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Background Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). In addition to glucose, other glucose-related indices, such as HbA1c, glucose-HbA1c ratio (GHR), and stress-hyperglycaemia ratio (SHR) are potential predictors of clinical outcomes following AMI. However, the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting 1-year all cause mortality in diabetic and non-diabetic ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients. Methods We undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values using the Youden’s formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-off values in the diabetic and non-diabetic subgroups, stratified by the type of AMI. Results There were 5841 STEMI and 4105 NSTEMI in the study. In STEMI patients, glucose, GHR, and SHR were independent predictors of 1-year all-cause mortality [glucose: OR 2.19 (95% CI 1.74–2.76); GHR: OR 2.28 (95% CI 1.80–2.89); SHR: OR 2.20 (95% CI 1.73–2.79)]. However, in NSTEMI patients, glucose and HbA1c were independently associated with 1-year all-cause mortality [glucose: OR 1.38 (95% CI 1.01–1.90); HbA1c: OR 2.11 (95% CI 1.15–3.88)]. In diabetic STEMI patients, SHR performed the best in terms of area-under-the-curve (AUC) analysis (glucose: AUC 63.3%, 95% CI 59.5–67.2; GHR 68.8% 95% CI 64.8–72.8; SHR: AUC 69.3%, 95% CI 65.4–73.2). However, in non-diabetic STEMI patients, glucose, GHR, and SHR performed equally well (glucose: AUC 72.0%, 95% CI 67.7–76.3; GHR 71.9% 95% CI 67.7–76.2; SHR: AUC 71.7%, 95% CI 67.4–76.0). In NSTEMI patients, glucose performed better than HbA1c for both diabetic and non-diabetic patients in AUC analysis (For diabetic, glucose: AUC 52.8%, 95% CI 48.1–57.6; HbA1c: AUC 42.5%, 95% CI 37.6–47. For non-diabetic, glucose: AUC 62.0%, 95% CI 54.1–70.0; HbA1c: AUC 51.1%, 95% CI 43.3–58.9). The optimal cut-off values for glucose, GHR, and SHR in STEMI patients were 15.0 mmol/L, 2.11, and 1.68 for diabetic and 10.6 mmol/L, 1.72, and 1.51 for non-diabetic patients respectively. For NSTEMI patients, the optimal glucose values were 10.7 mmol/L for diabetic and 8.1 mmol/L for non-diabetic patients. Conclusions SHR was the most consistent independent predictor of 1-year all-cause mortality in both diabetic and non-diabetic STEMI, whereas glucose was the best predictor in NSTEMI patients.

Although current evidence is in favor of metabolic health and nonobesity in the reduction of incident cardiovascular disease, little is known regarding the prognosis across the metabolic phenotypes once cardiovascular disease occurs. This study examined the prognosis of patients with significant aortic stenosis (AS) on the basis of the presence of metabolic health and obesity. This a retrospective cohort study on consecutive patients who presented with moderate-to-severe AS to a tertiary hospital between 2010 and 2015. Patients were allocated into 4 groups on the basis of obesity and metabolic health: metabolically healthy obese (MHO), metabolically healthy nonobese (MHNO), metabolically unhealthy obese (MUO), and metabolically unhealthy nonobese (MUNO). Metabolic health was defined in accordance to the Adult Treatment Panel III criteria. The primary outcome was all-cause mortality. Cox regression examined independent associations between mortality and metabolic phenotypes, adjusting for aortic valve area, ejection fraction, age, gender, chronic kidney disease, and aortic valve replacement as a time-dependent covariate. Of 727 patients, the majority (51.6%) were MUNO, followed by MUO (32.7%), MHNO (11.4%), and MHO (4.3%). MHNO had the highest mortality (43.0%), followed by the MUNO (37.5%), MUO (30.0%), and MHO (6.9%) groups (p = 0.001). Compared with MHNO, MHO (hazard ratio 0.159, 95% confidence interval 0.038 to 0.668, p = 0.012) and MUO (hazard ratio 0.614, 95% confidence interval 0.403 to 0.937, p = 0.024) were independently associated with lower all-cause mortality rates after adjusting for confounders. In patients who are obese, metabolic health had favorable survival compared with metabolically unhealthy (p = 0.015), but this protective impact of metabolic health was not observed in patients with overweight or normal weight. Obesity had favorable survival compared with overweight and normal weight in both patients who are metabolically healthy (p = 0.002) and unhealthy (p = 0.007). In conclusion, patients who are MHO with AS have the most favorable prognosis, whereas the seemingly healthy MHNO group had the worst survival. There should be a paradigm shift toward prioritizing metabolic health rather than weight reduction in patients with significant AS.

Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed the “smoker’s paradox.” Given the known detrimental effects of smoking on the cardiovascular system, it has been proposed that the beneficial effect of smoking on outcomes is due to age differences between smokers and non-smokers and is therefore a smoker’s pseudoparadox. The aim of this study was to evaluate the association between smoking status and clinical outcomes in ST-segment elevation (STEMI) and non-STEMI (NSTEMI) patients treated by percutaneous coronary intervention (PCI), using a national multi-ethnic Asian registry. In unadjusted analyses, current smokers had better clinical outcomes following STEMI and NSTEMI. However, after adjusting for age, the protective effect of smoking was lost, confirming a smoker’s pseudoparadox. Interestingly, although current smokers had increased risk for recurrent MI within 1 year after PCI in both STEMI and NSTEMI patients, there was no increase in mortality. In summary, we confirm the existence of a smoker’s pseudoparadox in a multi-ethnic Asian cohort of STEMI and NSTEMI patients and report increased risk of recurrent MI, but not mortality, in smokers.

BackgroundThere is limited contemporary data available on the subject of left ventricular thrombus (LVT) recurrence. This study aimed to evaluate the incidence, outcomes and predictors of patients with LVT recurrence after resolution.MethodsThis was a retrospective cohort study involving 346 patients with resolved LVT at baseline, derived from an echocardiography database at a tertiary medical centre, from March 2011 to January 2021. Patients were stratified based on the presence of LVT recurrence during follow-up, with subgroup analysis performed for patients who developed LVT post-acute myocardial infarction (AMI) over a median follow-up duration of 4.4 years.ResultsThe incidence of LVT recurrence was 11.8% (n=41/346) among all resolved LVT (mean age of 59.9±11.6 years, 86.4% male), and 12.0% (n=23/192) in patients with post-AMI resolved LVT. On multivariable regression analyses accounting for competing risks (all-cause mortality), active or previous malignancy was associated with LVT recurrence in both all (adjusted subdistribution HR (aSHR) 5.59, 95% CI 2.02 to 15.5, p<0.001) and patients with post-AMI (aSHR 13.9, 95% CI 4.05 to 47.7, p<0.001) resolved LVT. Initial LVT characteristics such as size (per cm) (aSHR 1.42, 95% CI 1.02 to 1.96, p=0.036) and protrusion (aSHR 5.46, 95% CI 1.38 to 21.6, p=0.016) were associated with recurrence in all and patients with post-AMI, respectively. On multivariable Cox regression analyses, LVT recurrence was associated with increased composite outcomes (comprising AMI, acute ischaemic stroke, acute decompensated heart failure, all-cause mortality) in all patients with resolved LVT (adjusted HR (aHR) 3.04, 95% CI 1.70 to 5.44, p<0.001), and in the post-AMI subgroup (aHR 2.77, 95% CI 1.21 to 6.32, p=0.016).ConclusionsActive or previous malignancy, and initial LVT imaging characteristics were associated with recurrent LVT. LVT recurrence was a marker of poor prognosis in terms of adverse composite outcomes in patients with resolved LVT.

Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70–0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55–0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66–0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68–0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57–0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40–0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48–0.86). This were consistent for left ventricular ejection fraction < 50% or ≥ 50%. In conclusion, in AMI managed with revascularization, both BB and ACEI/ARB were associated with a lower incidence of 12-month all-cause mortality. Combined BB and ACEI/ARB was associated with the lowest incidence of all-cause mortality and HF hospitalization.

Cognitive impairment (CI) is common in heart failure (HF). Patients with HF demonstrate reduced global cognition as well as deficits in multiple cognitive domains compared to controls. Degree of CI may be related to HF severity. HF has also been associated with an increased risk of dementia. Anatomical brain changes have been observed in patients with HF, including grey matter atrophy and increased white matter lesions. Patients with HF and CI have poorer functional independence and self-care, more frequent rehospitalisations as well as increased mortality. Pathophysiological pathways linking HF and CI have been proposed, including cerebral hypoperfusion and impaired cerebrovascular autoregulation, systemic inflammation, proteotoxicity and thromboembolic disease. However, these mechanisms are poorly understood. We conducted a search on MEDLINE, Embase and Scopus for original research exploring the connection between HF and CI. We then reviewed the relevant literature and discuss the associations between HF and CI, the patterns of brain injury in HF and their potential mechanisms, as well as the recognition and management of CI in patients with HF.

Objectives: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce serum urate in patients with type 2 diabetes mellitus. To evaluate if this effect applies to both patients with and without diabetes, we conducted a systematic review and meta-analysis of SGLT2 inhibitors on serum urate levels in this population. Methods: Four electronic databases (PubMed, Embase, Cochrane and SCOPUS) were searched on 25 September 2021 for articles published from 1 January 2000 up to 25 September 2021, for studies that examined the effect of SGLT2 inhibitors on serum urate in study subjects. Random-effects meta-analysis was performed, with subgroup analyses on the type of SGLT2 inhibitor agent administered, presence of type 2 diabetes mellitus, presence of chronic kidney disease and drug dose. Results: A total of 43 randomized controlled trials, with a combined cohort of 31,921 patients, were included. Both patients with [−31.48 μmol/L; 95% confidence interval (CI): −37.35 to −25.60] and without diabetes (−91.38 μmol/L; 95% CI: −126.53 to −56.24) on SGLT2 inhibitors had significantly lower urate levels when compared with placebo. This treatment effect was similarly observed across different types of SGLT2 inhibitors. However, in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease, the reduction in serum urate with SGLT2 inhibitors became insignificant (95% CI: −22.17 to 5.94, p < 0.01). Conclusion: This study demonstrated that SGLT2 inhibitors are beneficial in reducing serum urate in patients with and without diabetes. SGLT2 inhibitors could therefore contribute to the general treatment of hyperuricaemia.

ObjectiveTo investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV).Methods554 individuals (45 (IQR 33–57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses.ResultsDilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m2, 19.4±3.7 mm/m2, 16.5±3.8 mm/m2 and 20.4±4.5 mm/m2, respectively. After a median follow-up of 23 (4–82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m2), those with a dilated LAVI (≥35 mL/m2) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter.ConclusionsIn this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.

Yeo’s index, the product of the mitral leaflet separation index and dimensionless index of mitral valve (MV), was recently described to accurately identify severe rheumatic mitral stenosis (MS). We assess the association between Yeo’s index and clinical outcomes in patients with rheumatic MS. We studied 297 patients with rheumatic MS. Clinical and echocardiographic data were obtained from the electronic medical record and Yeo’s index was measured in all cases. The outcome studied was a composite of all cause death, heart failure (HF) hospitalisation, MV intervention and stroke or transient ischaemic attack. We also performed subgroup analysis of patients without pre-existing atrial fibrillation (AF) to assess for association with new onset AF. The median follow up was 6.3 years; 145 patients (48.8%) developed the composite outcome. Yeo’s index ( p  < 0.001), mitral valve area (MVA) by pressure half-time (PHT) ( p =  0.028) and planimetry ( p  < 0.001), age ( p  = 0.016), history of diabetes mellitus ( p  = 0.029), previous HF ( p  = 0.021), left ventricular ejection fraction ( p  = 0.022), and pulmonary artery systolic pressure ( p  = 0.007) were univariately associated with the composite outcome. Yeo’s index remained independently associated with the composite outcome in multivariate analysis ( p  < 0.001, HR 0.094, 95% CI 0.260–0.340). This was primarily driven by MV intervention. In a subgroup analysis of patients without pre-existing AF, Yeo’s index was independently associated with new onset AF ( p  = 0.024, HR 0.354, 95% CI 0.143–0.874). This demonstrated that Yeo’s index was independently associated with clinical outcomes in patients with rheumatic MS which was mainly driven by MV intervention.

This study sought to investigate the impact of pre-existing cognitive impairment on outcomes after transcatheter aortic valve implantation (TAVI). TAVI has been increasingly used in seniors, and evidence suggests better outcomes than surgical aortic valve replacement. Although frailty has been shown to be associated with poorer outcomes after TAVI, the effect of pre-existing cognitive impairment on patient outcomes after TAVI remains unclear. We searched the Medline, Embase, Scopus and Cochrane databases until May 14, 2022. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was short-term (6 months to 1 year) mortality, and secondary outcomes included long-term (1 year to 3 years) mortality, in-hospital mortality, and postoperative delirium. A total of 14 studies with 32,746 patients (5,098 patients with cognitive impairment at baseline, 27,648 without) were included in our meta-analysis. Among studies that reported the raw proportion of patients with mortality of postoperative delirium, cognitive impairment significantly increased mortality (risk ratio 2.10, 95% confidence intervals [CIs] 1.43 to 3.08, p = 0.0002) and postoperative delirium (risk ratio 2.27, 95% CI 1.76 to 2.93, p <0.0001). Studies which reported the hazards for mortality (pooled hazards ratio 1.97, 95% CI 1.50 to 2.60, p <0.0001) and odds of postoperative delirium (pooled odds ratio 2.40, 95% CI: 1.51 to 3.80, p = 0.0002) yielded results consistent with the primary meta-analysis. In conclusion, pre-existing cognitive impairment is a significant risk factor for poorer outcomes after TAVI and should be carefully considered in this group of patients. Guidelines and future studies should take cognitive impairment into consideration for preoperative risk stratification.