors of all-cause mortality. No independent relationship between ARB withdrawal and mortality was observed. Conclusion: ACEi and MRA withdrawal were associated with higher mortality. Strong consideration should be given to not discontinuing these medications during hospital admission.

Introdução: O uso crónico de inibidores da ECA (IECA) e de antagonistas dos recetores de aldosterona (ARA) não está associado a resultados piores em doentes com Covid-19. No entanto, a evidência relativa ao impacto da sua retirada durante a admissão hospitalar é escassa. O nosso objetivo foi determinar se a retirada do IECA, ARA e antagonistas dos recetores dos mineralocorticóides (ARM) está associada à mortalidade por todas as causas numa grande coorte real de doentes com infeção por SRA-CoV-2. Métodos: Estudo coorte observacional a partir de um grande centro de referência de 1 de março de 2020 a 20 de abril de 2020. A retirada dos inibidores do sistema RAAS foi definida como a ausência de qualquer dose recebida durante a admissão hospitalar em doentes que recebem tratamento prolongado. As prescrições durante a admissão foram confirmadas por dados do sistema informático da farmácia central. Resultados: Um total de 2042 doentes (idade média de 68,4 ±17,6, 57,1% do sexo masculino) com COVID-19 confirmado foram incluídos. Durante um acompanhamento médio de 57 (21-55) dias, 583 (28,6%) morreram. Conclusão: A retirada do IECA e do ARM foi associada a uma mortalidade mais elevada. Deve ser dada grande atenção para não interromper estes medicamentos durante a admissão hospitalar.

Characterization of myocardial injury in a cohort of patients with SARS-CoV-2 infection.

BACKGROUND: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19. METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. RESULTS: A total of 918 patients (mean age 63.2 ± 15.5 years, 60.1% male) with a median follow-up of 57 (49-63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7-18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57-4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates. CONCLUSION: Elevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes.

ANTECEDENTES: El daño miocárdico parece una complicación frecuente en pacientes con COVID-19. Sin embargo, la literatura al respecto presenta serias limitaciones, como definiciones incorrectas, heterogeneidad de las determinaciones de troponina o seguimientos cortos. Utilizando datos de una cohorte amplia, el objetivo del trabajo fue caracterizar adecuadamente el daño miocárdico en pacientes con COVID-19 utilizando una metodología adecuada. MÉTODOS: Se estudió a pacientes consecutivos con infección confirmada y determinaciones disponibles de troponina I de alta sensibilidad (hs-TnI), desde el 1 de marzo hasta el 20 de abril del 2020, que hubieran completado al menos un mes de seguimiento o fallecieran durante el periodo de estudio. RESULTADOS: Se incluyó a 918 pacientes (edad 63,2 ± 15,5 años, 60,1% varones) con un seguimiento mediano de 57 (49-63) días. De estos, 190 (20,7%) cumplían criterios estrictos de lesión miocárdica (21,1% crónica, 76,8% aguda no isquémica, 2,1% aguda isquémica). El tiempo desde el inicio de los síntomas hasta la hs-TnI máxima fue de 11 (7-18) días. Los eventos trombóticos y hemorrágicos, las arritmias, la insuficiencia cardíaca, la necesidad de ventilación mecánica y la muerte fueron significativamente más frecuentes en pacientes con concentraciones elevadas de hs-TnI, incluso por debajo del nivel de lesión miocárdica. La hs-TnI resultó un predictor independiente de mortalidad (HR 2,52 [(1,57-4,04] por cada 5 unidades logarítmicas). CONCLUSIÓN: La hs-TnI elevada es altamente prevalente entre los pacientes con COVID-19. Elevaciones leves muy por debajo del límite para definir lesión miocárdica se asociaron con más complicaciones y mayor mortalidad. La determinación protocolizada de hs-TnI en estos enfermos podría mejorar su estratificación pronóstica y los resultados clínicos.

Characterization of myocardial injury in a cohort of patients with SARS-CoV-2 infection / Caracterización de la lesión miocárdica en una cohorte de pacientes infectados por el SARS-CoV-2

Background: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19.MethodsConsecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied.ResultsA total of 918 patients (mean age 63.2±15.5 years, 60.1% male) with a median follow-up of 57 (49–63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7–18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57–4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates.ConclusionElevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes. (AU)

Antecedentes: El daño miocárdico parece una complicación frecuente en pacientes con COVID-19. Sin embargo, la literatura al respecto presenta serias limitaciones, como definiciones incorrectas, heterogeneidad de las determinaciones de troponina o seguimientos cortos. Utilizando datos de una cohorte amplia, el objetivo del trabajo fue caracterizar adecuadamente el daño miocárdico en pacientes con COVID-19 utilizando una metodología adecuada.MétodosSe estudió a pacientes consecutivos con infección confirmada y determinaciones disponibles de troponina I de alta sensibilidad (hs-TnI), desde el 1 de marzo hasta el 20 de abril del 2020, que hubieran completado al menos un mes de seguimiento o fallecieran durante el periodo de estudio.ResultadosSe incluyó a 918 pacientes (edad 63,2±15,5 años, 60,1% varones) con un seguimiento mediano de 57 (49-63) días. De estos, 190 (20,7%) cumplían criterios estrictos de lesión miocárdica (21,1% crónica, 76,8% aguda no isquémica, 2,1% aguda isquémica). El tiempo desde el inicio de los síntomas hasta la hs-TnI máxima fue de 11 (7-18) días. Los eventos trombóticos y hemorrágicos, las arritmias, la insuficiencia cardíaca, la necesidad de ventilación mecánica y la muerte fueron significativamente más frecuentes en pacientes con concentraciones elevadas de hs-TnI, incluso por debajo del nivel de lesión miocárdica. La hs-TnI resultó un predictor independiente de mortalidad (HR 2,52 [(1,57-4,04] por cada 5 unidades logarítmicas).ConclusiónLa hs-TnI elevada es altamente prevalente entre los pacientes con COVID-19. Elevaciones leves muy por debajo del límite para definir lesión miocárdica se asociaron con más complicaciones y mayor mortalidad. La determinación protocolizada de hs-TnI en estos enfermos podría mejorar su estratificación pronóstica y los resultados clínicos. (AU)

Characterization of myocardial injury in a cohort of patients with SARS-CoV-2 infection.

BACKGROUND: Myocardial injury has been identified as a common complication in patients with COVID-19. However, recent research has serious limitations, such as non-guideline definition of myocardial injury, heterogenicity of troponin sampling or very short-term follow-up. Using data from a large European cohort, we aimed to overcome these pitfalls and adequately characterize myocardial damage in COVID-19. METHODS: Consecutive patients with confirmed SARS-CoV-2 infection and available high-sensitive troponin I (hs-TnI), from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. RESULTS: A total of 918 patients (mean age 63.2±15.5 years, 60.1% male) with a median follow-up of 57 (49-63) days were included. Of these, 190 (20.7%) fulfilled strict criteria for myocardial injury (21.1% chronic, 76.8% acute non-ischemic, 2.1% acute ischemic). Time from onset of symptoms to maximum hs-TnI was 11 (7-18) days. Thrombotic and bleeding events, arrhythmias, heart failure, need for mechanical ventilation and death were significantly more prevalent in patients with higher hs-TnI concentrations, even without fulfilling criteria for myocardial injury. hs-TnI was identified as an independent predictor of mortality [HR 2.52 (1.57-4.04) per 5-logarithmic units increment] after adjusting for multiple relevant covariates. CONCLUSION: Elevated hs-TnI is highly prevalent among patients with SARS-CoV-2 infection. Even mild elevations well below the 99th URL were significantly associated with higher rates of cardiac and non-cardiac complications, and higher mortality. Future research should address the role of serial hs-TnI assessment to improve COVID-19 prognostic stratification and clinical outcomes.

Prediction of thromboembolic events and mortality by the CHADS2 and the CHA2DS2-VASc in COVID-19.

AIMS: Age, sex, and cardiovascular disease have been linked to thromboembolic complications and poorer outcomes in COVID-19. We hypothesize that CHADS2 and CHA2DS2-VASc scores may predict thromboembolic events and mortality in COVID-19. METHODS AND RESULTS: COVID-19 hospitalized patients with confirmed SARS-CoV-2 infection from 1 March to 20 April 2020 who completed at least 1-month follow-up or died were studied. CHADS2 and CHA2DS2-VASc scores were calculated. Given the worse prognosis of male patients in COVID-19, a modified CHA2DS2-VASc score (CHA2DS2-VASc-M) in which 1 point was given to male instead of female was also calculated. The associations of these scores with laboratory results, thromboembolic events, and death were analysed. A total of 3042 patients (mean age 62.3 ± 20.3 years, 54.9% male) were studied and 115 (3.8%) and 626 (20.6%) presented a definite thromboembolic event or died, respectively, during the study period [median follow 59 (50-66) days]. Higher score values were associated with more marked abnormalities of inflammatory and cardiac biomarkers. Mortality was significantly higher with increasing scores for CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M (P < 0.001 for trend). The CHA2DS2-VASc-M showed the best predictive value for mortality [area under the receiver operating characteristic curve (AUC) 0.820, P < 0.001 for comparisons]. All scores had poor predictive value for thromboembolic events (AUC 0.497, 0.490, and 0.541, respectively). CONCLUSION: The CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M scores are significantly associated with all-cause mortality but not with thromboembolism in COVID-19 patients. They are simple scoring systems in everyday use that may facilitate initial 'quick' prognostic stratification in COVID-19.

Characterization of NT-proBNP in a large cohort of COVID-19 patients.

AIMS: Extensive research regarding the association of troponin and prognosis in coronavirus disease 2019 (COVID-19) has been performed. However, data regarding natriuretic peptides are scarce. N-terminal pro B-type natriuretic peptide (NT-proBNP) reflects haemodynamic stress and has proven useful for risk stratification in heart failure (HF) and other conditions such as pulmonary embolism and pneumonia. We aimed to adequately characterize NT-proBNP concentrations using a large cohort of patients with COVID-19, and to investigate its association with prognosis. METHODS AND RESULTS: Consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and available NT-proBNP determinations, from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. Of 3080 screened patients, a total of 396 (mean age 71.8 ± 14.6 years, 61.1% male) fulfilled all the selection criteria and were finally included, with a median follow-up of 53 (18-62) days. Of those, 192 (48.5%) presented NT-proBNP levels above the recommended cut-off for the identification of HF. However, only 47 fulfilled the clinical criteria for the diagnosis of HF. Patients with higher NT-proBNP during admission experienced more frequent bleeding, arrhythmias and HF decompensations. NT-proBNP was associated with mortality both in the whole study population and after excluding patients with HF. A multivariable Cox model confirmed that NT-proBNP was independently associated with mortality after adjusting for all relevant confounders (hazard ratio 1.28, 95% confidence interval 1.13-1.44, per logarithmic unit). CONCLUSION: NT-proBNP is frequently elevated in COVID-19. It is strongly and independently associated with mortality after adjusting for relevant confounders, including chronic HF and acute HF. Therefore, its use may improve early prognostic stratification in this condition.

Heart failure in COVID-19 patients: prevalence, incidence and prognostic implications.

AIMS: Data on the impact of COVID-19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking. The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID-19 infection and a prior diagnosis of heart failure (HF). Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline-directed medical therapy (GDMT) and worse outcomes during hospitalization. METHODS AND RESULTS: Data for a total of 3080 consecutive patients with confirmed COVID-19 infection and follow-up of at least 30 days were analysed. Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs. 2.1%; P < 0.001) and had higher levels of N-terminal pro brain natriuretic peptide. In addition, patients with previous CHF had higher mortality rates (48.7% vs. 19.0%; P < 0.001). In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF. Arrhythmias during hospital admission and CHF were the main predictors of AHF. Patients developing AHF had significantly higher mortality (46.8% vs. 19.7%; P < 0.001). Finally, the withdrawal of beta-blockers, mineralocorticoid receptor antagonists and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in-hospital mortality. CONCLUSIONS: Patients with COVID-19 have a significant incidence of AHF, which is associated with very high mortality rates. Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID-19 diagnosis. The withdrawal of GDMT was associated with higher mortality.

Long term clinical outcomes in survivors after out-of-hospital cardiac arrest.

INTRODUCTION AND OBJECTIVES: Information regarding long-term outcomes in patients surviving out-of-hospital cardiac arrest (OHCA) is scarce. Our aim was to study the long-term clinical outcomes of a large cohort of OHCA patients surviving until hospital discharge and to identify predictors of mortality and cardiovascular events. METHODS: Consecutive OHCA patients admitted in the Acute Cardiac Care Unit who survived at least until hospital discharge between 2007 and 2019 were included. All received therapeutic hypothermia according to the local protocol. Pre- and intra-hospital clinical and analytical variables were analyzed, as well as the clinically relevant events during follow-up. RESULTS: A total of 201 patients were included, with a mean age of 57.6 ± 14.2 years, 168 (83.6%) were male. Thirty-six (17.9%) died during a median follow-up of 40.3 months (18.9-69.1), the most frequent causes of death being cardiovascular and neurological, followed by cancer. We calculated a predictive model for mortality during follow-up using Cox regression that included the following variables: poor neurological outcome [HR 3.503 (1.578-7.777)], non-shockable rhythm [HR 2.926 (1.390-6.163)], time to onset of CPR [HR 1.063 (0.997-1.134)], older age [1.036 (1.008-1.064)) and worse ejection fraction at discharge [1.033 (1.009-1.058)]. CONCLUSIONS: Even though few patients experience recurrent cardiac arrest events, survivors after OHCA face high morbidity and mortality during long-term follow-up. Therefore, they may benefit from multidisciplinary teams providing an integral management and ensuring continuity of care.

Dataset regarding baseline and follow-up characteristics of out-of-hospital cardiac arrest patients focused on neurological outcomes.

This data article contains the data related to the research article entitled "Long-term neurological outcomes in out-of-hospital cardiac arrest patients treated with targeted-temperature management" (Caro-Codón et al., 2018). In this dataset, we report details regarding the flow chart of the included patients and the specific exclusion criteria. We also include information on the difference between the patients who attended the structured personal interview (and therefore were finally included in the study) and those who did not attend. Neuropsychiatric and functional data before and after cardiac arrest are also reported. Finally, we list all the "de novo" focal neurological deficits identified after cardiac arrest in the related population.

Long-term neurological outcomes in out-of-hospital cardiac arrest patients treated with targeted-temperature management.

BACKGROUND: This study aimed to assess long-term cognitive and functional outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted-temperature management, investigate the existence of prognostic factors that could be assessed during initial admission and evaluate the usefulness of classic neurological scales in this clinical scenario. METHODS: Patients admitted due to OHCA from August 2007 to November 2015 and surviving at least one year were included. Each patient completed a structured interview focused on the collection of clinical, social and demographic data. All available information in clinical records was reviewed and a battery of neurocognitive and psychometric tests was performed. RESULTS: Seventy-nine patients were finally included in the analysis. Forty-three patients (54.4%) scored below the usual cut-off points for the diagnosis of mild cognitive impairment, even though most of these deficits went unnoticed when patients were assessed using CPC and modified Rankin scale. Nineteen (24%) developed certain degree of impairment in their attention capacity and executive functions. A significant proportion developed new memory-related disorders (43%), depressive symptoms (17.7%), aggressive/uninhibited behavior (12.7%) and emotional lability (8.9%). A greater number of weekly hours of intellectual activity and a qualified job were independent protective factors for the development of cognitive impairment. However, being older at the time of the cardiac arrest was identified as a poor prognostic factor. CONCLUSIONS: There is a high prevalence of long-term cognitive deficits and functional limitations in OHCA survivors. Most commonly used clinical scales in clinical practice are crude and lack sensitivity to detect most of these deficits.

Critical appraisal of trials for validation of 'risk-guided' cardiovascular disease prevention therapy.

Cardiovascular risk management in the primary prevention population is impeded by the fact that risk scores do not identify properly a low-moderate risk population that could benefit from the use of preventive strategies. Current risk scores are further limited by their complexity and the lack of applicability to special patient populations and the real-life clinical setting, which deters their use. Clinical trials with risk factor interventions have been based on either a treat-to-target or fire-and-forget strategy and have used cardiovascular mortality or major events as their primary endpoint. These endpoints may not be appropriate for assessing cardiovascular benefit in low-moderate risk patients. Cardiovascular risk assessment should guide the strategy for risk factor intervention; however, this needs to be more clearly defined in low-intermediate risk patients.