Exercise Intolerance in Post-Acute Sequelae of COVID-19 and the Value of Cardiopulmonary Exercise Testing- a Mini-Review.

Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with systemic organ damage in the most severe forms. Long-term complications of SARS-CoV-2 appear to be restricted to severe presentations of COVID-19, but many patients with persistent symptoms have never been hospitalized. Post-acute sequelae of COVID-19 (PASC) represents a heterogeneous group of symptoms characterized by cardiovascular, general, respiratory, and neuropsychiatric sequelae. The pace of evidence acquisition with PASC has been rapid, but the mechanisms behind it are complex and not yet fully understood. In particular, exercise intolerance shares some features with other classic respiratory and cardiac disorders. However, cardiopulmonary exercise testing (CPET) provides a comprehensive assessment and can unmask the pathophysiological mechanism behind exercise intolerance in gray-zone PASC. This mini-review explores the utility of CPET and aims to provide a comprehensive assessment of PASC by summarizing the current evidence.

Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19.

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). METHODS AND RESULTS: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. CONCLUSION: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.

Exercise Ventilatory Inefficiency in Post-COVID-19 Syndrome: Insights from a Prospective Evaluation.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. This study sought to identify clinical sequelae and their potential mechanism. METHODS: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up. An outpatient group was also evaluated. They underwent serial testing with a cardiopulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis, and quality of life questionaries. RESULTS: Patients with dyspnea (n = 41, 58.6%), compared with asymptomatic patients (n = 29, 41.4%), had a higher proportion of females (73.2 vs. 51.7%; p = 0.065) with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in the transthoracic echocardiogram and pulmonary function test. Patients who complained of persistent dyspnea had a significant decline in predicted peak VO2 consumption (77.8 (64-92.5) vs. 99 (88-105); p < 0.00; p < 0.001), total distance in the six-minute walking test (535 (467-600) vs. 611 (550-650) meters; p = 0.001), and quality of life (KCCQ-23 60.1 ± 18.6 vs. 82.8 ± 11.3; p < 0.001). Additionally, abnormalities in CPET were suggestive of an impaired ventilatory efficiency (VE/VCO2 slope 32 (28.1-37.4) vs. 29.4 (26.9-31.4); p = 0.022) and high PETCO2 (34.5 (32-39) vs. 38 (36-40); p = 0.025). INTERPRETATION: In this study, >50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest a potential ventilation/perfusion mismatch or hyperventilation syndrome.

Modelo predictivo de mortalidad hospitalaria en endocarditis infecciosa izquierda / Predictive model of in-hospital mortality in left-sided infective endocarditis

INTRODUCCIÓN Y OBJETIVOS: La endocarditis infecciosa (EI) es una enfermedad compleja con elevada mortalidad. La evaluación pronóstica es esencial en el tratamiento de la enfermedad; sin embargo, las guías internacionales no aportan una evaluación objetiva del riesgo individual. Se desarrolló un modelo predictivo de mortalidad hospitalaria en EI izquierda combinando las variables pronósticas propuestas por la guía europea. MÉTODOS: Se utilizaron 2 cohortes prospectivas de pacientes con EI izquierda. La cohorte 1 (n=1.002) se aleatorizó 2:1 para obtener 2 muestras: muestra de derivación (n=688) y muestra de validación interna (n=314). La cohorte 2 (n=133) se utilizó para la validación externa. RESULTADOS: El modelo incluyó edad, endocarditis protésica, comorbilidades, insuficiencia cardiaca, insuficiencia renal, shock séptico, Estafilococo aureus, hongos, complicaciones perianulares, disfunción ventricular y vegetaciones como predictores independientes de mortalidad hospitalaria. El modelo mostró buena capacidad discriminativa (área bajo la curva ROC=0,855; IC95%, 0,825-0,885) y calibración (p valor test Hosmer-Lemeshow=0,409) que se ratificaron en la validación interna (área bajo curva ROC=0,823; IC95%, 0,774-0,873) y externa (área bajo curva ROC=0,753; IC95%, 0,659-0,847). Para la muestra de validación interna (mortalidad 29,9%) el modelo predijo una mortalidad de 30,7% (IC95%, 27,7-33,7) y para la muestra de validación externa (mortalidad 27,1%) 26,4% (IC95%, 22,2-30,5). CONCLUSIONES: Se presenta un modelo predictivo de mortalidad hospitalaria en EII basado en las variables pronósticas propuestas por la guía europea de EI y con alta capacidad discriminativa

INTRODUCTION AND OBJECTIVES: Infective endocarditis (IE) is a complex disease with high in-hospital mortality. Prognostic assessment is essential to select the most appropriate therapeutic approach; however, international IE guidelines do not provide objective assessment of the individual risk in each patient. We aimed to design a predictive model of in-hospital mortality in left-sided IE combining the prognostic variables proposed by the European guidelines. METHODS: Two prospective cohorts of consecutive patients with left-sided IE were used. Cohort 1 (n=1002) was randomized in a 2:1 ratio to obtain 2 samples: an adjustment sample to derive the model (n=688), and a validation sample for internal validation (n=314). Cohort 2 (n=133) was used for external validation. RESULTS: The model included age, prosthetic valve IE, comorbidities, heart failure, renal failure, septic shock, Staphylococcus aureus, fungi, periannular complications, ventricular dysfunction, and vegetations as independent predictors of in-hospital mortality. The model showed good discrimination (area under the ROC curve=0.855; 95%CI, 0.825-0.885) and calibration (P value in Hosmer-Lemeshow test=0.409), which were ratified in the internal (area under the ROC curve=0.823; 95%CI, 0.774-0.873) and external validations (area under the ROC curve=0.753; 95%CI, 0.659-0.847). For the internal validation sample (observed mortality: 29.9%) the model predicted an in-hospital mortality of 30.7% (95%CI, 27.7-33.7), and for the external validation cohort (observed mortality: 27.1%) the value was 26.4% (95%CI, 22.2-30.5). CONCLUSIONS: A predictive model of in-hospital mortality in left-sided IE based on the prognostic variables proposed by the European Society of Cardiology IE guidelines has high discriminatory ability

Predictive model of in-hospital mortality in left-sided infective endocarditis.

INTRODUCTION AND OBJECTIVES: Infective endocarditis (IE) is a complex disease with high in-hospital mortality. Prognostic assessment is essential to select the most appropriate therapeutic approach; however, international IE guidelines do not provide objective assessment of the individual risk in each patient. We aimed to design a predictive model of in-hospital mortality in left-sided IE combining the prognostic variables proposed by the European guidelines. METHODS: Two prospective cohorts of consecutive patients with left-sided IE were used. Cohort 1 (n=1002) was randomized in a 2:1 ratio to obtain 2 samples: an adjustment sample to derive the model (n=688), and a validation sample for internal validation (n=314). Cohort 2 (n=133) was used for external validation. RESULTS: The model included age, prosthetic valve IE, comorbidities, heart failure, renal failure, septic shock, Staphylococcus aureus, fungi, periannular complications, ventricular dysfunction, and vegetations as independent predictors of in-hospital mortality. The model showed good discrimination (area under the ROC curve=0.855; 95%CI, 0.825-0.885) and calibration (P value in Hosmer-Lemeshow test=0.409), which were ratified in the internal (area under the ROC curve=0.823; 95%CI, 0.774-0.873) and external validations (area under the ROC curve=0.753; 95%CI, 0.659-0.847). For the internal validation sample (observed mortality: 29.9%) the model predicted an in-hospital mortality of 30.7% (95%CI, 27.7-33.7), and for the external validation cohort (observed mortality: 27.1%) the value was 26.4% (95%CI, 22.2-30.5). CONCLUSIONS: A predictive model of in-hospital mortality in left-sided IE based on the prognostic variables proposed by the European Society of Cardiology IE guidelines has high discriminatory ability.

Contemporary epidemiology and outcomes in recurrent infective endocarditis.

OBJECTIVE: Recurrent infective endocarditis (IE) is a major complication of patients surviving a first episode of IE. This study sought to analyse the current state of recurrent IE in a large contemporary cohort. METHODS: 1335 consecutive episodes of IE were recruited prospectively in three tertiary care centres in Spain between 1996 and 2015. Episodes were categorised into group I (n=1227), first-IE episode and group II (n=108), recurrent IE (8.1%). After excluding six patients, due to lack of relevant data, group II was subdivided into IIa (n=87), reinfection (different microorganism), and IIb (n=15), relapse (same microorganism within 6 months of the initial episode). RESULTS: The cumulative burden and incidence of recurrence was slightly lower in the second decade of the study (2006-2015) (7.17 vs 4.10 events/100 survivors and 7.51% vs 3.82, respectively). Patients with reinfections, compared with group I, were significantly younger, had a higher frequency of HIV infection, were more commonly intravenous drug users (IVDU) and prosthetic valve carriers, had less embolic complications and cardiac surgery, with similar in-hospital mortality. IVDU was found to be an independent predictor of reinfection (HR 3.92, 95% CI 1.86 to 8.28).In the relapse IE group, prosthetic valve endocarditis (PVE) and periannular complications were more common. Among patients treated medically, those with PVE had a higher relapse incidence (4.82% vs 0.43% in native valve IE, p=0.018). Staphylococcus aureus and PVE were independent predictors of relapse (HR 3.14, 95% CI 1.11 to 8.86 and 3.19, 95% CI 1.13 to 9.00, respectively) and in-hospital-mortality was similar to group I. Three-year all-cause mortality was similar in recurrent episodes compared with single episodes. CONCLUSION: Recurrent IE remains a frequent late complication. IVDU was associated with a fourfold increase in the risk of reinfection. PVE treated medically and infections caused by S. aureus increased the risk of relapse. In-hospital and long-term mortality was comparable among groups.

Nutritionally variant streptococci infective endocarditis: Report of 5 cases / Endocarditis infecciosa por variantes nutricionales de estreptococos: estudio de 5 casos

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Impact of Valve Culture in the Prognosis of Active Left-sided Infective Endocarditis.

BACKGROUND: The culture of removed cardiac tissues during cardiac surgery of left-sided infective endocarditis (LSIE) helps to guide antibiotic treatment. Nevertheless, the prognostic information of a positive valve culture has never been explored. METHODS: Among 1078 cases of LSIE consecutively diagnosed in 3 tertiary centers, we selected patients with positive blood cultures who underwent surgery during the active period of infection and in whom surgical biological tissues were cultured (n = 429). According to microbiological results, we constructed 2 groups: negative valve culture (n=218) and concordant positive valve culture (CPVC) (n=118). We compared their main features and performed a multivariable analysis of in-hospital mortality. RESULTS: Patients with CPVC presented more nosocomial origin (32% vs 20%, P = .014), more septic shock (21% vs 11%, P = .007), and higher Risk-E score (29% vs 21%, P = .023). Their in-hospital mortality was higher (35% vs 19%, P = .001), despite an earlier surgery (3 vs 11 days from antibiotic initiation, P < .001). Staphylococcus species (61% vs 42%, P = .001) and Enterococcus species (20% vs 9%, P = .002) were more frequent in the CPVC group, whereas Streptococcus species were less frequent (14% vs 42%, P < .001). Independent predictors for in-hospital mortality were renal failure (odds ratio [OR], 2.6 [95% confidence interval {CI}, 1.5-4.4]), prosthesis (OR, 1.9 [95% CI, 1.1-3.5]), Staphylococcus aureus (OR, 1.8 [95% CI, 1.02-3.3]), and CPVC (OR, 2.3 [95% CI, 1.4-3.9]). CONCLUSIONS: Valve culture in patients with active LSIE is an independent predictor of in-hospital mortality.

Endocarditis infecciosa por Leuconostoc species / Infective endocarditis due to leuconostoc species

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Surgery changes prognosis in infective endocarditis: The importance of post-surgical clinical evolution.

BACKGROUND: Left-sided infective endocarditis (LSIE) bears a grim prognosis and surgery is needed in more than half of the patients to improve survival. Our hypothesis has been that clinical complications developing after surgery impact prognosis. METHODS: Among 1075 consecutive episodes of LSIE, 654 (60.7%) underwent cardiac surgery. Of them, 41 patients (6.3%) died the same day of surgery, 112 (17.2%) died after the first day of surgery during hospital stay and 500 (76.5%) were successfully discharged. We compared the last two groups and performed a multivariable analysis of in-hospital mortality. RESULTS: Age (OR 1.02, 95% CI 1.01-1.04), periannular complications (OR 1.9, 95% CI 1.2-3.2) renal failure after surgery (OR 2.4, 95% CI 1.3-4.4) but not before surgery, and septic shock after surgery (OR 9.6, 95% CI 5.4-17.1) but not before surgery are predictive of in-hospital death among LSIE patients who underwent cardiac surgery. CONCLUSION: A thorough clinical assessment with prognostic purposes in infective endocarditis after surgery is mandatory. In-hospital mortality of patients with infective endocarditis who undergo surgery depends mainly on the clinical evolution after surgery.