Subclinical Cardiac Dysfunction Research Articles

Normalization of Cardiac Function After Bariatric Surgery Is Related to Autonomic Function and Vitamin D

PurposeSubclinical cardiac dysfunction is common in patients with obesity. Bariatric surgery is associated with normalization of subclinical cardiac function in 50% of the patients with obesity. The aim of this study was to identify predictors for a lack of improvement of subclinical cardiac dysfunction 1-year post-bariatric surgery.MethodsPatients who were referred for bariatric surgery were enrolled in a longitudinal study. Inclusion criteria were age 35–65 years and BMI ≥ 35 kg/m2. Patients with a suspicion of or known cardiovascular disease were excluded. Conventional and advanced echocardiography, Holter monitoring, and blood tests were performed pre- and 1-year post-bariatric surgery. Subclinical cardiac dysfunction was defined as either a reduced left ventricular ejection fraction, decreased global longitudinal strain (GLS), diastolic dysfunction, arrhythmia, or an increased BNP or hs Troponin I.ResultsA total of 99 patients were included of whom 59 patients had cardiac dysfunction at baseline. Seventy-two patients completed the 1-year follow-up after bariatric surgery. There was a significant reduction in weight and cardiovascular risk factors. Parameters of cardiac function, such as GLS, improved. However, in 20 patients cardiac dysfunction persisted. Multivariate analysis identified a decreased heart rate variability (which is a measure of autonomic function), and a decreased vitamin D pre-surgery as predictors for subclinical cardiac dysfunction after bariatric surgery.ConclusionAlthough there was an overall improvement of cardiac function 1-year post-bariatric surgery, autonomic dysfunction and a decreased vitamin D pre-bariatric surgery were predictors for a lack of improvement of subclinical cardiac dysfunction.Graphical abstract

Augmentation and Evaluation of an Olive Oil Based Polyherbal Combination against Diabetic Cardiomyopathy in Experimental Model of Rodents

Diabetes mellitus is a metabolic disorder that is prima facie a cause for numerous macro and micro vascular complications. A common macroscopic complication associated with diabetes is cardiomyopathy. Cardiomyopathy refers to diseases of the heart muscle, where the heart muscle becomes enlarged, thick, or rigid. As cardiomyopathy worsens, the heart becomes weaker and is unable to conduct the right amount of blood through the body and maintain a normal electrical rhythm. This can lead to heart failure or arrhythmias. Chronic diabetes is one of the instigating factors behind the etiology of this cardiac complication. Type-II diabetes is associated with impaired glucose metabolism that increases the dependence of a diabetic heart on fatty acid oxidation to meet its functional demands, resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction that finally gives way to heart failure. The increasing diabetic population with cardiac disorders and the ironically decreasing trend in newer medications to counter this complication leave us at a crossroads for pharmacological management of diabetic cardiomyopathy. Keeping this in view, the present study proclaims a newly developed polyherbal combination (PHC) with three herbs, namely Tinospora cordifolia, Withania somnifera and Boerhavia diffusa based in olive oil and administered in fixed dose (PHC-6 and PHC-10) to screen its cardioprotective potential against a well-established experimental model for diabetic cardiomyopathy. The three herbs mentioned have been known through the traditional literature for their antidiabetic and cardioprotective roles, hence they became the obvious choice. The study follows an experimental model proposed by Reed et al., where the capacity of the β-cell is unobtrusively impeded without totally compromising insulin release, bringing about a moderate disability in glucose resilience. Various sophisticated parameters, namely intraventricular septum thickness of hearts, Western blot of α/β- MHC monoclonal antibody (Ab), cardiac pyruvate dehydrogenase (PDH) activity, medium chain acyl coenzyme A dehydrogenase (MCAD) enzyme, etc. showed promising results where treatment with PHC (PHC-6 and PHC-10) significantly (*** p < 0.001 and **** p < 0.0001) prevented the symptoms of cardiomyopathy in subsequent groups when compared to disease control group.

RF02 | PMON308 Hyperglycemia Is the Main Determinant of Cardiac Autonomic Dysfunction in Youth With Obesity Across the Spectrum of Glycemic Regulation.

Abstract Heart Rate Variability (HRV) results from the autonomic nervous system activity, it is a non-invasive marker of cardiac autonomic function. Loss of parasympathetic function (PNS) and sympathetic (SNS) override, reflected in decreased HRV, is one of the earliest subclinical manifestations of cardiac autonomic dysfunction. Lower HRV is associated with increased risk of cardiac events in adults. We aimed to characterize HRV in normal weight and overweight children with and without dysglycemia and to investigate the determinants of HRV in these youth, including body composition, glycemia measures, beta-cell function and inflammatory markers. We evaluated 94 adolescents (50 males/44 females), age 15 ± 2.1 years; 21 normal weight with normal glucose tolerance (NW-NGT), 23 overweight with NGT (OW-NGT) and 50 overweight with impaired glucose regulation (OW-IGR) including prediabetes (n= 27) and type 2 diabetes (n= 23). They underwent assessment of anthropometrics, body composition (DXA scan), inflammatory markers (hs-CRP and TNF-α), fasting labs and 2-hour oral glucose tolerance test (OGTT) with determination of glucose and insulin concentration. EndoPat was used to measure HRV: frequency-domain indices [high-frequency (HF) reflecting PNS, low-frequency (LF) reflecting both PNS and SNS, and LF/HF (higher is worse) estimating the ratio between SNS and PNS] and time-domain indices [the inter-beat interval of normal sinus beats (NN) and the standard deviation of NN (SDNN) measuring overall HRV, the square root of the mean squared difference of successive NN (RMSSD) and the NN intervals differing by more than 50 milliseconds (NN50) measuring PNS activity]. LF/HF was higher in the OW-IGR group compared with NW and OW-NGT (p=0.005). After controlling for sex, race and Tanner stage, fasting glucose (FBG) negatively correlated with NN (r=-0.22,p=0.04), SDNN (r=-0.21,p=0.05), RMSSD (r=-0.3,p=0.004), NN50 (r=-0.27,p=0.01) and HF (r=-0.26,p=0.02). LF/HF was positively related to FBG (r=0.39,p<0.001), 2hr-glucose (r=0.31,p=0.004) and HbA1c (r=0.22,p=0.04), and negatively with the insulinogenic index (r=-0.27,p=0.02), but not fasting insulin or HOMA-IR; LF/HF also correlated with percent body fat (r=0.22,p=0.04), hs-CRP (r=0.33,p=0.002) and TNF-α (r=0.38,p=0.006). In a linear regression model with LnLF/HF as the dependent variable and percent body fat, hs-CRP, FBG and HOMA-IR as the independent variables, FBG (beta=0.39,p=0.003) and hs-CRP (beta=0.21,p=0.09) were the significant determinants of LnLF/HF independent of age, sex, race and Tanner stage as covariates (R2= 0.23,p=0.013). Youth with impaired glucose metabolism have evidence of early subclinical cardiac autonomic dysfunction with decreased HRV, loss of parasympathetic function and sympathetic overdrive as reflected by lower time-domain indices, lower HF and higher LF/HF, related to glycemia and systemic inflammation. Presentation: Saturday, June 11, 2022 1:00 p.m. - 2:00 p.m., Saturday, June 11, 2022 1:12 p.m. - 1:17 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Clinical Utility of Three-Dimensional Speckle-Tracking Echocardiography in Heart Failure.

Heart failure (HF) is an extremely major health problem with gradually increasing incidence in developed and developing countries. HF may lead to cardiac remodeling; thus, advanced imaging techniques are required to comprehensively evaluate cardiac mechanics. Recently, three-dimensional speckle-tracking echocardiography (3D-STE) has been developed as a novel imaging technology that is based on the three-dimensional speckle-tracking on the full volume three-dimensional datasets. Three-dimensional speckle-tracking echocardiography allows a more accurate evaluation of global and regional myocardial performance, assessment of cardiac mechanics, detection of subclinical cardiac dysfunction, and prediction of adverse clinical events in a variety of cardiovascular diseases. Therefore, this review summarizes the clinical usefulness of 3D-STE in patients with HF.

Long-term hepatic and cardiac health in patients diagnosed with Sheehan's syndrome.

Sheehan's syndrome (SS) is characterised by chronic pituitary insufficiency following a vascular insult to the pituitary in the peripartum period. There is a lack of substantial evidence on the long-term hepatic and cardiac consequences in these patients, following hormone replacement. Patients with a diagnosis of SS were recruited for the study. Detailed clinico-biochemical and radiological evaluation were performed in all patients (n = 60). Hepatic and cardiac complications were assessed using fibroscan and echocardiography (2D speckle-tracking) respectively, in a subset of patients (n = 29) as well as age-and BMI-matched controls (n = 26). Controlled attenuation parameter (for steatosis) and liver stiffness measurement (for fibrosis) were used to define non-alcoholic fatty liver disease (NAFLD). Diastolic cardiac function was evaluated using standard criteria and systolic function by ejection fraction and global longitudinal strain (GLS). The mean age of the cohort was 42.7 ± 11.6 years. Multiple (≥ 2) hormone deficiencies were present in 68.8% of patients, with hypothyroidism (91.4%), hypocortisolism (88.3%), and growth hormone (GH) deficiency (85.7%) being the most common. At a mean follow-up of 9.8 ± 6.8 years, NAFLD was present in 63% of patients, with 51% having severe steatosis, which was predicted by the presence of GH deficiency and higher body mass index. Though the ejection fraction was similar, increased left ventricular GLS (18.8 vs. 7.7%) was present in a significantly higher number of patients versus controls. NAFLD, especially severe hepatic steatosis, is highly prevalent in SS. Subclinical cardiac systolic dysfunction (impaired GLS) is also more common, but of mild intensity.

Cardiac dysfunction in relation to vascular brain injury, cognitive impairment and depressive symptoms; The Heart-Brain Connection Study

Abstract Introduction Cardiovascular disease is an independent contributor to cognitive impairment. With an imminent rise in chronic cardiovascular disease, a better understanding of its effects on brain health is warranted. Impaired blood flow to the brain is one of the main hypothesized mechanisms linking cardiovascular disease with abnormal brain aging. Purpose To investigate relations between (subclinical) cardiac dysfunction and vascular brain injury, cognitive impairment and depressive symptoms, with a side-by-side comparison of cardiac biomarkers and imaging parameters. Methods Multicenter, cross-sectional, observational cohort study among 559 participants: 431 with manifest cardiovascular disease (heart failure [HF], carotid occlusive disease or vascular cognitive impairment) and 128 control participants, all without dementia. Participants underwent 3T heart-brain MRI and cognitive testing. Determinants were cardiac biomarkers (NT-proBNP and high-sensitive Troponin-I) and left ventricular (LV) functional parameters by MRI (LV ejection fraction, cardiac output, LV global function index). Outcome measures were cerebral small vessel disease (CSVD) by MRI (presence of white matter hyperintensities, microbleeds, lacunar infarcts or perivascular spaces), CSVD score (0–4), cognitive impairment in ≥1 domain (memory, language, attention-psychomotor speed and executive functioning) and depressive symptoms (Geriatric Depression Scale-15 score >5). Interaction analyses were used to investigate effect modification by patient group; results are reported pooled or stratified accordingly. Results In patients with cardiovascular disease and controls, but not in those with manifest HF, LV functional parameters were associated with CSVD and cognitive impairment, with the following associations: LVEF <50% with CSVD (OR 4.67 [1.37–15.95]) and CSVD score (RR 1.38 [1.06–1.81]); LV global function index with CSVD (OR 0.71 [0.58–0.86]), CSVD score (RR 0.90 [0.84–0.96]) and cognitive impairment (OR 0.84 [0.72–0.97]). LV global function index (OR 0.82 [0.71–0.95]) and cardiac output (OR 0.81 [0.71–0.93]) were also associated with depressive symptoms in all. These relations were independent from age, sex, hypertension, diabetes, waist-hipratio, history of ischemic heart disease, transient ischemic attack or stroke. Cardiac biomarkers were univariably associated with brain outcome measures, but not in multivariable analysis. Conclusion This study indicates that subclinical cardiac dysfunction, as assessed by cardiovascular MRI, is independently associated with vascular brain injury, cognitive impairment and depressive symptoms. Of all parameters, LV global function index showed the most robust relations, indicating that global cardiac performance is more closely related to poorer brain outcome than merely LV systolic function. In those with clinically manifest HF, the severity of cardiac dysfunction was related to depressive symptoms but not to other brain outcome measures. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Netherlands CardioVascular Research Initiative; The Dutch Heart Foundation

Association of hepatic steatosis with subclinical cardiac dysfunction in asymptomatic people with type 2 diabetes

Abstract Introduction Non-alcoholic fatty liver disease is highly prevalent among people with type 2 diabetes (T2D) and is an emerging risk factor for heart failure with preserved ejection fraction (HFpEF). Whether excess liver adiposity is simply a marker of the coexisting adverse cardiometabolic risk profile or independently contributes to the development of HFpEF is unclear. Purpose To assess the association between liver fat fraction and subclinical cardiac dysfunction in adults with T2D. Methods Prospective cross-sectional study. Two-hundred and thirty-eight adults with T2D (mean age 63±7 years, 62% males, HbA1c 7.2±1.5%, diabetes duration 10±8 years) with no signs, symptoms, or evidence of cardiovascular disease and 40 age-, sex-, and ethnicity-matched non-diabetic controls (mean age 61±8 years, 63% males, HbA1c 5.2±1.2%) underwent comprehensive phenotyping with echocardiography and multiparametric cardiac MRI including adenosine stress and rest perfusion. Volumetric liver fat fraction (VLFF) was measured using a histologically validated, proprietary MRI technique blinded to all participant details. Inter-study reproducibility was assessed in participants (n=28) who underwent a repeat MRI within two weeks. Linear regression analysis was performed to assess any independent associations between VLFF and identified markers of subclinical cardiac dysfunction in subjects with T2D. Results People with T2D had evidence of concentric left ventricular (LV) remodelling (higher LV mass/volume), extracellular matrix expansion (higher ECV fraction), both systolic and diastolic dysfunction (lower global longitudinal systolic strain and E/A ratio, respectively), and coronary microvascular dysfunction (lower myocardial perfusion reserve) (Table 1). VLFF demonstrated excellent inter-study reproducibility with an intra-class correlation coefficient (ICC) of 0.988 (0.974–0.994). T2Ds had higher VLFF compared to controls [7.5 (3.8–13.7)% vs 2.9 (1.7–4.7)%, p<0.001]. In multivariable regression analysis adjusting for age, sex, ethnicity, body mass index, ambulatory systolic blood pressure, HbA1c, and low-density lipoprotein, VLFF (β=−0.161, p=0.027) was independently associated with E/A, but not other imaging measures of subclinical cardiac dysfunction. Conclusion Liver fat fraction is elevated in people with T2D and is independently associated with early LV diastolic dysfunction. These results add to the growing evidence that ectopic fat plays an important role in the pathogenesis of HFpEF and may be a potential target for intervention. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health Research (NIHR) United Kingdom through a Research Professorship award (RP-2017-08-ST2-007).British Heart Foundation through a Clinical Research Training Fellowship (FS/16/47/32190).

The impact of long COVID on myocardial work performance

Abstract Background Long COVID emerged as a new condition, following the acute episode of coronavirus disease 2019 (COVID-19),exerting a significant impact on patients' quality of life [1]. Several studies involving COVID-19 survivors emphasized the presence of cardiac abnormalities following the acute infection. However, data on possible mechanisms associated to long COVID remain limited. Clinical applications of myocardial work (MW) analysis, assessed by transthoracic echocardiography (TTE) have expended recently, showing an additional value in detecting cardiac dysfunction compared to standard parameters such as left ventricle ejection fraction (LVEF) or global longitudinal strain (GLS) in various pathologies, including COVID-19 [2]. Nevertheless, its potential role in detecting subclinical cardiac dysfunction in long COVID remained unexplored. Purpose We assessed the association between subclinical cardiac dysfunction evaluated by global work index (GWI) and global constructive work (GCW) and long COVID. Methods We included 310 COVID-19 patients hospitalized between March and April 2020. All patients were invited to a systematic one-year follow-up, including clinical evaluation, TTE with MW assessment, chest-computed tomography and spirometry. 140 patients completed the follow-up. Normal values for GWI and GCW were defined as 1926±247 mmHg% and 2224±229 mmHg% [3]. The primary endpoint was long COVID, characterized by a cluster of symptoms such as fatigue or dyspnea more than 3 months after the acute infection, without any other explanation. Results 140 patients (57.1±13.9 years, 90 (64.3%) males) had a mean follow-up of 337.1±34.5 days.The mean values of LVEF, GWI and GCW were 55.2±3.2%, 2105.9±403.3 mmHg% and 2377.8±446.2 mmHg%. 83 (61%) patients had long COVID. No significant differences in terms of comorbidities, clinical evaluation and COVID-19 severity were found between patients with and without long COVID. GCW (2276.7±410.3 vs 2516.5±458.6, p=0.006) and GWI (2008.5±358.9 vs 2242.2±427.0, p=0.003) were the only TTE parameters different between patients with and without long COVID. Multivariable regression analysis showed that GWI <1926 mmHg% (OR 6.095; CI: 2.024–18.355, p=0.001) and GCW <2224 mmHg% (OR 3.205; CI: 1.181–8.694, p=0.022) were the only MW parameters independently associated with long COVID, irrespective of age or the severity of the acute infection, at one year. In a subgroup analysis of 77 patients without previous cardiovascular diseases, long COVID was diagnosed in 45 (58.4%)patients. GWI <1926 mmHg% (OR 8.015; CI: 2.149–29.887, p=0.002) remained independently associated with long COVID at 1 year follow-up. Conclusions Long COVID, frequently observed in recovered COVID-19 patients may indicate the presence of subclinical cardiac dysfunction, reflected by a decrease of the left ventricle performance, assessed by GWI and GCW.Long-term follow-up including cardiac screening should be performed in order to identify patients at risk who would benefit from cardiac rehabilitation programs. Funding Acknowledgement Type of funding sources: None.

Aortic valve calcium in relation to subclinical cardiac dysfunction and risk of heart failure in the general population

Abstract Background Emerging evidence suggests that aortic valve calcium (AVC) is associated with adverse cardiovascular outcomes, while the association of (early) AVC with subclinical cardiac dysfunction and with risk of heart failure (HF) remains unclear. Purpose To determine the association of CT-assessed AVC with echocardiographic measurements of cardiac dysfunction, and with HF in the general population. Methods We included 2,348 participants (mean age 68.5 years, 52% women) of the Rotterdam Study, who had AVC measured between 2003 and 2006, and without a history of HF at baseline. Linear regression models were used to explore cross-sectional associations of AVC with echocardiographic measures at baseline. All participants were followed for HF event until December 2016. Cox proportional hazard models were used to assess the association of AVC with incident HF. Models were adjusted for potential confounders. Results The presence of AVC was associated with 3.14 g/m2 (95% CI, 1.50 to 4.79) higher mean left ventricular mass indexed by body surface area. One-unit larger log (AVC+1) was associated with 0.01 mm (95% CI 0.01 to 0.02) larger mean left atrial size. During a median follow-up of 9.8 years, 182 incident HF cases were identified. Presence of AVC was associated with 37% greater risk for HF (HR, 1.37; 95% CI, 1.01 to 1.87). One-unit larger log (AVC+1) was associated with 11% larger risk of HF (HR, 1.11; 95% CI, 1.04 to 1.18). Compared with the AVC =0, AVC ≥100 had 1.70 folded risk of HF (HR, 1.70; 95% CI, 1.17 to 2.49). Conclusions The levels of AVC were associated with markers of left ventricular structure and with risk of HF, independent of traditional cardiovascular risk factors. Larger CT-assessed AVC is an indicative of increased risk for development of HF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Netherlands Organization for the Health Research and Development (ZonMw)Dutch Heart Foundation (03-004-2021-T050)

Subclinical myocardial dysfunction in patients with persistent dyspnea one year after COVID-19

Abstract Introduction Coronavirus disease 2019 (COVID-19) rapidly spread across the globe,evolving into a global pandemic,with a crucial impact on healthcare systems. Several short-term follow-up studies emphasized the persistence of symptoms, referred as long COVID, in a significant number of discharged patients even without history of cardiopulmonary diseases, with dyspnea being one of the most frequent complaint [1–3]. Even though those reports on recovered COVID-19 patients did not describe major left ventricle (LV) function abnormalities, subtle cardiac changes may be present. Purpose We aimed to investigate the presence of subclinical cardiac dysfunction, assessed by transthoracic echocardiography (TTE) in recovered COVID-19 patients, without previous cardiopulmonary disease at 1 year follow-up. Methods 310 COVID-19 consecutive hospitalized patients were prospectively included between March and April 2020. 66 patients out of 251 recovered patients had no previous history of coronary artery disease, arrhythmia, arterial hypertension, valvular heart disease, asthma, chronic obstructive pulmonary disease and obstructive sleep apnea, respectively and were included in the final analysis (Figure 1). The follow-up consisted in 2 parts, a 6-months visit including clinical and physical examination, chest computed tomography and spirometry and a 12-months visit including clinical and physical examination, spirometry and TTE. Results 66 patients (mean age 51.39±11.15 years, 45 (68.2%) males) were included in the final analysis. 23 (34.8%) patients reported dyspnea at 1 year. TTE parameters were in the normal range, with a mean LV ejection fraction of 56.9±4.6%, mean global longitudinal strain (GLS) of −20.9±2.3%, global constructive work (GCW) of 2381.4±463.6 mmHg% and global work index (GWI) of 2132.5±419.2 mmHg%. Type 1 diastolic dysfunction was observed in 11 (16.7%) patients. One (1.5%) patient had type 2 diastolic dysfunction. A normal respiratory pattern was reported in 31 (47%) patients at 6 months spirometry, while 19 (28.8%) patients had a restriction pattern. No significant differences regarding clinical, laboratory or imaging findings at baseline were found between groups. The following TTE parameters were significantly different in patients with and without dyspnea at 1 year: GLS (−19.97±2.14 vs. −21.38±2.37, p=0.039), GCW (2183.72±487.93 vs. 2483.14±422.42, p=0.024) and GWI (1960.06±396.21 vs. 2221.17±407.99, p=0.030). Multivariable logistic regression showed that GCW and GWI were inversely and independently associated with persistent dyspnea, one year after COVID-19 (p=0.035, OR 0.998, 95% CI 0.997–1.000; p=0.040, OR 0.998, 95% CI 0.997–1.000) (Table 1). Conclusions Persistent dyspnea one year after COVID-19 was present in more than a third of patients without known cardiovascular or pulmonary diseases. GCW and GWI were the only echocardiographic parameters independently associated with symptoms, suggesting a decrease in myocardial performance in this population and subclinical cardiac dysfunction. Funding Acknowledgement Type of funding sources: None.

Impaired myocardial calcium handling in people with type 2 diabetes: an in vivo manganese-enhanced magnetic resonance imaging study

Abstract Background There is a high prevalence of subclinical cardiac dysfunction in people with type 2 diabetes (T2D) which is associated with subsequent development of heart failure. Dysregulated myocardial calcium handling has been demonstrated in animal models of T2D and may be a key mechanism driving the development of heart failure. Manganese-enhanced cardiac magnetic resonance imaging (MEMRI) provides a unique method to assess in vivo myocardial calcium handling. Purpose To determine whether myocardial calcium handling is perturbed in people with T2D with no history of cardiovascular disease. We hypothesised that myocardial manganese uptake would be reduced in people with T2D compared with healthy volunteers. Methods Cross-sectional case-control study, adults with (n=20) and without (n=9) T2D underwent both gadolinium-enhanced MRI and MEMRI. Standard gadolinium-enhanced MRI was used to assess cardiac structure, function and tissue characteristics. MEMRI scans were performed within two weeks of the initial scan. Native T1 maps were obtained in the mid-short axis slice position using a Modified Look-Locker Inversion recovery sequence. An intravenous infusion of manganese dipyridoxyl diphosphate (5 μmol/kg (0.1 mL/kg) at 1 mL/min) was administered and T1 maps at the same location were repetitively acquired every 2.5 min for 30 min. Regions of interest were drawn in the inferoseptal segment and blood pool for all T1 maps from 0 to 30 min by a single observer. The primary outcome was the rate of manganese uptake which was assessed by Patlak modelling as a measure of myocardial calcium handling. Manganese uptake constants were compared using analysis of co-variance, with age, sex and body mass index as co-variates. Results Subjects with T2D were older (62±7 vs. 57±5 years, p=0.046) but body mass index (29.0±4.5 vs. 26.2±3.4 kg/m2, p=0.106), systolic (135±16 vs. 134±17 mmHg, p=0.809) and diastolic (81±10 vs. 83±9 mmHg, p=0.736) blood pressures were similar. Compared to control subjects, participants with T2D had normal systolic function but more concentric left ventricular remodelling (mass/volume ratio 0.90±0.14 vs. 0.71±0.06 g/mL, p<0.001) and reduced peak early diastolic strain rate (0.64±0.17 vs. 0.91±0.26 s–1, p=0.002). Myocardial manganese uptake was substantially reduced in people with T2D compared with controls (6.51±1.46 vs. 8.45±2.52 ml/100 g of tissue/min, p=0.003) (Figure 1). Conclusions For the first time, we have demonstrated in vivo that despite no history of cardiovascular disease and normal systolic function, patients with T2D have marked impairment of myocardial calcium handling. This has potential major implications for the pathogenesis, diagnosis and treatment of diabetic cardiomyopathy. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation and National Institute for Health Research

Prognostic utility of left ventricular global longitudinal strain in patients with systemic amyloidosis

Abstract Background Myocardial deposition of amyloid proteins results in restrictive cardiomyopathy. Left ventricular global longitudinal strain (GLS) has emerged as a sensitive measure for detecting subclinical cardiac dysfunction over traditional echocardiographic parameters. However, multiple studies have provided differing conclusions regarding prognostic utility of impaired GLS in patients with systemic amyloidosis. Purpose We conducted a systematic review and meta-analysis to evaluate whether impaired GLS was associated with increased mortality or major adverse cardiovascular events (MACE) in patients with systemic amyloidosis. Methods We performed a literature search of Embase, Medline and Web of Science databases to identify studies that reported the association of GLS with clinical outcomes in patients with systemic amyloidosis (light chain or TTR amyloidosis). Outcomes of interest included all-cause mortality and MACE, defined as a composite of death or heart transplant or heart failure hospitalization. Unadjusted and adjusted hazard ratio (uHR and aHR respectively) were pooled using a random effects model. Heterogeneity among the studies was assessed using the Higgins I2 value. Results Out of 2139 initial citations, 28 observational studies with a total of 2713 patients were included in the analysis. The mean age ranged between 58–78 years and 62% of the patients were male. Most patients had cardiac amyloidosis (83%) and light-chain amyloidosis accounted for 69% of cases. Mean follow-up ranged between 1 and 5 years. GLS was significantly higher (less negative) (mean difference (MD) −3.69 [−5.94, −1.44], I2=87, p<0.01) in non-survivors compared with survivors. Similarly, patients who experienced MACE had a significantly higher mean GLS (MD −3.22, [−5.21, −1.22,], I2=82, p<0.01]. The risk of both mortality and MACE increased significantly for every −1% increase in GLS. In unadjusted models, a GLS above the defined threshold value was associated with a significantly higher risk of mortality (uHR: 1.66 [1.22, 5.21], I2=85.2, p<0.01) and MACE (uHR: 2.24 [1.28, 3.92], I2=39, p<0.01). In multivariable models an increase in GLS by −1% was an independent predictor of mortality (aHR: 1.09 [1.01,1.16], I2=53, p=0.02) and MACE (aHR: 1.24 [1.14,1.36], I2=0, p<0.01). Conclusion In patient with amyloidosis, the baseline left ventricular GLS may help identify patients with a higher risk of mortality and MACE. Funding Acknowledgement Type of funding sources: None.

Epicardial adipose tissue thickness is associated with reduced peak oxygen consumption and systolic reserve in patients with type 2 diabetes and normal heart function.

To investigate the impact of epicardial adipose tissue (EAT) thickness on cardiopulmonary performance in patients with type 2 diabetes (T2D) and normal heart function. We analysed EAT thickness in subjects with T2D and normal biventricular systo-diastolic functions undergoing a maximal cardiopulmonary exercise test combined with stress echocardiography, speckle tracking and pulmonary function assessment, as well as serum N-terminal pro B-type natriuretic peptide (NT-proBNP). In the 72 subjects enrolled, those with EAT thickness above the median (> 5 mm) showed higher body fat mass, smaller indexed left ventricular dimensions and marginally reduced diastolic function variables at rest. Higher EAT thickness was associated with lower peak oxygen uptake (VO2peak 17.1 ± 3.6 vs. 21.0 ± 5.7ml/min/kg, P=.001), reduced systolic reserve (ΔS' 4.6 ± 1.6 vs. 5.8 ± 2.5m/s, P=.02) and higher natriuretic peptides (NT-proBNP 64 [29-165] vs. 31 [26-139] pg/ml, P=.04), as well as chronotropic insufficiency and impaired heart rate recovery. Ventilatory variables and peripheral oxygen extraction were not different between groups. EAT was independently associated with VO2peak and linearly and negatively correlated with peak heart rate, heart rate recovery, workload, VO2 at the anaerobic threshold and at peak, and cardiac power output, and was directly correlated with natriuretic peptides. Higher EAT thickness in T2D is associated with worse cardiopulmonary performance and multiple traits of subclinical cardiac systolic dysfunction.

Effects of DPP-4 inhibitors on brain natriuretic peptide, neuropeptide Y, glucagon like peptide-1, substance P levels and global longitudinal strain measurements in type 2 diabetes mellitus patients

Introduction: Previously, a significant relationship between saxagliptin treatment and increased rate of hospitalization for congestive heart failure was reported. We aimed to investigate effects of vildagliptin and saxagliptin on brain natriuretic peptide (BNP), neuropeptide Y (NPY), substance P (SP), glucagon like peptide-1 (GLP-1) levels and left ventricular global longitudinal strain (GLS), assessed by 3-dimensional speckle tracking echocardiography in uncontrolled type 2 Diabetes mellitus (T2DM).
 Material and method: Thirty seven uncontrolled T2DM (HbA1c>7,5%) patients who were recently prescribed to either vildagliptin 50 mg BID (n=21) or saxagliptin 5 mg QD (n=16) were included in this study. Levels of BNP, NPY, SP, GLP-1 levels were measured at admission, first and third months of treatment. GLS was measured at admission and third month. 
 Results: In whole group, BNP and NPY values increased significantly at third month of treatment (p< 0.001, 0.004; respectively). In the vildagliptin group, BNP and NPY values increased significantly at third month of treatment (p=0.02 and p=0.04, respectively). In the saxagliptin group only BNP levels increased significantly (p=0.015). In both groups; SP, GLP-1 levels and GLS measurements did not change significantly during follow-up period. 
 Conclusion: The current study demonstrated that treatment with saxagliptin and vildagliptin, was associated with increased levels of BNP and NPY levels. No evidence of subclinical myocardial damage or cardiac dysfunction could be detected by GLS measurements. Since our study population had no previous clinical cardiac disorders, increases in BNP and NPY levels with these two DPP4 inhibitors can be considered as a safety signal.

Dexrazoxane Treatments Limits Subclinical Cardiac Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors Exposed to Doxorubicin Treatments.

Doxorubicin leads to dose dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. We investigated survivors' heart health using echocardiography and evaluated doxorubicin and dexrazoxane treatments on cardiac function. A total of 196 childhood ALL survivors were stratified (standard risk [SR], high risk with and without dexrazoxane (HR+DEX and HR). We performed a complete transthoracic echocardiographic assessment with M-mode echocardiography, Doppler, and Tissue Doppler. We used 2-dimensional and 3-dimensional echocardiography to measure the left ventricular ejection fraction, whereas myocardial strain imaging was used to obtain global strain indices. Although most cardiac and arterial dimension parameters were not different between groups, a difference was observed in posterior intima of the right carotid ( P =0.017). Diastolic functions analyses reported that LV shortening fraction and left and right ventricular lateral S' wave amplitudes were lower in HR than in SR and HR+DEX groups ( P =0.028, P =0.048, and P =0.005, respectively). The LV lateral E' in diastolic function was lower in the HR than in SR and HR+DEX groups ( P =0.036). The LV end-systolic wall stress was higher in HR than in SR and HR+DEX groups ( P =0.009). A decrease contractility was observed, while the effect was not group specific. Strain rate was not different between groups, as opposed to tissue Doppler measurements. This study showed that dexrazoxane treatments could limit subclinical cardiac dysfunction in childhood ALL survivors, whereas survivors in HR group who did not receive dexrazoxane had potential subclinical cardiac damage observable in heart failure patients. Echocardiographic screening for survivors must be part of the follow-up routine in cardio-oncology.

Do type 1 diabetic children have echocardiographic signs of subclinical cardiac dysfunction?

Background Diabetes mellitus is a major illness in which cardiac problems play a significant role in patient mortality. Objectives We aimed to evaluate whether children with diabetes mellitus type 1 have early echocardiographic signs of subclinical cardiac dysfunction and whether their sex, metabolic control, and duration of diabetes have an effect. Patients and methods A case–control study was performed from January 2022 to November 2022 that included 29 children and adolescents with type 1 diabetes aged from 4 to 15 years. A control group of 15 healthy children was also included. They were recruited from the pediatric endocrinology clinic, Al-Fayoum University Children’s Hospital, Al-Fayoum University, Egypt. Conventional echocardiographic study and tissue Doppler imaging measurements were done. Results With glycated hemoglobin levels less than 7%, the study group of diabetic children had inadequate glycemic control. There was a statistically significant low mean of fractional shortening and high mean of left ventricular septal wall thickness in diastole among diabetic children in comparison with controls, with P values of 0.04 and 0.038, respectively, but still within normal range. Conclusion Children with diabetes have poor glycemic control and scanty echocardiographic evidence of subclinical cardiac dysfunctions. According to the study, cardiac dysfunction in children with diabetes is uncommon. For the early identification of any potential cardiac dysfunctions, distant periodic cardiac examination using both conventional and tissue Doppler echocardiography is advised.

Evaluation of Fetal Cardiac Geometry and Contractility in Gestational Diabetes Mellitus by Two-Dimensional Speckle-Tracking Technology.

Background: The most commonly known cardiac effect of gestational diabetes mellitus (GD) in the fetus is hypertrophic cardiomyopathy, but recent studies show that it is preceded by subclinical cardiac dysfunction. This study aimed to assess the effect of GD on fetal cardiac geometry and contractility by two-dimensional speckle-tracking technology. Methods: We performed a prospective observational study that included 33 pregnant patients with GD and 30 healthy individuals. For all fetuses, a four-chamber 3 s cine-loop was recorded and analyzed with Fetal Heart Quantification (FetalHQ®), a novel proprietary speckle-tracking software. The following cardiac indices were calculated: global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC), and 24-segment end-diastolic diameter (EDD), fractional shortening (FS), and sphericity index (SI) for both ventricles. Demographic and cardiac differences between the two groups were analyzed, as well as intra-rater and inter-rater reliability. Results: There were significant changes in right ventricular FAC and FS for segments 4–24 in fetuses exposed to GD (−1 SD, p < 0.05). No significant differences were detected for GSI, GLS, EDD, or SI for either ventricle. Conclusions: Fetuses exposed to GD present impaired right ventricular contractility, especially in the mid and apical segments.

Detection of myocardial dysfunction using global longitudinal strain with speckle-tracking echocardiography in patients with vs without rheumatoid arthritis: a systematic review and meta-analysis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder primarily involving the peripheral joints. Systemic involvement can occur, including myocardial dysfunction. Speckle tracking echocardiography (STE) is a novel diagnostic study which is recently being used to detect subclinical cardiac dysfunction. Global longitudinal strain (GLS) by STE is more sensitive than standard echocardiographic parameters to detect occult cardiac dysfunction. A systematic search of PUBMED, EMBASE, Cochrane, and Google Scholar databases was performed to identify studies comparing the STE parameters between RA and non-RA patients. Left ventricular (LV) GLS was significantly lower in patients with RA compared to non-RA patients with a standard mean difference (SMD) of -1.09 (-1.48--0.70, P < 0.001). LV Global Circumferential Strain (GCS) was reported in five studies, and it was found to be lower in RA patients with an SMD of -1.25 (-2.59--0.10; P < 0.0010). Meta regression analysis studies failed to show any significant impact of disease duration, activity, age, sex and BMI on LV GLS and RV GLS. RA patients have lower LV GLS and LV GCS compared to controls suggesting impaired myocardial dysfunction. Further studies need to be done to delineate the importance of lower GLS in asymptomatic rheumatoid patients to guide disease management and risk factor modification in this selected population.

To assess the prevalence of clinical and subclinical cardiac autonomic dysfunction in adolescent with family history of hypertension and adolescent with prehypertension; correlating with adolescent anthropometric parameters

Objectives: Hypertension (HTN) is an inherited disorder and these patients manifest with cardiac autonomic dysfunction (CAD). The present study intends to assess the presence of pre HTN, clinical and subclinical CAD in adolescents with a family history of HTN, and to obtain its correlation with anthropometric values. Materials and Methods: After obtaining ethical clearance and informed consent, three groups containing 50 subjects each, of age 17–19 years were included in the study. (Group-I: Normotensives without a family history of HTN; Group-II: Normotensives with a family history of HTN and Group-III: prehypertensives). CAD was done by performing (1) resting tachycardia, (2) loss of sinus arrhythmia, and (3) heart rate response to the Valsalva manoeuvre. If any two of them are positive then the presence of CAD was confirmed. Results: Height, weight, BMI, SBP and DBP was significantly higher in group 3 (prehypertensives). Confirmed CAD findings was seen in 36% of group 2 and 46% of group 3 participants. Of the anthropometric parameters, a significant positive correlation was seen between weight and SBP, DBP and CAD parameters, and height with SBP and DBP. Conclusion: Clinical and subclinical CAD exists in adolescents with risk factors for HTN including heredity, obesity, and pre-HTN values. These risk factors show multiplicative effects for disease genesis and indicate high sympathetic and low parasympathetic drives. Extra care should be taken to curb the onset of clinical HTN and CAD in these young adults. Additional work needs to be done on pathophysiological mechanisms for the same.

Might female patients benefit more from bariatric surgery with respect to inflammation.

BackgroundBariatric surgery is an effective method for severe obesity and its related comorbidities, in which inflammation plays a crucial role. The aim of this study was to investigate the changes of Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in patients undergoing laparoscopic sleeve gastrectomy (LSG) and to explore the related factors including gender.MethodsWe retrospectively included 72 patients undergoing LSG in our hospital from 2017 to 2020. Clinical information, laboratory investigations as well as parameters derived from traditional and 2D strain echocardiography were collected. Univariate logistic model was used in myocardial performance index (MPI) and E/E′ analysis. Univariate and Multivariate logistic model were used in NLR analysis.ResultsAt baseline, all patients had normal left ventricular ejection fraction (LVEF). The myocardial performance index (MPI) (OR = 1.218 (95%CI 1.040, 1.426); p = 0.0142) and E/E′ (OR = 1.364 (95%CI 1.124, 1.655); p = 0.0017) were independently associated with CRP. LSG led to a significant decrease in inflammatory markers (NLR, 2.4 ± 1.59 vs.1.7 ± 0.86; CRP, 5.6 ± 3.17 vs. 2.1 ± 2.35 mg/L, respectively, both p < 0.001),which was more in NLR among female than male (OR = 3.14 (95%CI 1.112, 8.870); p = 0.031).ConclusionsThe present study indicated a significant correlation between subclinical cardiac dysfunction and CRP among obese patients. Furthermore, female patients might benefit more from bariatric surgery on inflammation.