617 Effects of SGLT2 inhibitors on left and right ventricular function in a real-world diabetic population

Aims Heart failure (HF) is a pandemic and despite improvements in therapy, the mortality rate has remained unacceptably high. Sodium glucose cotransporter-2 inhibitors (SGLT2i) have emerged as a promising new class of glucose-lowering drugs, reducing HF-related outcomes across all ejection fraction ranges in clinical trials. However, few studies have assessed their efficacy using echocardiography imaging in a real-world setting. Methods and results Type 2 diabetes mellitus (T2DM) patients treated with SGLT2i from 2015 to 2020 were enrolled in a retrospective observational study. Clinical, biochemical, and echocardiographic data at baseline and 6 and 12 months after treatment initiation were collected. Of the 459 patients screened, 312 (68%) patients completed 1 year of SGLT2i therapy. Side effects were developed in 92 (20%) patients leading them to stop treatment pre-maturely, while 55 (12%) were lost to follow-up. From the 312 patients who completed 1 year of treatment, 83 patients had echocardiography data before initiation and after either 6 or 12 months of treatment and were included in the data analysis. Sample’s average age was 65.78 ± 8.53 years, 23 (27.7%) were females, and the mean BMI was 32.10 ± 6.29 kg/m2. At baseline patients had Hb1Ac 7.94 ± 1.80% and the mean duration of diabetes was 11.19 ± 8.54 years. 59 (71.1%) patients were asymptomatic (NYHA I) at baseline. The mean left ventricular ejection fraction (LVEF) at baseline was 48.40 ± 10.89%, while mean left ventricular end-diastolic volume (LVEDV) was 127.96 ± 41.84 ml. Mean pulmonary artery systolic pressure (PASP) was 33.63 ± 7.89 mmHg and mean tricuspid annular plane systolic excursion (TAPSE) was 20.18 ± 4.17 mm before treatment started. Mean E/e′ ratio at baseline was 9.75 ± 3.50. Mean septal wall thickness before therapy was initiated was 12.05 ± 1.80 mm while mean anterior wall thickness was 11.22 ± 1.52 mm. Almost all of the patients had at least one cardiovascular risk factor, hypertension being the most common (77, 92.8%), while 53 (63.9%) patients had a history of coronary artery disease (CAD), of which 42 (50.6%) had suffered a myocardial infarction. All-cause HF was present in 31 (37.3%) patients (19 HFrEF, 7 HFmrEF, 5 HFpEF). After a mean of 12.94 ± 7.91 months of SGLT2i treatment, left ventricular function was improved as LVEF was increased to 50.62 ± 10.04% (+2.22%, P = 0.018), while LVEDV was reduced to 123.24 ± 41.41 ml (−4.72 ml, P = 0.052). A trend towards improvement of the right ventricular function was also observed as TAPSE increased to 21.45 ± 3.92 mm (+1.27 mm, P = 0.076). PASP remained rather stable (−0.83 mm, P = 0.620), as well as the E/e′ ratio (−0.11, P = 0.857). Septal wall thickness was found unchanged (−0.16 mm, P = 0.449), as well as the anterior wall thickness (−0.63 mm, P = 0.143). After 1 year of treatment the number of asymptomatic patients remained stable (60, P = 0.863). Conclusions SGLT2i improved left ventricular systolic function in a sample of real-world diabetic patients, as shown by the changes in LVEF and LVEDV. A trend towards right ventricular function improvement was also recorded, demonstrated by the TAPSE increase. These findings highlight SGLT2i action on ventricular function and might be hypothesis generating to further elucidate their cardiovascular mechanism of action, beyond their already noted diuretic effect.

Left Ventricular Hypertrophy (LVH) in Patients with Advanced Stages of Chronic Kidney Disease (CKD)

Objective: To determine the left ventricular hypertrophy (LVH) prevalence in patients admitted with advanced stage of Chronic kidney disease at Ziauddin hospital. Methodology: This was a cross-sectional study conducted in department of Nephrology of Ziauddin University Hospital, Karachi from January to July 2016. The inclusion criteria involved patients with CKD stages 3-5 undergoing two-dimensional M mode Doppler echocardiography. The sample size of the study was 147. LVH was considered as positive when Inter-ventricular-septal-wall-thickness in diastole (IVSd) >11 mm, Left-Ventricular-Septal-Wall-Thickness in diastole (LVPWd) >11 mm and Left-Ventricular-Mass-Index (LVMi) >131 g/m2 for men and > 100 g/m2 for women. The exclusion criteria included patients with terminal illness, on mechanical ventilator support, valvular heart diseases and congenital heart diseases, liver diseases and patients with acute kidney injury on chronic kidney disease. Results: 88 male and 59 female patients were included. The mean duration of CKD was 7.02±1.60 years. 94(63.9%) study subjects were observed with left ventricular hypertrophy. A significant association of LVH was observed with gender and CKD Stages. Conclusion: LVH can be easily diagnosed and assessed by M-mode or 2D echocardiography. The prevalence was high (60.5%) in stage 3–5 CKD patients.

Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET

Aim To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET). Methods We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland–Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients. Results High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001). Conclusion 15O-water PET might detect LV hypertrophy with high accuracy and precision.

Obesity in the absence of comorbidities is not related to clinically meaningful left ventricular hypertrophy

Obesity is associated with the development of left ventricular (LV) hypertrophy. Whether obesity in in the absence of comorbidities can cause LV hypertrophy to an extent which could create diagnostic uncertainty with pathological states (such as hypertrophic cardiomyopathy) is unknown. We used cine cardiovascular magnetic resonance imaging to precisely measure LV wall thickness in the septum and lateral wall in 764 people with body mass indices ranging from 18.5 kg/m2 to 59.2 kg/m2 in the absence of major comorbidities. Obesity was related to LV wall thickness across the cohort (basal septum r 0.30, P < 0.001 and basal lateral wall r 0.18, P < 0.001). Although no participant had hypertension, these associations remained highly significant after controlling for systolic blood pressure (all P < 0.01). Each 10 kg/m2 increase in BMI was associated with an increase in basal septal wall thickness of 1.0 mm males and 0.8 mm in females, with no statistically significant difference between genders (P = 0.1). Even in class 3 obesity (BMI > 40 kg/m2), no LV wall thickness > 13.4 mm in males or > 12.7 mm in females was observed in this cohort. We confirm that obesity in the absence of comorbidities is associated with LV hypertrophy, and establish that the magnitude of this change is modest even in severe obesity. LV hypertrophy > 14 mm cannot safely be attributed to obesity alone and alternative diagnoses should be considered.

Sex differences in ventricular remodeling and long-term heart failure outcomes following acute coronary syndrome

Background Compared with men, women are at increased risk of heart failure hospitalization following acute coronary syndrome (ACS). Purpose We sought to determine whether this increased hazard was associated with differing patterns in left ventricular (LV) remodeling over the first 12 months after ACS. Methods In a prospective multi-centre observational cohort study, 2,140 patients with ACS underwent echocardiography at 1, 4, and 12 months following the index event. Heart failure hospitalisation events were captured over a median 4.8 (IQR 3.4–6.5) years and relative risk compared between women and men using a multivariable Cox model adjusted for baseline demographics (age and systolic blood pressure) and echocardiographic variables (LV end diastolic and end systolic volumes, LV ejection fraction, interventricular septal wall thickness, and E/e') captured at baseline and 12 months. Results The 609 (28.5%) women were older (mean [SD] age 70 [12] versus 65 [12] years), had higher systolic blood pressure, demonstrated smaller increases in peak myocardial biomarkers, and were less likely to undergo coronary revascularization during the index admission (41.9% versus 62.0%; p&lt;0.001 for all). After indexing for body surface area, women had smaller LV end diastolic and end systolic volumes, greater LV ejection fractions, and greater septal wall thickness and diastolic filling pressure estimates (E/e' 14 versus 11; p&lt;0.001 for all). Diastolic volumes further diverged at 12 months (p=0.05) and septal wall thickness increased compared with men (p=0.016). In unadjusted and adjusted analyses women were at increased risk of future heart failure hospitalization (unadjusted HR 1.5, 95% CI 1.2–1.9, adjusted HR 1.6, 95% CI 1.1–2.4). Conclusions Women experience a more concentric remodeling pattern over the 12 months following ACS. Women remain at increased risk of long-term heart failure hospitalization after accounting for clinical and echocardiographic characteristics. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation of New Zealand, New Zealand Health Research Council

Maladaptive Changes Associated With Cardiac Aging Are Sex-Specific and Graded by Frailty and Inflammation in C57BL/6 Mice

We investigated whether late-life changes in cardiac structure and function were related to high levels of frailty and inflammation in male and female mice. Frailty (frailty index), ventricular structure/function (echocardiography), and serum cytokines (multiplex immunoassay) were measured in 16- and 23-month-old mice. Left ventricular (LV) mass and septal wall thickness increased with age in both sexes. Ejection fraction increased with age in males (60.4 ± 1.4 vs 68.9 ± 1.8%; p &lt; .05) but not females (58.8 ± 2.5 vs 62.6 ± 2.4%). E/A ratios declined with age in males (1.6 ± 0.1 vs 1.3 ± 0.1; p &lt; .05) but not females (1.4 ± 0.1 vs 1.3 ± 0.1) and this was accompanied by increased ventricular collagen levels in males. These changes in ejection fraction (r = 0.52; p = .01), septal wall thickness (r = 0.59; p = .002), E/A ratios (r = −0.49; p = .04), and fibrosis (r = 0.82; p = .002) were closely graded by frailty scores in males. Only septal wall thickness and LV mass increased with frailty in females. Serum cytokines changed modestly with age in both sexes. Nonetheless, in males, E/A ratios, LV mass, LV posterior wall thickness, and septal wall thickness increased as serum cytokines increased (eg, IL-6, IL-3, IL-1α, IL-1β, tumor necrosis factor-α, eotaxin, and macrophage inflammatory protein-1α), while ejection fraction declined with increasing IL-3 and granulocyte-macrophage colony stimulating factor. Cardiac outcomes were not correlated with inflammatory cytokines in females. Thus, changes in cardiac structure and function in late life are closely graded by both frailty and markers of inflammation, but this occurs primarily in males. This suggests poor overall health and inflammation drive maladaptive changes in older male hearts, while older females may be resistant to these adverse effects of frailty.

Significance of NT-proBNP and High-Sensitivity Troponin in Friedreich Ataxia

Background: Friedreich’s ataxia (FA) is a rare autosomal recessive mitochondrial disease resulting of a triplet repeat expansion guanine-adenine-adenine (GAA) in the frataxin (FXN) gene, exhibiting progressive cerebellar ataxia, diabetes and cardiomyopathy. We aimed to determine the relationship between cardiac biomarkers, serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and serum cardiac high-sensitivity troponin (hsTnT) concentrations, and the extent of genetic abnormality and cardiac parameters. Methods: Between 2013 and 2015, 85 consecutive genetically confirmed FA adult patients were prospectively evaluated by measuring plasma hsTnT and NT-proBNP concentrations, electrocardiogram, and echocardiography. Results: The 85 FA patients (49% women) with a mean age of 39 ± 12 years, a mean disease onset of 17 ± 11 years had a mean SARA (Scale for the Assessment and Rating of Ataxia) score of 26 ± 10. The median hsTnT concentration was 10 ng/L (3 to 85 ng/L) and 34% had a significant elevated hsTnT ≥ 14 ng/L. Increased septal wall thickness was associated with increased hsTnT plasma levels (p < 0.001). The median NT-proBNP concentration was 31 ng/L (5 to 775 ng/L) and 14% had significant elevated NT-proBNP ≥ 125 ng/L. Markers of increased left ventricular filling pressure (trans mitral E/A and lateral E/E’ ratio) were associated with increased NT-proBNP plasma levels (p = 0.01 and p = 0.01). Length of GAA or the SARA score were not associated with hsTnT or NT-proBNP plasma levels. Conclusion: hsTnT was increased in 1/3 of the adult FA and associated with increased septal wall thickness. Increased NT-proBNP remained a marker of increased left ventricular filling pressure. This could be used to identify patients that should undergo a closer cardiac surveillance.