Left Ventricular Diastolic Dimension Research Articles

Echocardiographic prognostication of new onset heart failure in a cohort of ischemic heart disease patients

Background Echocardiographic predictors for new onset heart failure in patients with ischemic heart disease with reduced left ventricular ejection fraction (HFrEF) or with preserved left ventricular ejection fraction (HFpEF) in Ethiopian and Sub-Saharan African is not well-known. Methods Two hundred twenty-eight patients with ischemic heart disease were retrospectively recruited and followed. Analysis on baseline clinical and echocardiographic characteristics of patients, and risk factors for new onset HFpEF and new onset HFrEF were done. The exclusion criteria were known heart failure at baseline and those who did not have echocardiography data. Results During the follow up period, heart failure developed in 62.2% (61/98) of ischemic heart disease patients with preserved left ventricular ejection fraction and in 70.1% (92/130) of ischemic heart disease patients with reduced left ventricular ejection fraction. We did not find significant difference between HFrEF and HFpEF in time to new onset heart failure. Systolic blood pressure, diastolic blood pressure, diabetes, left atrium and diastolic left ventricular dimension had significant association with new onset HFrEF on univariate regression analysis. Whereas new onset HFpEF was significantly associated with age, sex, presence of hypertension, Systolic blood pressure and diastolic left ventricular dimension. On cox regression analysis diastolic left ventricular dimension was associated with both new onset HFpEF and HFrEF. Age, diabetes, and dimension of left atrium were also associated with HFrEF. Conclusion This cohort study in ischemic heart disease patients suggests a key role for the diastolic left ventricular dimension, left atrium size, diabetes, sex and age as predictors of new onset HFrEF and HFpEF. Strategies directed to prevention and early treatment of diabetes, dilatation of left ventricle and left atrium may prevent a considerable proportion of HFrEF or HFpEF.

Predicting outcome in children with dilated cardiomyopathy: the use of repeated measurements of risk factors for outcome.

AimsWe aimed to determine whether in children with dilated cardiomyopathy repeated measurement of known risk factors for death or heart transplantation (HTx) during disease progression can identify children at the highest risk for adverse outcome.Methods and resultsOf 137 children we included in a prospective cohort, 36 (26%) reached the study endpoint (SE: all‐cause death or HTx), 15 (11%) died at a median of 0.09 years [inter‐quartile range (IQR) 0.03–0.7] after diagnosis, and 21 (15%) underwent HTx at a median of 2.9 years [IQR 0.8–6.1] after diagnosis. Median follow‐up was 2.1 years [IQR 0.8–4.3]. Twenty‐three children recovered at a median of 0.6 years [IQR 0.5–1.4] after diagnosis, and 78 children had ongoing disease at the end of the study. Children who reached the SE could be distinguished from those who did not, based on the temporal evolution of four risk factors: stunting of length growth (−0.42 vs. −0.02 length Z‐score per year, P < 0.001), less decrease in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) (−0.26 vs. −1.06 2log pg/mL/year, P < 0.01), no decrease in left ventricular internal diastolic dimension (LVIDd; 0.24 vs. −0.60 Boston Z‐score per year, P < 0.01), and increase in New York University Pediatric Heart Failure Index (NYU PHFI; 0.49 vs. −1.16 per year, P < 0.001). When we compared children who reached the SE with those with ongoing disease (leaving out the children who recovered), we found similar results, although the effects were smaller. In univariate analysis, NT‐proBNP, length Z‐score, LVIDd Z‐score, global longitudinal strain (%), NYU PHFI, and age >6 years at presentation (all P < 0.001) were predictive of adverse outcome. In multivariate analysis, NT‐proBNP appeared the only independent predictor for adverse outcome, a two‐fold higher NT‐proBNP was associated with a 2.8 times higher risk of the SE (hazard ratio 2.78, 95% confidence interval 1.81–3.94, P < 0.001).ConclusionsThe evolution over time of NT‐proBNP, LVIDd, length growth, and NYU PHFI identified a subgroup of children with dilated cardiomyopathy at high risk for adverse outcome. In this sample, with a limited number of endpoints, NT‐proBNP was the strongest independent predictor for adverse outcome.

Risk factors for new-onset heart failure with reduced or preserved ejection fraction in patients with ischemic heart disease: A cohort study

Background: Risk factors for heart failure (HF) with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF) in Ethiopian and Sub-Saharan African patients with ischemic heart disease (IHD) is not well-known. Methods: This is a cohort study where 228 patients with IHD were recruited and followed retrospectively over 24 months period. Exclusion criteria were known HF at baseline and absence of echocardiography data. From baseline clinical and echocardiographic patient characteristics, risk factors for incident HFpEF and incident HFrEF were analyzed. Results: New-onset HF was diagnosed in 67.1% (153/228) of the patients. Median time to HF diagnosis was 12.02 (3.42–13.31) months in HFrEF and 12.06 (2.66–15.28) months in HFpEF. There was no significant difference between HFrEF and HFpEF in time to incident HF. On univariate regression analysis risk factors for incident total HF were age, diabetes, and left atrium (LA) size. Diabetes, systolic blood pressure (SBP), diastolic blood pressure, LA and diastolic left ventricular dimension (LVD) had significant association with HFrEF. Age, sex, hypertension, SBP, and diastolic LVD were significantly associated with HFpEF. On cox regression analysis diabetes and LA dimension were associated with total HF while diastolic LVD was associated with incident HFpEF and HFrEF. Age, diabetes, and dimension of LA were also associated with HFrEF. Conclusion: These data suggest a major role for age, sex, diabetes, bigger LA size, and diastolic LVD as predictors of HFrEF and HFpEF in patients with IHD. Strategies directed to prevention and treatment of diabetes, dilatation of left ventricle and LA may prevent a considerable proportion of HFrEF or HFpEF.

Soluble Receptor for Advanced Glycation End-products regulates age-associated Cardiac Fibrosis.

Myocardial aging increases the cardiovascular risk in the elderly. The Receptor for Advanced Glycation End-products (RAGE) is involved in age-related disorders. The soluble isoform (sRAGE) acts as a scavenger blocking the membrane-bound receptor activation. This study aims at investigating RAGE contribution to age-related cardiac remodeling.We analyzed the cardiac function of three different age groups of female Rage-/- and C57BL/6N (WT) mice: 2.5- (Young), 12- (Middle-age, MA) and 21-months (Old) old. While aging, Rage-/- mice displayed an increase in left ventricle (LV) dimensions compared to age-matched WT animals, with the main differences observed in the MA groups. Rage-/- mice showed higher fibrosis and a larger number of α-Smooth Muscle Actin (SMA)+ cells with age, along with increased expression of pro-fibrotic Transforming Growth Factor (TGF)-β1 pathway components. RAGE isoforms were undetectable in LV of WT mice, nevertheless, circulating sRAGE declined with aging and inversely associated with LV diastolic dimensions. Human cardiac fibroblasts stimulated with sRAGE exhibited a reduction in proliferation, pro-fibrotic proteins and TGF-beta Receptor 1 (TGFbR1) expression and Smad2-3 activation. Finally, sRAGE administration to MA WT animals reduced cardiac fibrosis.Hence, our work shows that RAGE associates with age-dependent myocardial changes and indicates sRAGE as an inhibitor of cardiac fibroblasts differentiation and age-dependent cardiac fibrosis.

A retrospective study of 14 dogs with advanced heart failure treated with loopdiuretics and hydrochlorothiazide.

Background:The use of thiazide diuretics is recommended in the American College of Veterinary Internal Medicine guidelines for advanced heart failure due to mitral insufficiency (MI) in dogs. However, there are no large-scale reports of the use of thiazide diuretics in dogs with advanced heart failure.Aim:This retrospective study evaluated the therapeutic effect of concomitant hydrochlorothiazide (HTCZ) with loop diuretics in dogs with heart failure.Methods:The study included 14 dogs diagnosed with advanced pulmonary edema with MI at two facilities. In all cases, high-dose loop diuretics (torsemide; 0.78–4 mg/kg/day) did not improve pulmonary edema. The results of the echocardiography and renal function tests before and after the administration of HTCZ (0.2–0.84 mg/kg/day) in addition to torsemide were statistically compared.Results:The echocardiographic data demonstrated significant improvement in relation to cardiac stress; left atrium to the aorta ratio, normalized left ventricular internal dimension in diastole, and E wave velocity (m/s) after HTCZ administration. However, blood urea nitrogen and creatinine levels increased, and potassium levels decreased, indicating a decline in renal function following HTCZ administration.Conclusion:This study suggests that the administration of HTCZ in combination with loop diuretics may be beneficial during advanced heart failure due to MI in dogs. The results can also be extended to patients who are resistant to loop diuretics, resulting in the improvement of cardiac function. However, as the combination of HTCZ and loop diuretics can deteriorate renal function, caution should be exercised prior to making recommendations regarding its use, and renal function should be monitored.

Left ventricular outflow obstruction occurs immediately after exercise in patients with non-obstructive hypertrophic cardiomyopathy

We evaluated the hemodynamic and geometric determinants of latent obstruction (LO, trans-left ventricular outflow tract (LVOT) gradient ≥30 mmHg with provocation) in patients with non-obstructive hypertrophic cardiomyopathy (HCMP). A total of 35 patients with non-obstructive HCMP underwent stepwise supine bicycle exercise echocardiography. Trans-LVOT pressure gradients, mitral geometric parameters, left ventricular ejection fractions (LVEF) and left ventricular end-systolic and diastolic dimensions (LVESD, LVEDD) were measured at each stage. The highest peak LVOT pressure gradient predominantly occurred immediately after exercise (n = 32, 91.3%) rather than during peak exercise (n = 3, 8.7%). Significant LO developed in nine patients (25%). No significant differences were found in resting echocardiographic parameters. Compared to the remaining patients, however, patients with LO had longer residual mitral leaflets (defined as residual portions of leaflets after coaptation; 4 ± 4 vs. 13 ± 4 mm, respectively; p = 0.001) and higher resting LVOT pressure gradients (7.4 ± 3.7 vs. 12.9 ± 5.8 mmHg, respectively; p = 0.001). Substantial decreases in mitral annular diameters from peak exercise to recovery after exercise were observed in the LO group, while mitral annular diameters increased after exercise in the non-LO group. In conclusion, the highest peak LVOT pressure gradient predominantly occurred immediately after exercise rather than during peak exercise, regardless of LO. Abrupt decrease of mitral annular diameter immediately after exercise, a longer residual mitral leaflet and a higher resting LVOT pressure gradient at rest might be related to LO.

Nursing Measures of Microcirculation Disturbance in Emergency Patients with Acute Myocardial Infarction after Intervention

To explore the nursing measures taken for microcirculation disturbance in emergency patients with acute myocardial infarction after percutaneous coronary intervention. 100 cases of emergency acute myocardial infarction patients underwent percutaneous coronary intervention in our hospital from November 2017 to November 2019 were selected and randomly divided into the control group (50 cases) and the observation group (50 cases). The control group received routine nursing, while the observation group received targeted nursing measures on the basis of the control group. The incidence of microcirculation disturbance, left ventricular end diastolic dimension, left ventricular end systolic dimension, left ventricular ejection fraction and major adverse cardiac events were compared between the two groups. Compared with the control group (58.00 %), the incidence of microcirculation disturbance was significantly lower in the observation group (28.00 %) the difference was statistically significant (p<0.05). Compared with before nursing, left ventricular end diastolic dimension and left ventricular end systolic dimension in the two groups were significantly lower, left ventricular ejection fraction was significantly higher, the change range in the observation group was significantly greater than that in the control group and the differences were statistically significant (p<0.05). Compared with the control group (32.00 %), the incidence of mace in the observation group was significantly lower, and the difference was statistically significant (p<0.05). Active and effective nursing measures can not only effectively reduce the risk of microcirculation disturbance in emergency acute myocardial infarction patients after percutaneous coronary intervention, but also improve the cardiac function and reduce the incidence of mace, which is worthy of clinical reference.

Longitudinal Prediction of Transplant-Free Survival by Echocardiography in Pediatric Dilated Cardiomyopathy

BackgroundThe prognostic significance of serial echocardiography and its rate of change in children with dilated cardiomyopathy (DCM) is incompletely defined. MethodsWe retrospectively analysed up to 4 serial echocardiograms. Associations between mortality/transplant and echocardiographic parameters over time and between outcomes and the rate of change of echocardiographic parameters were analysed. Estimation of patient-specific intercepts and slopes was done using linear regression models. ResultsFifty-seven DCM children were studied (50% male; median age, 0.6 year; average follow-up, 2.1 ± 2.4 years). The median time to transplant or death was 2.0 years. Increased left ventricular (LV) diastolic (LVEDD) and systolic (LVESD) dimensions and myocardial performance index (MPI) were associated with increased mortality and transplant risk. Increased LV ejection fraction, mitral E-deceleration time, right ventricular (RV) fractional area change, and tricuspid annular plane systolic excursion were associated with reduced mortality and transplant risk. Transplant/mortality likelihood increased by 41.6% and 19.8% for each unit increase in LVEDD and LVESD z scores, respectively (LVEDD: hazard ratio [HR], 1.416; 95% confidence interval [CI], 1.285-1.560; P < 0.001; LVESD: HR, 1.198; 95% CI, 1.147-1.251; P < 0.001). A higher monthly change in LVESD z score increased transplant/mortality likelihood by 85.6% (HR, 1.856; 95% CI, 1.572-2.191; P = 0.015). Greater changes in mitral E/eʹ (HR, 0.707; 95% CI, 0.636-0.786; P < 0.001) and RV MPI (HR, 0.412; 95% CI, 0.277-0.613; P < 0.001) were associated with reduced mortality and transplant risk. ConclusionsLV and RV systolic and diastolic dimensions and function over time and their rate of change are associated with risk for transplant and mortality in childhood DCM. Serial changes in these parameters may be useful to predict clinical outcomes.

Two-dimensional echocardiographic measures of left ventricular dimensions agree with M-mode measurements in dogs

IntroductionClinicians measure left ventricular dimensions in dogs from both M-mode and two-dimensional images. Little information currently exists as to whether these two methods provide measurements similar enough to be interchangeable. AnimalsThe animals included in this study are 206 client-owned dogs: 68 healthy, 105 with myxomatous mitral valve disease, 33 with other cardiac or extracardiac disease. Materials and methodsInvestigators measured left ventricular diastolic and systolic dimensions from archived M-mode and two-dimensional images obtained from the right parasternal short-axis view. Agreement between the pairs of measurements was examined using limits of agreement (Bland-Altman) plots. ResultsLeft ventricular diastolic dimensions showed no fixed or proportional bias but did show heteroscedasticity. Ninety-five percent limits of agreement for normalized differences approximated ±10%; 95% of the absolute differences for any pair of measurements were <3.9 mm regardless of bodyweight and <2.7 mm for dogs <15 kg. Left ventricular systolic dimensions showed slight proportional bias, with two-dimensional measurements being progressively larger than M-mode measurements as ventricular size increased. Ninety-five percent limits of agreement for normalized differences approximated ±20%; 95% of the absolute differences for any pair of measurements were <4.6 mm regardless of bodyweight and <3.5 mm for dogs <15 kg. Mitral valve disease did not appreciably affect these findings. ConclusionsLeft ventricular internal dimensions in dogs with and without cardiac disease measured from two-dimensional right parasternal short-axis images are interchangeable with those measured from M-mode images using the same view.

Echocardiographic assessment of left ventricular size and systolic function in Warmblood horses using linear measurements, area-based indices, and volume estimates: A retrospective database analysis.

BackgroundEchocardiographic assessment of left ventricular (LV) size and function using area‐based indices and volumetric estimates is not well established in horses.ObjectiveTo report reference intervals and measurement variability for uni‐, 2‐, and 3‐dimensional echocardiographic indices of LV size and systolic function in Warmblood horses and to provide proof of concept for allometric scaling of variables to body weight. Unidimensional indices were to be compared to area‐based indices and LV volume estimates to establish their clinical use.AnimalsThirty healthy Warmblood horses and 70 Warmblood horses with a primary diagnosis of mitral regurgitation or aortic regurgitation.MethodsEchocardiographic indices of LV size and systolic function were measured using an existing echocardiography database. Weight‐related variables were scaled to body weight (BWT). Reference intervals and measurement variability were calculated, the influence of valvular regurgitation on LV size and function was investigated and agreement between different variables for detection of reduced, normal, and increased LV size and systolic function was assessed.ResultsReference values for healthy Warmblood horses were reported. Measurement variability was sufficiently low for clinical use of all variables. Allometric scaling was effective to correct diastolic LV dimensions and cardiac output for differences in BWT. Various echocardiographic indices resulted in different conclusions regarding identification of LV enlargement and systolic dysfunction in healthy horses and horses with valvular regurgitation.Conclusions and Clinical ImportanceEchocardiographic assessment of LV size and systolic function should include joint assessment of multiple uni‐ and multidimensional indices. Area‐based or volumetric indices that reflect LV long‐axis motion should be included.

Abstract 13898: A Comparison of Rate Control Agents in Patients With Atrial Fibrillation: Follow-up Investigation of Affirm Study

Introduction: There is limited data from randomized controlled trials comparing rate control agents in patients with atrial fibrillation (AF). We used patient-level data from the AFFIRM trial to compare outcomes in patients randomized to the rate control arm who were treated with a single rate control agent at baseline, including beta-blockers (BB), calcium channel blockers (CCB), or digoxin. Methods: Patient-level data from the AFFIRM trial was provided through the NHLBI BioLINCC biologic specimens and data repository information coordinating center. Different data sets were used to obtain the data for analysis. The independent variable for this analysis was the initial study drug used, which was classified as BB, CCB, or digoxin. The dependent variables were time to first hospitalization and time to death. Cox proportional hazards survival models were used to control for baseline differences between groups. Results: We analyzed 1144 out of 2027 participants assigned to the rate control group who were on a single rate control agent at the start of the trial. 485 (42.5%) participants were in the BB group, 344 (30%) in the CCB group, and 315 (27.5%) in the digoxin group. The mean age was 69.6 ± 8.0 and the majority of participants (62.9%) were male. Significant differences in baseline characteristics were present between groups, including sex, history of heart disease, left ventricular (LV) ejection fraction, LV diastolic dimension, and history of pulmonary disease. Hospitalization and death occurred in 55.9% and 12.5% of those in the BB group, 58.4% and 16.7% in the CCB group, and 55.2% and 21.1% in the digoxin group, respectively. After adjustment for differences in baseline characteristics, there were no significant differences in time to hospitalization or death for any group compared to another. Conclusions: In the AFFIRM trial, the initial rate control drug used was not associated with statistically significant differences in time to hospitalization or death after controlling for differences in baseline characteristics. There is limited data at present to guide the selection of rate control agents in patients with AF.

Abstract 15413: Building New Arteriogenic Therapy for Ischemic Cardiomyopathyusing Notch-induced Mesenchymal Stem Cell Patch

Introduction: The induction of arteriogenesis is a promising approach for treatment of ischemic cardiomyopathy. Notch signaling has been reported to be a key regulator of arteriogenesis. Hypothesis: We hypothesized that Notch-induced human mesenchymal stem cell (SB623) sheet transplantation would induce arteriogenesis in ischemic lesion, leading to improvement of left ventricular function in ischemic cardiomyopathy model rats. Methods: Two weeks after the ischemic induction, SB623-patches were transplanted to myocardial infarction model rats (SB group, n=10) or shame operations were performed (Control group, n=10). We evaluated cardiac performance and histology six weeks after the treatment in vivo. In vitro, we performed RNA-sequencing of human umbilical vein endothelial cells (HUVECs) cocultured with SB623s. Results: Left ventricular ejection fraction was significantly improved 6 weeks after SB623-sheets transplantation (LVEF, 52±7% vs. 34±5%, p&lt;0.001). Similarly, the attenuation of LV remodeling was observed at 6 weeks (LV diastolic dimension, 73±7 mm vs. 85±5 mm, p&lt;0.001). Histological findings revealed that fibrosis was decreased in SB group (11±1% vs. 22±4%, p=0.02). Furthermore, vWF-positive capillary vessels (vessels, 516±110 /mm 2 vs. 248±26 /mm 2 , p&lt;0.001) and αSMA- and vWF-positive arterioles with over 20μm diameter (arterioles, 25±8 /mm 2 vs. 6±3 /mm 2 , p=0.002) were significantly increased in SB group, suggesting the induction of angiogenesis and arteriogenesis. In vitro, whole transcriptome analysis showed that Notch signaling pathway was significantly upregulated (p&lt;0.001) in HUVECs co-cultured with SB623s. Similarly, pathway analysis revealed upregulated “fluid shear stress and atherosclerosis” pathway (p&lt;0.001) in vitro, suggesting an arteriogenic response of endothelial cell. In vivo study, upregulations of ephrin-B2 (p=0.03) and EphB4 (p=0.01) gene expressions in SB group were confirmed, indicating both arterial and venous remodeling induced by Notch signaling. Conclusions: SB623 patch transplantation induces arteriogenesis with functional recovery via Notch signaling in rat myocardial infarction model, proposing a new strategy for the treatment of ischemic cardiomyopathy.

Abstract 13868: Effects of Chronic Electronic Cigarette Vapor Exposures on the Cardiovascular Function in Rats

Background: We investigated the effects of chronic electronic cigarettes with nicotine (E-Cig) exposure on cardiovascular function in rats. Methods: Adult Sprague Dawley rats were exposed to either pure air (n=10) or E-Cig (n=14) for 12 weeks. After 12 weeks of exposure, flow-mediated vasodilation was measured in anesthetized rats with ultrasound to measure femoral artery diameter. Femoral artery flow velocity was measured before and 5 minutes after reperfusion of a 5-minute femoral artery occlusion. Cardiac function was assessed by echocardiogram. A Millar catheter was used to record systemic arterial and LV pressures. Cardiac output was measured using a themodilution catheter. Results: The femoral artery internal diameter and blood flow velocity were comparable between the 2 groups before and after artery occlusion. However, in the E-cig group, blood flow velocity significantly decreased from 55.5 ± 5.2 cm/s prior to occlusion to 41.3 ± 4.1 cm/s after reperfusion (p = 0.005); it remained similar prior to (47.8 ± 3.4 cm/s) and after (47.8 ± 5.5 cm/s) occlusion in the air group. There were no statistically significant differences in left ventricular diastolic and systolic dimensions, LV fractional shortening, heart rate or mean blood pressure (80 ± 3 mmHg in air and 79 ± 5 mmHg in E-cig group) , LV end-diastolic pressure (Ped), end-systolic pressure (Pes), peak -dP/dt, Tau, or cardiac output (48.3 ± 3.3 ml/min in air and 47.6 ± 3.9 ml/min in E-cig group) between the E-Cig and the pure air group. There was a trend toward a reduction in peak LV +dP /dt in the E-Cig group (5574 ± 341 mmHg/s) compared to the air group (6166 ± 238 mmHg/s). LV weight and wall thickness were similar between groups. Conclusions: Twelve weeks of E-Cig exposure did not affect heart rate or blood pressure; but did tend to reduce contractility. E-cigarette exposure slowed the flow-mediated blood flow velocity probably at a microvascular level, possibly by altering endothelial function.

Abstract 14254: Pharmacodynamic Effects of a Single Dose of CK-3773274 in Cats With Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) hypertrophy in the absence of known causes. HCM can be due to genetic mutations that affect sarcomeric proteins, leading to myocardial hypercontractility. HCM is often complicated by left ventricular outflow tract obstruction (LVOTO) and patients may be at greater risk of cardiovascular death. Medications targeted to address the pathophysiology of HCM and ameliorate LVOTO are needed. CK-3773274 (CK-274) is a novel small molecule cardiac myosin inhibitor that reduces myocardial contractility in vitro and in vivo . Cats have naturally occurring HCM commonly complicated by LVOTO and are an excellent large animal model for investigation of HCM therapeutics. In this study, we aim to characterize the pharmacodynamic effect of a single oral dose of CK-274 on cardiac function in cats with hypertrophic cardiomyopathy and LVOTO. Methods: Eight purpose-bred cats with naturally occurring HCM and LVOTO due to the A31P mutation in cardiac myosin binding protein C (cMyBP-C) were included in a randomized, controlled, crossover study. Cats were randomized to receive vehicle, 0.3 mg/kg, or 1 mg/kg CK-274 treatment, and received echocardiograms at baseline, 6, 24, and 48 hours post-treatment. All cats were crossed over to all treatment groups. Results: CK-274 (1 mg/kg) reduced mean LV fractional shortening at 6, 24 and 48 hours post-treatment (mean reduction 13.6%, p=0.03; 15.4%, p=0.01; 11.6% p=0.02, respectively). CK-274 (1 mg/kg) increased LV systolic internal dimension at 6 and 24-hours post-treatment (mean increase 0.21 cm, p=0.046; 0.25 cm, p=0.03), and did not affect LV diastolic internal dimension. LVOT peak pressure gradient was reduced with CK-274 (0.3 mg/kg) treatment [median pressure gradient at baseline 27.1 mmHg (IQR 18.3-33.3) vs 24 hours post-drug, 7.3 mmHg (IQR 14.2-19.7) p=0.01]. Heart rate did not change for any treatment group over time. No differences were noted following vehicle administration at any time point. Conclusion: In HCM affected cats with the cMyBP-C A31P mutation, the cardiac myosin inhibitor CK-274 is well tolerated at the studied doses and caused dose-related changes in LV systolic function and reductions in LVOT peak pressure gradient.

Abstract 13764: Chronic Electronic Cigarette Vapor Exposure Leads to Impaired Cardiac Function in Experimental Rat Myocardial Ischemia/reperfusion Model

Background: We investigated the effects of long-term electronic cigarettes with nicotine (eC) vaping on cardiac function and structure in rats subjected to myocardial infarction (MI). Methods: After 8 weeks of exposure to either pure air (n=20) or eC (n=20), rats were anesthetized, and were subjected to 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. Cardiac function was assessed by echocardiogram and pressure measurements of the aorta and left ventricle (LV). Cardiac output (CO) was measured using a thermodilution catheter. At 3 hours of reperfusion, ischemic risk zone, no-reflow and infarct areas were determined. Results: Prior to coronary artery occlusion, chronic eC exposure was associated with a lower CO (45 ± 2 ml/min ) compared to air (55 ± 4 ml/min; p&lt;0.05)) and a decrease in +dP/dt (5226 ± 294 mmHg/s versus 6062 ± 271 mmHg/s; p=0.05). After 30 minutes of coronary occlusion and 2.5 hours of reperfusion, CO and LV + dp/dt fell in both groups, but remained significantly lower in eC compared to the pure air group (Table). LV systolic and diastolic dimensions were significantly smaller in the E-Cig group compared to the air group. Systolic and diastolic anterior LV wall thickness were significantly thicker in the eC group after reperfusion. The ischemic risk size was comparable between the 2 groups. MI size was 48.8 ± 4.8% of the ischemic risk zone in the air group and 45.4 ± 4.4 % in the eC group (p=0.603). The area of no reflow was 26.7 ± 4.0% of the ischemic risk zone in the air group and 21.1 ± 3.5% in the E-C group (p=0.298). Chronic eC exposure did not change heart rate and blood pressure, but the significantly increased the systemic arterial resistance. Conclusions: Chronic exposure to eC significantly impaired cardiac function in rats prior to and during ischemia/reperfusion, increased arterial resistance, but did not increase infarct size or no-reflow zone. Increased LV wall thickness of the risk zone suggested that eC may have increased edema.

Factors associated with the cardiac allograft vasculopathy after heart transplantation

Abstract Introduction Cardiac allograft vasculopathy (CAV) is a major threat to long-term survival after heart transplantation (HT). The frequency of CAV is estimated to be 8% at 1 year after HT, 30% at the 5-year follow-up, and as high as 50% within 10 years after the procedure. Therefore, it is necessary to select those factors that are closely associated with the presence of CAV and facilitate the proper, fast and minimally invasive diagnosis of this disease. Purpose The aim of this study was determine risk factors associated with CAV detection in patients after HT. Material and methods We analyzed 299 consecutive patients after HT who underwent routine visits in our institution between 2015 and 2017. During the visit, echocardiography, routine coronary angiography, laboratory tests and immunosuppressive drug serum concentrations were performed in all patients. In addition, 10 ml of peripheral blood was collected to determine human interleukin 33 (IL-33) and IL-1 Receptor Like 1 (IL1RL1). IL-33 and IL1RL1 concentrations were measured by sandwich enzyme-linked immunosorbent assay (ELISA) with the commercially available kit. The diagnosis of CAV was based on the results of coronary angiography and defined according to the current International Society for Heart and Lung Transplantation (ISHLT) criteria.The Medical University Local Institutional Review Board approved the study protocol, and all patients provided informed consent. Results Patients' median age was 59.00 (45.00–66.00) years, and 74.2% were men. The median time from HT to study inclusion was 9.03 (6.02–13.01) years. The frequency of CAV according to the ISHLT criteria in the analysed population was 47.5%. At the time of enrolment all patients were receiving immunosuppressive therapy with calcineurin inhibitor and mycophenolate mofetil, and were free from acute rejection (diagnosed either by echocardiography or biopsy), clinical signs of infection or symptoms of acute heart failure. Multivariate analysis using logistic regression confirmed that IL-33 OR 0.958 (0.944–0.972), p&amp;lt;0.0001 as well as IL1RL1 OR 1.061 (1.040–1.083), p&amp;lt;0.0001) serum concentrations, donor age OR 1.046 (1.009–1.085) p=0.015, left ventricular diastolic dimension OR 1.081 (1.016–1.149) p=0.015, and time from HT to blood collection OR 1.256 (1.151–1.371), p&amp;lt;0.0001 were independent factors of CAV detection. Conclusions Lower IL-33 and higher IL1RL1 serum concentrations, as well as donor age, left ventricular diastolic dimension and time from HT to blood collection are independently associated with CAV. This study provides non-invasive, low-cost, and simple indicators for CAV detection. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of Silesia, Katowice, Poland

Klotho protein, albumin level, left ventricular and left atrium dimensions are independently associated with moderate and severe cardiac allograft vasculopathy in heart transplant recipients

Abstract Background Cardiac allograft vasculopathy (CAV) is one of the main risk factors influencing graft loss and patients survival. An important element of monitoring the patient after heart transplantation (HT) is the assessment of non-invasive indicators associated with the occurrence and progression of CAV. Therefore, new noninvasive sensitive and specific tools are necessary for detecting CAV early, which may result in the modification of immunosuppressive therapy, increase in statin doses, and intensive treatment of CAV-related comorbidities. Purpose The aim of the study was to research for factors associated with occurrence of moderate to severe CAV in heart transplant recipients. Methods Our analysis included consecutive adult patients after HT with CAV who underwent routine visits in our institution between 2015–2017. Exclusion criteria included history of kidney diseases, hepatitis B and C, autoimmune diseases, chronic pancreatitis or thyroid diseases, and cerebrovascular accidents. During each visit, all patients underwent echocardiography, laboratory tests, immunosuppressive drugs serum concentration analyses, and coronary angiographies. In addition, Klotho protein concentration was measured in all patients using sandwich enzyme-linked immunosorbent assay (ELISA) with the commercially available kit. Coronary angiographies of all patients enrolled to the study were reviewed by two independent interventional cardiologists to accurately classify coronary artery lesions according to International Society for Heart and Lung Transplantation (ISHLT) guidelines. Then, patients were divided into a group with mild CAV (1) and moderate to severe CAV (2/3). The local institutional review board of the Medical University of Silesia approved the study protocol, and all patients provided informed consent. Results The final group consisted of 141 patients with CAV. The age of the patients was 60.0 (53.0–66.0) and 77.5% of them were male. The median time from HT to include in the study was 11.6 (8.5–15.0) years. The frequency of CAV 2/3 in the analysed population was 36.6%. All included patients received optimal immunosuppressive therapy consisting of a calcineurin inhibitor (tacrolimus or cyclosporin) and mycophenolate mofetil. Multivariate analysis of logistic regression showed that Klotho protein (OR = 0.719 [0.598–0.866], p&amp;lt;0.001), albumin (OR=0.790 [0.686–0.910] p&amp;lt;0.001), left ventricular diastolic dimension (OR =1.135 [1.054–1.222], p&amp;lt;0.001), and left atrium dimension (OR=1.058 [1.013–1.106] p=0.012) were independent factors of CAV 2/3 presence. Conclusions Lower Klotho and albumin levels, as well as left ventricular and left atrium dimensions are the independent factors of moderate to severe CAV presence. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): MEdical University of Silesia, Katowice, Poland

Clinical implication of symptom for long-term outcomes after elective percutaneous coronary intervention

Abstract Background The appropriate treatment for silent myocardial ischemia (SMI) is controversial. The prognosis of asymptomatic patients after percutaneous coronary intervention (PCI) is unknown. Asymptomatic patients might be sicker and have delay of diagnosis when they have coronary events in clinical course. We, thus, hypothesized SMI are associate with the poor outcomes after PCI for stable coronary artery disease (CAD). Purpose The present study compared the long-term outcomes of patients with SMI vs. stable angina pectoris (SAP) after elective PCI. Methods Our prospective registry database included 923 consecutive patients with CAD who underwent PCI from October 2015 to August 2018. Patients with emergent PCI, acute coronary syndrome at admission, or chronic total occlusion patients were not included. A total 613 patients (71.4±11.2 years, 75.7% male) who underwent elective PCI were studied. The end points included all-cause mortality, non-fatal myocardial infarction, and repeat revascularization. Results They were divided into 2 groups according to symptom status: SMI (n=392) and SAP (n=221). SMI patients were predominantly men, and more frequently had diabetes mellitus (197 [50.4%] vs. 91 [41.2%], p=0.028), previous myocardial infarction (44 [11.3%] vs. 8 [3.6%], p=0.001) and heart failure hospitalization.Echocardiography showed SMI groups had reduced ejection fraction (56.9±12.6 vs 63.3±9.1, P&amp;lt;0.001), extended left ventricular internal dimension in diastole (48.5±6.2 vs 47.4±5.8, p=0.048) and left ventricular diameter at end systole (32.8±7.6 vs 30.5±7.5, p=0.001). Mean duration of follow-up was 20.9±10.6 months. The incidence of non-fatal myocardial infarction and repeat revascularization was similar between the 2 groups (10 [2.6%] vs. 5 [2.3%], p=0.82, and 50 [12.8%] vs. 30 [13.6%], p=0.77, respectively). The incidence of all-cause and cardiovascular mortality was more frequent in SMI patients (26 [6.6%] vs. 6 [2.7%], p=0.036, and 9 [3.1%] vs 1 [0.5%], p=0.035, respectively). Kaplan-Meier survival curves indicated that SMI patients had significantly higher all cause-mortality than SAP patients (log-rank, p=0.0184, Hazard ratio 1.24 (1.05–1.47), p=0.013). In multivariable analysis, SMI was an independent predictor of all cause-mortality (Hazard-ratio 5.17, 95% CI 1.35–34.29, p=0.014). Conclusion In patients with stable CAD undergoing elective PCI, SMI was associated with an increase in mortality. Optimal care for SMI patients after PCI should be clarified in future studies. Funding Acknowledgement Type of funding source: None

Targeting MEF2 acetylation improves myocardial recovery and overall survival in mice

Abstract Background Post-myocardial infarct remodeling is a complex process that is strongly associated with the eventual development of heart failure, and involves myocyte hypertrophy, specific alterations in gene expression and mitochondrial metabolism, myocyte death, fibrosis, and incursion of inflammatory mediators. Many of these alterations involve dynamic changes in lysine acetylation (KAc), a key regulatory post-transcriptional modification in the nucleus and cytosol, and can be blocked by small molecules with broad activity against histone deacetylases (HDACi). The downstream targets of HDACi and other KAc modulators remain to be established, and the safety of this class of agent for long-term administration in heart failure is similarly unknown. We recently reported that a small molecule probe (8MI) selectively blocking acetylation of transcription factor MEF2 is effective in preventing and reversing pressure overload hypertrophy in vivo, without altering overall histone acetylation. Hypothesis Treatment with a MEF2-selective KAc modulator will accelerate cardiac functional recovery after myocardial infarction. Methods The left coronary artery was permanently ligated (PCO) in 8–10 week C57BL/6J mice; controls underwent thoracotomy only (Sham). Within each group, half received 8MI (20–100mg/kg) by gavage daily, beginning at 30 min, and half received diluent only (DMSO). Treatment was continued for 31 days with weekly echocardiography. Mice from each group (n=3–6) were euthanized weekly for gross and histological analysis. Separately, mice were subjected to transverse aortic banding (TAC) +/− 8MI. Comparative LV RNASeq data were analysed using Gene Set Enrichment Analysis at 4 weeks, and median survival was determined. Results At 24 hours all PCO vs. Sham mice had reduced ejection fraction (62.1±1.08% vs. 80.9±1.08%), increased LV diastolic dimensions, and decreased systolic wall thickening (n =min. 8 per group, p &amp;lt; E-001). Over 4 weeks, heart weights progressively increased in PCO mice together with lung and liver congestion. 8MI dose-dependently improvedeach of these parameters, with near-normal function and organ weights at 4 weeks in higher-dose groups. 8MI also reduced infarct size, compensatory hypertrophy, and fibrosis at 4 weeks. In parallel, 8MI extended median survival by 1.67-fold after TAC (127.5 vs 76 days, p&amp;lt;0.0001, 8MI vs DMSO). RNASeq +GSEA analysis revealed that 8MI treatment blocked MEF2 target gene induction, while enriching for gene sets Oxidative Phosphorylation and Myc Targets (FDR q values 0.000 and 0.041) compared with DMSO. Conclusion An inhibitor of MEF2 acetylation promoted significant functional and pathological recovery in a mouse model of myocardial infarction, associated with suppression of MEF2-dependent transcription. These findings point to a novel approach to preventing myocardial functional decline, and improving survival, after myocardial injury. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health; Miami Heart Research Institute

Pregnancy Effect on Echocardiographic Parameters in Great Dane Bitches.

Simple SummaryIn women, as well as in bitches, pregnancy is associated with the adaptation of the left ventricular function. Pregnancy mainly represents a status of increased volume load of the maternal heart driven by the need to supply an adequate blood flow through an augmented uterine perfusion to the developing fetuses. Consequently, cardiac morpho-functional changes are expected. Cardiac morphology and function in pregnant bitches that would develop complications may differ from those with a normal outcome. Thus, the assessment of the maternal cardiovascular function may be a useful screening tool to detect pregnancy complications in dogs. Few studies investigated the cardiac maternal adaptation in different gestational ages in dogs. Breed is a known source of variation in echocardiographic values; hence, the cardiac performance during pregnancy may also be prone to a breed-related variation. For these purposes, due to possible breed-related variations in cardiac parameters and function, and to the specific predisposition for myocardial diseases, echocardiographic changes along pregnancy in healthy Great Dane bitches were evaluated. A significant effect of the age of gestation on the increase of functional and diastolic parameters and on the decrease of systolic parameters was reported.Pregnancy is associated with adaptation of the left ventricular (LV) function. Due to differences between breeds in baseline echocardiographic values and specific predispositions for myocardial diseases, breed-specific echocardiographic parameters may be helpful to evaluate whether the systolic function varies during pregnancy. This study enrolled nine healthy Great Dane bitches with uncomplicated pregnancy. Echocardiographic M-mode and B-mode data were collected before ovulation and within 7 days of the predicted parturition term. Evaluated parameters were: LV dimension in diastole (LVd) and systole (LVs), end-diastolic (EDVI) and end-systolic (ESVI) volumes indexed to body surface area (BSA), end-diastolic (EDV) and end-systolic (ESV), end-point-septal-separation (EPSS), left atrium to aortic root ratio (LA/Ao), sphericity index (SI), ejection fraction (EF), fractional shortening (FS), stroke volume (SV), heart rate (HR), and cardiac output (CO). The ANOVA showed a statistical effect of the age of gestation (p < 0.01) on the increase of diastolic dimensions and functional parameters and on the decrease of systolic dimensions. The CO increase parallels the rise in SV and HR (p < 0.01). No statistical differences were observed for EPSS, LA/Ao, and SI. The changes in cardiac chambers and function are likely to reflect maternal adaptation to allow the fetal development in uncomplicated pregnancy. The present study provides specific echocardiographic values in uncomplicated pregnancy of Great Danes, showing that the systolic function is enhanced and that the increase in preload, observed during gestation, is the likely mechanism.