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 During the study period, 216 (46.2%), 193 (56.3%) and 41 (49.4%) were withdrawn from the corresponding drug.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.

Influence of statin treatment in a cohort of patients admitted for COVID-19.

Aims and objectives: Statins have been proposed as potentially useful agents for modulating the host response in COVID-19. However, solid evidence-based recommendations are still lacking. Our aim was to study the association between statin use and clinical outcomes in a large cohort of hospitalized patients with SARS-CoV-2 infection, as well as the specific consequences of chronic treatment withdrawal during hospital admission. Material and methods: Retrospective observational study including 2191 hospitalized patients with confirmed SARS-CoV-2 infection. Results: Mean age was 68.0±17.8 years and 597 (27.3%) patients died during follow-up. A total of 827 patients (37.7% of the whole sample), received chronic treatment with statins. Even though they underwent more frequent admissions in critical care units, chronic treatment with statins was not independently associated with all-cause mortality [HR 0.95 (0.72-1.25)]. During the whole hospital admission, 371 patients (16.9%) received at least one dose of statin. Although these patients had a significantly worse clinical profile, both treatment with statins during admission [HR 1.03 (0.78-1.35)] and withdrawal of chronic statin treatment [HR 1.01 (0.78-1.30)] showed a neutral effect in mortality. However, patients treated with statins presented more frequently hepatic cytolysis, rhabdomyolysis and thrombotic/hemorrhagic events. Conclusions: In this large cohort of hospitalized COVID-19 patients, statins were not independently associated with all-cause mortality during follow-up. Clinically relevant statin-associated adverse effects should be carefully monitored during hospital admission.

Antecedentes y objetivos: Se ha especulado que las estatinas pueden ser de utilidad en el tratamiento de pacientes con COVID-19, pero no existen evidencias clínicas sólidas. El objetivo de este trabajo es conocer su utilidad en una cohorte de gran tamaño de pacientes hospitalizados por COVID-19, así como si su retirada se asocia con un peor pronóstico. Material y métodos: Estudio retrospectivo observacional. Se incluyeron 2.191 pacientes hospitalizados con infección confirmada con SARS-CoV-2. Resultados: La edad media fue de 68,0 ± 17,8 años y fallecieron un total de 597 (27,3%) pacientes. Un total de 827 pacientes (37,7% de la muestra) estaban tratados previamente con estatinas. Aunque precisaron con mayor frecuencia de ingreso en camas de críticos, dicho grupo terapéutico no resultó un factor predictor independiente de muerte en el seguimiento [HR 0,95 (0,72-1,25)]. Un total de 371 pacientes (16,9%) recibió al menos una dosis de estatina durante el ingreso. A pesar de ser una población con un perfil clínico más desfavorable, tanto su uso [HR 1,03 (0,78-1,35)] como la suspensión durante el ingreso en pacientes que las recibían crónicamente [HR 1,01 (0,78-1,30)] presentaron un efecto neutro en la mortalidad. No obstante, el grupo con estatinas desarrolló con mayor frecuencia datos de citolisis hepática, rabdomiolisis y más eventos trombóticos y hemorrágicos. Conclusiones: En nuestra muestra, las estatinas no se asociaron de forma independiente a una menor mortalidad en pacientes con COVID-19. En aquellos pacientes que tengan indicación de recibirlas por su patología previa es necesario monitorizar estrechamente sus potenciales efectos adversos durante el ingreso hospitalario.

Bispectral index and suppression ratio after cardiac arrest: are they useful as bedside tools for rational treatment escalation plans?

INTRODUCTION AND OBJECTIVES: Myocardial dysfunction contributes to early mortality (24-72 hours) among survivors of a cardiac arrest (CA). The benefits of mechanical support in refractory shock should be balanced against the patient's potential for neurological recovery. To date, these early treatment decisions have been taken based on limited information leading mainly to undertreatment. Therefore, there is a need for early, reliable, accessible, and simple tools that offer information on the possibilities of neurological improvement. METHODS: We collected data from bispectral index (BIS) and suppression ratio (SR) monitoring of adult comatose survivors of CA managed with targeted temperature management (TTM). Neurological status was assessed according to the Cerebral Performance Category (CPC) scale. RESULTS: We included 340 patients. At the first full neurological evaluation, 211 patients (62.1%) achieved good outcome or CPC 1-2. Mean BIS values were significantly higher and median SR lower in patients with CPC 1-2. An average BIS> 26 during first 12 hours of TTM predicted good outcome with 89.5% sensitivity and 75.8% specificity (AUC of 0.869), while average SR values> 24 during the first 12 hours of TTM predicted poor outcome (CPC 3-5) with 91.5% sensitivity and 81.8% specificity (AUC, 0.906). Hourly BIS and SR values exhibited good predictive performance (AUC> 0.85), as soon as hour 2 for SR and hour 4 for BIS. CONCLUSIONS: BIS/SR are associated with patients' potential for neurological recovery after CA. This finding could help to create awareness of the possibility of a better outcome in patients who might otherwise be wrongly considered as nonviable and to establish personalized treatment escalation plans.

Cardiac monitoring during trastuzumab therapy in metastatic breast cancer: early incidence of cardiac dysfunction.

Trastuzumab therapy has dramatically changed breast cancer prognosis. Consensus documents recommend a close monitoring during therapy, not always feasible, especially in metastatic breast cancer. The purpose of this study is to describe trastuzumab cardiotoxicity in metastatic breast cancer patients to understand how to improve cardiovascular monitoring. We retrospectively studied metastatic breast cancer patients scheduled for trastuzumab therapy (2001-2018). All patients underwent a baseline evaluation and monitoring during therapy. Cardiotoxicity was defined as symptomatic heart failure or asymptomatic decrease in left ventricular ejection fraction > 10% from baseline and < 53%. Ninety-two women were included, mean age 61 years (±14.43), median follow-up 42.5 months (IQR 26-74). Fourteen percent developed cardiotoxicity:  two heart failure with preserved left ventricular ejection fraction, three heart failure with reduced left ventricular ejection fraction, and eight asymptomatic decreased in left ventricular ejection fraction. Eighty-one percent of cardiac dysfunction cases occurred within the first 4 years and on median of 31 months from trastuzumab initiation. Thus, in metastatic breast cancer patients, trastuzumab-mediated cardiotoxicity occurred more frequently during the first 4 years. These data should be considered to optimize follow-up protocols.

Influence of statin treatment in a cohort of patients admitted for COVID-19. / Influencia del tratamiento con estatinas en una cohorte de pacientes ingresados por COVID-19.

AIMS AND OBJECTIVES: Statins have been proposed as potentially useful agents for modulating the host response in COVID-19. However, solid evidence-based recommendations are still lacking. Our aim was to study the association between statin use and clinical outcomes in a large cohort of hospitalized patients with SARS-CoV-2 infection, as well as the specific consequences of chronic treatment withdrawal during hospital admission. MATERIAL AND METHODS: Retrospective observational study including 2191 hospitalized patients with confirmed SARS-CoV-2 infection. RESULTS: Mean age was 68.0±17.8 years and 597 (27.3%) patients died during follow-up. A total of 827 patients (37.7% of the whole sample), received chronic treatment with statins. Even though they underwent more frequent admissions in critical care units, chronic treatment with statins was not independently associated with all-cause mortality [HR 0.95 (0.72-1.25)]. During the whole hospital admission, 371 patients (16.9%) received at least one dose of statin. Although these patients had a significantly worse clinical profile, both treatment with statins during admission [HR 1.03 (0.78-1.35)] and withdrawal of chronic statin treatment [HR 1.01 (0.78-1.30)] showed a neutral effect in mortality. However, patients treated with statins presented more frequently hepatic cytolysis, rhabdomyolysis and thrombotic/hemorrhagic events. CONCLUSIONS: In this large cohort of hospitalized COVID-19 patients, statins were not independently associated with all-cause mortality during follow-up. Clinically relevant statin-associated adverse effects should be carefully monitored during hospital admission.

Cardiovascular risk factors during cancer treatment. Prevalence and prognostic relevance: insights from the CARDIOTOX registry.

AIMS: The actual usefulness of cardiovascular (CV) risk factor assessment in the prognostic evaluation of cancer patients treated with cardiotoxic treatment remains largely unknown. Prospective multicentre study in patients scheduled to receive anticancer therapy related with moderate/high cardiotoxic risk. METHODS AND RESULTS: A total of 1324 patients underwent follow-up in a dedicated cardio-oncology clinic from April 2012 to October 2017. Special care was given to the identification and control of CV risk factors. Clinical data, blood samples, and echocardiographic parameters were prospectively collected according to protocol, at baseline before cancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years after initiation of cancer therapy. At baseline, 893 patients (67.4%) presented at least one risk factor, with a significant number of patients newly diagnosed during follow-up. Individual risk factors were not related with worse prognosis during a 2-year follow-up. However, a higher Systemic Coronary Risk Estimation (SCORE) was significantly associated with higher rates of severe cardiotoxicity (CTox) and all-cause mortality [hazard ratio (HR) 1.79 (95% confidence interval, CI 1.16-2.76) for SCORE 5-9 and HR 4.90 (95% CI 2.44-9.82) for SCORE ≥10 when compared with patients with lower SCORE (0-4)]. CONCLUSIONS: This large cohort of patients treated with a potentially cardiotoxic regimen showed a significant prevalence of CV risk factors at baseline and significant incidence during follow-up. Baseline CV risk assessment using SCORE predicted severe CTox and all-cause mortality. Therefore, its use should be considered in the evaluation of cancer patients.

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.

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.

Comparison of Noninvasive Cardiac Test Strategies for Newly Diagnosed Chagas Disease in a Non-Endemic Zone.

Chagas disease is an emerging infectious disease in Europe and other non-endemic areas, mainly owing to migration from endemic areas. We aimed at investigating the value of advanced echocardiography (ECHO) and cardiac magnetic resonance (CMR) in patients newly diagnosed with Chagas disease to compare findings with those of electrocardiogram (ECG) and conventional ECHO and thus detecting cardiac abnormalities. We included consecutive patients with newly diagnosed Chagas disease and registered cardiac test results (ECG, ECHO, and CMR). We divided ECHO parameters into three tiers: 1) left ventricular ejection fraction, regional wall motion abnormality, and left ventricular diastolic dimension (ECHO-1); 2) other common ECHO parameters (ECHO-2); and 3) global longitudinal strain (GLS) (ECHO-3). Cardiac magnetic resonance included global and segmental biventricular function, the presence of myocardial fibrosis, and edema. The study comprised 100 patients from South America. The mean age was 43.9 ± 0.9 years, and 66% were women. Mean time living in Spain was 9.7 ± 0.5 years. The ECG revealed ≥ 2 abnormal findings in 47% of patients. ECHO-1 was abnormal in 22% of patients, ECHO-2 in 52%, and GLS in 16%. Cardiac magnetic resonance was abnormal in 50% of cases, and in 3% of these, ECHO was normal. When ECG and conventional ECHO were taken together, abnormalities were detected in 83% of patients. This value increased to 86% and 92% for GLS and CMR, respectively. These findings suggest that ECG and conventional ECHO should be used routinely as standard cardiac tests for newly diagnosed cases of Chagas disease. The value of advanced ECHO techniques and CMR is low.