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Internal Medicine Journal Jun 2024Cancer therapy-related cardiac dysfunction (CTRCD) is a complication of selected cancer therapy agents associated with decline in left ventricular ejection fraction... (Review)
Review
Prevention of anthracycline-t and trastuzumabinduced decline in left ventricular ejection fraction with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker: a narrative systematic review of randomised controlled trials.
Cancer therapy-related cardiac dysfunction (CTRCD) is a complication of selected cancer therapy agents associated with decline in left ventricular ejection fraction (LVEF). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have established benefits in heart failure with reduced ejection fraction, but their efficacy for preventing CTRCD remains controversial. This narrative systematic review assessed the efficacy and safety of ACEI/ARB in the prevention of cancer therapy LVEF decline. We systematically searched PubMed, Embase and Cochrane from January 1980 to June 2022. Studies of interest were randomised controlled trials of patients with normal LVEF and active malignancy receiving cancer therapy, randomised to receive either an ACEI or ARB compared with a control group. The outcome was the change in LVEF from baseline to the end of the follow-up period. Death, clinical heart failure and adverse drug reactions were recorded. A total of 3731 search records were screened and 12 studies were included, comprising a total of 1645 participants. Nine studies assessed the prevention of anthracycline-induced LVEF decline, of which five showed a beneficial effect (1%-14% higher LVEF in treated groups), whereas four studies showed no effect. Three studies assessed the prevention of trastuzumab-induced LVEF decline, of which one showed a beneficial effect (4% higher LVEF) in a subset of participants. There are mixed data regarding the efficacy of ACEI/ARB in preventing the LVEF decline in patients undergoing anthracycline or trastuzumab therapy, with evidence suggesting no clinically meaningful benefit observed in recent studies.
PubMed: 38874281
DOI: 10.1111/imj.16437 -
Vascular Jun 2024A current and ongoing challenge is to reduce patient mortality after endovascular abdominal aortic repair (EVAR). This study aimed to assess the predictors of all-cause...
OBJECTIVES
A current and ongoing challenge is to reduce patient mortality after endovascular abdominal aortic repair (EVAR). This study aimed to assess the predictors of all-cause mortality after EVAR.
METHODS
Data regarding the demographic characteristics, comorbidities, laboratory values, selected anatomical factors, post-EVAR treatment, surveillance and complications of patients who underwent elective EVAR for non-ruptured abdominal aortic aneurysm (AAA) between January 2010 and January 2021 were evaluated. Mortality was assessed until 10 October 2023. Multivariate analyses were performed after adjusting for age, hypertension, diabetes mellitus, dyslipidaemia, sex, smoking, number of lumbar arteries, patency of inferior mesenteric artery (IMA), IMA diameter and reinterventions.
RESULTS
This study included 196 patients (183 men and 13 women) with a mean age of 72.4 ± 7.67 years. The overall mortality rate during a mean follow-up period of 5.75 ± 3.1 years was 50.0% ( = 98). The 2-, 5- and 10-year mortality rates were 9.7%, 32.0% and 66.6%, respectively. The mortality rates decreased by 59% in patients with reinterventions (hazard ratio [HR]: 0.41; 95% confidence interval [CI]: 0.23-0.73; = .002) and by 59% in patients treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (HR: 0.41; 95% CI: 0.26-0.66; < .001). Chronic anticoagulation was associated with 2.09-fold higher mortality (HR: 2.09; 95% CI: 1.19-3.67; = .010), and coronary artery disease (CAD) was associated with 1.74-fold higher mortality (HR: 1.74; 95% CI: 1.09-2.78; = .021). Pre-EVAR AAA diameter and 1-year post-EVAR sac diameter were positively associated with mortality (HR: 1.05; 95% CI: 1.03-1.08; < .001, and HR: 1.05; 95% CI: 1.03-1.07; < .001, respectively), that is, an increase of pre-EVAR and/or 1-year post-EVAR AAA diameter by 1 mm was associated with a 5% higher risk of all-cause mortality.
CONCLUSIONS
Reinterventions and treatment with ACE inhibitors or ARBs may be associated with decreased post-EVAR mortality. A greater pre-EVAR, a post-EVAR AAA diameter, CAD and chronic anticoagulation were associated with higher all-cause mortality post-EVAR.
PubMed: 38872254
DOI: 10.1177/17085381241262350 -
PloS One 2024Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor...
BACKGROUND
Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated.
METHODS
Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications.
RESULTS
A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118).
CONCLUSION
In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis.
Topics: Humans; Metformin; Male; Female; Middle Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver Cirrhosis; Gastrointestinal Hemorrhage; Esophageal and Gastric Varices; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cohort Studies
PubMed: 38870117
DOI: 10.1371/journal.pone.0302811 -
Heliyon Jun 2024Anti-SARS-CoV-2 and immunomodulatory drugs are important for treating clinically severe patients with respiratory distress symptoms. Alpha- and gamma-mangostins (AM and...
BACKGROUND
Anti-SARS-CoV-2 and immunomodulatory drugs are important for treating clinically severe patients with respiratory distress symptoms. Alpha- and gamma-mangostins (AM and GM) were previously reported as potential 3C-like protease (3CL) and Angiotensin-converting enzyme receptor 2 (ACE2)-binding inhibitors .
OBJECTIVE
We aimed to evaluate two active compounds, AM and GM, from for their antivirals against SARS-CoV-2 in live virus culture systems and their cytotoxicities using standard methods. Also, we aimed to prove whether 3CL and ACE2 neutralization were major targets and explored whether any additional targets existed.
METHODS
We tested the translation and replication efficiencies of SARS-CoV-2 in the presence of AM and GM. Initial and subgenomic translations were evaluated by immunofluorescence of SARS-CoV-2 3CL and N expressions at 16 h after infection. The viral genome was quantified and compared with the untreated group. We also evaluated the efficacies and cytotoxicities of AM and GM against four strains of SARS-CoV-2 (wild-type B, B.1.167.2, B.1.36.16, and B.1.1.529) in Vero E6 cells. The potential targets were evaluated using cell-based anti-attachment, time-of-drug addition, 3CL activities, and ACE2-binding using a surrogated viral neutralization test (sVNT). Moreover, additional targets were explored using combinatorial network-based interactions and Chemical Similarity Ensemble Approach (SEA).
RESULTS
AM and GM reduced SARS-CoV-2 3CL and N expressions, suggesting that initial and subgenomic translations were globally inhibited. AM and GM inhibited all strains of SARS-CoV-2 at EC of 0.70-3.05 μM, in which wild-type B was the most susceptible strain (EC 0.70-0.79 μM). AM was slightly more efficient in the variants (EC 0.88-2.41 μM), resulting in higher selectivity indices (SI 3.65-10.05), compared to the GM (EC 0.94-3.05 μM, SI 1.66-5.40). GM appeared to be more toxic than AM in both Vero E6 and Calu-3 cells. Cell-based anti-attachment and time-of-addition suggested that the potential molecular target could be at the post-infection. 3CL activity and ACE2 binding were interfered with in a dose-dependent manner but were insufficient to be a major target. Combinatorial network-based interaction and chemical similarity ensemble approach (SEA) suggested that fatty acid synthase (FASN), which was critical for SARS-CoV-2 replication, could be a target of AM and GM.
CONCLUSION
AM and GM inhibited SARS-CoV-2 with the highest potency at the wild-type B and the lowest at the B.1.1.529. Multiple targets were expected to integratively inhibit viral replication in cell-based system.
PubMed: 38867992
DOI: 10.1016/j.heliyon.2024.e31987 -
European Heart Journal Supplements :... Apr 2024Arterial hypertension represents the most important cardiovascular risk factor with a direct responsibility for a large share of cardiovascular mortality and morbidity...
Arterial hypertension represents the most important cardiovascular risk factor with a direct responsibility for a large share of cardiovascular mortality and morbidity in the world. Despite the wide availability of antihypertensive therapies with documented effectiveness, blood pressure control still remains largely unsatisfactory in large segments of the population. Guidelines for the management of arterial hypertension suggest the preferential use of five classes of drugs-angiotensin-converting enzyme inhibitors, angiotensin II type I receptor inhibitors, calcium channel blockers, thiazide/thiazide-like diuretics, and beta-blockers-recommending the use of combination therapy, preferably in pre-established combinations, for the majority of hypertensive patients. The evidence of a non-negligible heterogeneity in the response to different antihypertensive drugs in different patients suggests the opportunity for personalization of treatment. The notable phenotypic heterogeneity of the population of hypertensive patients in terms of genetic structure, behavioural aspects, exposure to environmental factors, and disease history imposes the need to consider all the potential determinants of the response to a specific pharmacological treatment. The progressive digitalization of healthcare systems is making enormous quantities of data available for machine learning systems which will allow the development of management algorithms for truly personalized antihypertensive therapy in the near future.
PubMed: 38867857
DOI: 10.1093/eurheartjsupp/suae019 -
Lung Jun 2024Chronic cough (persisting for ≥ 8 weeks) is a common disorder that includes refractory chronic cough (RCC; cough that persists despite treatment of underlying...
INTRODUCTION
Chronic cough (persisting for ≥ 8 weeks) is a common disorder that includes refractory chronic cough (RCC; cough that persists despite treatment of underlying disease) and unexplained chronic cough (UCC; cough with no identifiable cause). We evaluated self-reported health-related quality of life (HR-QoL) and work/activity impairment associated with RCC/UCC in Canada.
METHODS
Our exploratory study included Canadians in the Leger Opinion Panel with RCC or UCC. Key entry criteria were ≥ 18 years of age, cough for ≥ 8 weeks, not currently smoking/quit ≥ 1 year ago, no serious respiratory disease or lung cancer, and not taking angiotensin-converting enzyme inhibitors. Respondents completed a 30-min online survey with general and cough-specific HR-QoL questionnaires, including the EuroQol (EQ) visual analogue scale (VAS), EQ-5-dimension 5-level (EQ-5D-5L), cough severity VAS, Leicester Cough Questionnaire (LCQ), and Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SPH).
RESULTS
Of 49,076 individuals who completed the chronic cough screening questionnaire (July 30-September 1, 2021), 1,620 (3.3%) met entry criteria for RCC/UCC and 1,046 (2.1%) completed the survey. The mean age of respondents was 45 years and 61% were female. Respondents reported impairments in global HR-QoL (EQ-VAS 73.8, 61% with anxiety/depression on the EQ-5D-5L) and cough-specific HR-QoL (mean cough severity VAS score 29.7, LCQ index 15.2). Work and non-work activities were reduced by 34% and 30%, respectively, on the WPAI-SPH.
CONCLUSION
RCC/UCC is prevalent in Canada and associated with impaired HR-QoL, particularly in mental health domains. Additional support and management options may be required to fully address this burden.
PubMed: 38867086
DOI: 10.1007/s00408-024-00714-1 -
Chemical & Pharmaceutical Bulletin Jun 2024In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases...
In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Topics: Glycosides; Angiotensin-Converting Enzyme 2; Molecular Docking Simulation; Humans; Coumarins; SARS-CoV-2; COVID-19; Rutaceae; COVID-19 Drug Treatment; Antiviral Agents; Plant Roots; Angiotensin-Converting Enzyme Inhibitors
PubMed: 38866495
DOI: 10.1248/cpb.c23-00844 -
Cardiovascular Drugs and Therapy Jun 2024This study aims to compare the addition of SGLT2 inhibitors or doubling the diuretic dose in patients receiving treatment with beta-blockers, angiotensin-converting...
INTRODUCTION
This study aims to compare the addition of SGLT2 inhibitors or doubling the diuretic dose in patients receiving treatment with beta-blockers, angiotensin-converting enzyme inhibitors (ACEi), or angiotensin receptor blockers (ARB), as well as mineralocorticoid receptor antagonists (MRA), for heart failure with reduced ejection fraction (HFrEF) who present to the emergency department with decompensated heart failure.
METHODS
This study is a single-center and prospective analysis. A total of 980 decompensated heart failure (HFrEF) patients receiving optimal medical therapy (OMT) according to the 2021 European heart failure guidelines were randomized in a 2:1 ratio into the furosemide and empagliflozin treatment arms. The analysis includes patient clinical characteristics, laboratory results, and echocardiographic data. Factors influencing rehospitalization were identified through multivariate Cox regression analysis. Log-rank analysis was employed to assess factors affecting rehospitalization.
RESULTS
The mean age of the patients was 67.9 years, with 52.1% being men. There was no significant impact of demographic, clinical, or echocardiographic factors on rehospitalization at 1 month; only the effect of treatment subgroups on rehospitalization was observed (p = 0.039). Significant echocardiographic and clinical improvements were seen in both treatment arms. The empagliflozin group exhibited significant improvements in 6-min walk distance, heart rate, body weight, NT-pro BNP levels, and eGFR level compared to the furosemide group. The rate of rehospitalization in the first month was significantly lower in those receiving empagliflozin (28.7%) compared to those receiving a double dose of furosemide (40.2%) (log-rank p = 0.013).
DISCUSSION AND CONCLUSION
This study provides valuable insights into the management of decompensated HFrEF and demonstrates that SGLT2 inhibitors offer benefits beyond glycemic control in this patient group. The significant reduction in rehospitalization rates and improvements in echocardiographic parameters underscore the potential of SGLT2 inhibitors in reducing acute heart failure episodes.
PubMed: 38864970
DOI: 10.1007/s10557-024-07593-x -
Frontiers in Pharmacology 2024Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure...
Effect of sacubitril-valsartan on left ventricular remodeling in patients with acute myocardial infarction after primary percutaneous coronary intervention: a systematic review and meta-analysis.
BACKGROUND
Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure (HF). However, the effect of sacubitril-valsartan in patients with acute myocardial infarction (AMI) remains controversial. Therefore, we conducted this meta-analysis to investigate whether sacubitril-valsartan could reverse left ventricular remodeling and reduce cardiovascular adverse events in AMI patients after primary percutaneous coronary intervention (PPCI).
MATERIALS AND METHODS
Two researchers independently retrieved the relevant literature from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database. The retrieval time was limited from inception to 1 June 2023. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analyzed.
RESULTS
In total, 21 RCTs involving 2442 AMI patients who underwent PPCI for revascularization were included in this meta-analysis. The meta-analysis showed that compared with the angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril-valsartan treatment in AMI patients after PPCI significantly reduced left ventricular end-diastolic dimension (LVEDD) (weighted mean difference (WMD) -3.11, 95%CI: -4.05∼-2.16, < 0.001), left ventricular end-diastolic volume (LVEDV) (WMD -7.76, 95%CI: -12.24∼-3.27, = 0.001), left ventricular end-systolic volume (LVESV) (WMD -6.80, 95%CI: -9.45∼-4.15, < 0.001) and left ventricular end-systolic dimension (LVESD) (WMD -2.53, 95%CI: -5.30-0.24, < 0.001). Subgroup analysis according to the dose of sacubitril-valsartan yielded a similar result. Meanwhile, PPCI patients using sacubitril-valsartan therapy showed lower risk of major adverse cardiac events (MACE) (OR = 0.36, 95%CI: 0.28-0.46, < 0.001), myocardial reinfarction (OR = 0.54, 95%CI: 0.30-0.98, = 0.041) and HF (OR = 0.35, 95%CI: 0.26-0.47, < 0.001) without increasing the risk of renal insufficiency, hyperkalemia, or symptomatic hypotension. At the same time, the change of LV ejection fraction (LVEF) (WMD 3.91, 95%CI: 3.41-4.41, < 0.001), 6 min walk test (6MWT) (WMD 43.56, 95%CI: 29.37-57.76, < 0.001) and NT-proBNP level (WMD -130.27, 95%CI: -159.14∼-101.40, < 0.001) were statistically significant.
CONCLUSION
In conclusion, our meta-analysis indicates that compared with ACEI/ARB, sacubitril-valsartan may be superior to reverse left ventricular remodeling, improve cardiac function, and effectively reduce the risk of MACE, myocardial reinfarction, and HF in AMI patients after PPCI during follow-up without increasing the risk of adverse reactions including renal insufficiency, hyperkalemia, and symptomatic hypotension.
PubMed: 38863978
DOI: 10.3389/fphar.2024.1366035 -
ESC Heart Failure Jun 2024Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide...
AIMS
Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide implementation of guideline-directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution.
METHODS AND RESULTS
Between 2011 and 2020, a total of 12 428 patients (6518 men and 5910 women, mean age 73.50 ± 14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40 ± 13.43 vs. 71.20 ± 15.67 years old, P < 0.0001) with more coexisting hypertension, diabetes, hyperlipidaemia and moderate to severe chronic kidney disease, but less with ischaemic heart disease, cerebrovascular disease and chronic obstructive pulmonary disease (P < 0.0001). In echocardiography measurement parameters, women had smaller left ventricular and left atrial dimensions, higher left ventricular mass index, higher left ventricular ejection fraction (LVEF) and more in HF with preserved ejection fraction (EF) category (LVEF > 50%) than men (P < 0.0001). In HF therapy, women compared with men received more guideline-directed medical HF therapies including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, but similar beta-blockers and mineralocorticoid receptor antagonists (P < 0.0001). Post-discharge long-term clinical outcomes after multivariate-adjusted analysis revealed that women compared with men had lower all-cause mortality [adjusted hazard ratio (aHR): 0.89, 95% confidence interval (CI): 0.84-0.93], lower cardiovascular mortality (aHR: 0.89, 95% CI: 0.80-0.99) and lower 1 year mortality (aHR: 0.91, 95% CI: 0.84-0.99) but similar HF rehospitalization rate (aHR: 1.02, 95% CI: 0.95-1.09) over 8 years of follow-up. The superiority of women over men in all-cause mortality was shown in HF with preserved EF (>50%) and HF with mildly reduced EF (40%-50%), but not in HF with reduced EF (<40%) category. Subgroup forest plot analysis showed body mass index, coexisting hypertension and chronic obstructive pulmonary disease as significant interacting factors.
CONCLUSIONS
With more coronary risk factors and medical comorbidities, less cardiac remodelling and better adherence to guideline-directed HF therapy, women hospitalized for acute decompensated HF demonstrated superiority over men in long-term post-discharge clinical outcomes, including all-cause mortality, cardiovascular mortality and 1 year mortality, and mainly in HF with preserved and mid-range EF categories, in the Asian HF cohort.
PubMed: 38863210
DOI: 10.1002/ehf2.14888