Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Effects of sacubitril/valsartan on exercise capacity: a prognostic improvement that starts during uptitration.

PURPOSE: Sacubitril/valsartan is a mainstay of the treatment of heart failure with reduced ejection fraction (HFrEF); however, its effects on exercise performance yielded conflicting results. Aim of our study was to evaluate the impact of sacubitril/valsartan on exercise parameters and echocardiographic and biomarker changes at different drug doses. METHODS: We prospectively enrolled consecutive HFrEF outpatients eligible to start sacubitril/valsartan. Patients underwent clinical assessment, cardiopulmonary exercise test (CPET), blood sampling, echocardiography, and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sacubitril/valsartan was introduced at 24/26 mg b.i.d. dose and progressively uptitrated in a standard monthly-based fashion to 97/103 mg b.i.d. or maximum tolerated dose. Study procedures were repeated at each titration visit and 6 months after reaching the maximum tolerated dose. RESULTS: Ninety-six patients completed the study, 73 (75%) reached maximum sacubitril/valsartan dose. We observed a significant improvement in functional capacity across all study steps: oxygen intake increased, at peak exercise (from 15.6 ± 4.5 to 16.5 ± 4.9 mL/min/kg; p trend = 0.001), while minute ventilation/carbon dioxide production relationship reduced in patients with an abnormal value at baseline. Sacubitril/valsartan induced positive left ventricle reverse remodeling (EF from 31 ± 5 to 37 ± 8%; p trend < 0.001), while NT-proBNP reduced from 1179 [610-2757] to 780 [372-1344] pg/ml (p trend < 0.0001). NYHA functional class and the subjective perception of limitation in daily life at KCCQ-12 significantly improved. The Metabolic Exercise Cardiac Kidney Index (MECKI) score progressively improved from 4.35 [2.42-7.71] to 2.35% [1.24-4.96], p = 0.003. CONCLUSIONS: A holistic and progressive HF improvement was observed with sacubitril/valsartan in parallel with quality of life. Likewise, a prognostic enhancement was observed.

The double anaerobic threshold in heart failure: MECKI score database overview.

AIMS: In heart failure (HF), anaerobic threshold (AT) may be indeterminable but its value held a relevant prognostic role. AT is evaluated joining three methods: V-slope, ventilatory equivalent, and end-tidal methods. The possible non-concordance between the V-slope (met AT) and the other two methods (vent AT) has been highlighted in healthy individuals and named double threshold (DT). METHODS AND RESULTS: We reanalysed 1075 cardiopulmonary exercise tests of HF patients recruited in the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score database. We identified DT in 43% of cases. Met AT precedes vent AT being met-ventΔVO2 221 (interquartile range: 129-319) mL/min. Peak VO2 , 1307 ± 485 vs. 1343 ± 446 mL/min (63 ± 17 vs. 63 ± 17 percentage of predicted), was similar between DT+ and DT- patients. Differently, DT+ showed a lower ventilatory vs. carbon dioxide production (VE/VCO2 ) slope (29.6 ± 6.1 vs. 31.0 ± 6.3), a lower peak exercise end-tidal oxygen tension (PetO2 ) 115.3 (111.5-118.9) vs. 116.4 (112.4-120.2) mmHg, and a higher carbon dioxide tension (PetCO2 ) 34.2 (30.9-37.1) vs. 32.4 (28.7-35.5) mmHg. Vent AT showed a significant higher VO2 , 957 ± 318 vs. 719 ± 252 mL/min, VCO2 , 939 ± 319 vs. 627 ± 226 mL/min, ventilation, 31.0 ± 8.3 vs. 22.5 ± 6.3 L/min, respiratory exchange ratio, 0.98 ± 0.08 vs. 0.87 ± 0.07, PetO2 , 108 (104-112) vs. 105 (101-109) mmHg, PetCO2 , 37 (34-40) vs. 36 (33-39) mmHg, and VE/VO2 ratio, 33.5 ± 6.7 vs. 32.6 ± 6.9, but lower VE/VCO2 ratio, 33 (30-37) vs. 36 (32-41), compared with met AT. At 2 year survival by Kaplan-Meier analysis, even adjusted for confounders, DT resulted not associated with survival. CONCLUSIONS: Double threshold is frequently observed in HF patients. DT+ is associated to a decreased ventilatory response during exercise.

Unexpected Huge Prevalence of Intracardiac Extension of Wilms Tumor-A Single Center Experience from a Ugandan Hospital.

Wilms tumor (WT) is the most common primary renal malignancy in young children. WT vascular extension to the inferior vena cava (IVC) occurs in 4-10% of cases and can reach the right atrium (RA) in 1%. Data on WT clinical presentation and outcome in developing countries are limited. The aim of the present study is to describe the prevalence of intracardiac extension in a consecutive population of WT patients observed in a large non-profit Ugandan hospital. A total of 16 patients with a histological diagnosis of 29 WT were screened in a 6-month period. Patient n°2, a 3 y/o child, presented with a 3-week history of abdominal distension, difficulty in breathing, and swelling of the lower limbs. A cardiovascular system exam showed rhythmic heart sounds, a heart rate of 110 beats per minute, and a pansystolic murmur on the tricuspid area; the abdomen was grossly distended with a palpable mass in the right flank, hepatomegaly, and splenomegaly. An abdomen ultrasound showed an intra-abdominal tumor, involving the right kidney and the liver and extended to the IVC. An ultrasound guided biopsy showed a picture consistent with WT. Cardiac echo showed a huge, mobile, cardiac mass attached to the right side of the interatrial septum, involving the tricuspid valve annulus, causing a "functional" tricuspid stenosis. The patient died of cardiogenic shock 7 days after admission. Patient n°3, a 3 y/o child, presented with analogue symptoms and the same diagnosis. The cardiac echo showed a round mass in the RA. Thirteen more patients were screened with cardiac echo, showing a normal heart picture. In our limited series, we found WT cardiac extension in three patients over 16 (19%). Cardiac echo performed routinely can lead to a better staging, prognostic, and therapeutic assessment. In our setting, the intra-cardiac extension could be more frequent than previously reported and might have prognostic implications.

Brisk walking can be a maximal effort in heart failure patients: a comparison of cardiopulmonary exercise and 6 min walking test cardiorespiratory data.

AIMS: Cardiopulmonary exercise test (CPET) and 6 min walking test (6MWT) are frequently used in heart failure (HF). CPET is a maximal exercise, whereas 6MWT is a self-selected constant load test usually considered a submaximal, and therefore safer, exercise, but this has not been tested previously. The aim of this study was to compare the cardiorespiratory parameters collected during CPET and 6MWT in a large group of healthy subjects and patients with HF of different severity. METHODS AND RESULTS: Subjects performed a standard maximal CPET and a 6MWT wearing a portable device allowing breath-by-breath measurement of cardiorespiratory parameters. HF patients were grouped according to their CPET peak oxygen uptake (peakV̇O2 ). One hundred and fifty-five subjects were enrolled, of whom 40 were healthy (59 ± 8 years; male 67%) and 115 were HF patients (69 ± 10 years; male 80%; left ventricular ejection fraction 34.6 ± 12.0%). CPET peakV̇O2 was 13.5 ± 3.5 mL/kg/min in HF patients and 28.1 ± 7.4 mL/kg/min in healthy subjects (P < 0.001). 6MWT-V̇O2 was 98 ± 20% of the CPET peakV̇O2 values in HF patients, while 72 ± 20% in healthy subjects (P < 0.001). 6MWT-V̇O2 was >110% of CPET peakV̇O2 in 42% of more severe HF patients (peakV̇O2  < 12 mL/kg/min). Similar results have been found for ventilation and heart rate. Of note, the slope of the relationship between V̇O2 at 6MWT, reported as a percentage of CPET peakV̇O2 vs. 6MWT V̇O2 reported as the absolute value, progressively increased as exercise limitation did. CONCLUSIONS: In conclusion, the last minute of 6MWT must be perceived as a maximal or even supramaximal exercise activity in patients with more severe HF. Our findings should influence the safety procedures needed for the 6MWT in HF.

Sacubitril/valsartan use in a real-world population of patients with heart failure and reduced ejection fraction.

AIMS: Practice guidelines recommend sacubitril/valsartan for heart failure with reduced ejection fraction. The aim of our study was to describe the use of sacubitril/valsartan in real-world clinical practice to help identify patients best able to tolerate titration to higher doses. METHODS: We retrospectively analyzed clinical data for 201 patients with heart failure with reduced ejection fraction prescribed sacubitril/valsartan at our heart failure clinic (Centro Cardiologico Monzino) between September 2016/December 2018. Patients had a mean age of 67.2 years, mean left ventricular ejection fraction of 30.1%, New York Heart Association class II (65%), class III (35%), and poor cardiopulmonary exercise capacity. Median 2-year risk of death/urgent cardiac transplantation was 8.9% [Metabolic Exercise Cardiac Kidney Index (MECKI) score]. RESULTS: After a median follow-up of 230 (interquartile interval: 105-366) days, 57 patients achieved higher-dose sacubitril/valsartan, 103 tolerated medium/low doses, nine died, and 20 interrupted treatment. The highest dose of sacubitril/valsartan was reached by younger patients with better hemoglobin (Hb) levels, renal function, and blood pressure (BP). Patients continuing on sacubitril/valsartan had significantly higher serum Hb and sodium, better BP, and lower MECKI scores than patients who discontinued treatment or died during follow-up. Our patients were older and frailer than those in the pivotal PARADIGM-HF trial. CONCLUSION: In our experience, more than one-third of the patients were able to tolerate the higher dose of sacubitril/valsartan, and these patients were younger, had higher Hb, and better BP and renal function. MECKI score stratification was useful to discriminate patients who continued treatment from those who did not. Future prospective studies should test if these clinical variables can guide the up-titration of sacubitril/valsartan.