Left Ventricular Concentric Remodeling Research Articles

P446 INDEPENDENT EFFECTS OF TYPE 2 DIABETES AND OBESITY ON CARDIOPULMONARY PERFORMANCE IN SUBJECTS AT HIGH CARDIOVASCULAR RISK

Abstract Background Both obesity and type 2 diabetes (T2D) are associated with effort intolerance and heart failure. Since the two conditions often coexist and overlap, their distinct effect on cardiopulmonary performance remains to be elucidated. Methods Patients at high cardiovascular risk, free from any clinical or instrumental evidence of heart disease, with a wide range of body mass index (BMI) values, and with or without T2D underwent combined echocardiography–cardiopulmonary exercise test (eCPET). Patients were divided in T2D and controls, as well as in lean (BMI <25 kg/m2), overweight (BMI 25 – 30 kg/m2), and obese (BMI >30 kg/m2). Results A total of 206 patients was analyzed, divided in 109 patients with T2D and 97 controls. Increased BMI is associated with multiple cardiovascular dysfunctions including chronotropic insufficiency, subclinical systolic dysfunction (reduced global longitudinal strain, GLS), and impaired systolic reserve, achieving significantly lower oxygen uptake and workload. Obesity is associated with reduced lung volumes and mild ventilatory alterations at peak exercise, irrespective of diabetes. T2D patients showed more frequent LV concentric remodeling, worse systolic and diastolic performance at rest with diminished ameliorations during exercise, and worse sympatho–vagal balance as expressed by the higher prevalence of chronotropic insufficiency and delayed heart rate recovery. Nonetheless, when divided in BMI subclasses, the differences between T2D and controls were only evident among lean subjects. In fact, while no difference between T2D and controls was evident among overweight and obese patients, lean individuals with T2D display worse cardiopulmonary performance than lean controls, achieving lower workload and lower VO2peak, revealing systolic dysfunction (lower GLS) and higher LV filling pressures (E/e’). Unlike glycated hemoglobin, strong linear relationships were proven between fat mass and oxygen uptake, workload, systolic, and diastolic indices. Conclusions T2D affects LV dimensions and geometry, systo–diastolic functions, autonomic balance, cardiopulmonary capacity, and exercise tolerance, independently of the presence of obesity. Nonetheless, increased BMI is an even more powerful independent negative determinant of systolic function, autonomic balance, and effort tolerance. These early alterations might partly explain the increased risk of developing heart failure associated with diabetes and obesity.

Obesity, Preserved Ejection Fraction Heart Failure, and Left Ventricular Remodeling.

Owing to the overwhelming obesity epidemic, preserved ejection fraction heart failure commonly ensues in patients with severe obesity and the obese phenotype of preserved ejection fraction heart failure is now commonplace in clinical practice. Severe obesity and preserved ejection fraction heart failure share congruent cardiovascular, immune, and renal derangements that make it difficult to ascertain whether the obese phenotype of preserved ejection fraction heart failure is the convergence of two highly prevalent conditions or severe obesity enables the development and progression of the syndrome of preserved ejection fraction heart failure. Nevertheless, the obese phenotype of preserved ejection fraction heart failure provides a unique opportunity to assess whether sustained and sizeable loss of excess body weight via metabolic bariatric surgery reverses the concentric left ventricular remodeling that patients with preserved ejection fraction heart failure commonly display.

Abstract P666: Prevalence and Determinants of Left Ventricular Structural Abnormalities and Diastolic Dysfunction in Asymptomatic Mexican Americans Living in South Texas

Left ventricular hypertrophy (LVH) and concentric LV remodeling (CR) are precursors to development of clinical heart failure (HF), and are associated with obesity, hypertension (HTN) and diabetes mellitus (DM), which are highly prevalent in Mexican Americans. Our study aimed to determine the prevalence of subclinical LV structural abnormalities (LVH or CR) and LV diastolic dysfunction (LVDD) in a sample of asymptomatic Mexican Americans in South Texas and determinants of these LV structural abnormalities. Methods: Demographic, cardiometabolic biomarkers, and body composition data were obtained in 1208 participants (66.3% females, mean age 53.0±0.4 years) without any CVD history from the community-based Cameron County Hispanic Cohort study. Echocardiography was used to determine LVH/CR (linear method) and LVDD was assessed using national guidelines. Those with LV systolic dysfunction (n=26) were excluded. Abdominal adiposity was determined by abdominal visceral fat mass (VAT) from dual-energy X-ray absorptiometry. Weighted ordinal logistic regression analyses were conducted adjusting for demographic and clinical covariates. Results: Weighted prevalence rates of LVH (16.6% ± 1.7%), CR (40.7% ± 2.0%) and LVDD (24.2% ± 1.8%) were high in this cohort. In men, age (p<0.01), obesity (p=0.04) and HTN (p<0.001) were positively related to LV abnormalities. In women, age (p<0.001), obesity (p<0.01), education (p=0.02), HTN (p<0.01) and DM (p<0.01) were related to LV abnormalities. VAT was associated with LV abnormalities in women (p=0.02), but not in men (p=0.08). Conclusion: More than half of this asymptomatic Hispanic cohort had evidence of LV structural abnormalities and almost a quarter had subclinical diastolic dysfunction. We noted a gender interaction, with diabetes and abdominal obesity seen to be significantly related to cardiac abnormalities only in women. Identifying subclinical changes in cardiac function in these high-risk patients may mitigate progression to clinical HF by early intervention.

Hepatocyte Growth Factor and 10-Year Change in Left Ventricular Structure: The Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundHepatocyte growth factor (HGF) is a cytokine linked to incident heart failure (HF), particularly HF with preserved ejection fraction (HFpEF). Increases in left ventricular (LV) mass and concentric remodelling defined by increasing mass-to-volume (M:V) ratios are imaging risk markers for HFpEF. We aimed to determine if HGF is associated with adverse LV remodelling. MethodsWe studied 4907 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), free of cardiovascular disease and HF at baseline, who had HGF measured and cardiac magnetic resonance imaging (CMR) performed at baseline. Of these, 2921 completed a second CMR at 10 years. We examined the cross-sectional and longitudinal associations of HGF and LV structural parameters using multivariable-adjusted linear mixed-effect models, adjusting for cardiovascular disease risk factors and N-terminal pro B-type natriuretic peptide. ResultsThe mean (SD) for age was 62 (10) years; 52% were female. Median (interquartile range) for HGF level was 890 pg/mL (745-1070). At baseline, the highest HGF tertile, compared to the lowest, was associated with a greater M:V ratio (relative difference 1.94 [95% confidence interval [CI]: 0.72, 3.17]) and lower LV end-diastolic volume (–2.07 mL [95% CI: –3.72, –0.42)]. In longitudinal analysis, the highest HGF tertile was associated with increasing M:V ratio (10-year difference: 4.68 [95% CI: 2.64, 6.72]) and decreasing LV end-diastolic volume (–4.74 [95% CI: –6.87, –2.62]). ConclusionsIn a community-based cohort, higher HGF levels were independently associated with a concentric LV remodelling pattern of increasing M:V ratio and decreasing LV end-diastolic volume by CMR over 10 years. These associations may reflect an intermediate phenotype explaining the association of HGF with HFpEF risk.

Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans.

South Asians (SA) constitute a quarter of the global population and are disproportionally affected by both type 2 diabetes (T2D) and heart failure. There remains limited data of the acceptability and efficacy of low-energy meal replacement plans to induce remission of T2D in SA. The objective of this exploratory secondary analysis of the DIASTOLIC study was to determine if there was a differential uptake, glycometabolic and cardiovascular response to a low-energy meal replacement plan (MRP) between SA and White European (WE) people with T2D. Obese adults with T2D without symptomatic cardiovascular disease were allocated a low-energy (~810 kcal/day) MRP as part of the DIASTOLIC study (NCT02590822). Comprehensive multiparametric cardiovascular magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing and metabolic profiling were undertaken at baseline and 12 weeks. A comparison of change at 12 weeks between groups with baseline adjustment was undertaken. Fifteen WE and 12 SAs were allocated the MRP. All WE participants completed the MRP versus 8/12 (66%) SAs. The degree of concentric left ventricular remodelling was similar between ethnicities. Despite similar weight loss and reduction in liver fat percentage, SA had a lower reduction in Homeostatic Model Assessment for Insulin Resistance [-5.7 (95% CI: -7.3, -4.2) versus -8.6 (-9.7, -7.6), p = 0.005] and visceral adiposity compared to WE [-0.43% (-0.61, -0.25) versus -0.80% (-0.91, -0.68), p = 0.002]. Exercise capacity increased in WE with no change observed in SA. There was a trend towards more reverse remodelling in WE compared to SAs. Compliance to the MRP was lower in SA versus WE. Overall, those completing the MRP saw improvements in weight, body composition and indices of glycaemic control irrespective of ethnicity. Whilst improvements in VAT and insulin resistance appear to be dampened in SA versus WE, given the small sample, larger studies are required to confirm or challenge this potential ethnic disparity. NCT02590822.

Prognostic implication of left ventricular hypertrophy regression after antihypertensive therapy in patients with hypertension.

Left ventricular (LV) hypertrophy (LVH) in patients with hypertension is a significant risk factor for cardiovascular mortality and morbidity. However, the prognostic implication of LVH regression after antihypertensive therapy has not been clearly investigated. Patients who underwent echocardiography at the time of the diagnosis of hypertension and repeated echocardiography at an interval of 6-18 months were retrospectively identified. LVH was defined as LV mass index (LVMI) >115 g/m2 (men) and >95 g/m2 (women). LVH regression was defined as LVH at initial echocardiography with normal geometry or concentric LV remodeling at follow-up echocardiography. Cardiovascular mortality, hospitalization for heart failure (HHF), coronary revascularization, stroke, and aortic events were analyzed according to changes in LVMI and geometry. Of 1,872 patients, 44.7% (n = 837) had LVH at the time of diagnosis; among these, 30.7% showed LVH regression. The reduction in LVMI was associated with the reduction in BP, especially in those with LVH at baseline. During follow up (median, 50.4 months; interquartile range, 24.9-103.2 months), 68 patients died of cardiovascular causes, 127 had HHF, and 162 had vascular events (coronary revascularization, stroke, and aortic events). Persistent or newly developed LVH during antihypertensive therapy was a significant predictor of cardiovascular mortality and events, especially HHF. On multivariable analysis, women, diabetes, atrial fibrillation, coronary artery disease, larger LVMI and end-diastolic dimension, and less reduction in systolic BP were associated with persistent or newly developed LVH. LVH regression in patients with hypertension is associated with a reduction in cardiovascular events and can be used as a prognostic marker.

Extent of Left Ventricular Mass Regression and Impact of Global Left Ventricular Afterload on Cardiac Events and Mortality after Aortic Valve Replacement.

Patient-prosthesis mismatch (PPM) causes a high transvalvular pressure gradient and residual left ventricular (LV) hypertrophy, consequently influencing long-term results. This study aimed to find the relationships between hemodynamic parameters and LV mass regression and determine the risk predictors of major adverse cardiovascular and cerebral events (MACCE) after aortic valve replacement (AVR) for aortic stenosis. Methods and Results: Preoperative and postoperative Doppler echocardiography data were evaluated for 120 patients after AVR. The patients' mean age was 67.7 years; 55% of the patients were male. Forty-four (37%) patients suffered from MACCE during a mean follow-up period of 3.6 ± 2 years. The following hemodynamic parameters at follow-up were associated with lower relative indexed LV mass (LVMI) regression: lower postoperative indexed effective orifice area, greater mean transvalvular pressure gradient (MPG), greater stroke work loss (SWL), and concentric or eccentric LV remodeling mode. The following hemodynamic parameters at follow-up were associated with a higher risk of MACCE: higher valvuloarterial impedance (ZVA), greater SWL, greater MPG, greater relative wall thickness, greater LVMI, and hypertrophic LV remodeling mode. Lower relative LVMI regression was associated with a higher risk of MACCE (hazard ratio, 1.01: 95% confidence interval, 1.003-1.03). The corresponding cutoff of relative LVMI regression was -14%. Conclusions: Changes in hemodynamic parameters were independently associated with relative LVMI regression. Impaired reverse remodeling and persistent residual LV hypertrophy were independent risk predictors of MACCE. An LVMI regression lower than 14% indicated higher MACCE. A postoperative ZVA greater than 3.5 mmHg/mL/m2 was an independent risk predictor of cardiac events and mortality after AVR. Preventive strategies should be used at the time of the operation to avoid PPM.

Abstract 13809: Multiparametric CMR Tissue Characterization Distinguishes Pathological From Physiological Cardiac Hypertrophy and Correlates With CPET Findings

Introduction: Physiological and pathological cardiac hypertrophy differ in terms of mechanisms, phenotypes, and outcomes. We aimed to characterize the cardiac tissue phenotype of athletes and HF patients. Methods: Prospectively enrolled participants underwent CMR and CPET. HF patients (NYHA class II-III) were classified as HFpEF (LVEF>=45%) or HFrEF (LVEF<45%). Results: One-hundred and eighty participants were categorized in four groups: athletes (n=44, 32±12 years), HFpEF (n=47, 61±11 years, H2FPEF score 5±2), HFrEF (n=47, 54±10 years), and healthy controls (n=42, 41±13 years). LVEF was markedly reduced in HFrEF (athletes 65±6%, HFpEF 59±11, HFrEF 29±9, controls 66±4, p<.001). LV mass index (athletes 65±6%, HFpEF 59±11, HFrEF 29±9, controls 66±4, p<.001) and cardiomyocyte mass index (athletes 64±15g/m 2 , HFpEF 66±24, HFrEF 82±36, controls 42±8, p<.001) were greater in athletes and in HF patients (Fig 1A). Athletes and HFpEF patients had concentric LV remodeling, while HFrEF patients showed eccentric remodeling (Fig 1B). Intracellular lifetime of water was longer in athletes and shorter in HFrEF (athletes .17±.07s, HFpEF .15±.05, HFrEF .13±.05, controls .14±.05, p<.001) (Fig 2A). ECV was similarly increased in both HF groups (athletes .28±.04%, HFpEF .31±.05, HFrEF .31±.05, controls .28±.04, p<.001) (Fig 2B). Native T1 (athletes 1175±55ms, HFpEF 1261±61, HFrEF 1274±61, controls 1229±75, p=.01) correlated with CPET maximal oxygen consumption (VO 2 max) in HF patients (r=-.023, p=.048) (athletes 52±10, HFpEF 18±6, HFrEF 17±4, controls 29±9, p<.001). Conclusion: Physiological hypertrophy was characterized by increased cardiomyocyte diameter, normal ECV, and shorter native T1 due to its greater cardiomyocyte volume. Contrastingly, pathological hypertrophy’s longer native T1 was a result of its higher ECV and correlated with VO 2 max in HF. Cardiomyocyte diameter was smaller in HFrEF than in HFpEF.

Abstract 11174: Hypertension in Hispanics/Latinos is Associated with Adverse Alterations in Cardiac Structure and Function

Introduction: Hispanic/Latino adults have been reported to be less aware of their hypertension (HTN) diagnosis and less likely to be on treatment compared to non-Hispanic white and black adults. These disparities suggest that Hispanic adults with HTN are at high risk for developing structural heart disease. Yet, limited data exist regarding how HTN affects cardiac structure and function in this population. Hypothesis: Higher long-term antecedent blood pressure (BP) level is associated with adverse changes in cardiac structure and function in Hispanic/Latino adults. Methods: The study sample consisted of 6,144 participants of the Hispanic Community Health Study/Study of Latinos free of prior cardiovascular disease who had BP measured at visits 1 and 2 (2010-2011 and 2014-2017, respectively) and underwent echocardiography at visit 2. Mean systolic and diastolic BP were averaged across visits 1 and 2. Those who were taking antihypertensive medications were imputed as follows: values for systolic BP (+10 mmHg) and diastolic BP (+5 mmHg). Results: Mean age was 57±10 years, 54% were women. 48% had imputed mean systolic BP ≥130 or diastolic BP ≥80 mmHg. Increasing age, body mass index (BMI), diabetes prevalence, and worsening kidney function were associated with more severe hypertension. Increasing mean BP was associated with increased prevalence of concentric remodeling and concentric left ventricular (LV) hypertrophy. Higher BP was also associated with adverse changes in diastolic function parameters including left atrial volume index, septal e’, E/A ratio, and E/e’. These differences persisted after adjusting for age, sex, Hispanic subgroup, BMI, kidney function, diabetes, alcohol use, and cholesterol level. LV ejection fraction did not significantly differ across BP groups. Conclusions: Increased prevalence of HTN in a Hispanic/Latino adult population is associated with LV hypertrophy, concentric remodeling, and diastolic dysfunction.

Abstract 13211: Dysregulated Myocardial Calcium Handling is a Driver of Early Heart Failure in Type 1 and Type 2 Diabetes

Introduction: Dysregulated myocardial calcium handling may be a precursor for heart failure in type 1 (T1D) and type 2 diabetes (T2D). Manganese-enhanced magnetic resonance imaging (MEMRI) is a novel non-invasive method of assessing in vivo myocardial calcium handling. Hypothesis Myocardial calcium handling is impaired in patients with either T1D or T2D, despite normal left ventricular (LV) systolic function. Methods Prospective, multicentre, study in patients with T1D (n=19), T2D (n=30), and healthy volunteers (n=28), all of whom were free of known cardiovascular disease. Cardiac MRI was performed including MEMRI, during which T1 mapping was performed at baseline and every 2.5 min for 30 min after manganese infusion (Figure 1a). The rate of myocardial manganese uptake, determined by Patlak modelling [1]. Results No difference in LV systolic function was observed between groups, but those with T2D had more concentric LV remodelling compared to T1Ds and healthy volunteers (LV mass:volume 0.90±0.16 vs. 0.75±0.09 vs. 0.74±0.10 g/mL, respectively; p=0.001, Table 1). Mean myocardial manganese uptake was significantly lower in both T1Ds (6.47±0.99 mL/100g/min) and T2Ds (6.43±0.77 mL/100g/min) compared with healthy volunteers (8.33±0.77 mL/100g/min; p<0.001 for both, Figure 1b). Conclusion For the first time, we have demonstrated that myocardial calcium handling is impaired in patients with either T1D or T2D despite apparently normal LV systolic function. This may be a precursor to the development of diabetic cardiomyopathy and has implications for developing novel therapeutic targets for its prevention and treatment. [1] Skjold, A et al. J Magn Reson Imag 2006;24:1047-1055 graphic_{ECFA3EC4-96D0-4ADC-8599-3D854C84F04F}graphic_{F1770AC6-718C-4C39-B107-4A5DD60957A8}

Association between left ventricular geometry and global myocardial work in patients with heart failure with preserved ejection fraction: assessment using strain-pressure loop.

Concentric LV remodeling and hypertrophy are common structural abnormalities in patients with heart failure with preserved ejection fraction (HFpEF) and tend to be accompanied by impaired LV function. Assessment of global myocardial work (GMW) using strain-pressure loop may provide more comprehensive assessment of LV myocardial function, overcoming the limitations of the conventional parameters. We investigated the value of GMW in patients with HFpEF and assessed the relationship of GMW with concentric remodeling and hypertrophy. Consecutive patients with HFpEF (n = 107) and sex-matched healthy controls (n = 32) were prospectively enrolled. Clinical and conventional echocardiography variables were obtained. Further analyses of offline data were performed to obtain GMW indices including global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE). Association of concentric remodeling and hypertrophy with GMW was analyzed by univariate and multivariate analysis. HFpEF patients showed lower GWE (94% vs 96%, P < 0.001) and higher GWW (114mmHg% vs 78mmHg%, P = 0.003) than control group, while GWI (2111mmHg% vs 2146mmHg%, P = 0.877) and GCW (2369mmHg% vs 2469mmHg%, P = 0.733) were comparable in the two groups. HFpEF patients with relative wall thickness (RWT) > 0.42 had reduced GWE (94% vs 95%, P = 0.034) compared to HFpEF patients with RWT ≤ 0.42, while GWI, GCW, and GWW were comparable between these two subgroups. Multivariate analysis showed an independent association of RWT with GWI, GCW, and GWE, respectively. Impaired global myocardial work was detected in patients with HFpEF. Impaired LV GMW may be associated with increased RWT.

Lifestyle intervention in obese pregnancy and cardiac remodelling in 3-year olds: children of the UPBEAT RCT

Background/ObjectivesObesity in pregnancy has been associated with increased childhood cardiometabolic risk and reduced life expectancy. The UK UPBEAT multicentre randomised control trial was a lifestyle intervention of diet and physical activity in pregnant women with obesity. We hypothesised that the 3-year-old children of women with obesity would have heightened cardiovascular risk compared to children of normal BMI women, and that the UPBEAT intervention would mitigate this risk.Subjects/MethodsChildren were recruited from one UPBEAT trial centre. Cardiovascular measures included blood pressure, echocardiographic assessment of cardiac function and dimensions, carotid intima-media thickness and heart rate variability (HRV) by electrocardiogram.ResultsCompared to offspring of normal BMI women (n = 51), children of women with obesity from the trial standard care arm (n = 39) had evidence of cardiac remodelling including increased interventricular septum (IVS; mean difference 0.04 cm; 95% CI: 0.018 to 0.067), posterior wall (PW; 0.03 cm; 0.006 to 0.062) and relative wall thicknesses (RWT; 0.03 cm; 0.01 to 0.05) following adjustment. Randomisation of women with obesity to the intervention arm (n = 31) prevented this cardiac remodelling (intervention effect; mean difference IVS −0.03 cm (−0.05 to −0.008); PW −0.03 cm (−0.05 to −0.01); RWT −0.02 cm (−0.04 to −0.005)). Children of women with obesity (standard care arm) compared to women of normal BMI also had elevated minimum heart rate (7 bpm; 1.41 to 13.34) evidence of early diastolic dysfunction (e prime) and increased sympathetic nerve activity index by HRV analysis.ConclusionsMaternal obesity was associated with left ventricular concentric remodelling in 3-year-old offspring. Absence of remodelling following the maternal intervention infers in utero origins of cardiac remodelling.Clinical trial registry name and registration numberThe UPBEAT trial is registered with Current Controlled Trials, ISRCTN89971375.

White Coat Hypertension: When Office Blood Pressure Impacts Cardiac Mechanics More Than Ambulatory. Is This Really So?

Hypertensive heart disease, characterized by left ventricular (LV) hypertrophy, left atrial enlargement, and LV dysfunction, represents a relatively advanced stage of hypertension-mediated organ damage (HMOD) typically associated with unrecognized or inadequately controlled systemic hypertension. However, a growing amount of evidence supports the view that subtle cardiac morphofunctional abnormalities such as LV concentric remodeling and mild impairment in LV relaxation can develop very early in the natural history of hypertension. Furthermore, an increased risk of initial cardiac HMOD has also been reported for long-held innocent conditions such as prehypertension and white coat hypertension (WCH). WCH is a common condition in which blood pressure (BP) measured in the medical environment is elevated while ­out-of-office BP (i.e., home and/or ambulatory BP [ABP]) is ­normal.1 The relationship between WCH and cardiac HMOD, an intermediate step linking hypertension with overt cardiovascular disease, has been investigated by numerous individual studies and their meta-analyses. Pooled data from 25 studies, including a total of 7.382 untreated individuals (2.493 true normotensives, 1.705 WCH, and 3.184 sustained hypertensives), showed that LV mass index (LVMI) gradually increased from normotensive, WCH, to sustained hypertensive patients. A meta-regression analysis restricted to WCH group documented a significant direct correlation between LVMI and office systolic BP (r = 0.42, P < 0.01); this was not the case for daytime systolic BP (r = 0.18, P = 0.17). Of note, the meta-analysis suggested that LV relaxation (in parallel with a greater left atrial size) but not LV ejection fraction (LVEF) was impaired in WCH.2

A prediction model for aberrant cardiac remodelling in women after preeclampsia; Queen of Hearts study

Abstract Background Preeclampsia, a hypertensive pregnancy disorder, is strongly associated with aberrant left ventricular remodelling up to ten years after delivery and heart failure later in life. To detect occult cardiac abnormalities, echocardiography is necessary but not feasible for all these women. A prediction model for aberrant cardiac remodelling to be used in primary care may guide towards intensified follow-up for those at risk or tempered follow-up for low-risk individuals. Purpose To develop a prediction model for aberrant left ventricular remodelling in former pregnant women weighing their complicated pregnancy. Methods In this large cohort study, we included women (aged ≥18 years) with a history of preeclampsia or normotensive pregnancy at a postpartum interval of 6 months until 30 years. Comprehensive cardiovascular assessment was performed, including echocardiography, 30-minutes blood pressure measurements and circulating biomarkers. The procedures were in accordance with institutional guidelines and adhered to the principles of the Declaration of Helsinki. Aberrant cardiac remodelling based on echocardiography was defined as either left ventricular concentric remodelling or left ventricular hypertrophy. A prediction model based on clinical and circulating markers was developed using univariable and multivariable logistic regression with backward elimination. Internal validation was performed using Heuristic shrinkage factor. Performance of the final model was evaluated in terms of discrimination by the area under the receiver operating characteristic (AUC-ROC) curve. Results We included 1466 women, of which 93 (6.3%) with left ventricular concentric remodelling and/or left ventricular hypertrophy (mean ± SD age, 43±10 years) and 1373 (93.7%) without left ventricular concentric remodelling and/or left ventricular hypertrophy (40±8 years). The final prediction model was based on the predictors age, waist circumference, systolic blood pressure, Homeostatic Model Assessment of Insulin Resistance (HOMAIR), and preeclampsia (y/n) (Table 1). After internal validation, this prediction model showed a good discriminative ability of AUC-ROC-curve 0.71 (95% CI 0.661–0.758) (Figure 1). Conclusion We developed a good-performing prediction model for aberrant cardiac remodelling in former pregnant women based on five conventional variables that could contribute to risk-guided follow-up after preeclampsia aiming at intensifying follow-up for those at risk and tempered follow-up for low-risk women. Funding Acknowledgement Type of funding sources: None.

Female-specific reference values for blood pressure and its relationship with subclinical echocardiographic findings in women with a history of preeclampsia: the Queen of Hearts study

Abstract Introduction Hypertension is the most crucial modifiable risk factor for cardiovascular disease (CVD). Sex differences in what is considered optimal blood pressure (BP) might deviate from current sex-blinded guidelines for hypertension. In women, an obstetric history of preeclampsia relates to postpartum hypertension and substantially increases the risk of premature CVD. Purpose To establish female-specific reference values for BP in relatively young women and assess its association with subclinical aberrant echocardiographic findings in a high-risk female population. Methods Data was used from the Queen of Hearts study; a cross-sectional cohort study on early detection of heart failure among young women with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancy. The control group was used to non-parametrically establish reference values for BP (95th percentile). The association between the derived reference values and the risk of subclinical aberrant echocardiographic findings was evaluated in the former preeclamptic group using logistic regression. All women were admitted to a standardized cardiovascular assessment including transthoracic echocardiography and 30-minutes BP measurement. Subclinical echocardiographic findings included left ventricular (LV) hypertrophy (LVH), LV concentric remodelling (LCVR), diastolic dysfunction (DD) and impaired LV ejection fraction (LVEF, &amp;lt;55%). Results A total of 429 women in the healthy control group and 856 in the former preeclamptic group were included (44±8 and 38±8 years, respectively). In the healthy control group, 97.7% and 99.8% of women had a systolic (SBP) and diastolic BP (DBP) value below the European Society of Cardiology (ESC) guidelines for hypertension. Overall, the derived reference value for SBP and DBP in our control group was 133 and 82 mmHg, respectively. Age-specific reference curves are presented in Figure 1 and 2. In the subgroup of former preeclamptic women 10.4% and 14.6% had SBP and DBP levels above 133 mmHg and 82mmHg, respectively. In this group, the Odds Ratio (OR) for subclinical aberrant echocardiographic findings when having SBP ≥133mmHg was 5.3 (95% CI 2.3–12.3) for LVH, 1.4 (95% CI 0.6–3.2) for LVCR, 5.9 (95% CI 3.3–10.7) for DD and 1.3 (95% CI 0.3–6.0) for impaired LVEF. For DBP ≥82mmHg, the OR for LVH was 3.5 (95% CI 1.5–8.0), LVCR 1.3 (95% CI 0.6–2.7), DD 3.4 (95% CI 1.9–6.0) and impaired LVEF 1.5 (95% CI 0.4–5.3). Conclusions Upper limits for SBP and DBP values in current guidelines correspond with the value of less than 2% of women in our healthy (no pre-eclampsia) population. We derived new reference values with the upper limit corresponding with the upper 5th centile. Values above this level, even below decision limits for hypertension, are associated with abnormal subclinical cardiac function and geometry in a high-risk young female population. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation

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&amp;lt;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

Changes in adipose tissue depots and cardiac geometry following bariatric surgery

Abstract Introduction Cardiac geometry is affected by body composition, with total body adipose volume being related to left ventricular (LV) dilatation (due to increased intravascular volume and cardiac output), and visceral adipose tissue (VAT) to smaller LV cavity size and concentric remodelling (because of insulin resistance) [1]. As such we hypothesised that changes in VAT and total body weight during weight loss would have a differential impact on cardiac geometry. Alongside this, we hypothesised that, as the pericardium is a fixed volume, changes in epicardial adipose tissue (EAT), may have an additional mechanical effect by reducing pericardial restraint. Purpose We sought to investigate long term changes in VAT, total weight and EAT following bariatric surgery and relate them to changes in cardiac geometry. Methods Forty patients underwent cardiac magnetic resonance (CMR) imaging before and after bariatric surgery, including 21 who underwent short-term (median 209 days), 28 medium-term (median 428 days) and 12 long-term (median 1030 days) imaging follow up. Cardiac volumes (left atrial (LA), LV end-diastolic volume (LVEDV) and stroke volume (LVSV)) were assessed using cardiac MRI. VAT was assessed at L5 using a T1 weighted, water suppressed sequence. EAT volumes were calculated by manual contouring in end-ventricular systole on short axis slices from the mitral valve to the apex. Percentage changes in volumes were calculated between scans for each individual. Results Patients on average lost 32kg within the first 428 days following bariatric surgery (54% excess weight loss, p&amp;lt;0.0001), with no significant change in weight at the longer-term time point (Figure 1A). Most VAT loss occurred in the first 209 days (−42%, p&amp;lt;0.0001) with no subsequent change observed at the final two timepoints (Figure 1B). Similarly, EAT loss occurred in the first 209 days (−13%, mean 10ml, p&amp;lt;0.0001) with non-significant changes thereafter (Figure 1C). There was a significant decrease in both LA (13%, mean 12ml, p&amp;lt;0.0001) and LVEDV (4%, mean 8ml, p=0.0249) at 209 days post-surgery. Both LA volume and LVEDV had returned to baseline by the longest term time point of 1030 days (Figure 2). LVSV followed a similar pattern being reduced at 209 days (by 10%, mean 9ml, p=0.0019), then returning to levels similar to those pre-weight loss at 1030 days (p=0.44) (Figure 2C). Conclusions Cardiac volumes show a biphasic response to weight loss, initially becoming smaller and then returning to baseline by 1030 days. We hypothesise that the early drop in LA and LV cavity size is a response to reduced volume from body mass reduction. In contrast, we propose that the increase in LA and LVEDV that follows results from the longer-term effects of reducing VAT, and increased space within the pericardium resulting from EAT loss allowing expansion to occur. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): We acknowledge support from the British Heart Foundation Oxford Center of Research Excellence

Female sex and systolic blood pressure are independently associated with coronary microvascular dysfunction in asymptomatic adults with type 2 diabetes

Abstract Introduction Coronary microvascular dysfunction is frequently reported in people with type 2 diabetes (T2D), is associated with reduced exercise capacity, and is a prognostic marker. Identifying modifiable risk factors associated with microvascular dysfunction may facilitate early intervention to improve outcomes in these patients. Purpose To identify independent determinants of myocardial perfusion reserve (MPR) in asymptomatic adults with T2D and no prevalent cardiovascular disease. Methods Prospective cross-sectional study. People with and without T2D and no signs, symptoms or evidence of cardiovascular disease underwent comprehensive phenotyping with echocardiography, coronary artery calcium scoring, and multiparametric cardiac MRI including adenosine stress and rest perfusion with automated pixel-wise myocardial blood flow (MBF) mapping. Participants with regional perfusion defects indicating obstructive coronary disease or silent myocardial infarct on late-gadolinium enhancement were excluded from analysis. Univariable and multivariable linear regression was performed to identify independent determinants of MPR. Results Two-hundred people with T2D (diabetes duration 11±8 years) were compared with 39 sex- and ethnicity-matched non-diabetic controls (Table 1). People with T2D had higher body mass index (BMI) and ambulatory 24-hour systolic blood pressure (SBP). There was evidence of concentric left ventricular (LV) remodelling (higher LV mass/volume), extracellular matrix expansion (higher ECV fraction), and both systolic and diastolic dysfunction (lower global longitudinal systolic strain and E/A ratio, respectively) in those with T2D. Resting MBF was similar between groups, but stress MBF tended to be lower in T2D compared to controls with significantly reduced MPR in T2Ds (2.87±0.86 vs 3.18±0.82, p=0.043). In univariable analysis, MPR correlated with sex, 24-hour SBP, and E/e' ratio. In a multivariable model adjusting for clinical (age, sex, smoking status, BMI, ambulatory SBP, diabetes duration, HbA1c, low-density lipoprotein, albuminuria) and imaging variables (E/e' ratio, LV mass/volume, global longitudinal strain, myocardial ECV, coronary calcium score) known to affect coronary perfusion, female sex (β=−0.227, p=0.013) and 24-hour SBP (β=−0.275, p=0.001) were the only variables independently associated with MPR. Conclusion Female sex is associated with coronary microvascular dysfunction in asymptomatic people with T2D but not LV mass or myocardial extracellular volume. Systolic BP is the only modifiable independent determinant of MPR and may be an early target for intervention to prevent heart failure development in these patients. 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 award (FS/16/47/32190).

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&amp;lt;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).

Epicardial adipose tissue volume and density is associated with cardiac dysfunction in asymptomatic people with type 2 diabetes

Abstract Background Type 2 diabetes (T2D) is associated with several perturbations of cardiac structure and function, which are precursors to the development of heart failure. Excess accumulation of epicardial adipose tissue (EAT) may contribute to cardiac dysfunction in individuals with T2D. Lipid-laden adipocytes have a lower computed tomography (CT) attenuation and can be readily identified using cardiac CT. Using a multimodality cardiac imaging approach, we aimed to assess the association of total and low attenuation EAT volume with early markers of cardiac dysfunction in people with T2D. Methods Prospective case-control study, in which participants with and without T2D and no known cardiovascular disease, underwent comprehensive cardiovascular phenotyping including multiparametric cardiac magnetic resonance imaging (MRI), echocardiography and non-contrast cardiac CT. EAT volume was measured from CT scans using a deep learning method and volumes indexed to body surface area. Total EAT was defined according to CT adipose tissue attenuation range of −30 to −190 Hounsfield Units (HU) and low attenuation EAT as −90 to −190 HU. Left ventricular (LV) volumes, function and strain measurements were derived from cardiac MRI images and diastolic function also assessed using echocardiography. Markers of early cardiac dysfunction in those with T2D were assessed for associations with EAT in T2D participants using multivariable linear regression analyses. Results Two hundred and fifty-four participants were included: demographic, anthropometric and imaging variables are displayed in Table 1. Subjects with T2D had increased LV concentric remodelling (higher LV mass/volume ratio), diastolic dysfunction (lower circumferential peak early diastolic strain rate (PEDSR) and average E/e') and reduced systolic function (global longitudinal strain, GLS) compared with controls. Total and low attenuation indexed EAT volumes were 1.6-fold and 2-fold higher, respectively, in participants with T2D compared to controls (Figure 1). After adjustment for age, gender, ethnicity, insulin resistance, systolic blood pressure and waist/hip ratio, total and low attenuation indexed EAT volume were independently associated with LV mass/volume ratio (total indexed EAT volume: β=0.002, p=0.02, low attenuation indexed EAT volume: β=0.004, p=0.01) and LV GLS (total indexed EAT volume: β=−0.02, p&amp;lt;0.01, low attenuation indexed EAT volume: β=−0.04, p=0.02) in subjects with T2D, but not indices of diastolic dysfunction. Conclusion Total and low attenuation EAT volumes are higher in individuals with T2D, and excess EAT accumulation is independently associated with early markers of cardiac dysfunction. Further studies into the underlying mechanisms of this interaction may facilitate the development of interventions targeted at EAT, which could mitigate against the development of heart failure in people with T2D. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): United Kingdom National Institute for Health Research