Incidence and determinants of high-sensitivity troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

BACKGROUND: Myocardial involvement in the course of coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. The aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. METHODS: In this multicenter observational study, we analyzed data from n = 111 patients. Cardiac biomarkers subgroups were identified according to values beyond reference range. RESULTS: Increased hs-Troponin and NP were found in 38 and 56% of the cases, respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and had more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03, respectively). Both hs-Troponin and NP were higher in patients with in-hospital mortality (p = 0.001 and p = 0.002, respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B = - 0.212, p = 0.013; and B = 0.179, p = 0.037, respectively) and of NP with age and previous CVD (B = 0.480, p < 0.001; and B = 0.253, p = 0.001, respectively). CONCLUSIONS: Myocardial involvement at admission is common in COVID-19 pneumonia. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point toward existing different mechanisms leading to their elevation in this setting.

265 Incidence, determinants and prognostic relevance of HS-troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

Aims: myocardial involvement in the course of Coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. Aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. Methods and results: in this multicenter observational study, we analyzed data from n = 111 COVID-19 patients admitted to dedicated "COVID-19" medical units. Hs-Troponin was assessed in n = 103 patients and NP in n = 82 patients on admission; subgroups were identified according to values beyond reference range. increased hs-Troponin and NP were found in 38% and 56% of the cases respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP only (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03 respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B=-0.212, p = 0.013 and B = 0.179, p = 0.037 respectively), and of NP with age and previous CVD (B = 0.480, p < 0.001 and B = 0.253, p = 0.001 respectively). In patients with in-hospital mortality (n = 23, 21%) hs-Troponin and NP were both higher (p = 0.001 and p = 0.002 respectively), while increasing hs-troponin and NP were associated with worse in-hospital prognosis [OR 4.88 (95% CI 1.9-12.2), p = 0.001 (adjusted OR 3.1 (95% CI 1.2-8.5), p = 0.025) and OR 4.67 (95% CI 2-10.8), p < 0.001 (adjusted OR 2.89 (95% CI 1.1-7.9), p = 0.04) respectively]. Receiver operator characteristic curves showed good ability of hs-Troponin and NP in predicting in-hospital mortality (AUC = 0.869 p < 0.001 and AUC = 0.810, p < 0.001 respectively). Conclusion: myocardial involvement at admission is common in COVID-19 pneumonia and associated to worse prognosis, suggesting a role for cardiac biomarkers assessment in COVID-19 risk stratification. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point towards existing different mechanisms leading to their elevation in this setting.

Significance of Patent Foramen Ovale in Patients with GOLD Stage II Chronic Obstructive Pulmonary Disease (COPD).

Background: Patent foramen ovale (PFO) is a common finding in adults. A PFO is associated with right to left shunting but its importance in the aetiology of hypoxia in early COPD remains uncertain, although it has not proved possible to demonstrate a role for PFOs in the aetiology of hypoxia in patients with Global Initiative for chronic Obstructive Lung Disease (GOLD) stage III/IV disease. We compared the characteristics of GOLD stage II patients with or without a PFO and assessed its impact on exercise performance. Methods: In 22 GOLD stage II COPD patients we measured exercise performance, arterial oxygen tension and lung function and used contrast transcranial Doppler ultrasonography (TCD) to assess the presence of a PFO. Patients (n=20) underwent TCD measurements during incremental cycle ergometry with respiratory pressures measured using an esophageal balloon catheter (n=13). Results:Twelve individuals (54%) had a PFO. Patients with a PFO were more hypoxic; mean(SD) partial pressure of oxygen in arterial blood (PaO2)10.2(1.1) kilopascals (kPa) vs. 11.7(0.9)kPa (p<0.01), but the presence of a PFO was not associated with reduced exercise performance either on cycle ergometry or a 6 Minute Walk Test (6MWT). A strong relationship was noted between the esophageal pressure swing (PSwingEs) and the degree of shunting observed during exercise (r=0.7; p<0.001). Conclusions:The presence of a PFO in GOLD stage II COPD patients does not appear to influence exercise performance despite increased right-to-left shunting.

Respiratory muscle fatigue following exercise in patients with interstitial lung disease.

BACKGROUND: It is not known whether respiratory muscle fatigue occurs as a consequence of exercise in patients with interstitial lung disease (ILD) and, if so, to what extent it is related to changes in dynamic lung volumes. OBJECTIVES: To assess the development of respiratory muscle fatigue in patients with ILD and relate it to the respiratory pattern during exercise. METHODS: Sixteen ILD patients (11 women) performed incremental, symptom-limited cycle ergometry with inspiratory capacity manoeuvres used to measure changes in end-expiratory lung volume (EELV). Twitch transdia-phragmatic pressure (TwPdi) and twitch gastric pressure (TwT10Pga), in response to magnetic stimulation, were used to assess the development of fatigue. RESULTS: TwPdi did not differ significantly before and after exercise (21.8 ± 8 vs. 20.2 ± 8 cm H2O; p = 0.10), while TwT10Pga fell from 28.6 ± 18 to 25.2 ± 14 cm H2O (p = 0.02). EELV fell from 2.18 ± 0.65 to 1.91 ± 0.59 liters following exercise (p = 0.04). The fall in TwT10Pga correlated with peak oxygen uptake at peak of exercise (r = -0.52, p = 0.041), increase in heart rate (r = 0.53, p = 0.032) and with the decrease of EELV during exercise (r = 0.57, p = 0.021). Abdominal muscle fatiguers (n = 9, 56%), defined as having a ≥10% fall in TwT10Pga, had a fall in EELV of 22 ± 22% compared to 0.7 ± 8% in non-fatiguers (p = 0.016). CONCLUSION: Abdominal muscle fatigue develops during exercise in some ILD patients in association with increased expiratory muscle activity manifested by reduced EELV.

Muscle function in COPD: a complex interplay.

The skeletal muscles play an essential role in life, providing the mechanical basis for respiration and movement. Skeletal muscle dysfunction is prevalent in all stages of chronic obstructive pulmonary disease (COPD), and significantly influences symptoms, functional capacity, health related quality of life, health resource usage and even mortality. Furthermore, in contrast to the lungs, the skeletal muscles are potentially remedial with existing therapy, namely exercise-training. This review summarizes clinical and laboratory observations of the respiratory and peripheral skeletal muscles (in particular the diaphragm and quadriceps), and current understanding of the underlying etiological processes. As further progress is made in the elucidation of the molecular mechanisms of skeletal muscle dysfunction, new pharmacological therapies are likely to emerge to treat this important extra-pulmonary manifestation of COPD.

A simplified approach for the estimation of the ventilatory compensation point.

UNLABELLED: Incremental cardiopulmonary exercise test with gas exchange measurement is the gold standard for the identification of the ventilatory compensation point (VCP). It has previously been demonstrated that the change in the slope of increment of minute ventilation over HR (ΔV˙E/ΔHR) can be used alternatively to the ventilatory equivalent for CO2 (V˙E/V˙CO2) method for detection of VCP in healthy subjects undergoing cycle ergometer (C) incremental exercise. The same evaluation during treadmill (T) incremental exercise and comparison between C and T have not yet been performed. PURPOSE: We analyzed, during both C and T incremental exercises, the V˙E/HR and the respiratory rate (RR)/HR relationships, expressed either as slope or as an absolute value. We hypothesized that changes in the slope of increment of the two relationships could represent a reliable method for VCP detection, regardless of exercise mode and protocol. METHODS: Fourteen healthy male subjects (age = 31 ± 7 yr (mean ± SD)) underwent two T incremental exercises--fast (FT) and slow (ST) protocols (8 km·h⁻¹, 2% (F(T)) and 1% (S(T)) grade per minute)--and one C incremental exercise (30 W·min⁻¹). O2 uptake (V˙O2), V˙CO2, V˙E, HR, and RR were measured breath by breath. RESULTS: A good between-method agreement in the detection of VCP by the ΔV˙(E)/ΔV˙CO2, ΔV˙(E)/ΔHR, and the ΔRR/ΔHR slope changes was found in both T protocols and C. No differences (C vs T and F(T) vs S(T)) were found in the slope of the ΔV˙(E)/ΔHR and ΔRR/ΔHR relationships after the VCP and in the V˙(E)/HR and RR/HR absolute values at VCP. CONCLUSIONS: In healthy young males, the ΔV˙E/ΔHR and ΔRR/ΔHR relationships during T and C incremental exercises can be reliably used to detect the VCP as an alternative to the ventilatory equivalent method.

Cardiopulmonary exercise testing (CPET) in pulmonary emphysema.

In patients affected by chronic obstructive pulmonary disease (COPD), cardiopulmonary response to exercise was never related to the severity of emphysema (E) measured by high resolution computed tomography (HRCT). Sixteen patients (age=65±8 yrs; FEV(1)=54±18%pred; RV=160±28%pred) with moderate to severe E (quantified by lung HRCT as % voxels <-910 HU) were exercised on a cycle-ergometer to exhaustion. Oxygen uptake (V˙(O2)), carbon dioxide output (V˙(CO2)), ventilation (V˙(E)), tidal volume (V(T)), and end-tidal P(CO2) (PET(CO2)) derived variables were measured breath-by-breath. The % of E correlated with: (1) the ratio V(Tpeak) (r=0.74; p=0.001); (2) the V˙(E)/V˙(CO2) slope (r=-0.77; p=0.0004); (3) PET(CO2) values at peak exercise (r=0.80; p=0.0001). Also, the %E was strongly predicted by the following exercise equation: %E(EST) = 58.1 + 11.9 × ΔV˙(E)/V˙(CO2) (r=0.94; p<0.0001). A V(Tpeak)/FEV1 ratio>1 is typically observed in severe E patients; furthermore, the V˙(E)/V˙(CO2) slope and the PET(CO2peak) values decrease and increase respectively as more as the emphysema is severe.

Bronchodilator effect on ventilatory, pulmonary gas exchange, and heart rate kinetics during high-intensity exercise in COPD.

Respiratory mechanical abnormalities in patients with chronic obstructive pulmonary disease (COPD) may impair cardiodynamic responses and convective oxygen delivery during exercise, resulting in slower ventilatory, pulmonary gas exchange (PGE), and heart rate (HR) kinetics compared with normal. We reasoned that bronchodilators and the attendant reduction of operating lung volumes should accelerate ventilatory, PGE, and HR kinetics in the transition from rest to high-intensity exercise. Twelve clinically stable COPD patients undertook constant-work rate cycle testing at 75% of each individual's maximum work capacity after receiving either combined nebulized bronchodilators (BD) or placebo (PL), randomly. Mean response time (MRT) and amplitude of slow component for oxygen uptake (V'O(2)), carbon dioxide production (V'CO(2)), ventilation (V'(E)), and HR together with operating dynamic end-expiratory lung volume (EELV) were measured. Resting and exercise EELV decreased significantly by 0.38 L after BD compared with PL. After BD, V'O(2), V'CO(2), V'(E), and HR MRT accelerated (p < 0.05) by an average of 12, 22, 27, and 22 s, respectively (i.e., 15, 18, 22 and 27%, respectively). The slow component for V'O(2) declined by an average of 55 ml/min compared with PL. Speeded MRT for V'O(2) correlated with indices of reduced lung hyperinflation, such as resting EELV (r = -0.64, p = 0.025) and EELV at isotime (r = -0.77, p = 0.0032). The results confirm an important interaction between abnormal dynamic respiratory mechanics and indices of cardio-circulatory function in the rest-to-exercise transition in COPD patients.

Estimation of the exercise ventilatory compensation point by the analysis of the relationship between minute ventilation and heart rate.

Cardiopulmonary exercise test is the gold standard for the identification of the ventilatory compensation point (VCP), an important threshold for exercise training prescription. We hypothesized that changes in the slope of increment in minute ventilation (V'(E)) over heart rate (HR) during incremental exercise can be utilized, as alternative to the ventilatory equivalents method, for VCP detection. In 14 healthy subjects (ten males, four females, age 31 +/- 10 SD) we studied the ventilatory, cardiovascular and gas exchange adaptations during two incremental cycle ergometer exercise: (F) fast work rate increments (30-20 watt/min, M-F), (S) slow work rate increments (15-10 watt/min, M-F). A good between-method agreement in VCP detection in terms of oxygen uptake (V'O(2)) was found in both F and S protocols (F: -7 +/- 118 V'O(2) ml/min; S: -36 +/- 144 V'O(2) ml/min). VCP occurred at the same percentage of peak V'O(2) in both protocols. The changes in the V'(E) versus HR slope during incremental exercise can be used to detect the VCP as alternative to the ventilatory equivalents method.