Nir Ayalon

Rationale: Despite increasing recognition of mixed cardiogenic shock—particularly in patients with concomitant sepsis—there remains limited guidance on optimal inotropic selection, and the comparative effectiveness of different inotropes in this population is unclear. Objective: To examine the association between inotrope selection and in-hospital outcomes, including all-cause mortality, among patients with cardiogenic shock and sepsis. Methods: Using the PINC AI enhanced-claims database (2016-2022), we identified patients with cardiogenic shock and sepsis using International Classification of Diseases, Tenth Revision codes (ICD-10) that were present on hospital admission and a pharmacy charge code for dobutamine or milrinone within 2 days of hospitalization. The primary outcome was all-cause hospital mortality. Secondary outcomes included inotrope duration, in-hospital length of stay, atrial arrhythmia, initiation of renal replacement therapy, use of mechanical circulatory support devices, and heart transplantation. We used greedy nearest neighbor matching on the propensity score (dobutamine vs milrinone) followed by g-computation to estimate effects of inotrope selection on outcomes. We examined heterogeneity of treatment effect in patients with renal disease, congestive heart failure, pulmonary circulatory diseases, and on epinephrine prior to inotrope initiation. Results: Out of 10 447 included patients, 74.4% received dobutamine and 25.6% received milrinone. Postmatching characteristics between the milrinone and dobutamine groups were similar (all standardized mean differences <0.1). The primary outcome all-cause mortality was similar between the postmatched milrinone and dobutamine groups (41.6% vs 42.7%; risk difference, -1.4% [95% CI, -3.7% to 1.5%]; P = .40). Patients initiated on milrinone (vs dobutamine) had longer inotrope durations (5.1 vs 3.5 days; mean difference, 1.7 [95% CI, 1.4-1.9] days; P < .001), longer in-hospital length of stay (10.0 vs 9.1 days; mean difference, 0.9 [95% CI, 0.4-1.3] days; P < .001), and more usage of anti-arrhythmic agents (56.0% vs 44.5%; mean difference, 11.5% [95% CI, 8.9%-14.1%]; P < .001). We did not observe any heterogeneity of treatment effect for all-cause mortality based on the preexisting conditions of interest. Conclusions: Using a large, multicenter cohort, we identified no differences in all-cause mortality between dobutamine and milrinone among patients with concurrent cardiogenic shock and sepsis overall. However, secondary outcomes favored dobutamine.

Background: The American Heart Association's framework “ideal cardiovascular health” (CVH) focuses on modifiable risk factors to reduce cardiovascular disease (CVD). Metabolomics provides important pathobiological insights into risk factors and CVD development. We hypothesized that metabolomic signatures associate with CVH status, and that metabolites, at least partially, mediate the association of CVH score with atrial fibrillation (AF) and heart failure (HF). Methods and Results: We studied 3056 adults in the FHS (Framingham Heart Study) cohort to evaluate CVH score and incident outcomes of AF and HF. Metabolomics data were available in 2059 participants; mediation analysis was performed to evaluate the mediation of metabolites in the association of CVH score and incident AF and HF. In the smaller cohort (mean age, 54 years; 53% women), CVH score was associated with 144 metabolites, with 64 metabolites shared across key cardiometabolic components (body mass index, blood pressure, and fasting blood glucose) of the CVH score. In mediation analyses, 3 metabolites (glycerol, cholesterol ester 16:1, and phosphatidylcholine 32:1) mediated the association of CVH score with incident AF. Seven metabolites (glycerol, isocitrate, asparagine, glutamine, indole‐3‐proprionate, phosphatidylcholine C36:4, and lysophosphatidylcholine 18:2), partly mediated the association between CVH score and incident HF in multivariable‐adjusted models. Conclusions: Most metabolites that associated with CVH score were shared the most among 3 cardiometabolic components. Three main pathways: (1) alanine, glutamine, and glutamate metabolism; (2) citric acid cycle metabolism; and (3) glycerolipid metabolism mediated CVH score with HF. Metabolomics provides insights into how ideal CVH status contributes to the development of AF and HF.

Background: Obesity is a precursor to heart failure with preserved ejection fraction. Biomarkers that identify preclinical metabolic heart disease ( MHD ) in young obese patients would help identify high‐risk individuals for heart failure prevention strategies. We assessed the predictive value of GAL3 (galectin–3), FSTL3 (follistatin‐like 3 peptide), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) to identify stage B MHD in young obese participants free of clinically evident cardiovascular disease. Methods and Results: Asymptomatic obese patients (n=250) and non‐obese controls (n=21) underwent echocardiographic cardiac phenotyping. Obese patients were classified as MHD positive ( MHD ‐ POS ; n=94) if they had abnormal diastolic function or left ventricular hypertrophy and had estimated pulmonary artery systolic pressure ≥35 mm Hg. Obese patients without such abnormalities were classified as MHD negative (MHD‐NEG; n=52). Serum biomarkers timed with echocardiography. MHD ‐ POS and MHD‐NEG individuals were similarly obese, but MHD ‐ POS patients were older, with more diabetes mellitus and metabolic syndrome. Right ventricular coupling was worse in MHD ‐ POS patients ( P P P =0.04). Conclusions: In young obese individuals without known cardiovascular disease, GAL 3 is associated with the presence of preclinical MHD . GAL 3 may be useful in screening for preclinical MHD and identifying individuals with increased risk of progression to obesity‐related heart failure with preserved ejection fraction.

Objective: Metabolic syndrome (MetS) can lead to myocardial fibrosis, diastolic dysfunction, and eventual heart failure. This study evaluated alterations in myocardial microstructure in people with MetS by using a novel algorithm to characterize ultrasonic signal intensity variation.Methods: Among 254 participants without existing cardiovascular disease (mean age 42 ± 11 years, 75% women), there were 162 with MetS, 47 with obesity without MetS, and 45 nonobese controls. Standard echocardiography was performed, and a novel validated computational algorithm was used to investigate myocardial microstructure based on sonographic signal intensity and distribution. The signal intensity coefficient (SIC [left ventricular microstructure]) was examined.Results: The SIC was significantly higher in people with MetS compared with people with (P < 0.001) and without obesity (P = 0.04), even after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, and the ratio of triglyceride (TG) to high‐density lipoprotein (HDL) cholesterol (P < 0.05 for all). Clinical correlates of SIC included TG concentrations (r = 0.21, P = 0.0007) and the TG/HDL ratio (r = 0.2, P = 0.001).Conclusions: This study's findings suggest that preclinical MetS and dyslipidemia in particular are associated with altered myocardial signal intensity variation. Future studies are needed to determine whether the SIC may help detect subclinical diseases in people with metabolic disease, with the ultimate goal of targeting preventive efforts.

Background—: Despite the substantial overlap of obesity and metabolic disease, there is heterogeneity with respect to cardiovascular risk. We sought to investigate preclinical differences in systolic and diastolic function in obesity, and specifically compare obese individuals with and without metabolic syndrome (MS). Methods and Results—: Obese individuals without cardiac disease with (OB/MS+, n=124) and without (OB/MS−, n=37) MS were compared with nonobese controls (n=29). Diastolic function was assessed by transmitral and tissue Doppler. Global longitudinal strain (LS) and time-based dyssynchrony were assessed by speckle tracking. Both OB/MS− and OB/MS+ groups had similar ejection fraction but worse systolic mechanics as assessed by LS and dyssynchrony when compared with nonobese controls. Specifically, OB/MS− had 2.5% lower LS (SE, 0.7%; P =0.001 in multivariable-adjusted analyses) and 10.8 ms greater dyssynchrony (SE, 3.3 ms; P =0.002), and OB/MS+ had 1.0% lower LS (SE, 0.3%; P P <0.001) when compared with controls. Obesity was associated with impaired diastolic function regardless of MS status, as evidenced by greater left atrial diameter and left ventricular mass although diastolic dysfunction was more pronounced in OB/MS+ than in OB/MS− individuals. Conclusions—: Obesity is associated with subclinical differences in both systolic and diastolic function regardless of the presence or absence of MS although MS seems to be associated with worse diastolic dysfunction. When compared with controls, metabolically healthy obese had lower LS, greater dyssynchrony, and early diastolic dysfunction, supporting the notion that obesity per se may have adverse cardiovascular effects regardless of metabolic disease.

Background: Metabolic disease can lead to intrinsic pulmonary hypertension in experimental models. The contributions of metabolic syndrome (MetS) and obesity to pulmonary hypertension and right ventricular dysfunction in humans remain unclear. We investigated the association of MetS and obesity with right ventricular structure and function in patients without cardiovascular disease. Methods and Results: A total of 156 patients with MetS (mean age 44 years, 71% women, mean body mass index 40 kg/m ² ), 45 similarly obese persons without MetS, and 45 nonobese controls underwent echocardiography, including pulsed wave Doppler measurement of pulmonary artery acceleration time ( PAAT ) and ejection time. Pulmonary artery systolic pressure was estimated from PAAT using validated equations. MetS was associated with lower tricuspid valve e′ (right ventricular diastolic function parameter), shorter PAAT , shorter ejection time, and larger pulmonary artery diameter compared with controls ( P P for ANOVA P =0.002 versus obese). This association persisted after accounting for left ventricular structure and function and after exclusion of participants with obstructive sleep apnea. Conclusions: MetS is associated with abnormal right ventricular and pulmonary artery hemodynamics, as shown by shorter PAAT and subclinical right ventricular diastolic dysfunction. Estimated pulmonary artery systolic pressures are higher in MetS and preclinical metabolic heart disease and raise the possibility that pulmonary hypertension contributes to the pathophysiology of metabolic heart disease.