A review of the conservative versus invasive management of ischemic heart failure with reduced ejection fraction.

Heart failure is increasing in terms of prevalence, morbidity, and mortality rates. Clinical trials and studies are focusing on heart failure as it is the destiny end-stage for several cardiovascular disorders. Recently, medical therapy has dramatically progressed with novel classes of medicines providing better quality of life and survival outcomes. However, heart failure remains a heavy impactful factor on societies and populations. Current guidelines from the American and European cardiac societies are not uniform with respect to the class and level of treatment recommendations for coronary artery disease patients with heart failure and reduced ejection fraction. The discrepancy among international recommendations, stemming from the lack of evidence from adequately powered randomized trials, challenges physicians in choosing the optimal strategy. Hybrid therapy including optimal medical therapy with revascularization strategies are commonly used for the management of ischemic heart failure. Coronary artery bypass graft (CABG) has proved its efficacy on improving long term outcome and prognosis while no large randomized clinical trials for percutaneous coronary intervention (PCI) are still available. Regardless of the lack of data and recommendations, the trends of performing PCI in ischemic heart failure prevailed over CABG whereas lesion complexity, chronic total occlusion and complete revascularization achievement are limiting factors. Lastly, regenerative medicine seems a promising approach for advanced heart failure enhancing cardiomyocytes proliferation, reverse remodeling, scar size reduction and cardiac function restoration.

Long-Term Survival Outcomes After Transcatheter Aortic Valve Replacement: A Real-World Experience of a Large Tertiary Center.

Transcatheter aortic valve replacement (TAVR) becomes the leading therapeutic choice for severe aortic stenosis. There is a growing body of knowledge on long-term survival outcomes, but available data from real-world observational studies are scarce. An observational cohort study was conducted on 705 consecutive patients who underwent TAVR at Strasbourg University Hospital between February 2010 and June 2017. We observed the living status (dead or alive) for each study participants by March 2023. The primary end point was to evaluate the all-cause mortality rate beyond 5 years after TAVR, compare the survival outcomes according to valve type, and identify predictors of mortality. Of the 705 study participants, 91.8% of the TAVR procedures were performed through the common femoral artery and 60.6% were treated with a balloon-expandable valve. Over a mean study period of 5.4 ± 3 years, the all-cause mortality rate was 45.8%. No difference in survival outcomes according to valve type was observed (p = 0.449). All-cause mortality rate was associated with age ≥90 years (hazard ratio [HR] 1.625, 1.109 to 2.380, p = 0.013), female gender (HR 0.228, 0.176 to 0.294, p <0.001), diabetes mellitus (HR 1.356, 1.070 to 1.719, p = 0.012), post-TAVR stroke (HR = 2.867, 1.690 to 4.865, p <0.001), and post-TAVR acute kidney injury (HR 1.977, 1.445 to 2.703, p <0.001). In conclusion, the present real-world large tertiary center experience showed that more than half of patients who underwent TAVR are alive beyond 5 years from procedure's date. All-cause mortality is mainly determined by advanced age and co-morbid conditions, and valve type has no advantage on the survival outcomes.

Spontaneous Coronary Artery Dissection: A Review of Epidemiology, Pathophysiology and Principles of Management.

Spontaneous coronary artery dissection (SCAD) is a sudden rupture of coronary artery wall leading to false lumen and intramural hematoma formation. It commonly occurs in young and middle-aged women lacking typical cardiovascular risk factors. Fibromuscular dysplasia and pregnancy are strongly associated with SCAD. To date, the "inside-out" and "outside-in" are the 2 proposed hypothesis for the pathogenesis of SCAD. Coronary angiography is the gold standard and first line diagnostic test. Three types of SCAD have been described according to coronary angiogram. Intracoronary imaging modalities are reserved for patients with ambiguous diagnosis or to guide percutaneous coronary intervention view the increased risk of secondary iatrogenic dissection. The management of SCAD includes conservative approach, coronary revascularization strategies accounting for percutaneous coronary intervention and coronary artery bypass graft, and long-term follow-up. The overall prognosis of patients with SCAD is favorable marked by a spontaneous healing in a large proportion of cases.

Comparison of in-hospital outcomes and long-term survival for valve-in-valve transcatheter aortic valve replacement versus the benchmark native valve transcatheter aortic valve replacement procedure.

Background: In recent years, the number of patients with failed surgically implanted aortic bioprostheses and the number of candidates for valve-in-valve transcatheter aortic valve replacement (VIV-TAVR) have been increasing. Objectives: The purpose of this study is to evaluate the efficacy, safety, and long-term survival outcomes of VIV-TAVR compared with the benchmark native valve transcatheter aortic valve replacement (NV-TAVR). Methods: A cohort study was conducted on patients who underwent TAVR in the department of cardiology at Toulouse University Hospital, Rangueil, France between January 2016 and January 2020. The study population was divided into two groups: NV-TAVR (N = 1589) and VIV-TAVR (N = 69). Baseline characteristics, procedural data, in-hospital outcomes, and long-term survival outcomes were observed. Results: In comparison with NV-TAVR, there are no differences in TAVR success rate (98.6 vs. 98.8%, p = 1), per-TAVR complications (p = 0.473), and length of hospital stay (7.5 ± 50.7 vs. 4.4 ± 2.8, p = 0.612). The prevalence of in-hospital adverse outcomes did not differ among study groups, including acute heart failure (1.4 vs. 1.1%), acute kidney injury (2.6, 1.4%), stroke (0 vs. 1.8%, p = 0.630), vascular complications (p = 0.307), bleeding events (0.617), and death (1.4 vs. 2.6%). VIV-TAVR was associated with a higher residual aortic gradient [OR = 1.139, 95%CI (1.097-1.182), p = 0.001] and a lower requirement for permanent pacemaker implantation [OR = 0.235 95%CI (0.056-0.990), p = 0.048]. Over a mean follow-up period of 3.44 ± 1.67 years, no significant difference in survival outcomes has been observed (p = 0.074). Conclusion: VIV-TAVR shares the safety and efficacy profile of NV-TAVR. It also represents a better early outcome but a higher non-significant long-term mortality rate.

Effect of molybdenum treatment on molybdenum concentration and nitrate reduction in maize seedlings.

Since 1940 molybdenum has been known as an essential trace element in plant nutrition and physiology. It has a central role in nitrogen metabolism, and its deficiency leads to nitrate accumulation in plants. In this study, we cultivated maize seedlings (Zea mays L. cv. Norma SC) in nutrient solution and soil (rhizoboxes) to investigate the effect of molybdenum treatment on the absorption of molybdenum, sulfur and iron. These elements have been previously shown to play important roles in nitrate reduction, because they are necessary for the function of the nitrate reductase enzyme. We also investigated the relationship between molybdenum treatments and different nitrogen forms in maize. Molybdenum treatments were 0, 0.96, 9.6 and 96 µg kg(-1) in the nutrition solution experiments, and 0, 30, 90, 270 mg kg(-1) in the rhizobox experiments. On the basis of our results, the increased Mo level produced higher plant available Mo concentration in nutrient solution and in soil, which resulted increased concentration of Mo in shoots and roots of maize seedlings. In addition it was observed that maize seedlings accumulated more molybdenum in their roots than in their shoots at all treatments. In contrast, molybdenum treatments did not affect significantly either iron or sulfur concentrations in the plant, even if these elements (Mo, S and Fe) play alike important roles in nitrogen metabolism. Furthermore, the physiological molybdenum level (1× Mo = 0.01 µM) reduced NO3-N and enhanced the NH4-N concentrations in seedlings, suggesting that nitrate reduction was more intense under a well-balanced molybdenum supply.

Effects of short term iron citrate treatments at different pH values on roots of iron-deficient cucumber: a Mössbauer analysis.

Alkaline pH values and bicarbonate greatly reduce the mobility and uptake of Fe, causing Fe deficiency chlorosis. In the present work, the effects of pH and bicarbonate on the uptake and accumulation of Fe in the roots of cucumber were studied by Mössbauer spectroscopy combined with physiological tests and diaminobenzidine enhanced Perls staining. Mössbauer spectra of Fe-deficient cucumber roots supplied with 500 µM (57)Fe(III)-citrate at different pH values showed the presence of an Fe(II) and an Fe(III) component. As the pH was increased from 4.5 to 7.5, the root ferric chelate reductase (FCR) activity decreased significantly and a structural change in the Fe(III) component was observed. While at pH 4.5 the radial intrusion of Fe reached the endodermis, at pH 7.5, Fe was found only in the outer cortical cell layers. The Mössbauer spectra of Fe-deficient plants supplied with Fe(III)-citrate in the presence of bicarbonate (pH 7.0 and 7.5) showed similar Fe components, but the relative Fe(II) concentration compared to that measured at pH values 6.5 and 7.5 was greater. The Mössbauer parameters calculated for the Fe(II) component in the presence of bicarbonate were slightly different from those of Fe(II) alone at pH 6.5-7.5, whereas the FCR activity was similarly low. Fe incorporation into the root apoplast involved only the outer cortical cell layers, as in the roots treated at pH 7.5. In Fe-sufficient plants grown with Fe(III)-citrate and 1mM bicarbonate, Fe precipitated as granules and was in diffusely scattered grains on the root surface. The "bicarbonate effect" may involve a pH component, decreasing both the FCR activity and the acidification of the apoplast and a mineralization effect leading to the slow accumulation of extraplasmatic Fe particles, forming an Fe plaque and trapping Fe and other minerals in biologically unavailable forms.

Industrial side-products as possible soil-amendments.

The protection of our environment is a common task. All pollution that expose our soils, plants or in the narrower and wider sense environment will appear sooner or later in the food chain and in human beings who are at the top of the food-chain pyramid. The aim of our work is to give a brief overview about the effects of some industrial wastes on the physiological parameters of plants. Compost, black soot, sewage sludge and lime sludge dust was examined. Sunflower seeds were used in the experiments. The filtrates of examined materials were added to the nutrient solution in different quantities because of different solubility. The contents of sample elements and uptake of the element were measured by ICP, the relative chlorophyll contents by SPAD 502. Disadvantageous and advantageous physiological effects of compost, black soot, sewage sludge and lime sludge were proved. Larger concentrations of aluminium were measured in the roots than in the shoots. The concentrations of chrome were below the control value in the shoots when black soot, compost, lime sludge and sewage sludge were added to the nutrient solution. The concentrations of zinc, phosphorous, magnesium and copper were very low when black soot was used, and it was lower than the control. The dry matter of shoots increased when compost and sewage sludge was used, but the growth of roots remained under the control level.

Chelator-enhanced lead accumulation in Agropyron elongatum cv Szarvasi-1 in hydroponic culture.

Hydroponic culture was applied to compare the efficiency of K2EDTA and citrate in mobilizing Pb for accumulation in Agropyron elongatum cv. Szarvasi-1 and their effects on some physiological characteristics of the plants. The plants were grown in nutrient solutions containing 0, 10, and 100 microM Pb(NO3)2 combined with chelating agents added to the nutrient solutions after 21 days of growth, in 3 concentrations (0, 100, and 500 microM). The effects were measured after eight days. The energy grass proved to be greatly resistant to the treatments, as was reflected in the slight inhibition of growth, the resistance of the photosynthetic electron transport chain and the chlorophyll composition and the lack of change in the malone-dialdehyde content. Fundamental differences can be identified between the effects of EDTA and citrate. Citrate had only a little effect on the physiological parameters, which may be due to the strongly increasing lead accumulation with increasing concentration of Pb in the nutrient solution. Additionally, citrate ensured a higher biomass yield with higher shoot Pb accumulation compared to EDTA in almost all treatments. Concerning biomass reduction, 10 microM Pb applied together with K2EDTA has the most deleterious effects on energy grass. The effects correlated with the concentration of EDTA.

Impact of moderate Fe excess under Cd stress on the photosynthetic performance of poplar (Populus jacquemontiana var. glauca cv. Kopeczkii).

Cadmium interference with Fe nutrition has a strong impact on the development and efficiency of the photosynthetic apparatus. To shed more light on the interaction between Fe and Cd, it was studied how iron given in moderate excess under Cd stress affects the development and functioning of chlorophyll-protein complexes. Poplar plants grown in hydroponics up to four-leaf stage were treated with 10 µM Cd(NO3)2 in the presence of 50 µM Fe([III])-citrate as iron supply (5xFe + Cad) for two weeks. Though leaf area growth was inhibited similarly to that of Cad (10 µM Cd(NO3)2 + 10 µM Fe([III])-citrate) plants, chlorophyll content, ¹4CO2 fixation and quenching parameters calculated from PAM fluorescence induction measurements were control-like in 5xFe+Cad leaves. Increased chloroplast iron content (measured photometrically by the bathophenanthroline disulfonate method) without changes in the iron and cadmium content of leaves (determined by inductively coupled plasma mass spectrometry) pointed out that a key factor in the observed protection of photosynthesis is the iron-excess-induced redistribution of iron in the leaf. However, the chlorophyll a/b ratio and the chlorophyll-protein pattern obtained by Deriphat PAGE remained similar to that of Cad leaves. The decreased amount of PSII core and PSI in mature and developing leaves, respectively, refers to developmental stage-dependent remodelling of thylakoids in the presence of Cd. The results underline not only the beneficial effect of iron excess under Cd stress, but also refer to the importance of a proper Fe/Cd ratio and light environment to avoid its possible harmful effects.

Cd affects the translocation of some metals either Fe-like or Ca-like way in poplar.

In plants, Cd causes perturbation of root metal uptake and is known to interfere with the metal translocation to the shoot. The most significant effect is the strongly reduced transport of Fe. Fe accumulation in roots under Cd stress revealed that it is not the Fe acquisition but the Fe loading to xylem elements that is blocked by Cd, which can be a result of competition between Fe and Cd for the transporters. However, in animal cells as well as in plant stomata guard cells, Cd was shown to move through Ca channels. To clarify whether the perturbation of metal translocation/xylem loading caused by Cd show any regularity, translocation ability was tested by the determination of the metal content in leaves of hydroponically cultured (» Hoagland nutrient solution, Fe source: 10 µM Fe((III))-citrate) poplar plants grown for three weeks with or without 10 µM Cd(NO3)2 treatment. Metals could be classified into two groups according to the behavior of their translocation under Cd treatment: alkaline earth metals (except Mg), Zn and Mn were influenced similarly to Ca, but other transition metals (together with alkali metals and Al) behaved like the Fe. Based on the translocation pattern, Cd seems to inhibit the transport of Ca-like metals competitively, but a different type of inhibition is exerted on the transition metal transport, with which Cd can share a common translocation system. The strongly decreased translocation of chelator-dependent transition metals may indicate Cd related disturbances in signalling pathways and gene expression of xylem transporters or chelators.

Impact of iron supply on the kinetics of recovery of photosynthesis in Cd-stressed poplar (Populus glauca).

BACKGROUND AND AIMS: Cadmium (Cd) causes Fe-deficiency-like symptoms in plants, and strongly inhibits photosynthesis. To clarify the importance of Cd-induced Fe deficiency in Cd effects on photosynthesis, the recovery processes were studied by supplying excess Fe after the Cd symptoms had developed. METHODS: Fe-citrate at 10 microm or 50 microm was given with or without 10 microm Cd(NO3)2 to hydroponically cultured poplars (Populus glauca 'Kopeczkii') with characteristic Cd symptoms. Ion, chlorophyll and pigment contents, amount of photosynthetic pigment-protein complexes, chlorophyll fluorescence and carbon assimilation were measured together with the mapping of healing processes by fluorescence imaging. KEY RESULTS: In regenerated leaves, the iron content increased significantly, while the Cd content did not decrease. As a result, the structural (increase in the amount of photosynthetic pigments and pigment-protein complexes, decrease in the F690/F740 ratio) and functional (elevation of CO2 fixation activity and DeltaF/Fm') recovery of the photosynthetic machinery was detected. Cd-induced, light-stress-related changes in non-photochemical quenching, activity of the xanthophyll cycle, and the F440/F520 ratio were also normalized. Imaging the changes in chlorophyll fluorescence, the recovery started from the parts adjacent to the veins and gradually extended to the interveinal parts. Kinetically, the rate of recovery depended greatly on the extent of the Fe supply, and chlorophyll a/b ratio and DeltaF/Fm' proved to be the most-rapidly reacting parameters. CONCLUSIONS: Iron deficiency is a key factor in Cd-induced inhibition of photosynthesis.

Evaluation of the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention: the randomized, double-blind, placebo-controlled, multicenter Verapamil Slow-Release for Prevention of Cardiovascular Events After Angioplasty (VESPA) Trial.

OBJECTIVES: We investigated the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention (PCI). BACKGROUND: Thus far, there is no established systemic pharmacologic approach for the prevention of restenosis after PCIs. Five small studies reported encouraging results for calcium channel blockers. METHODS: Our randomized double-blind trial included 700 consecutive patients with successful PCI of a native coronary artery. Patients received the calcium channel blocker verapamil, 240 mg twice daily for six months, or placebo. Primary clinical end point was the composite rate of death, myocardial infarction, and target vessel revascularization (TVR) during one-year follow-up; the angiographic end point was late lumen loss at the six-month follow-up angiography. RESULTS: We obtained complete clinical follow-up in 95% of the patients, and scheduled angiography was performed in 94%. The proportion of patients treated with stents was 83%. The primary clinical end point was reached in 67 (19.3%) patients on verapamil and in 103 (29.3%) patients on placebo (relative risk [RR] 0.66 [95% confidence interval (CI) 0.48 to 0.89]; p = 0.002). This difference between the groups was driven by TVR (17.5% with verapamil vs. 26.2% with placebo; RR 0.67 [95% CI 0.49 to 0.93]; p = 0.006). Late lumen loss was 0.74 +/- 0.70 mm with verapamil and 0.81 +/- 0.75 mm with placebo (p = 0.11). Compared with placebo, verapamil reduced the rate of restenosis > or =75% (7.8% vs. 13.7%; RR 0.57 [95% CI 0.35 to 0.92]; p = 0.014). CONCLUSIONS: Verapamil compared with placebo improves long-term clinical outcome after PCI of native coronary arteries by reducing the need for TVR. This was caused by a reduction in the rate of high-grade restenosis.