The obesity paradox in patients with significant tricuspid regurgitation: effects of obesity on right ventricular remodeling and long-term prognosis

Background: Obesity may cause right ventricular (RV) remodeling due to volume overload. However, obesity is also associated with better prognosis compared with normal weight in patients with various cardiac diseases. The aim of this study was to assess the impact of obesity on RV remodeling and long-term prognosis in patients with significant (moderate and severe) tricuspid regurgitation (TR).Methods: A total of 951 patients with significant TR (median age, 70 years; interquartile range, 61-77 years; 50% men) were divided into three groups according to body mass index (BMI): normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI >= 30 kg/m(2)). Patients with congenital heart disease, peripheral edema, active endocarditis, and BMI < 18.5 kg/m(2) were excluded. RV size and function for each group were measured using transthoracic echocardiography and compared with reference values of healthy study populations. The primary end point was all-cause mortality. Event rates were compared across the three BMI categories.Results: Four hundred seventy-six patients (50%) with significant TR had normal weight, 356 (37%) were over-weight, and 119 (13%) were obese. RV end-diastolic and end-systolic areas were larger in overweight and obese patients compared with normal-weight patients. However, no differences in RV systolic function were observed. During a median follow-up period of 5 years, 358 patients (38%) died. Five-year survival rates were significantly better in overweight and obese patients compared with patients with normal weight (65% and 67% vs 58%, respectively, P < .001 and P = .005). In multivariate analysis, overweight and obesity were independently associated with lower rates of all-cause mortality compared with normal weight (hazard ratios, 0.628 [95% CI, 0.493-0.800] and 0.573 [95% CI, 0.387-0.848], respectively).Conclusions: In patients with significant TR, overweight and obese patients demonstrated more RV remodeling compared with patients with normal weight. Nevertheless, a higher BMI was independently associated with better long-term survival, confirming the obesity paradox in this context.Cardiolog

Renal function in patients with significant tricuspid regurgitation: pathophysiological mechanisms and prognostic implications

Background The pathophysiological mechanisms linking tricuspid regurgitation (TR) and chronic kidney disease (CKD) remain unknown. This study aimed to determine which pathophysiological mechanisms related to TR are independently associated with renal dysfunction and to evaluate the impact of renal impairment on long-term prognosis in patients with significant (>= moderate) secondary TR.Methods A total of 1234 individuals (72 [IQR 63-78] years, 50% male) with significant secondary TR were followed up for the occurrence of all-cause mortality and the presence of significant renal impairment (eGFR of <60 mL min(-1) 1.73 m(-2)) at the time of baseline echocardiography.Results Multivariable analysis demonstrated that severe right ventricular (RV) dysfunction (TAPSE < 14 mm) was independently associated with the presence of significant renal impairment (OR 1.49, 95% CI 1.11 to 1.99, P = 0.008). Worse renal function was associated with a significant reduction in survival at 1 and 5 years (85% vs. 87% vs. 68% vs. 58% at 1 year, and 72% vs. 64% vs. 39% vs. 19% at 5 years, for stage 1, 2, 3 and 4-5 CKD groups, respectively, P < 0.001). The presence of severe RV dysfunction was associated with reduced overall survival in stage 1-3 CKD groups, but not in stage 4-5 CKD groups.Conclusions Of the pathophysiological mechanisms identified by echocardiography that are associated with significant secondary TR, only severe RV dysfunction was independently associated with the presence of significant renal impairment. In addition, worse renal function according to CKD group was associated with a significant reduction in survival.Cardiolog

Sex-specific differences in etiology and prognosis in patients with significant tricuspid regurgitation

Cardiolog

Ratio between vena contracta width and tricuspid annular diameter: prognostic value in secondary tricuspid regurgitation

Background: Conventional approaches for the assessment of secondary tricuspid regurgitation (STR) severity do not correct for right heart dimensions. The authors hypothesized that STR severity can be proportional or disproportional to the dilation of the tricuspid annulus (TA) and investigated the prognostic impact of this novel definition. Methods: A total of 334 patients with moderate to severe STR and preserved left ventricular systolic function were included. The ratio between vena contracta (VC) width and tricuspid annular diameter was calculated. The cutoff value for VC/TA ratio associated with increased risk for all-cause death was identified using spline-curve analysis. Results: The cutoff value of VC/TA ratio associated with a mortality excess was 0.24, and 165 patients (49%) had VC/TA ratios >_ 0.24. Compared with those with VC/TA ratios _ 0.24 had a higher prevalence of moderate to severe mitral regurgitation, had higher pulmonary pressures, and were more frequently treated with diuretics. During a median follow-up period of 62 months (interquartile range, 28-101 months), 128 patients (38%) died. The cumulative 5-year survival rate was significantly worse in patients with VC/TA ratios >_ 0.24 (55% vs 71%, P = .001). VC/TA ratio >_ 0.24 was independently associated with poor outcomes on multivariate analysis (hazard ratio, 1.567; 95% CI, 1.044-2.352; P = .030) together with coronary artery disease, renal impairment, right ventricular systolic function (evaluated using either tricuspid annular plane systolic excursion or right ventricular free wall strain), and pulmonary pressures. Conclusions: VC/TA ratio >_ 0.24 is independently associated with poor prognosis in patients with STR. This parameter may be considered as a marker of disproportionate STR and could improve risk stratification and clinical decision-making. (J Am Soc Echocardiogr 2021;34:944-54.)Cardiolog

Prognostic implications of a novel algorithm to grade secondary tricuspid regurgitation

OBJECTIVES A novel tricuspid regurgitation (TR) grading system, using vena contracta (VC) width and effective regurgitant orifice area (EROA), was proposed and validated based on its prognostic usefulness.BACKGROUND The clinical need of a new grading system for TR has recently been emphasized to depict the whole spectrum of TR severity, particularly beyond severe TR (massive or torrential).METHODS TR severity was characterized in 1,129 patients with moderate or severe secondary TR (STR). Recently proposed cutoff values of VC width were more effective in differentiating the prognosis of patients with moderate STR, whereas EROA cutoff values performed better in characterizing the risk of patients with more severe STR. Therefore, these 2 parameters were combined into a novel grading system to define moderate (VC = 7 mm and EROA = 7 mm and EROA >= 80 mm(2)) STR.RESULTS A total of 143 patients (13%) showed moderate STR, whereas 536 patients (47%) had severe STR, and 450 (40%) had torrential STR. Patients with torrential STR had larger right ventricular (RV) dimensions, lower RV systolic function, and were more likely to receive diuretics. The cumulative 10-year survival rate was 53% for moderate, 45% for severe, and 35% for torrential STR (p = 0.007). After adjusting for potential confounders, torrential STR retained an association with worse prognosis compared with other STR grades (hazard ratio: 1.245; 95% confidence interval: 1.023 to 1.516; p = 0.029).CONCLUSIONS A novel STR grading system was able to capture the whole range of STR severity and identified patients with torrential STR who were characterized by a worse prognosis. (C) 2021 by the American College of Cardiology Foundation

Right ventricular reverse remodeling after tricuspid valve surgery for significant tricuspid regurgitation

Background: Changes in right ventricular (RV) dimensions and function after tricuspid valve (TV) surgery and their association with long-term outcomes remain largely unexplored. The current study evaluated RV reverse remodeling, based on changes in RV dimensions and function, after TV surgery for significant (moderate or severe) tricuspid regurgitation (TR) and their association with outcome. Methods: A total of 121 patients (mean age 63 +/- 12 years, 47% males) with significant TR treated with TV surgery were included in this analysis. The population was stratified by tertiles of percentage reduction of RV end-systolic area (RVESA) and absolute change of RV fractional area change (RVFAC). Five-year mortality rates were compared across the tertiles of RV remodeling and independent associates of mortality were investigated. Results: Tertile 3 consisted of patients presenting with a reduction in RVESA >= 17.2% and an improvement in RVFAC >= 2.3% after TV surgery. Cumulative survival rates were significantly better in patients within tertile 3 of RVESA reduction: 90% vs. 49% for tertile 1 and 69% for tertile 2 (log-rank p = 0.002) and within tertile 3 of RVFAC improvement: 87% vs. 57% for tertile 1 and 65% for tertile 2 (log-rank p = 0.02). Tertiles 3 of RVESA reduction and RVFAC improvement were both independently associated with better survival after TV surgery compared to tertiles 1 (hazard ratio: 0.221 [95% CI: 0.074-0.658] and 0.327 [95% CI: 0.118-0.907], respectively). Conclusions: The extent of RV reverse remodeling, based on reduction in RVESA and improvement in RVFAC, was associated with better survival at 5-year follow-up of TV surgery for significant TR.Thoracic Surger

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Comparison of the usefulness of strain imaging by echocardiography versus computed tomography to detect right ventricular systolic dysfunction in patients with significant secondary tricuspid regurgitation

Assessment of right ventricular (RV) systolic function in patients with significant secondary tricuspid regurgitation (STR) remains challenging. In patients with severe aortic stenosis treated with transcatheter aortic valve implantation (TAVI), STR and RV enlargement have been associated with poor outcomes. In these patients, speckle tracking echocardiography (STE) may detect RV systolic dysfunction better than 3-dimensional (3D) RV ejection fraction (EF). The purpose of this study was to investigate the prevalence of RV dysfunction when assessed with STE in patients with significant STR (>= 3+) compared with patients without significant STR (= 3+) was observed in 67 patients. Patients with STR >= 3+ had larger RVEDVi, larger RVESVi, lower LVEF, and more impaired RVFWS compared with patients with STR= 3+ (n = 53) had significantly more impaired RVFWS compared with patients with STR<3+ (n = 53): -18.2 +/- 5.0% versus -21.1 +/- 3.7%, p = 0.001. In conclusion, patients with significant STR have more pronounced RV systolic dysfunction as assessed with STE than the patients without significant STR despite having similar 3D RV dimensions and RVEF on dynamic CT. (c) 2020 The Author(s). Published by Elsevier Inc