Prognostic Impact of the Pulmonary Artery Pulsatility Index in Patients with Chronic Heart Failure and Severe Mitral Regurgitation Undergoing Percutaneous Edge-to-Edge Repair.

BACKGROUND: Pulmonary artery (PA) pulsatility index (PAPi), calculated as (PA systolic pressure - PA diastolic pressure)/right atrial pressure, emerged as a novel predictor of right ventricular failure in patients with acute inferior myocardial infarction, advanced heart failure, and severe pulmonary hypertension. However, the prognostic utility of PAPi in transcatheter mitral valve repair (TMVR) using the MitraClip® system has never been tested. OBJECTIVE: To assess the prognostic impact of PAPi in patients with severe functional mitral regurgitation (MR) and chronic heart failure (CHF) undergoing TMVR. METHODS: Consecutive patients with severe functional MR (grade 3+ or 4+) and CHF who underwent successful TMVR (MR ≤2+ at discharge) were enrolled and divided into 3 groups according to PAPi (A: low PAPi ≤2.2; B: intermediate PAPi 2.21-3.99; C: high PAPi ≥4.0). The primary endpoint was a composite of all-cause mortality and rehospitalization due to CHF during a mean follow-up period of 16 ± 4 months. The impact of PAPi on prognosis was assessed by a receiver-operating characteristic (ROC) analysis and a multivariable Cox proportional hazard regression analysis investigating independent predictors for outcome. RESULTS: 78 patients (A: n = 27, B: n = 28, C: n = 23) at high operative risk (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation] 18.8 vs. 21.5 vs. 20.6%; nonsignificant) were enrolled. Mean PAPi was 1.6 ± 0.41 vs. 2.9 ± 0.53 vs. 6.8 ± 3.5; p < 0.001). Patients with low PAPi showed significantly higher rates of early rehospitalization for heart failure at the 30-day follow-up (14.9 vs. 7.1 vs. 4.3%; p = 0.04). In the long term, a significantly lower event-free survival for the combined primary endpoint was observed in the low PAPi group (44.4 vs. 25.0 vs. 20.3%; log-rank p = 0.016). ROC curve analysis revealed that optimal sensitivity and specificity were achieved using a PAPi cutoff of 2.46 (sensitivity 83%, specificity 78.3%, area under the curve 0.82 [0.64-0.99]; p = 0.01). In Cox regression analysis, PAPi ≤2.46 was an independent predictor for the combined primary endpoint (hazard ratio 2.85; 95% confidence interval 1.15-7.04; p = 0.023). CONCLUSIONS: PAPi is strongly associated with clinical outcome among patients with CHF and functional MR undergoing TMVR. A PAPi value ≤2.46 predicts a worse prognosis independent of other important clinical, echocardiographic, and hemodynamic factors. Therefore, PAPi may serve as a new parameter to improve patient selection for TMVR.

Right Ventricular Cardiac Power Index Predicts 1 Year Outcome After Transcatheter Edge-to-Edge-Repair for Severe Tricuspid Valve Regurgitation.

Tricuspid transcatheter edge-to-edge repair (T-TEER) for severe tricuspid regurgitation (TR) emerged as a novel treatment option for patients not amenable to surgery. However, knowledge regarding independent risk factors for a worse prognosis is rarely available. The study sought to investigate the impact of right ventricular cardiac power index (RVCPi) on 1-year outcomes in patients with severe symptomatic TR who underwent T-TEER. Consecutive patients with severe TR who underwent T-TEER from August 2020 to March 2022 were included and followed prospectively. Baseline clinical and invasive hemodynamic variables, changes in echocardiographic parameters and New York Heart Association functional class, and periprocedural and in-hospital major adverse events were assessed. Primary end point was defined as a composite of all-cause mortality and heart failure hospitalization at 1 year after T-TEER. A multivariable Cox proportional-hazards regression analysis was performed to identify independent risk factors for combined primary end point. RVCPi was calculated as: (cardiac index × mean pulmonary pressure) × K (conversion factor 2.22 × 10-3) = W/m². Receiver operator characteristic analysis was used to determine discriminative capacity of RVCPi. The prognostic value of RVCPi threshold was tested using Kaplan-Meier analysis. In total, 102 patients (mean age 81 ± 6 years, 51% women) at high operative risk underwent T-TEER for severe TR. Primary end point occurred in 30 patients (32%). Receiver operator characteristic curve analysis demonstrated that RVCPi was associated with an area under the curve of 0.69 (95% confidence interval 0.56 to 0.82; p = 0.003). With a RVCPi threshold of 0.17 W/m² (maximally selected rank statistics), the event-free survival was significantly higher in the RVCPi <0.17 W/m² group compared with those with RVCPi ≥0.17 W/m² (71% vs 35%, log-rank p <0.001). In the multivariable Cox regression analysis, RVCPi was an independent predictor for the combined primary end point (hazard ratio 2.6, 95% confidence interval 1.4 to 5.1, p = 0.003). In conclusion, RVCPi is associated with outcome in patients who underwent T-TEER for severe TR and this hemodynamic predictor is useful in risk stratification of T-TEER candidates.

Impact of Ventricular Stroke Work Indices on Mortality in Heart Failure Patients After Percutaneous Mitral Valve Repair.

Optimal patient selection for transcatheter mitral valve repair (TMVR) remains challenging. The aim of the study was to assess the impact of left and right ventricular stroke work index (LVSWi, RVSWi) on mortality in patients with chronic heart failure (CHF) undergoing TMVR. One hundred-forty patients (median age 74 ± 9.9 years, 67.9% male) with CHF who underwent successful TMVR were included. Primary end point was defined as all-cause mortality after 16 ± 9 months of follow-up. LVSWi was calculated as: Stroke volume index (SVi) * (mean arterial pressure - postcapillary wedge pressure) * 0.0136 = g/m-1/m2. RVSWi was calculated as: SVi * (mean pulmonary artery pressure - right atrial pressure) * 0.0136 = g/m-1/m2. Receiver operating characteristic (ROC) analysis determined an optimal threshold of 24.8 g/m-1/m2 for LVSWi (sensitivity 80.4%, specificity 40.2%, area under the curve (AUC) 0.71 [0.60 to 0.81]; p = 0.001) and 8.3 g/m-1/m2 for RVSWi (sensitivity 67.4%, specificity 57.0%, AUC 0.67 [0.56 to 0.78]; p = 0.006), respectively. Kaplan-Meier analysis showed significantly lower survival in patients with LVSWi ≤24.8 g/m-1/m2 (20.0% vs 39.4%; log-rank p = 0.038) and in patients with RVSWi ≤8.3 g/m-1/m2 (22.1% vs 43.7%; log-rank p = 0.026), respectively. LVSWi of ≤24.8 g/m-1/m2 and RVSWi of ≤8.3 g/m-1/m2 were independent predictors for all-cause mortality (hazard ratio (HR) 2.83; 95% confidence interval (CI) 1.1 to 7.6; p = 0.04; HR 2.52; 95% CI 1.04 to 6.1; p = 0.041). A risk-score incorporating LVSWi and RVSWi cut-off values from ROC analysis powerfully predicts long-term survival after successful TMVR (log-rank p = 0.02). In conclusion, LVSWi and RVSWi independently predict mortality in patients with CHF undergoing TMVR and might be useful in risk stratification of TMVR candidates.

Influence of the ratio of mean arterial pressure to right atrial pressure on outcome after successful percutaneous edge-to-edge repair for severe mitral valve regurgitation.

BACKGROUND: It is important to identify further predictors of outcome after successful transcatheter mitral valve repair (TMVR), as optimal patient selection remains difficult. OBJECTIVE: The study investigates the prognostic benefit of the mean arterial pressure (MAP) to right atrial pressure (RAP) ratio (MAP/RAP ratio) after successful TMVR in patients with congestive heart failure (CHF) and severe mitral regurgitation (MR). METHOD: Patients with CHF and severe MR were enrolled after successful TMVR (MR ≤ 2+ at discharge). The primary endpoint was a composite of all-cause mortality or hospitalisation for heart failure. The median follow-up time was 16 ± 9 months. Receiver Operating Characteristic (ROC) analysis was applied to assess the discriminatory power of the MAP/RAP ratio. The predictive value of the MAP/RAP ratio threshold was investigated using a Kaplan-Meier analysis. Multivariable logistic regression analysis was conducted to evaluate independent risk factors for the combined primary endpoint. RESULTS: 145 patients (median age 76 [69-80 years], 60.3% male) were included. ROC curve analysis showed that MAP/RAP ratio was associated with an area under the curve of 0.62 (95% confidence interval (CI) 0.53-0.71; p = 0.01). A MAP/RAP ratio threshold of 7.13 was associated with 67.4% sensitivity and 57.0% specificity for the combined primary endpoint. Event-free survival was significantly lower in the MAP/RAP ratio < 7.13 group compared to those with MAP/RAP ratio ≥ 7.13 (62.2% versus 39.4%; log-rank p = 0.022). In logistic regression analysis MAP/RAP ratio was an independent predictor for the combined primary endpoint (odds ratio 0.75; 95% CI 0.62-0.90; p = 0.002). CONCLUSIONS: The MAP/RAP ratio is associated with an unfavorable outcome in patients undergoing successful TMVR. Therefore, this new index could improve prognostic assessment of TMVR candidates.

Brief Report: Increased Frequency of CD39+ CD56bright Natural Killer Cells in HIV-1 Infection Correlates With Immune Activation and Disease Progression.

The expression pattern of the ectonucleotidases CD39 and CD73 on natural killer (NK) cells was examined in peripheral blood mononuclear cell of 61 HIV-1-infected patients. Increased frequencies of CD39CD56 NK cells were detectable in untreated HIV patients, which was associated with high viral load, low CD4 T-cell count, and CD8 T-cell activation. Additionally, levels of CD39 on NK cells were inducible by in vitro stimulation of NK cells, correlating with aryl hydrocarbon receptor and interleukin 10 expression. Here, we provide the first evidence of increased CD39CD56 NK cell frequencies during HIV infection, which might have consequences for NK cell function and HIV pathogenesis.

Down-regulation of CD73 on B cells of patients with viremic HIV correlates with B cell activation and disease progression.

Recently, alterations of the T cell expression of the ectonucleotidases, CD39 and CD73, during HIV infection have been described. Here, peripheral (n = 70) and lymph nodal B cells (n = 10) of patients with HIV at different stages of disease as well as uninfected individuals were analyzed via multicolor flow cytometry with regard to expression of CD39 and CD73 and differentiation, proliferation, and exhaustion status. Patients with chronic, untreated HIV showed a significantly decreased frequency of CD73-expressing B cells (P < 0.001) compared with healthy controls. Decreased frequencies of CD39+CD73+ B cells in patients with HIV correlated with low CD4+ counts (P < 0.0256) as well as increased proliferation and exhaustion status as determined by Ki-67 and programmed death-1 expression. Down-regulation of CD73 was observed in naive and memory B cells as determined by CD27 and CD21. Neither HIV elite controller patients nor antiretroviral therapy-treated patients had significantly lower CD39 and CD73 expression on B cells compared with healthy controls. Of importance, low CD73+ expression on B cells was associated with modulated in vitro B cell function. Further in vivo studies are warranted to evaluate the in vivo role of phenotypic loss of CD73 in B cell dysregulation in HIV.