Pulmonary artery to aorta ratio for the detection of pulmonary hypertension: cardiovascular magnetic resonance and invasive hemodynamics in heart failure with preserved ejection fraction.

BACKGROUND: Previous work indicates that dilatation of the pulmonary artery (PA) itself or in relation to the ascending aorta (PA:Ao ratio) predicts pulmonary hypertension (PH). Whether these results also apply for heart failure with preserved ejection fraction (HFpEF) is unknown. In the present study we evaluated the diagnostic and prognostic power of PA diameter and PA:Ao ratio on top of right ventricular (RV) size, function, and septomarginal trabeculation (SMT) thickness by cardiovascular magnetic resonance (CMR) in HFpEF. METHODS AND RESULTS: 159 consecutive HFpEF patients were prospectively enrolled. Of these, 111 underwent CMR and invasive hemodynamic evaluation. By invasive assessment 64 % of patients suffered from moderate/severe PH (mean pulmonary artery pressure (mPAP) ≥30 mmHg). Significant differences between groups with and without moderate/severe PH were observed with respect to PA diameter (30.9 ± 5.1 mm versus 26 ± 5.1 mm, p < 0.001), PA:Ao ratio (0.93 ± 0.16 versus 0.78 ± 0.14, p < 0.001), and SMT diameter (4.6 ± 1.5 mm versus 3.8 ± 1.2 mm; p = 0.008). The strongest correlation with mPAP was found for PA:Ao ratio (r = 0.421, p < 0.001). By ROC analysis the best cut-off for the detection of moderate/severe PH was found for a PA:Ao ratio of 0.83. Patients were followed for 22.0 ± 14.9 months. By Kaplan Meier analysis event-free survival was significantly worse in patients with a PA:Ao ratio ≥0.83 (log rank, p = 0.004). By multivariable Cox-regression analysis PA:Ao ratio was independently associated with event-free survival (p = 0.003). CONCLUSION: PA:Ao ratio is an easily measureable noninvasive indicator for the presence and severity of PH in HFpEF, and it is related with outcome.

Non-professional efferocytosis of Salmonella-infected intestinal epithelial cells in the neonatal host.

The intestinal epithelium is the first line of defense against enteric pathogens. Removal of infected cells by exfoliation prevents mucosal translocation and systemic infection in the adult host, but is less commonly observed in the neonatal intestine. Instead, here, we describe non-professional efferocytosis of Salmonella-infected enterocytes by neighboring epithelial cells in the neonatal intestine. Intestinal epithelial stem cell organoid cocultures of neonatal and adult cell monolayers with damaged enterocytes replicated this observation, confirmed the age-dependent ability of intestinal epithelial cells for efferocytosis, and identified the involvement of the "eat-me" signals and adaptors phosphatidylserine and C1q as well as the "eat-me" receptors integrin-αv (CD51) and CD36 in cellular uptake. Consistent with this, massive epithelial cell membrane protrusions and CD36 accumulation at the contact site with apoptotic cells were observed in the infected neonatal host in vivo. Efferocytosis of infected small intestinal enterocytes by neighboring epithelial cells may represent a previously unrecognized mechanism of neonatal antimicrobial host defense to maintain barrier integrity.

The right heart in heart failure with preserved ejection fraction: insights from cardiac magnetic resonance imaging and invasive haemodynamics.

AIMS: Recent data indicate that right ventricular systolic dysfunction (RVSD) by cardiac magnetic resonance imaging (CMR) is a strong predictor of outcome in heart failure. However, the prognostic significance of RVSD by CMR in heart failure with preserved ejection fraction (HFpEF) is unknown. METHODS AND RESULTS: We prospectively enrolled 171 HFpEF patients who underwent CMR in addition to invasive and non-invasive testing. RVSD, defined as right ventricular (RV) EF <45% by CMR, was present in 33 (19.3 %) patients. Patients were followed for 573 ± 387 days, during which 41 had a cardiac event. Patients with RVSD presented with more frequent history of AF (P = 0.038), significantly higher resting heart rate (P = 0.009), shorter 6-min walk distance (P = 0.036), and higher NT-pro BNP serum levels (P < 0.001), and were more symptomatic (P < 0.001). With respect to haemodynamic parameters, RVSD was associated with respect to haemodynamic parameters, RVSD was associated with higher diastolic pulmonary artery pressure (P = 0.045), with higher pulmonary vascular resistance (P = 0.048), higher transpulmonary gradient (P = 0.042), and higher diastolic pulmonary vascular pressure gradient (P = 0.007). In the multivariable Cox analysis, RVSD (P < 0.001) remained significantly associated with cardiac events, in addition to diabetes (P = 0.011), 6-min walk distance (P = 0.018), and systolic pulmonary artery pressure (P = 0.003). CONCLUSIONS: Although HFpEF is considered a disease of the left ventricle, respective imaging parameters are not related to outcome. In contrast, RVSD by CMR is independently associated with mortality and clinical status in these patients, and provides a useful tool for risk stratification.

T1 Mapping by CMR Imaging: From Histological Validation to Clinical Implication.

OBJECTIVES: The purpose of this study was to prospectively investigate the diagnostic and prognostic impact of cardiac magnetic resonance (CMR) T1 mapping and validate it against left ventricular biopsies. BACKGROUND: Extracellular volume (ECV) expansion is a key feature of heart failure. CMR T1 mapping has been developed as a noninvasive technique to estimate ECV; however, the diagnostic and prognostic impacts of this technique have not been well established. METHODS: A total of 473 consecutive patients referred for CMR (49.5% female, age 57.8 ± 17.1 years) without hypertrophic cardiomyopathy, cardiac amyloidosis, or Anderson-Fabry disease were studied. T1 mapping with the modified Look-Locker inversion recovery (MOLLI) sequence was used for ECV calculation (CMR-ECV). For methodological validation, 36 patients also underwent left ventricular biopsy, and ECV was quantified by TissueFAXS analysis (TissueFAXS-ECV). To assess the prognostic value of CMR-ECV, its association with hospitalization for cardiovascular reasons or cardiac death was tested in a multivariable Cox regression model. RESULTS: TissueFAXS-ECV was 26.3 ± 7.2% and was significantly correlated with CMR-ECV (r = 0.493, p = 0.002). Patients were followed up for 13.3 ± 9.0 months and divided into CMR-ECV tertiles for Kaplan-Meier analysis (tertiles were ≤ 25.7%, 25.8% to 28.5%, and ≥ 28.6%). Significantly higher event rates were observed in patients with higher CMR-ECV (log-rank p = 0.013). By multivariable Cox regression analysis, CMR-ECV was independently associated with outcome among imaging variables (p = 0.004) but not after adjustment for clinical parameters. CONCLUSIONS: CMR T1 mapping allows accurate noninvasive quantification of ECV and is independently associated with event-free survival among imaging parameters. Its prognostic value on top of established clinical risk factors warrants further investigation in long-term studies.

Right ventricular dysfunction, but not tricuspid regurgitation, is associated with outcome late after left heart valve procedure.

BACKGROUND: Significant tricuspid regurgitation (TR) late after left heart valve procedure is frequent and associated with increased morbidity. Surgical correction carries a significant mortality risk, whereas the impact of TR on survival in these patients is unclear. OBJECTIVES: This study sought to assess the impact of significant TR late after left heart valve procedure. METHODS: A total of 539 consecutive patients with previous left heart valve procedure (time interval from valve procedure to enrollment 50 ± 30 months) were prospectively followed for 53 ± 15 months. RESULTS: Significant TR (defined as moderate or greater severity by echocardiography) was present in 91 (17%) patients (65% female). Patients with TR presented with more symptoms (New York Heart Association functional class ≥II 55% vs. 31%), lower glomerular filtration rates (61 ± 19 ml/min vs. 68 ± 18 ml/min), and a higher likelihood of atrial fibrillation (41% vs. 20%), all statistically significant. Right ventricular (RV) systolic function was worse in patients with significant TR (RV fractional area change 43 ± 11% vs. 47 ± 9%, p < 0.001). A total of 117 (22%) patients died during follow-up. By Kaplan-Meier analysis, overall survival was significantly worse in patients with significant TR (log-rank p < 0.001). However, by multivariable Cox analysis, only RV fractional area change, age, left atrial size, diabetes, and previous coronary artery bypass graft procedure were significantly associated with mortality, but not tricuspid regurgitation. CONCLUSIONS: RV dysfunction, but not significant TR, is independently associated with survival late after left heart valve procedure.