This research aims to identify and analyse the challenges faced by the energy-power supply chain (LNG Power) in Pakistan a developing economy from combined perspectives of supply chain sustainability ...and resilience in the context of the Triple Bottom Line framework, UN SDGs 7, 13 and energy security. The significance of this research increases many folds as energy-power supply chains have been severely disrupted by events such as COVID-19, the Russia-Ukraine war and massive devastation caused by floods in Pakistan. Pakistan meets more than 60% of its energy-power needs from natural gas (including LNG), being less harmful than coal and oil power generation. The industry is in a state of deep crisis as it faces a complex set of challenges. Exploratory research design using a mixed method case study approach was used for the identification and shortlisting of challenges. Later these were ranked using group BWM. Major challenges were lack of strategy, top management commitment, weak compliance to UN SDGs, stalled structural reforms, disasters, lack of supply chain orientation, risk management culture, financial instability, LNG non-availability, demand uncertainty, infrastructure inadequacies and lack of awareness of Industry 4.0. The research enables policy-making besides providing energy practitioners a roadmap to overcome these challenges.
1–3 Despite being classically identified as a ‘simple’ intestinal dysfunction, the main hypothesis is currently focused on the role of inflammation and oxidative stress as a consequence of the ...intestinal wall ischaemia and/or congestion induced by HF, determining a gut barrier dysfunction and resulting in an increased gut bacterial translocation. 1–3 With this in mind, two main mechanisms have been proposed to link gut dysfunction and HF; (i) metabolism dependent, via gut-derived metabolites entering the systemic circulation and exerting pro-atherogenic effects and pro-inflammatory effects and (ii) metabolism independent, via bacterial components (e.g. lipopolysaccharides and endotoxins) translocating in the systemic circulation and contributing to the systemic inflammatory state with its well-known negative effects on HF. 4 To date, most of the research has identified a choline and L-carnitine metabolic by-product, trimethylamine N-oxide (TMAO), derived by the gut microbiota from the precursor trimethylamine (TMA) and subsequent oxidation via the liver enzyme flavin-containing monooxygenase 3 (FMO3) (see Figure 1), as the key useful prognostic biomarker in several cardiovascular diseases (e.g. coronary artery disease, acute myocardial infarction, and HF), with an interesting role in risk stratification. 5,6 Notably, TMAO, produced through the anaerobic metabolism of choline and carnitine containing molecules, is widely considered as the possible missing link between the consumption of a Western diet and the well-known increased cardiovascular diseases risk observed in the Western population. 7 Indeed, TMAO is produced through the anaerobic metabolism of choline and L-carnitine, of which eggs and red meat are rich in the Western diet (i.e., based on high fat foods), and diet can be considered as one the of most important factors affecting the gut microbiota composition. 8 Figure 1. From a pathophysiological point of view, TMAO pathway affects HF in different ways. 1,3 First, TMAO increases the risk of conditions determining HF (i.e. cardiac ischemic diseases), through its pro-atherosclerotic effects mediated by an increase in the expression of macrophage scavenger receptors with development of foam cells in the arterial wall, increasing thrombosis, increasing platelet reactivity, and causing endothelial dysfunction. 1,3 Second, TMAO increases HF susceptibility, directly acting on myocardial remodelling and fibrosis; in addition, it has been speculated that TMAO, being an organic osmolyte, altered cellular osmosis; lastly, it has been showed that TMAO worsens cardiomyocyte contractility, by acting on calcium cellular fluxes. 1,3 Worthy to be mentioned is the relationship between TMAO and renal function, with a possible effect on renal fibrosis and tubular injury further aggravating HF clinic. 1,3 Table 1 Main reports for associations between trimethylamine N-oxide and outcome in heart failure patients First author; year of publication Location Study population Follow-up length Main findings Trimethylamine N-oxide levels (μmol/L) Tang WH 2014 9 USA CHF, N = 720 5 years TMAO levels are associated with all-cause mortality 5.0 (3.0–8.5) Tang WH 2015 10 USA CHF, N = 112 5 years TMAO levels are associated with all-cause mortality and heart transplantation 5.8 (3.6–12.1) Trøseid M 2015 11 Norway CHF N = 115 5.2 years TMAO levels are associated with all-cause mortality and heart transplantation 13.5 ± 18.5 (CAD), 7.1 ± 5.6 (DCM) Suzuki T 2016 12 UK AHF, N = 972 1 years TMAO levels are associated with all-cause mortality and a composite mortality/rehospitalization 5.6 (3.4–10.5) Schuett K 2017 22 Germany CHF (pEF and rEF), N = 823 9.7 years TMAO levels are associated with all-cause mortality and cardiovascular mortality 4.7 (3.4–6.8) rEF, 4.7 (3.2–6.9) pEF Hayashi T 2018 13 Japan Decomp HF, N = 22 Cross-sectional TMAO levels (during decompensation and during compensation phases) and gut microbiome composition were altered compared with control subjects 17.3 ± 11.7 (Decomp), 17.7 ± 12.6 (Comp) Salzano A 2019 23 UK CHF (pEF and rEF), pEF = 118 vs rEF = 38 vs C = 40, N = 196 5 years TMAO levels are associated with mortality in pEF Use of levels of TMAO for risk stratification of long-term mortality in pEF 6.6 (4.3–12.2) pEF, 8.4 (3.7–13.8) rEF Suzuki T 2019 14 11 European countries Worsening or new-onset HF, N = 2234 3 years TMAO levels are associated with all-cause mortality and a composite of mortality/rehospitalization 5.9 (3.6–10.8) Yazaki Y 2019 31 11 European countries Worsening or new-onset HF, N = 2234 2 years TMAO levels of HF patients differed by region TMAO levels associated with risk of mortality CE > NW/S 6.2 (4.8–7.8) CE, 7.2 (5.5–8.8) NW, 6.5 (5.0–8.2) S Zhou X 2020 16 China HFrEF after MI, N = 1208 4 years TMAO levels are associated with major adverse cardiac events (MACE): all-cause mortality, HF rehospitalization, or recurrent MI, and all-cause mortality 4.5 Yazaki Y 2020 28 UK AHF, N = 1087 1 year TMAO levels are associated with a composite of all-cause mortality and/or rehospitalization 5.2–22.8 (Japanese), 3.6–10.8 (Caucasian), 3.1–8.4 (South Asian) Guo F 2020 24 China HFpEF, N = 228 5 years TMAO levels are independent predictor of new onset HF TMAO levels are independent risk factor of renal dysfunction 12.65 (9.32–18.66) Emoto T 2021 25 CHF (pEF and rEF), CHF = 22 vs C = 11, N = 33 TMAO levels are increased in Japanese HF compared to Caucasian/South Asian HF abundance of cntA/B positively correlated with TMAO 4.5–34.5 Papandreou C 2021 17 Spain CHF (pEF and rEF), AF = 509 vs C = 618, CHF = 326 vs C = 426, N = 1879 10 years TMAO levels are not associated with AF and HF incidence 3.0–8.5 Kinugasa Y 2021 26 Japan HFpEF, N = 146 5 years TMAO levels are associated with a composite endpoint of cardiac mortality and hospitalization for HF 20.37 Israr MZ 2021 30 UK AHF, N = 806 1 years TMAO levels are associated with all-cause mortality and a composite of all-cause mortality and/or rehospitalization caused by HF 10.2 (5.8–18.7) Dong Z 2021 27 China HFpEF, CHF = 61 vs C = 57, N = 118 1 years TMAO levels are independent risk factor for HFpEF 6.84 Yuzefpolskaya M 2021 18 USA CHF, N = 341 2 years + 8 months TMAO levels increased with HF severity and were similarly elevated, long term after LVAD and HT. TMAO levels positively related to biomarkers of inflammation (TNF-α and ET-1), endotoxemia (sCD14), and oxidative stress 6.96 (HF), 5.81 (LVAD), 5.35 (HT) Mollar A 2021 19 Spain Decomp HF, N = 102 1 years TMAO related with recent HF Wargny M 2022 32 France AHF, AHF = 209 vs C = 1140, N = 1468 7.3 years TMAO is not associated with occurrence of HF requiring hospitalization (HFrH) and composite event HFrH and/or cardiovascular mortality and all-cause mortality. 8.8 (5.3–17.0) Li N 2022 29 China AMI and HF, N = 985 1 years TMAO levels independently correlated with poor prognosis (i.e.: MACE, and all-cause mortality) and recurrence of MI in patients with AMI complicated by HF, especially in those with higher hsCRP levels TMAO the difference for rehospitalization due to HF is not statistically significant 6.7 (4.0, 11.7) Wei H 2022 20 China HFrEF, N = 955 8 years TMAO levels are associated with the composite outcome of cardiovascular death or heart transplantation 2.52 (1.18–4.06) Israr MZ 2022 21 UK HFrEF, N = 1783 3 years TMAO levels are associated with the composite outcome of HF hospitalization or death at 3 years 6.4 (3.9–11.6) Abbreviations: AF, atrial fibrillation; AMI, acute myocardial infarction; AHF, acute heart failure; BUN, blood urea nitrogen; C, controls; CAD, coronary artery disease; CE, Central/Eastern group (Germany, Poland, Serbia, and Slovenia); CHF, chronic heart failure; cntA/B, carnitine oxygenase/reductase; Comp, compensated; DCM, dilated cardiomyopathy; Decomp, decompensated; ET-1, endothelin-1; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; hsCRP, high-sensitivity C-reactive protein; HT, heart transplant; LVAD, left ventricular assist device; MACE, major adverse cardiac events; MI, myocardial infarction; NT-proBNP, N-terminal pro-brain type natriuretic peptide; NYHA, New York Heart Association; NW, the Northern/Western group (France, Netherlands, Norway, Sweden, and United Kingdom); S, Southern group (Greece and Italy); sCD14, soluble CD14; TMAO, trimethylamine N-oxide; TNF-α, tumour necrosis factor alpha. From a clinical point of view, since the first investigations regarding the association between TMAO and HFrEF as of about 10 years ago, 9 several studies have demonstrated that TMAO levels were higher in CHF when compared with healthy controls showing associations between TMAO and clinical and biochemical parameters (i.e., renal function, age, comorbidities, and CRP), severity of disease (NYHA classes), 15,18 and clinical outcomes
Heart failure with preserved ejection fraction (HFpEF) represents the most common HF phenotype of patients aged > 65 years, with an incidence and a prevalence that are constantly growing. The HFpEF ...cardinal symptom is exercise intolerance (EI), defined as the impaired ability to perform physical activity and to reach the predicted age-related level of exercise duration in the absence of symptoms—such as fatigue or dyspnea—and is associated with a poor quality of life, a higher number of hospitalizations, and poor outcomes. The evidence of the protective effect between exercise and adverse cardiovascular outcomes is numerous and long-established. Regular exercise is known to reduce cardiovascular events and overall mortality both in apparently healthy individuals and in patients with established cardiovascular disease, representing a cornerstone in the prevention and treatment of many cardio-metabolic conditions. Several studies have investigated the role of exercise in HFpEF patients. The present review aims to dwell upon the effects of exercise on HFpEF. For this purpose, the relevant data from a literature search (PubMed, EMBASE, and Medline) were reviewed. The analysis of these studies underlines the fact that exercise training programs improve the cardiorespiratory performance of HFpEF patients in terms of the increase in peak oxygen uptake, the 6 min walk test distance, and the ventilatory threshold; on the other hand, diastolic or systolic functions are generally unchanged or only partially modified by exercise, suggesting that multiple mechanisms contribute to the improvement of exercise tolerance in HFpEF patients. In conclusion, considering that exercise training programs are able to improve the cardiorespiratory performance of HFpEF patients, the prescription of exercise training programs should be encouraged in stable HFpEF patients, and further research is needed to better elucidate the pathophysiological mechanisms underpinning the beneficial effects described.
Myocarditis is a disease caused by cardiac inflammation that can progress to dilated cardiomyopathy, heart failure, and eventually death. Several etiologies, including autoimmune, drug-induced, and ...infectious, lead to inflammation, which causes damage to the myocardium, followed by remodeling and fibrosis. Although there has been an increasing understanding of pathophysiology, early and accurate diagnosis, and effective treatment remain challenging due to the high heterogeneity. As a result, many patients have poor prognosis, with those surviving at risk of long-term sequelae. Current diagnostic methods, including imaging and endomyocardial biopsy, are, at times, expensive, invasive, and not always performed early enough to affect disease progression. Therefore, the identification of accurate, cost-effective, and prognostically informative biomarkers is critical for screening and treatment. The review then focuses on the biomarkers currently associated with these conditions, which have been extensively studied via blood tests and imaging techniques. The information within this review was retrieved through extensive literature research conducted on major publicly accessible databases and has been collated and revised by an international panel of experts. The biomarkers discussed in the article have shown great promise in clinical research studies and provide clinicians with essential tools for early diagnosis and improved outcomes.
Aims
The aim of this study was to investigate whether ethnicity influences the associations between trimethylamine N‐oxide (TMAO) levels and heart failure (HF) outcomes.
Methods and results
...Trimethylamine N‐oxide levels were measured in two cohorts with acute HF at two sites. The UK Leicester cohort consisted mainly of Caucasian (n = 842, 77%) and South Asian (n = 129, 12%) patients, whereas patients in the Japanese cohort (n = 116, 11%) were all Japanese. The primary endpoint was the measurement of all‐cause mortality and/or HF rehospitalization within 1 year post‐admission. Association of TMAO levels with outcome was compared in the entire population and between ethnic groups after adjustment for clinical parameters. TMAO levels were significantly higher in Japanese patients median (interquartile range): 9.9 μM (5.2–22.8) than in Caucasian 5.9 μM (3.6–10.8) and South Asian 4.5 μM (3.1–8.4) (P < 0.001) patients. There were no differences in the rate of mortality and/or HF rehospitalization between the ethnic groups (P = 0.096). Overall, higher TMAO levels showed associations with mortality and/or rehospitalization after adjustment for confounders ( P = 0.002). Despite no differences between ethnicity and association with mortality/HF after adjustment (P = 0.311), only in Caucasian patients were TMAO levels able to stratify for a mortality/HF event (P < 0.001).
Conclusions
Differences were observed in the association of mortality and/or rehospitalization based on circulating TMAO levels. Elevated TMAO levels in Caucasian patients showed increased association with adverse outcomes, but not in non‐Caucasian patients.
Heart failure (HF) is a clinical syndrome consisting of typical symptoms and signs due to structural and/or functional abnormalities of the heart, resulting in elevated intracardiac pressures and/or ...inadequate cardiac output. The vascular system plays a crucial role in the development and progression of HF regardless of ejection fraction, with endothelial dysfunction (ED) as one of the principal features of HF. The main ED manifestations (i.e., impaired endothelium-dependent vasodilation, increased oxidative stress, chronic inflammation, leukocyte adhesion, and endothelial cell senescence) affect the systemic and pulmonary haemodynamic and the renal and coronary circulation. The present review is aimed to discuss the contribution of ED to HF pathophysiology-in particular, HF with preserved ejection fraction-ED role in HF patients, and the possible effects of pharmacological and non-pharmacological approaches. For this purpose, relevant data from a literature search (PubMed, Scopus, EMBASE, and Medline) were reviewed. As a result, ED, assessed via venous occlusion plethysmography or flow-mediated dilation, was shown to be independently associated with poor outcomes in HF patients (e.g., mortality, cardiovascular events, and hospitalization due to worsening HF). In addition, SGLT2 inhibitors, endothelin antagonists, endothelial nitric oxide synthase cofactors, antioxidants, and exercise training were shown to positively modulate ED in HF. Despite the need for future research to better clarify the role of the vascular endothelium in HF, ED represents an interesting and promising potential therapeutic target.
Elastin degradation is implicated in the pathology of vulnerable plaque. Recent studies show promising results for plasma desmosine (pDES), an elastin-specific degradation product, as a marker of ...cardiovascular disease (CVD) outcomes. The aim of this study was to investigate the potential role of pDES as a marker of clinical outcome in patients with acute myocardial infarction (AMI).
In this case-control study, we studied 236 AMI patients: 79 patients who had death and/or myocardial infarction (MI) at 2 years, and 157 patients who did not have an event at 2 years. pDES was measured using a validated liquid chromatography-tandem mass spectrometry method. Association of pDES with adverse outcomes, and the incremental value of pDES to global registry of acute coronary events (GRACE) score for risk stratification was assessed.
pDES levels were elevated in patients with the composite outcome of death/MI at 2 years (
= 0.002). Logistic regression analyses showed pDES to be associated with death/MI at 2 years Odds ratio (OR) 5.99 (95% CI 1.81-19.86)
= 0.003. pDES remained a significant predictor of death/MI at 2 years even after adjustment for age, sex, history of CVD, revascularisation, blood pressure, medications on discharge, Troponin I, and NT-proBNP levels.OR 5.60 (95% CI 1.04-30.04)
= 0.044. In another multivariable model including adjustment for eGFR, pDES was significantly associated with the composite outcome at 6 months, but not at 2 years follow up. DES was also able to reclassify risk stratification for death/MI at 6 months, when added to the GRACE risk model Net Reclassification Index (NRI) 41.2 (95% CI 12.0-70.4)
= 0.006.
pDES concentrations predict clinical outcomes in patients with AMI, demonstrating its potential role as a prognostic marker in AMI.
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