Preserved Left Ventricular Systolic Function Research Articles

Elevated Glycated Albumin in Serum Is Associated with Adverse Cardiac Outcomes in Patients with Acute Coronary Syndrome Who Underwent Revascularization Therapy.

Aims: The associations between increased glycated albumin (GA) in the serum and diabetic complications and mortality have been revealed in the general population. However, less is known regarding the prognostic value of GA in patients diagnosed with acute coronary syndrome (ACS). Methods: In this study, all patients admitted for ACS who underwent a successful percutaneous coronary intervention (PCI) at our center from January 2018 to February 2019 were retrospectively examined. Clinical characteristics, laboratory results (e.g., serum GA levels), and procedural details were collected. The primary outcome included a composite of major adverse cardio-cerebral events (MACCE), such as death, myocardial infarction, stroke, and unplanned revascularization. The association between serum GA levels and clinical outcomes was tested in three multivariable models using Cox proportional hazard analysis. Subgroup analysis was performed in patients who were diagnosed with diabetes versus patients without diabetes. Results: A total of 1,806 ACS patients (mean age of 59.4 years; 77.8% were men; 44.9% were diagnosed with diabetes) were enrolled in this study, where the majority exhibited unstable angina (81.6%) and showed preserved left ventricular systolic function. Patients in the high GA level group were commonly female and were more likely to have metabolic disorders and to exhibit severe CAD (all p ＜0.05). MACCE occurred in 126 patients (7.0%) during a mean follow-up time of 17.2 months. The cumulative risk of MACCE at the 18-month follow-up visit significantly increased in a stepwise fashion along with increased GA levels (log-rank p =0.018) in the serum. The association between serum GA levels and MACCE was further determined after adjusting traditional risk factors and hemoglobin A1c (HbA1c) (GA, per 1% increase: hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.06–1.13; GA, higher vs. lower tertial: HR 1.92, 95% CI 1.01–3.67). In a subgroup analysis, the prognostic role of serum GA only existed in diabetic patients, even when adjusting for traditional risk factors and HbA1c levels. Conclusions: Elevated GA levels in the serum were associated with poor intermediate-term outcomes in low-risk ACS patients who underwent PCI, especially in patients with preexisting diabetes.

Angiotensin Receptor Blocker and Neprilysin Inhibitor Suppresses Cardiac Dysfunction by Accelerating Myocardial Angiogenesis in Apolipoprotein E-Knockout Mice Fed a High-Fat Diet.

Materials and Methods Male apolipoprotein E-knockout mice fed a high-fat diet were divided into control (CTL), valsartan (30 mg/kg) (VAL), sacubitril (30 mg/kg) (SAC), and valsartan plus sacubitril (30 mg/kg each) (VAL/SAC) groups after 4 weeks of prefeeding and were subsequently treated for 12 weeks. Results The VAL/SAC group exhibited significantly higher serum brain natriuretic peptide levels; more subtle changes in left ventricular systolic diameter, fractional shortening, and ejection fraction, and significantly higher expression levels of natriuretic peptide precursor B and markers of angiogenesis, including clusters of differentiation 34, vascular endothelial growth factor A, and monocyte chemotactic protein 1, than the CTL group. Conclusions Valsartan plus sacubitril preserved left ventricular systolic function in apolipoprotein E-knockout mice fed a high-fat diet. This result suggests that myocardial angiogenic factors induced by ARNI might provide cardioprotective effects.

Changes in Left Ventricle Mechanics in Patients with Anderson - Fabry Disease under Enzyme Replacement Therapy

Background: Sixty percent of patients with Fabry disease (FD) have cardiovascular involvement at the time of diagnosis. Among patients with heart failure of all causes, about 50% show normal or preserved left ventricular systolic function. We reported the evolution and echocardiographic findings of five patients with Fabry disease before undergoing enzyme replacement therapy and after 48 months of follow-up. Method: Systolic and diastolic functions were assessed in 5 patients with FD using transthoracic echocar- diography. They were matched with echocardiography performed between 36 to 48 months after treatment was started. Results: At initial evaluation, heart failure symptoms were positive in 3 patients. No history of fainting or cardiac arrhythmia was found on the initial approach. The mean LVEF before ERT was 57.25 ± 3.3. After 48 months of follow-up we observed a significant change increased on the LVEF to 68.7 ± 4.2 (p=0.04). All patients had increased interventricular septum thickness (IVT). The mean relative parietal thickness decreased from 0.63 to 0.59, after 48 months. Patients with mutation c.971T>A were more likely to increase the RPT. If the patient was free of dialysis the RWT tends to decrease. Diastolic function assessment revealed significantly higher E velocities, E wave increase from 73.6 to 81 m sec (p=0.04). But E/A ratio did not change after 48 months of ERT (1 vs. 1.1, p=NS). Two patients had diastolic dysfunction before ERT. After 2 years, four patients have diastolic dysfunction grade II. Before starting enzyme replacement therapy, all strain measures were abnormal. However, it was observed that their measurements did not worsen after ERT was started. The left ventricular twist was assessed, finding a decrease in it with a mean pre-ERT of 10o ± 4 vs. 13.7o ± 2.5 at 48 months (normal value 20 ± 7.3°), this was not significant. Conclusion: After 2 years of follow-up, we found an improvement in LVEF, a decrease in the ventricular septum. We found no progression in diastolic dysfunction. Even though enzyme replacement therapy in Fabry has proven efficacy, there are very few evaluation and monitoring tools to assess its effects at the cardio- vascular level. Systolic function is affected only in the late stages of the disease, although the diastolic function is affected earlier, it does not vary greatly over time once ERT has started. We found that conventional parameters, ven- tricular mass and septum diameter are useful as a baseline evaluation.

Epicardial adipose tissue is associated with increased systolic pulmonary artery pressure in patients with chronic obstructive pulmonary disease.

Pulmonary hypertension (PHT) is one of the essential predictors of mortality in chronic obstructive pulmonary disease (COPD). It is thought that PHT is due to vasoconstriction secondary to hypoxia caused by airway obstruction in COPD patients; however, loss of capillary bed with emphysema, inflammation, and endothelial dysfunction may also play a role in the development of PHT. Epicardial adipose tissue (EAT) has a role as a metabolically active endocrine organ and secretes various proinflammatory cytokines. We hypothesized that EAT thickness in COPD patients might be associated with the systolic pulmonary arterial pressure (PAPs) level, and we aimed to test it. The present study included 129 consecutive patients with the diagnosis of COPD. All patients underwent transthoracic echocardiographic evaluation. The relationship between PAPs and EAT thickness was evaluated. Positive correlations with PAPs were reported with age, EAT, white blood cell (WBC) and GOLD grade score (range 0.197-0.275, P values 0.026 to 0.002), negative correlations with body-mass index (BMI), hyperlipidemia, FEV1 (% predicted) and pO2 (range -0.216 to -0.340, P values .014 to <.001). In stepwise linear regression analysis, BMI (P = .003), EAT (P = .002), WBC (P = .001), and FEV1 (% predicted) (P = .010), were independently associated with PAPs. EAT thickness in COPD patients with preserved left ventricular systolic function is associated with increased PAPs, and this association is independent of the parameters indicating the severity of COPD.

Value of a comprehensive exercise echocardiography assessment for patients with hypertrophic cardiomyopathy

Background: Exercise echocardiography (ExE) may assess left ventricular (LV) systolic and diastolic function, LV outflow tract (LVOT) obstruction, and mitral regurgitation (MR). We aimed to evaluate the prognostic value of these assessments during exercise in patients with hypertrophic cardiomyopathy (HCM).Methods: LV systolic function, LV-derived filling pressures, LVOT gradients, and MR were prospectively evaluated during treadmill ExE in 285 patients with HCM and preserved LV ejection fraction (EF) (≥50%). Recordings were obtained at rest and peak exercise for LV systolic function and at rest and post-exercise for LVOT gradients, MR, and ratio of early LV inflow velocity to early tissue Doppler annulus velocity (E/e´).Results: Thirty-seven patients (13%) had LVOT obstruction at rest, and 76 (27%) developed exercise-induced LVOT obstruction. New wall motion abnormalities were detected in 38 patients (13%). E/e´>14 was observed in 129 patients at rest (45%) and in 134 at post-exercise (47%). Corresponding figures for significant MR (moderate or severe) were 21 (7%) and 17 (6%). During follow-up (3.9 ± 2.5 years), 27 patients had a hard event, 39 a combined event (hard plus new atrial fibrillation or syncope), and 58 a combined event or intervention. Exercise electrocardiographic testing, exercise LVEF, and the combination of positive ExE and increased E/e´ with exercise predicted outcome. The worst event rate corresponded to patients with raised E/e’ values at post-exercise and positive ExE (annualized hard event-rate of 5.9%).Conclusions: A comprehensive assessment during ExE is feasible for patients with HCM and preserved LV systolic function, and provides significant incremental prognostic information.

Prognostic Markers and Long-Term Outcomes After Aortic Valve Replacement in Patients With Chronic Aortic Regurgitation.

BackgroundThe objectives of the present study were (1) to evaluate the echocardiographic prognostic factors associated with improved left ventricular (LV) systolic function after aortic valve replacement, and (2) to compare the long‐term outcomes after aortic valve replacement in chronic aortic regurgitation (AR) patients with or without LV dysfunction.Methods and ResultsA total of 280 patients who underwent aortic valve replacement because of chronic aortic regurgitation were studied. Patients with reduced LV systolic function (LV ejection fraction [LVEF] <50%; group reduced LVEF [rEF]; N=80) were compared with those with preserved LV systolic function (LVEF ≥50%; group preserved LVEF; N=200). Postoperative clinical outcomes, overall survival, and freedom from cardiac death were compared. Postoperative echocardiographic examinations were reviewed, and changes in echocardiographic parameters were analyzed. The parameters related to LVEF improvement or normalization were evaluated, and risk factors affecting long‐term survival were identified. Follow‐up was complete in 100% of patients, with a median follow‐up of 104.8 months. Overall and cardiac mortality‐free survival rates at postoperative 10 years were 80.1% and 92.9% and 87.3% and 97.2% in groups rEF and preserved LVEF, respectively (P=0.036 and P=0.058, respectively). LVEF tended to decrease in the early postoperative period but improved thereafter in both groups. Preoperative early diastolic transmitral flow velocity/mitral annular tissue velocity ratio was a parameter of postoperative improvement or normalization of LVEF in all patients (area under the curve, 0.719; P=0.003) and in group rEF patients (area under the curve, 0.726; P=0.011) with a cutoff value of 12.73. Preoperative early diastolic transmitral flow velocity/mitral annular tissue velocity ratio also was the parameter of overall survival in all patients (hazard ratio [HR], 1.08; P=0.001) and in group rEF patients (HR, 1.08; P=0.005).ConclusionsLong‐term outcomes and survival after aortic valve replacement were related to preoperative LV function in patients with chronic aortic regurgitation. Preoperative early diastolic transmitral flow velocity/mitral annular tissue velocity ratio was correlated with the postoperative improvement or normalization of LVEF and long‐term survival, especially in group rEF patients.

Three-dimensional guided selective right ventricular septal pacing preserves ventricular systolic function and synchrony in pediatric patients

Nonfluoroscopic 3-dimensional (3D) electroanatomic mapping systems (EAMs) have been developed to guide cardiac catheter navigation and reduce fluoroscopy. Selective right ventricular (RV) septal pacing could prevent pacing-induced left ventricular (LV) dysfunction. The purpose of this study was to determine whether EAM-guided selective RV septal pacing preserves LV contractility/synchrony in pediatric patients with complete atrioventricular block (CAVB) and no other congenital heart defects. Prospective analysis of children/adolescents who underwent EAM-guided selective RV pacing was performed. A 3D pacing map guided ventricular lead implantation at septal sites with narrow paced QRS. Serial echocardiograms were obtained after pacemaker implantation to monitor for function (volumes, ejection fraction [EF], global longitudinal/circumferential strain) and synchrony (interventricular mechanical delay, septal to posterior wall motion delay, systolic dyssynchrony index). Data are reported as median (25th-75th percentile). Thirty-two CAVB patients (age 9.8 [7.0-14.0] years; 11 with a previous pacing system) underwent selective RV septal pacing (13 DDD, 19 VVIR pacemaker; midseptum 22, parahisian 7, RV outflow tract 3) with narrow paced QRS (110 [100-120] ms) and low radiation exposure. Follow-up over 24 (5-33) months showed preserved LV function and synchrony, without significant differences between pacing sites (midseptum-parahisian) and mode (VVIR-DDD). EF decreased after implantation in patients without previous pacing, although values were mainly within normal limits. Three parahisian patients underwent early lead repositioning. EAM-guided selective RV septal pacing is a feasible technique associated with preserved LV systolic function and synchrony and low radiation exposure in pediatric patients with CAVB.

Evaluation of diastolic function in newly diagnosed hyperthyroid patients with preserved left ventricular systolic function.

BackgroundDiastolic dysfunction has been reported as a cardiovascular effect of hyperthyroidism, and is also supposed to be a cause of heart failure manifestations in the patients with preserved ejection fraction (EF).MethodsFor evaluation of diastolic function in hyperthyroid patients and also diastolic function during performing exercise stress echocardiography, we conducted this study on 25 newly diagnosed hyperthyroid patients compared to 26 healthy subjects as control group. Diastolic function of the patients at rest was assessed using these parameters as follows: left atrium volume index, tricuspid regurgitation (TR) velocity, mitral inflow early diastolic flow (E wave), tissue Doppler of mitral annular velocity (e′), E/e′ ratio, and isovolumic relaxation time (IVRT); and during exercise stress echocardiography, we judged diastolic response by measuring E/e′ ratio and TR velocity at the peak of stress.ResultsThe mean age of the patients was 39.64 ± 12.23 years old and 52% of them were female. History of exertional dyspnea was found in 64% of patients. All the patients had normal diastolic function at the time of resting and there was no significant difference in diastolic parameters between the two groups except for IVRT, which was lower in hyperthyroid patients. Interestingly, no patients developed diastolic dysfunction during exercise stress echocardiography.ConclusionOur finding did not show diastolic dysfunction in hyperthyroid patients neither at rest nor during exercise echocardiography and did not support the hypothesis that diastolic dysfunction can be a cause of exertional intolerance and dyspnea in the patients with preserved EF.

Risk stratification refinement and implantable cardioverter defibrillator protection for the coronary artery disease patients with a preserved left ventricular systolic function with a two-step programmed ventricular stimulation-inclusive approach.

Risk stratification refinement and implantable cardioverter defibrillator protection for the coronary artery disease patients with a preserved left ventricular systolic function with a two-step programmed ventricular stimulation-inclusive approach.

Unusual Case of Hepatic Sinusoidal Obstruction Syndrome Induced By Low Dose Oral Cyclophosphamide

Hepatic sinusoidal obstruction syndrome (SOS) has been reported in patients receiving high dose intravenous (IV) cyclophosphamide especially as a part of preparative regimen for hematopoietic stem cell transplantation. Hepatic SOS from low dose oral cyclophosphamide has not been reported. Here we present a rare case of hepatic SOS induced by low dose oral cyclophosphamide. A 78-year-old male with history of coronary artery disease status post coronary artery bypass graft (CABG) was initially seen in hematology clinic for evaluation of normocytic anemia. During workup, bone marrow biopsy revealed NK cell large granular lymphocytic leukemia (LGL). He was then started on low dose oral cyclophosphamide 50 mg daily. After 2 months, his dose was reduced to 25 mg daily due to severe neutropenia. He then tolerated cyclophosphamide well and his hemoglobin (Hb) improved from his baseline 8 gm/dl to 12 gm/dl in 4 months. After 6 months of treatment, he was admitted to the hospital for abdominal distension, ascites and 15 pounds weight gain over 3 weeks. Labs most prominent on admission were Hb of 12.5 gm/dL , WBC 5.3 x 103/µL, Platelets 197 x 103/µL, total bilirubin 1.6 mg/dL, aspartate aminotransferase (AST) 89 U/L , alanine aminotransferase (ALT) 35 U/L and alkaline phosphatase (ALP) 283 U/L. Workup of ascites included abdominal paracentesis which revealed serum ascites albumin gradient(SAAG) &amp;lt;1.1 and fluid cytology was negative for carcinoma. Ultrasound of abdomen showed diffuse parenchymal heterogeneity and increased echogenicity of liver with patent hepatic vessels with normal direction of blood flow. Echocardiogram revealed preserved left ventricular systolic function with estimated left ventricular ejection fraction of 60%. He then underwent transjugular liver biopsy which revealed chronic lymphoproliferative disorder of NK cells, prominent centrilobular sinusoidal dilatation and congestion, lobular disarray, cholestasis and sinusoidal fibrosis suggestive of veno-occlusive disease secondary to drug/toxin induced liver injury. The Naranjo adverse drug reaction probability scale indicated a probable relationship between hepatic SOS and cyclophosphamide. Cyclophosphamide was held. Bone marrow biopsy showed the patient was in remission. His liver enzymes are improving and hematologic counts continue to be stable while on observation. High dose of IV cyclophosphamide given as myeloablative therapy in combination of total body irradiation or busulfan (or other agents) in preparation for hematopoietic stem cell transplantation can induce hepatic SOS, which can be severe leading to acute liver failure and death. The diagnosis is usually based on clinical features of tender hepatomegaly, weight gain, ascites and jaundice. Liver biopsy is usually diagnostic. Mechanism of injury is related to direct toxic effects of cyclophosphamide on sinusoidal cells in the liver, causing their necrosis and release into the sinusoids, obstruction and obliteration of hepatic veins. This case demonstrates that hepatic SOS can also be caused by low dose oral cyclophosphamide. Given this rare occurrence, it is prudent for the clinicians to keep an open mind and consider hepatic SOS as a potential side effect even with oral cyclophosphamide. Disclosures Yacoub: Novartis: Speakers Bureau; Agios: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Hylapharm: Current equity holder in private company; Cara Therapeutics: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Dynavax: Current equity holder in publicly-traded company; Roche: Other: Support of parent study and funding of editorial support.

Impact of baseline feature tracking multi-detector row computed tomography-derived left ventricular global longitudinal strain on left ventricular functional recovery in TAVI patients

Abstract Background Advances in left ventricular (LV) analysis with dynamic multi-detector row computed tomography (MDCT) permit measurement of LV global longitudinal strain (GLS) and have shown their impact on risk stratification of patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Purpose To evaluate the influence of baseline feature tracking (FT) MDCT- derived LV GLS on LV functional recovery in severe AS patients undergoing TAVI. Methods A total of 194 patients with severe AS (50% male, 80±7 years) with dynamic MDCT data allowing LV GLS measurement with a novel FT algorithm and having complete echocardiography evaluation at baseline, at 3–6 months and at 1 year follow-up were evaluated. FT MDCT-derived LV GLS was measured at baseline and the study population was divided according to a cut-off value of MDCT LV GLS −14% (≤−14% [more preserved LV systolic function] vs. &amp;gt;−14% [more impaired LV systolic function]). Results Transthoracic echocardiography (TTE)-derived Left ventricular ejection fraction (LVEF) increased over time in both groups: in patients with preserved and reduced MDCT LV GLS, and reached a higher value in patients with preserved MDCT LV GLS (52±7% at baseline, 55±7% at 3–6 months, 58±7% at 1 year follow-up vs. 43±10% at baseline, 49±10% at 3–6 months, 53±11% at 1 year follow-up; p=0.016) (Figure 1). TTE-derived LV GLS also showed greater improvement for patients with preserved MDCT LV GLS (−17±3% at baseline, −18±3% at 3–6 months, −20±3% at 1 year follow-up vs. −12±3% at baseline, −15±3% at 3–6 months, −16±3% at 1 year follow-up; p=0.027) (Figure 1). Conclusions In severe AS patients treated with TAVI, LV function improves significantly at 3–6 and at 12 months' follow-up and shows superior recovery in patients with more preserved baseline MDCT LV GLS, suggesting that MDCT-derived LV GLS has an important impact on LV functional recovery after TAVI. Funding Acknowledgement Type of funding source: None

Sex-related differences in cardiac and myofilament function in rats with pressure-overload induced left ventricular hypertrophy

Abstract Introduction Recent findings indicate that sex is a major determinant of left ventricular (LV) structure in pressure overload (PO)-induced LV myocardial hypertrophy (LVH). However, data are scare regarding sex-related differences in LV function in case of PO-evoked LVH. Aim Hence, in the present study we aimed at comprehensively investigating sex-related functional differences on the global cardiac level and also on the myofilament level in PO-induced LVH. Method Abdominal aortic banding (AB) was carried out to induce chronic PO for 6 or 12 weeks in male and female rats. Age- and sex-matched sham-operated animals served as controls. The development of LVH was followed by serial echocardiography. The extent of cardiomyocyte hypertrophy and myocardial fibrosis were evaluated by histology. Cardiac function was assessed by pressure-volume analysis. Force measurement was carried out in permeabilized cardiomyocytes to compute myofilament function. Results At week 6, robust myocardial hypertrophy, concentric LV geometry and moderate interstitial fibrosis were detected in both male and female AB rats. This early stage of PO-induced LVH was associated with increased LV contractility (slope of end-systolic pressure-volume relationship [ESPVR, mmHg/μl]: 3.09±0.18 Male-AB-wk6 vs. 1.79±0.22 Male-Sham-wk6 P&amp;lt;0.05; 3.68±0.77 Female-AB-wk6 vs. 1.87±0.21 Female-Sham-wk6 P&amp;lt;0.05) and enhanced myofilament Ca2+ sensitivity in both sexes (pCa50: 5.86±0.01 Male-AB-wk6 vs. 5.73±0.02 Male-Sham-wk6 P&amp;lt;0.05; 5.94±0.03 Female-AB-wk6 vs. 5.73±0.01 Female-Sham-wk6 P&amp;lt;0.05). At week 6, the augmented LV contractility effectively counterbalanced the increased afterload in both male and female AB groups. Hence, ventricular-arterial coupling (VAC) was maintained and LV systolic function was preserved in the AB groups in both sexes. In contrast, at week 12, marked sex differences could be observed. At this later stage, LVH was characterized by eccentric remodeling and intensified collagen accumulation in male AB rats. The initial LV contractility augmentation (slope of ESPVR, mmHg/μl: 1.74±0.13 Male-AB-wk12 vs. 1.31±0.17 Male-Sham-wk12 n.s.) as well as the enhanced myofilament Ca2+ sensitivity (pCa50: 5.78±0.02 Male-AB-wk12 vs. 5.75±0.01 Male-Sham-wk12 n.s.) diminished, leading to impaired VAC and reduced LV systolic function. On the contrary, in female AB rats, cardiac contractility (ESPVR, mmHg/ μl: 3.97±0.50 Female-AB-wk12 vs. 2.08±0.17 Female-Sham-wk12 P&amp;lt;0.05) and myofilament Ca2+ sensitivity (pCa50:5.85±0.02 Female-AB-wk12 vs. 5.78±0.01 Female-Sham-wk12 P&amp;lt;0.05) remained increased, resulting in adequate VAC and preserved LV systolic function at late-stage of PO-induced LVH as well. Conclusion The initially augmented LV contractility and enhanced myofilament Ca2+ sensitivity declines in male but not in female AB rats at later time points. Hence, characteristically different alterations occur in LV systolic function between the two sexes in late-stage of PO-evoked LVH. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NVKP_16-1-2016-0017.

Association between insulin resistance and left ventricular diastolic dysfunction in non-diabetic general population

Abstract Background Insulin resistance due to visceral fat accumulation plays a central role in the development of diabetic mellitus and subsequent cardiovascular disease. Abdominal obesity and diabetic mellitus are associated with the progression of left ventricular diastolic dysfunction which is the major structural abnormality in patients with heart failure. However, whether insulin resistance influences left ventricular diastolic dysfunction in non-diabetic subjects is unclear. Purpose In this study, we aimed to clarify the association between insulin resistance and left ventricular diastolic dysfunction in non-diabetic general population. Methods We examined 2,572 non-diabetic subjects with preserved left ventricular systolic function (ejection fraction ≥50%) and without a past history of diabetic mellitus, heart failure, coronary artery disease, atrial fibrillation, stroke, moderate to severe valvular disease, who underwent medical check-ups at the University of Tokyo Hospital from January 2009 to December 2018. Diabetes mellitus was defined as fasting glucose level ≥126 mg/dL or a subject's use of oral antidiabetic medications or insulin. We calculated the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) score [HOMA-IR = fasting glucose (mg/dL) × insulin (μU/mL) / 405], and defined insulin resistance as HOMA-IR ≥2.5. Left ventricular diastolic function was assessed by echocardiography, using tissue doppler analysis (E/E' ratio in septal and lateral). Visceral adiposity was assessed as visceral fat volume measured by computed tomography scanner. Results Mean age was 53.3±9.8 years, and 1,746 subjects (67.9%) were male. Overall, HOMA-IR was 1.1 on average, and HOMA-IR ≥2.5 was observed in 5.0% of study population. BMI and the prevalence of obesity were higher in subjects with HOMA-IR ≥2.5 than in those without. There was no significant difference in left ventricular ejection fraction between HOMA-IR ≥2.5 and ≤2.5. E/E' ratio in septal and lateral were higher in subjects with HOMA-IR ≥2.5 than in those without. Multivariable logistic regression analysis demonstrated that obesity and waist circumference, visceral fat volume were independently associated with HOMA-IR ≥2.5, however, age, hypertension, hypercholesterolemia were not. Further, multiple regression analysis including insulin resistance, age, male gender, obesity, hypertension, hypercholesterolemia, cigarette smoking and visceral fat volume, showed that insulin resistance was an independent determinant of increasing E/E' in both septal and lateral, whereas visceral fat volume was not (Figure 1). Conclusion The results of the present study suggest that insulin resistance due to visceral fat accumulation might be associated with the development of left ventricular diastolic dysfunction in non-diabetic general population without overt cardiovascular disease. Figure 1 Funding Acknowledgement Type of funding source: None

Elevation of high-sensitivity cardiac troponin T and left ventricular remodelling in hypertrophic cardiomyopathy.

AimsHypertrophic cardiomyopathy (HCM) is generally associated with mild disability and normal life expectancy. On the other hand, once the end‐stage phase of HCM characterized by left ventricular (LV) ejection fraction < 50% is established, patients with this subtype have a poor prognosis. This study clarifies the clinical parameters associated with progression to end‐stage HCM.Methods and resultsWe retrospectively studied 157 HCM patients (age 59.9 ± 14.2 years, 104 men) with preserved LV systolic function in whom subsequent echocardiographic data were obtained for a period of >1 year. HCM progressed to end‐stage HCM in 13 patients (8.3%) of the 157 patients during a mean follow‐up period of 6.3 ± 2.8 years. Compared with patients who did not reach end‐stage HCM at the last evaluation, patients with progression to the end‐stage phase had lower ejection fraction, larger LV size, more enlarged left atrial diameter, longer follow‐up period, and higher frequency of an elevated concentration of high‐sensitivity cardiac troponin T (hs‐cTnT; >0.014 ng/mL) at registration. Multivariate analysis revealed that elevated hs‐cTnT was a significant predictor independent of lower LV ejection fraction for progression to end‐stage HCM. Furthermore, in patients with elevated hs‐cTnT levels, LV ejection fraction became significantly lower, LV end‐diastolic diameter increased, and LV wall thickness decreased during the follow‐up period, whereas those parameters did not change in the normal hs‐cTnT group.ConclusionsIn patients with HCM, an elevated hs‐cTnT was associated with progression of LV remodelling, and this biomarker can be useful for predicting progression to the end‐stage phase.

Characterization of left ventricular myocardial sodium-glucose cotransporter 1 expression in patients with end-stage heart failure

BackgroundWhereas selective sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently showed cardiovascular protective effects in large outcome trials independent of the presence of type 2 diabetes mellitus (T2DM), the cardiovascular effects of dual SGLT1/2 inhibitors remain to be elucidated. Despite its clinical relevance, data are scarce regarding left ventricular (LV) SGLT1 expression in distinct heart failure (HF) pathologies. We aimed to characterize LV SGLT1 expression in human patients with end-stage HF, in context of the other two major glucose transporters: GLUT1 and GLUT4.MethodsControl LV samples (Control, n = 9) were harvested from patients with preserved LV systolic function who went through mitral valve replacement. LV samples from HF patients undergoing heart transplantation (n = 71) were obtained according to the following etiological subgroups: hypertrophic cardiomyopathy (HCM, n = 7); idiopathic dilated cardiomyopathy (DCM, n = 12); ischemic heart disease without T2DM (IHD, n = 14), IHD with T2DM (IHD + T2DM, n = 11); and HF patients with cardiac resynchronization therapy (DCM:CRT, n = 9, IHD:CRT, n = 9 and IHD-T2DM:CRT, n = 9). We measured LV SGLT1, GLUT1 and GLUT4 gene expressions with qRT-PCR. The protein expression of SGLT1, and activating phosphorylation of AMP-activated protein kinase (AMPKα) and extracellular signal-regulated kinase 1/2 (ERK1/2) were quantified by western blotting. Immunohistochemical staining of SGLT1 was performed.ResultsCompared with controls, LV SGLT1 mRNA and protein expressions were significantly and comparably upregulated in HF patients with DCM, IHD and IHD + T2DM (all P < 0.05), but not in HCM. LV SGLT1 mRNA and protein expressions positively correlated with LVEDD and negatively correlated with EF (all P < 0.01). Whereas AMPKα phosphorylation was positively associated with SGLT1 protein expression, ERK1/2 phosphorylation showed a negative correlation (both P < 0.01). Immunohistochemical staining revealed that SGLT1 expression was predominantly confined to cardiomyocytes, and not fibrotic tissue. Overall, CRT was associated with reduction of LV SGLT1 expression, especially in patients with DCM.ConclusionsMyocardial LV SGLT1 is upregulated in patients with HF (except in those with HCM), correlates significantly with parameters of cardiac remodeling (LVEDD) and systolic function (EF), and is downregulated in DCM patients with CRT. The possible role of SGLT1 in LV remodeling needs to be elucidated.

Left atrial myocardial function and compliance in pre-eclampsia with preserved left ventricular systolic and diastolic function.

Left atrial (LA) adaptive changes associated with pre-eclampsia (PE) have not been adequately addressed. This study aimed to evaluate the usefulness of LA myocardial function indices in detecting early cardiac alterations in PE. Using speckle tracking echocardiography (STE), LA volumetric and myocardial parameters were acquired in PE women with preserved left ventricular (LV) systolic and diastolic function based on standard criteria and normotensive controls. LA compliance was assessed by the ratio of reservoir strain (LASr) to the estimated LA pressure (E/e'). Subtle systolic and diastolic abnormalities were identified as LV global longitudinal strain < 17.8% and mitral tissue e' velocity < 7cm/s septal or < 10cm/s lateral, respectively. LASr/(E/e') was prior to other LA measurements in detecting early LA function changes in PE. The rate of LASr/(E/e') < 3 was significantly greater in the patients with subtle systolic impairments than those without (P < 0.05) in spite of similar proportion of LASr < 31% between them. Among PE women with subtle diastolic damages, the frequencies of anomaly and the values in both LASr/(E/e') and LASr were significantly different to those without (P < 0.05). Moreover, the rate of LASr/(E/e') < 3 was markedly higher than that of LASr < 31% in PE cases with subtle cardiac abnormalities (P < 0.05). In the setting of PE with preserved systolic and diastolic function, STE-derived LA strain and estimated LA compliance may be beneficial to identifying earlier cardiac alternations. LA compliance could outperform LASr in detecting cardiac anomalies earlier during a PE pregnancy with preserved LV performance.

Differential clinical impact of chronic total occlusion revascularization based on left ventricular systolic function

BackgroundThe effect of chronic total occlusion (CTO) revascularization on survival remains controversial. Furthermore, data regarding outcome differences for CTO revascularization based on left ventricular systolic function (LVSF) are limited.The differential outcomes from CTO revascularization in patients with preserved LVSF (PLVSF) versus reduced LVSF (RLVSF) were assessed.MethodsA total of 2,173 CTO patients were divided into either a PLVSF (n = 1661, Ejection fraction ≥ 50%) or RLVSF (n = 512, < 50%) group. Clinical outcomes were compared between successful CTO revascularization (SCR) versus optimal medical therapy (OMT) within each group. The primary endpoint was a composite of all-cause death or non-fatal myocardial infarction. Inverse probability of treatment weighting for endpoint analysis and a contrast test for comparison of survival probability differences according to LVSF were used.ResultsPatients with RLVSF had a mean 37% ejection fraction (EF) and 19% had EF < 30%. The median follow-up duration was 1,138 days. Regardless of LVSF, the primary endpoint incidence was significantly lower in patients treated with SCR [RLVSF: 29.7% vs. 49.7%, hazard ratio (HR) = 0.46, 95% confidence interval (CI): 0.36–0.62, p < 0.0001; PLVSF 7.3% vs. 16.9%, HR = 0.68, 95% CI: 0.54–0.93, p = 0.0019], which was mainly driven by a reduction in cardiac death. The difference in survival probability was greater and became more pronounced over time in patients with RLVSF than with PLVSF (1-year, p = 0.197; 3-years, p = 0.048; 5-years, p = 0.036).ConclusionsSCR was associated with better survival benefit than OMT regardless of LVSF. The benefit was greater and became more significant over time in patients with RLVSF versus PLVSF.Graphic abstract

Echocardiographic index E/e' in association with cerebral white matter hyperintensity progression.

Cerebral white-matter hyperintensities (WMHs) on MRI is associated with reduced compliance of the cerebral arterioles. We hypothesized that an echocardiography index for left ventricular (LV) diastolic function, E/e’, might reflect the cerebral arteriolar compliance and evaluated the association between E/e’ and long-term progression rate of the cerebral WMH volume. This retrospective study included individuals who were ≥ 50 years of age, with a preserved LV ejection fraction (≥ 50%) and neurological function status (modified Rankin scale score ≤1), and underwent initial and follow-up MRI evaluations within intervals of 34–45 months. Baseline clinical, laboratory, and echocardiography markers such as ejection fraction, LV mass index, and E/e' were obtained. WMH volume progression rate between the baseline and follow-up MRIs was designated as the outcome factor. 392 individuals (57.1% men; mean age: 66.7±8.4 years) were followed-up for 38.2±3.4 months. The mean WMH volume progression rate was 1.35±2.65 mL/year. The log-transformed value of WMH volume progression rate was linearly associated with the log-transformed E/e’ (B coefficient = 0.365; 95% confidence interval [CI] 0.180−0.551; P = 0.001), along with the log-transformed values of baseline WMH volume (B = 0.142; 95% CI 0.106−0.179; P<0.001) and glomerular filtration rate (B = -0.182; 95% CI -0.321−0.044; P = 0.010). Additionally, a subgroup with an E/e’ ≥15 exhibited a significantly higher WMH progression rate compared to the subgroups with lower E/e’ values (P<0.001), especially in the lower quartiles (quartiles 1 and 2) of the baseline WMH volume. We concluded that echocardiographic marker E/e’ is associated with the long-term progression rate of cerebral WMHs in population with preserved LV systolic function.

Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials.

Revascularization is often performed in patients with stable ischemic heart disease. However, whether revascularization reduces death and other cardiovascular outcomes is uncertain. We conducted PUBMED/EMBASE/Cochrane Central Register of Controlled Trials searches for randomized trials comparing routine revascularization versus an initial conservative strategy in patients with stable ischemic heart disease. The primary outcome was death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), heart failure, stroke, unstable angina, and freedom from angina. Trials were stratified by percent stent use and by percent statin use to evaluate outcomes in contemporary trials. Fourteen randomized clinical trials that enrolled 14 877 patients followed up for a weighted mean of 4.5 years with 64 678 patient-years of follow-up fulfilled our inclusion criteria. Most trials enrolled patients with preserved left ventricular systolic function and low symptom burden, and excluded patients with left main disease. Revascularization compared with medical therapy alone was not associated with a reduced risk of death (relative risk [RR], 0.99 [95% CI, 0.90-1.09]). Trial sequential analysis showed that the cumulative z-curve crossed the futility boundary, indicating firm evidence for lack of a 10% or greater reduction in death. Revascularization was associated with a reduced nonprocedural MI (RR, 0.76 [95% CI, 0.67-0.85]) but also with increased procedural MI (RR, 2.48 [95% CI, 1.86-3.31]) with no difference in overall MI (RR, 0.93 [95% CI, 0.83-1.03]). A significant reduction in unstable angina (RR, 0.64 [95% CI, 0.45-0.92]) and increase in freedom from angina (RR, 1.10 [95% CI, 1.05-1.15]) was also observed with revascularization. There were no treatment-related differences in the risk of heart failure or stroke. In patients with stable ischemic heart disease, routine revascularization was not associated with improved survival but was associated with a lower risk of nonprocedural MI and unstable angina with greater freedom from angina at the expense of higher rates of procedural MI. Longer-term follow-up of trials is needed to assess whether reduction in these nonfatal spontaneous events improves long-term survival.

Normoxic re-oxygenation ameliorates end-organ injury after cardiopulmonary bypass

BackgroundIn a rabbit model of cardiopulmonary bypass (CPB) and cardioplegic arrest, we previously showed that hyperoxic myocardial reperfusion was associated with increased left ventricular (LV) systolic dysfunction and myocardial injury compared with normoxic reperfusion. The aim of this study was to evaluate in our experimental model the impact of post-CPB reperfusion conditions on other organs potentially vulnerable to ischemic injury such as the brain and kidney.MethodsAfter 60 min of CPB, aortic cross-clamp, and cold cardioplegic arrest, rabbits were reperfused under hyperoxic or normoxic conditions for 120 min. Left ventricular systolic contractility (LV + dP/dt) and diastolic relaxation (LV –dP/dt) were continuously recorded, and end-organ injury was assessed by measuring circulating biomarkers specific for kidney (cystatin C and creatinine) and brain injury [S100B and neuron specific enolase (NSE)]. At completion of the protocol, kidney and brain tissues were harvested for measuring oxidant stress (OS), inflammation and apoptosis.ResultsFollowing aortic cross-clamp removal, rabbits exposed to normoxic reperfusion demonstrated preserved LV systolic and diastolic function compared with hyperoxic reperfusion (LV + dP/dt: 70 ± 14% of pre-CPB vs. 36 ± 21%, p = 0.018; LV -dP/dt: 72 ± 36% of pre-CPB vs. 33 ± 20%, p = 0.023). Similarly, CPB increased plasma creatinine, S100B and NSE that were significantly attenuated by normoxic reperfusion compared with hyperoxic reperfusion (creatinine: 4.0 ± 0.5 vs. 7.1 ± 0.8 mg/dL, p = 0.004; S100B: 4.0 ± 0.8 vs. 6.7 ± 1.0 ng/mL, p = 0.047; NSE: 57.7 ± 6.8 vs. 101.3 ± 16.1 pg/mL, p = 0.040). Furthermore, both kidney and brain tissues showed increased mRNA expression and activation of pathways for OS, inflammation, and apoptosis, that were reduced under normoxic compared with hyperoxic conditions.ConclusionsNormoxic reperfusion ameliorates cardiac, renal and neural injury compared with hyperoxic reperfusion in an in vivo animal model of CPB and cardioplegic arrest. This protective effect of normoxic reperfusion may be due to a reduction in signaling pathways for OS, inflammation, and apoptosis.