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• In those with cardiac amyloidosis and heart failure-related cardiogenic shock, there was significant augmentation of cardiac index after intra-aortic balloon pump (IABP) and significant decreases in left ventricular and right ventricular filling pressures. • Predictors of lack of response to IABP by cardiac index were a smaller baseline left ventricular end-diastolic diameter size per centimeter and higher pre-IABP systemic vascular resistance. • Most patients with Society for Cardiovascular Angiography and Interventions stage C heart failure-related cardiogenic shock were stabilized successfully and bridged to advanced therapies with IABP alone. In those with heart failure-related cardiogenic shock (HF-CS), an intra-aortic balloon pump (IABP) may improve hemodynamics and be useful as a bridge to advanced therapies. We explore whether those with cardiac amyloidosis and HF-CS might experience hemodynamic improvement and describe the hemodynamic response after IABP. We retrospectively identified consecutive patients with a diagnosis of cardiac amyloid, either light chain or transthyretin, who were admitted to our intensive care unit with HF-CS. Patients were excluded if an IABP was placed during heart transplant or for shock related to acute myocardial infarction. Invasive hemodynamics before and after IABP placement were assessed. We identified 23 patients with cardiac amyloid who had an IABP placed for HF-CS. The 1-year survival rate was 74% and most (65%) were bridged to heart transplant, although 1 patient was bridged to destination left ventricular assist device. After IABP, the mean arterial pressure, cardiac index, and cardiac power index were significantly increased, whereas mean right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure were all significantly decreased. A smaller left ventricular end-diastolic diameter (per cm) was associated with a higher likelihood of a cardiac index of <2.2 L/min/m2 after IABP (odds ratio 0.16, 95% confidence interval 0.01–0.93, P =.04). IABP significantly improved cardiac index while decreasing right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure in cardiac amyloidosis patients with HF-CS. [Display omitted] [ABSTRACT FROM AUTHOR]

Bile acids (BAs) are cholesterol-derived compounds that regulate glucose, lipid, and energy metabolism. Despite their significance in glucose homeostasis, the association between specific BA molecular species and their synthetic pathways with diabetes is unclear. Here, we used a recently validated, stable-isotope dilution, high-performance liquid chromatography with tandem mass spectrometry method to quantify a panel of BAs in fasting plasma from 2,145 study participants and explored structural and genetic determinants of BAs linked to diabetes, insulin resistance, and obesity. Multiple 12α-hydroxylated BAs were associated with diabetes (adjusted odds ratio [aOR] range, 1.3–1.9; P < 0.05 for all) and insulin resistance (aOR range, 1.3–2.2; P < 0.05 for all). Conversely, multiple 6α-hydroxylated BAs and isolithocholic acid (iso-LCA) were inversely associated with diabetes and obesity (aOR range, 0.3–0.9; P < 0.05 for all). Genome-wide association studies revealed multiple genome-wide significant loci linked with 9 of the 14 diabetes-associated BAs, including a locus for iso-LCA (rs11866815). Mendelian randomization analyses showed genetically elevated deoxycholic acid levels were causally associated with higher BMI, and iso-LCA levels were causally associated with reduced BMI and diabetes risk. In conclusion, comprehensive, large-scale, quantitative mass spectrometry and genetics analyses show circulating levels of multiple structurally specific BAs, especially DCA and iso-LCA, are clinically associated with and genetically linked to obesity and diabetes. Article Highlights: The association between specific circulating bile acid (BA) molecular species and diabetes in humans is not extensively studied. In the present study, we found that multiple 12α-hydroxylated BAs are positively associated with diabetes and insulin resistance, whereas multiple 6α-hydroxylated BAs are inversely associated with diabetes and obesity. Mendelian randomization analyses show isolithocholic acid levels are causally associated with reduced risk for diabetes and obesity, and deoxycholic acid levels are causally associated with obesity risk. The findings of this study provide new avenues for investigating the role of BAs in metabolic diseases and may have substantial therapeutic implications. [ABSTRACT FROM AUTHOR]

Aim: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all‐cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half‐life, but direct supportive evidence is lacking. Methods and results: The TRANSFORM‐HF trial randomized patients hospitalized for HF to a long‐term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post‐hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30–<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ‐CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30–<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all‐cause mortality and all‐cause (re)‐hospitalizations, both when assessing eGFR categorically or continuously (p‐value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ‐CSS (p‐value for interaction all >0.052) when assessing eGFR categorically or continuously. Conclusion: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient‐reported outcomes between torsemide and furosemide, irrespective of renal function. [ABSTRACT FROM AUTHOR]

Aim: Phenylacetylglutamine (PAGln) is a phenylalanine‐derived metabolite produced by gut microbiota with mechanistic links to heart failure (HF)‐relevant phenotypes. We sought to investigate the prognostic value of PAGln in patients with stable HF. Methods and results: Fasting plasma PAGln levels were measured by stable‐isotope‐dilution liquid chromatography–tandem mass spectrometry (LC‐MS/MS) in patients with stable HF from two large cohorts. All‐cause mortality was assessed at 5‐year follow‐up in the Cleveland cohort, and HF, hospitalization, or mortality were assessed at 3‐year follow‐up in the Berlin cohort. Within the Cleveland cohort, median PAGln levels were 4.2 (interquartile range [IQR] 2.4–6.9) μM. Highest quartile of PAGln was associated with 3.09‐fold increased mortality risk compared to lowest quartile. Following adjustments for traditional risk factors, as well as race, estimated glomerular filtration rate, amino‐terminal pro‐B‐type natriuretic peptide, high‐sensitivity C‐reactive protein, left ventricular ejection fraction, ischaemic aetiology, and HF drug treatment, elevated PAGln levels remained predictive of 5‐year mortality in quartile comparisons (adjusted hazard ratio [HR] [95% confidence interval, CI] for Q4 vs Q1: 1.64 [1.07–2.53]). In the Berlin cohort, a similar distribution of PAGln levels was observed (median 3.2 [IQR 2.0–4.8] μM), and PAGln levels were associated with a 1.92‐fold increase in 3‐year HF hospitalization or all‐cause mortality risk (adjusted HR [95% CI] for Q4 vs Q1: 1.92 [1.02‐3.61]). Prognostic value of PAGln appears to be independent of trimethylamine N‐oxide levels. Conclusion: High levels of PAGln are associated with adverse outcomes independent of traditional cardiac risk factors and cardio‐renal risk markers. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions The clinical utility of pulmonary hypertension (PH) risk scores in non‐group 1 PH with pulmonary vascular disease (PVD) remains unresolved.We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH‐related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c‐statistic to predict death was compared separately in (i) pre‐capillary PH groups 3/4/5, and (ii) combined post‐ and pre‐capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular–pulmonary artery (RV‐PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c‐statistic for predicting death (0.699, 95% confidence interval [CI] 0.660–0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656–0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c‐statistic difference −0.072, 95% CI −0.123 to −0.020, p = 0.006, and −0.043, 95% CI −0.067 to −0.018, p = 0.0007, respectively). RV function and RV‐PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non‐invasively identified non‐group 1 PH with more advanced PVD with worse exercise capacity, RV‐PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all).Non‐invasive REVEAL risk predicts mortality in non‐group 1 PH without incremental prognostic value from detailed RV function or RV‐PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non‐invasively identifies greater pulmonary vascular dysfunction and right heart‐related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non‐group 1 PH. [ABSTRACT FROM AUTHOR]