Noninvasive Prediction of Pulmonary Capillary Wedge Pressure in Patients With Normal Left Ventricular Ejection Fraction: Comparison of Cardiac Magnetic Resonance With Comprehensive Echocardiography.

BACKGROUND: Cardiac magnetic resonance (CMR) was recently reported to predict mean pulmonary capillary wedge pressure (PCWP). However, there is a paucity of data on its accuracy for estimation of PCWP in patients with normal left ventricular (LV) ejection fraction (EF). We sought to examine its accuracy against the invasive gold standard and to compare it with the accuracy of comprehensive echocardiography. METHODS: Stable patients with EF of ≥50% who underwent right heart catheterization, CMR, and echocardiographic imaging within 1 week were included. Pulmonary capillary wedge pressure was estimated by CMR using a previously validated equation where PCWP is estimated based on the left atrial maximum volume and LV mass. Echocardiographic estimation of PCWP was based on 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines, taking into account the presence of myocardial disease. RESULTS: The mean age of the 79 patients was 55 ± 15 years, and 58.2% were female. There were 33 patients with PCWP >15 mm Hg by right heart catheterization. Cardiac magnetic resonance prediction of PCWP had an area under the curve (AUC) = 0.72. In comparison, echocardiographic prediction of PCWP showed a higher accuracy (AUC = 0.87 vs AUC = 0.72; P = .008). CONCLUSIONS: In patients with normal LV EF, CMR estimation of mean PCWP based on LV mass and left atrial volume has modest accuracy for detecting patients with mean PCWP >15 mm Hg. Comprehensive echocardiography predicts elevated PCWP with higher accuracy in comparison with CMR.

Effects of Inoculation with Stress-Tolerant Rhizobia on the Response of Alfalfa (Medicago sativa L.) to Combined Salinity and Cadmium Stress.

Agricultural soil salinization, which is often combined with heavy-metal contamination, is an ever-growing problem in the current era of global change. Legumes have a high potential for nitrogen fixation and are ideal crops for the reclamation of degraded soils. Alfalfa (Medicago sativa) is a valuable forage crop cultivated worldwide. Alfalfa plants fertilized with nitrogen or inoculated with a salt- and cadmium-tolerant Sinorhizobium meliloti strain were subjected to combined NaCl and CdCl2 stresses. Our results showed that inoculated plants presented higher aerial biomass than nitrogen-fertilized plants when they were exposed to salinity and cadmium together. To assess the mechanisms involved in the plant response to the combined stresses, superoxide dismutase and catalase antioxidant enzymatic activities were determined. Both increased upon stress; however, the increase in catalase activity was significantly less marked for inoculated plants, suggesting that other tolerance mechanisms might be active. Cd accumulation was lower in inoculated plants than in fertilized plants, which appears to imply that inoculation somehow prevented cadmium uptake by the plant roots. Expression analyses of several involved genes suggested that inoculation stimulated the biosynthesis of proline, phytochelatins, and homophytochelatins, together indicating that inoculated plants might be better suited to withstand combined salinity and cadmium stress effects.

The Beneficial Effects of Inoculation with Selected Nodule-Associated PGPR on White Lupin Are Comparable to Those of Inoculation with Symbiotic Rhizobia.

Nodule endophytes and associated bacteria are non-symbiotic bacteria that colonize legume nodules. They accompany nodulating rhizobia and can form beneficial associations, as some of them are plant growth-promoting rhizobacteria (PGPR) that are able to promote germination and plant growth and increase tolerance to biotic and abiotic stress. White lupin (Lupinus albus) is a legume crop that is gaining relevance as a suitable alternative to soybean as a plant protein source. Eleven nodule-associated bacteria were isolated from white lupin nodules grown in a Tunisian soil. They belonged to the genera Rhizobium, Ensifer, Pseudomonas and Bacillus. Their plant growth-promoting (PGP) and enzymatic activities were tested in vitro. Strains Pseudomonas sp., L1 and L12, displayed most PGP activities tested, and were selected for in planta assays. Inoculation with strains L1 or L12 increased seed germination and had the same positive effects on all plant growth parameters as did inoculation with symbiotic Bradyrhizobium canariense, with no significant differences among treatments. Inoculation with efficient nitrogen-fixing rhizobia must compete with rhizobia present in the soil that sometimes nodulate efficiently but fix nitrogen poorly, leading to a low response to inoculation. In such cases, inoculation with highly effective PGPR might represent a feasible alternative to boost crop productivity.

Lupin, a Unique Legume That Is Nodulated by Multiple Microsymbionts: The Role of Horizontal Gene Transfer.

Lupin is a high-protein legume crop that grows in a wide range of edaphoclimatic conditions where other crops are not viable. Its unique seed nutrient profile can promote health benefits, and it has been proposed as a phytoremediation plant. Most rhizobia nodulating Lupinus species belong to the genus Bradyrhizobium, comprising strains that are phylogenetically related to B. cytisi, B. hipponenese, B. rifense, B. iriomotense/B. stylosanthis, B. diazoefficiens, B. japonicum, B. canariense/B. lupini, and B. retamae/B. valentinum. Lupins are also nodulated by fast-growing bacteria within the genera Microvirga, Ochrobactrum, Devosia, Phyllobacterium, Agrobacterium, Rhizobium, and Neorhizobium. Phylogenetic analyses of the nod and nif genes, involved in microbial colonization and symbiotic nitrogen fixation, respectively, suggest that fast-growing lupin-nodulating bacteria have acquired their symbiotic genes from rhizobial genera other than Bradyrhizobium. Horizontal transfer represents a key mechanism allowing lupin to form symbioses with bacteria that were previously considered as non-symbiotic or unable to nodulate lupin, which might favor lupin's adaptation to specific habitats. The characterization of yet-unstudied Lupinus species, including microsymbiont whole genome analyses, will most likely expand and modify the current lupin microsymbiont taxonomy, and provide additional knowledge that might help to further increase lupin's adaptability to marginal soils and climates.

Differences in Cardiac Remodeling in Left-Sided Valvular Regurgitation: Implications for Optimal Definition of Significant Aortic Regurgitation.

BACKGROUND: Grading of aortic regurgitation (AR) and mitral regurgitation (MR) is similar in the cardiology guidelines despite distinct differences in left ventricular (LV) adaptive pathophysiology. OBJECTIVES: This study compared differences in LV remodeling in patients with similar degrees of AR and MR severity and evaluated optimal cutoffs for significant AR in relation to the outcome of aortic valve replacement or repair (AVR) during follow-up. METHODS: From 2008 to 2018, consecutive patients with isolated AR or MR who had cardiac magnetic resonance (CMR) were identified and CMR parameters were compared. Patients with left ventricular ejection fraction (LVEF) <50%, ischemic scar >5%, valve stenosis, or concomitant regurgitation were excluded. Patients were followed longitudinally for AVR. RESULTS: Baseline characteristics of isolated AR (n = 418) and isolated MR (n = 1,073) were comparable except for higher male proportion and hypertension in AR, while heart failure was more prevalent in MR. Indexed LV end-diastolic and end-systolic volumes and mass were higher in AR compared with MR at the same level of regurgitant fraction. During follow-up (mean 2.1 years), 18.7% of AR patients underwent AVR based on symptoms or LV remodeling. Interestingly, 38.0% of patients that underwent AVR within 3 months after CMR did not meet severe AVR by current guidelines of AR severity. AR regurgitant fraction>35% had high sensitivity (86%) and specificity (88%) for identifying patients who underwent AVR. CONCLUSIONS: For similar regurgitation severity, LV remodeling is different in AR compared with MR. Cardiac symptoms and significant LV remodeling in AR requiring AVR occur frequently in patients with less severity than currently proposed. The study findings suggest that the optimal threshold for severe AR with CMR is different than MR and is lower than currently stated in the guidelines.

Nitrogen and Phosphorus Interplay in Lupin Root Nodules and Cluster Roots.

Nitrogen (N) and phosphorus (P) are two major plant nutrients, and their deficiencies often limit plant growth and crop yield. The uptakes of N or P affect each other, and consequently, understanding N-P interactions is fundamental. Their signaling mechanisms have been studied mostly separately, and integrating N-P interactive regulation is becoming the aim of some recent works. Lupins are singular plants, as, under N and P deficiencies, they are capable to develop new organs, the N2-fixing symbiotic nodules, and some species can also transform their root architecture to form cluster roots, hundreds of short rootlets that alter their metabolism to induce a high-affinity P transport system and enhance synthesis and secretion of organic acids, flavonoids, proteases, acid phosphatases, and proton efflux. These modifications lead to mobilization in the soil of, otherwise unavailable, P. White lupin (Lupinus albus) represents a model plant to study cluster roots and for understanding plant acclimation to nutrient deficiency. It tolerates simultaneous P and N deficiencies and also enhances uptake of additional nutrients. Here, we present the structural and functional modifications that occur in conditions of P and N deficiencies and lead to the organogenesis and altered metabolism of nodules and cluster roots. Some known N and P signaling mechanisms include different factors, including phytohormones and miRNAs. The combination of the individual N and P mechanisms uncovers interactive regulation pathways that concur in nodules and cluster roots. L. albus interlinks N and P recycling processes both in the plant itself and in nature.

Coenzyme Q10 for Patients With Cardiovascular Disease: JACC Focus Seminar.

Coenzyme Q10 (CoQ10) is a naturally occurring compound that is found in animals and all humans. It has a fundamental role in cellular energy production. Although it is produced in the body, tissue deficiency can occur due to medications such as statins, which inhibit the mevalonate pathway. The clinical syndromes of statin-associated muscle symptoms (SAMS) and some of the features observed in patients with heart failure (HF) may be related to blood and tissue deficiency of CoQ10. Numerous clinical trials of CoQ10 in SAMS have yielded conflicting results. Yet, the weight of evidence as reflected in meta-analyses supports the use of exogenous CoQ10 in SAMS. In patients with HF, large-scale randomized clinical trials are lacking, although one relatively contemporary trial, Q-SYMBIO, suggests an adjunctive role for CoQ10. The possibility that statin-related CoQ10 deficiency may play a role in patients with diastolic HF is an intriguing hypothesis that warrants further exploration.

Extracellular Volume in Primary Mitral Regurgitation.

OBJECTIVES: This study used cardiovascular magnetic resonance (CMR) to evaluate whether elevated extracellular volume (ECV) was associated with mitral valve prolapse (MVP) or if elevated ECV was a consequence of remodeling independent of primary mitral regurgitation (MR) etiology. BACKGROUND: Replacement fibrosis in primary MR is more prevalent in MVP; however, data on ECV as a surrogate for diffuse interstitial fibrosis in primary MR are limited. METHODS: Patients with chronic primary MR underwent comprehensive CMR phenotyping and were stratified into an MVP cohort (>2 mm leaflet displacement on a 3-chamber cine CMR) and a non-MVP cohort. Factors associated with ECV and replacement fibrosis were assessed. The association of ECV and symptoms related to MR and clinical events (mitral surgery and cardiovascular death) was ascertained. RESULTS: A total of 424 patients with primary MR (229 with MVP and 195 non-MVP) were enrolled. Replacement fibrosis was more prevalent in the MVP cohort (34.1% vs. 6.7%; p < 0.001), with bi-leaflet MVP having the strongest association with replacement fibrosis (odds ratio: 10.5; p < 0.001). ECV increased with MR severity in a similar fashion for both MVP and non-MVP cohorts and was associated with MR severity but not MVP on multivariable analysis. Elevated ECV was independently associated with symptoms related to MR and clinical events. CONCLUSIONS: Although replacement fibrosis was more prevalent in MVP, diffuse interstitial fibrosis as inferred by ECV was associated with MR severity, regardless of primary MR etiology. ECV was independently associated with symptoms related to MR and clinical events. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823).

Adaptive Mechanisms Make Lupin a Choice Crop for Acidic Soils Affected by Aluminum Toxicity.

Almost half of the world's agricultural soils are acidic, and most of them present significant levels of aluminum (Al) contamination, with Al3+ as the prevailing phytotoxic species. Lupin is a protein crop that is considered as an optimal alternative to soybean cultivation in cold climates. Lupins establish symbiosis with certain soil bacteria, collectively known as rhizobia, which are capable of fixing atmospheric nitrogen. Moreover, some lupin species, especially white lupin, form cluster roots, bottlebrush-like structures specialized in the mobilization and uptake of nutrients in poor soils. Cluster roots are also induced by Al toxicity. They exude phenolic compounds and organic acids that chelate Al to form non-phytotoxic complexes in the rhizosphere and inside the root cells, where Al complexes are accumulated in the vacuole. Lupins flourish in highly acidic soils where most crops, including other legumes, are unable to grow. Some lupin response mechanisms to Al toxicity are common to other plants, but lupin presents specific tolerance mechanisms, partly as a result of the formation of cluster roots. Al-induced lupin organic acid secretion differs from P-induced secretion, and organic acid transporters functions differ from those in other legumes. Additionally, symbiotic rhizobia can contribute to Al detoxification. After revising the existing knowledge on lupin distinct Al tolerance mechanisms, we conclude that further research is required to elucidate the specific organic acid secretion and Al accumulation mechanisms in this unique legume, but definitely, white lupin arises as a choice crop for cultivation in Al-rich acidic soils in temperate climate regions.

Resolving the Disproportionate Left Ventricular Enlargement in Mitral Valve Prolapse Due to Barlow Disease: Insights From Cardiovascular Magnetic Resonance.

OBJECTIVES: This study hypothesized that left ventricular (LV) enlargement in Barlow disease can be explained by accounting for the total volume load that consists of transvalvular mitral regurgitation (MR) and the prolapse volume. BACKGROUND: Barlow disease is characterized by long prolapsing mitral leaflets that can harbor a significant amount of blood-the prolapse volume-at end-systole. The LV in Barlow disease can be disproportionately enlarged relative to MR severity, leading to speculation of Barlow cardiomyopathy. METHODS: Cardiac magnetic resonance (CMR) was used to compare MR, prolapse volume, and heart chambers remodeling in patients with Barlow disease (bileaflet prolapse [BLP]) and in single leaflet prolapse (SLP). RESULTS: A total of 157 patients (81 with BLP, 76 with SLP) were included. Patients with SLP were older and more had hypertension. Patients with BLP had more heart failure. Indexed LV end-diastolic volume was larger in BLP despite similar transvalvular MR. However, the prolapse volume was larger in BLP, which led to larger total volume load compared with SLP. Increasing tertiles of prolapse volume and MR both led to an incremental increase in LV end-diastolic volume in BLP. Using the total volume load improved the correlation with indexed LV end-diastolic volume in the BLP group, which closely matched that of SLP. A multivariable model that incorporated the prolapse volume explained left heart chamber enlargement better than a MR-based model, independent of prolapse category. CONCLUSIONS: The prolapse volume is part of the total volume load exerted on the LV during the cardiac cycle and could help explain the disproportionate LV enlargement relative to MR severity noted in Barlow disease.

Natural History of Functional Tricuspid Regurgitation Quantified by Cardiovascular Magnetic Resonance.

BACKGROUND: Quantitation of tricuspid regurgitant (TR) severity can be challenging with conventional echocardiographic imaging and may be better evaluated using cardiovascular magnetic resonance (CMR). OBJECTIVES: In patients with functional TR, this study sought to examine the relationship between TR volume (TRVol) and TR fraction (TRF) with all-cause mortality. METHODS: We examined 547 patients with functional TR using CMR to quantify TRVol and TRF. The primary outcome was all-cause mortality. Thresholds for mild, moderate, and severe TR were derived based on natural history outcome data. RESULTS: During a median follow-up of 2.6 years (interquartile range: 1.7 to 3.3 years), there were 93 deaths, with an estimated 5-year survival of 79% (95% confidence interval [CI]: 73% to 83%). After adjustment of clinical and imaging variables, including RV function, both TRF (adjusted hazard ratio [AHR] per 10% increment: 1.26; 95% CI: 1.10 to 1.45; p = 0.001) and TRVol (AHR per 10-ml increment: 1.15; 95% CI: 1.04 to 1.26; p = 0.004) were associated with mortality. Patients in the highest-risk strata of TRVol ≥45 ml or TRF ≥50% had the worst prognosis (AHR: 2.26; 95% CI: 1.36 to 3.76; p = 0.002 for TRVol and AHR: 2.60; 95% CI: 1.45 to 4.66; p = 0.001 for TRF). CONCLUSIONS: This is the first study to use CMR to assess independent prognostic implications of functional TR. Both TRF and TRVol were associated with increased mortality after adjustment for clinical and imaging covariates, including right ventricular ejection fraction. A TRVol of ≥45 ml or TRF of ≥50% identified patients in the highest-risk strata for mortality. These CMR thresholds should be used for patient selection in future trials to determine if tricuspid valve intervention improves outcomes in this high-risk group.

Myocardial Fibrosis in Patients With Primary Mitral Regurgitation With and Without Prolapse.

BACKGROUND: Recent studies reported left ventricular (LV) fibrosis in patients with primary mitral regurgitation (MR) thought to be principally due to mitral valve prolapse (MVP). OBJECTIVES: This study sought to evaluate the prevalence, characteristics, and prognostic implications of LV fibrosis in a large cohort of primary MR patients with and without MVP using cardiovascular magnetic resonance (CMR). METHODS: Patients referred for contrast CMR assessment of chronic primary MR were enrolled and underwent comprehensive assessment of cardiac remodeling, severity of MR, and LV replacement fibrosis. Primary MR patients were stratified into: an MVP group if there was >2 mm mitral leaflet displacement on cine-CMR, or a non-MVP group. Patients were followed for arrhythmic events (sudden cardiac death, aborted sudden cardiac arrest, and sustained or inducible ventricular arrhythmia). RESULTS: A total of 356 primary MR patients (177 MVP and 179 non-MVP) were enrolled. LV fibrosis was more prevalent in the MVP group than the non-MVP group (36.7% vs. 6.7%; p < 0.001). The presence of MVP had the strongest association (odds ratio: 6.82; p < 0.001) with LV fibrosis even after adjustment for clinical variables, measures of cardiac remodeling, and MR severity. During follow-up (median 1,354 days), MVP patients with LV fibrosis had the highest event rate for arrhythmic events. CONCLUSIONS: In primary MR patients, LV fibrosis is more prevalent in MVP than non-MVP, suggesting a unique pathophysiology beyond volume overload in MVP. LV fibrosis in primary MR may represent a risk marker of arrhythmic events.

Prognostic value of delayed enhancement cardiac magnetic resonance imaging in mitral valve repair.

BACKGROUND: The objective of this study was to examine the prognostic utility of cardiac magnetic resonance imaging (CMR) in patients with chronic mitral regurgitation undergoing mitral valve repair. METHODS: This study is a prospectively enrolled observational cohort study of 48 consecutive patients with chronic mitral regurgitation who had preoperative evaluation with CMR including delayed-enhancement CMR for assessment of myocardial fibrosis before undergoing mitral valve repair. Postoperative adverse clinical events were defined as intensive care unit readmission, needs of permanent cardiac pacemaker, and rehospitalization for cardiac reasons. RESULTS: The cohort comprised 33 (69%) men with a mean age of 61±13 years and mean left ventricular ejection fraction of 0.63±0.12. Preoperative myocardial fibrosis was detected in 40% of the patients. Median fibrosis was 4% (interquartile range, 2% to 10%). Mean follow-up duration was 11 months (interquartile range, 1 to 24 months). Adverse clinical events occurred in 16 patients. In multivariate analysis, the presence of myocardial fibrosis was independently associated with postoperative adverse clinical events (hazard ratio, 4.775; 95% confidence interval, 1.100 to 20.729; p=0.037). The addition of the presence of myocardial fibrosis to the preoperative characteristics model significantly improved overall predictive performance (p=0.04). CONCLUSIONS: The presence of preoperative myocardial fibrosis assessed with delayed-enhancement CMR was an independent predictor of increased adverse clinical outcomes in patients with chronic mitral regurgitation undergoing mitral valve repair. Our findings suggest that in this population, preoperative delayed-enhancement CMR may be of clinical utility.