Improved Left Ventricle Function Research Articles

Effects of sacubitril/valsartan in patients with cancer therapy-related heart failure

To evaluate the effect of Sacubitril/Valsartan (S/V) on the functional status, systolic and diastolic function of the left ventricle (LV), tolerability of therapy and to determine predictors of its effectiveness in patients with cancer therapy-related heart failure (СTRHF). Forty patients 58 [46; 65.5] years of age with HF associated with anthracycline-containing cancer therapy were enrolled. Clinical examination, echocardiography, and assessment of potassium and creatinine levels were performed at baseline and after 6 months of S/V therapy. NYHA functional class (FC) improvement was observed in 22 (64.7%) patients. Radiation therapy (RT) decreased (OR 0.091; 95% CI 0.01-0.83; p=0.03) while baseline low LV EF increased (OR 9.0; 95% CI 1.78-45.33; p=0.008) the odds of FC improvement. LV EF increased from 37.3 [30; 42.5] % to 45 [38; 48] % (p<0.0001) and exceeded 50% in 7 (20.6%) patients. The odds of LV EF recovery increased when S/V therapy was initiated ≤1 year after anthracycline therapy (OR 10.67; 95% CI 1.57-72.67; p=0.0016) and decreased in patients with the history of RT (OR 0.14; 95% CI 0.02-0.89; p=0.0037) and in patients over 58 years (OR 0.07; 95% CI 0.01-0.68; p=0.022). LV diastolic function improvement included E/e' descent from 13.6 [10; 18.3] to 8.9 [6.9; 13.7] (p=0.0005), and decrease in diastolic dysfunction grade in 18 (45%) patients (p=0.0001). No significant change in serum potassium (4.45 [4.2; 4.8] versus 4.5 [4.3; 4.8]; p=0.5) and creatinine (75.4 [67.6; 85.1] versus 75.5 [68.2; 98.3]; p=0.08) levels were observed. S/V therapy is associated with improvement of EF, systolic and diastolic LV function, demonstrates a favorable tolerability profile in patients with СTRHF. Lack of RT and low baseline LV EF increased the odds of LV EF improvement; lack of RT, early (≤1 year) start of treatment after discontinuation of anthracycline therapy, and age <58 years increased the odds of LV EF recovery.

Right ventricle to pulmonary artery coupling after transcatheter aortic valve implantation-Determinant factors and prognostic impact.

Right ventricular (RV) dysfunction and pulmonary hypertension (PH) have been previously associated with unfavorable outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI), but little is known about the effect of right ventricle (RV) to pulmonary artery (PA) coupling. Our study aimed to evaluate the determinant factors and the prognostic value of RV-PA coupling in patients undergoing TAVI. One hundred sixty consecutive patients with severe AS were prospectively enrolled, between September 2018 and May 2020. They underwent a comprehensive echocardiogram before and 30 days after TAVI, including speckle tracking echocardiography (STE) for myocardial deformation analysis of the left ventricle (LV), left atrium (LA), and RV function. Complete data on myocardial deformation was available in 132 patients (76.6 ± 7.5 years, 52.5% men) who formed the final study population. The ratio of RV free wall longitudinal strain (RV-FWLS) to PA systolic pressure (PASP) was used as an estimate of RV-PA coupling. Patients were analyzed according to baseline RV-FWLS/PASP cut-off point, determined through time-dependent ROC curve analysis, as follows: normal RV-PA coupling group (RV-FWLS/PASP ≥0.63, n = 65) and impaired RV-PA coupling group (RV-FWLS/PASP < 0.63, n = 67). A significant improvement of RV-PA coupling was observed early after TAVI (0.75 ± 0.3 vs. 0.64 ± 0.3 before TAVI, p < 0.001), mainly due to PASP decrease (p < 0.001). LA global longitudinal strain (LA-GLS) is an independent predictor of RV-PA coupling impairment before and after TAVI (OR = 0.837, p < 0.001, OR = 0.848, p < 0.001, respectively), while RV diameter is an independent predictor of persistent RV-PA coupling impairment after TAVI (OR = 1.174, p = 0.002). Impaired RV-PA coupling was associated with a worse survival rate (66.3% vs. 94.9%, p-value < 0.001) and emerged as an independent predictor of mortality (HR = 5.97, CI = 1.44-24.8, p = 0.014) and of the composite endpoint of death and rehospitalization (HR = 4.14, CI = 1.37-12.5, p = 0.012). Our results confirm that relief of aortic valve obstruction has beneficial effects on the baseline RV-PA coupling, and they occur early after TAVI. Despite significant improvement in LV, LA, and RV function after TAVI, RV-PA coupling remains impaired in some patients, it is mainly related to persistent pulmonary hypertension and is associated with adverse outcomes.

Evaluation of the effectiveness of thyrostatics in the treatment of comorbid patients with thyrotoxicosis

Objective: to evaluate the effect of thyrostatics on clinical symptoms, the frequency of cardiac arrhythmias and morpho-functional parameters of the left heart in patients with a combination of thyrotoxicosis and ischemic heart failure. Materials and methods: 85 patients participated in the study. Group 1st — patients with CHF of functional class II-III (FC) on the background of coronary heart disease and concomitant thyrotoxicosis (n=40), average age 58.6±4.6 years; group 2nd — patients with manifest thyrotoxicosis without cardiovascular pathology (n=45), average age 46.7± 4.1 years. When included in the study and after 6 months of therapy with the addition of thyrostatics, the clinical condition of patients and physical activity were evaluated, daily monitoring of an electrocardiogram and an echocardiographic study (EchoCG) were performed. Results: after 6 months of combined therapy with the inclusion of thyrostatics against the background of persistent drug-induced euthyroidism, exercise tolerance increased in comorbid patients (group 1) (p&lt;0.001), the severity of clinical symptoms of CHF decreased, and the frequency of cardiac arrhythmias significantly decreased (p&lt;0.05). The analysis of the dynamics of EchoCG results in group 1 patients revealed a significant increase in the index of shock ejection (p=0.04), left ventricular ejection fraction (p=0.01), shock volume (p=0.03), a decrease in the value of myocardial stress (p=0.02) and parameters characterizing the transmittal flow (E/A, p&lt;0.05), which allowed us to judge the improvement of systolic and diastolic function of the left ventricle (LV) under conditions of drug compensation thyrotoxicosis. Conclusion: the inclusion of thyrostatics in combination therapy and normalization of thyroid function contributed to the reduction of clinical symptoms of heart failure, the frequency of cardiac arrhythmias, improvement of systolic and diastolic LV function in comorbid patients with ischemic CHF and concomitant thyrotoxicosis.

Colchicine prevents disease progression in viral myocarditis via modulating the NLRP3 inflammasome in the cardiosplenic axis.

AimThe acute phase of a coxsackievirus 3 (CVB3)‐induced myocarditis involves direct toxic cardiac effects and the systemic activation of the immune system, including the cardiosplenic axis. Consequently, the nucleotide‐binding oligomerization domain‐like receptor pyrin domain‐containing‐3 (NLRP3) inflammasome pathway is activated, which plays a role in disease pathogenesis and progression. The anti‐inflammatory drug colchicine exerts its effects, in part, via reducing NLRP3 activity, and has been shown to improve several cardiac diseases, including acute coronary syndrome and pericarditis. The aim of the present study was to evaluate the potential of colchicine to improve experimental CVB3‐induced myocarditis.Methods and resultsC57BL6/j mice were intraperitoneally injected with 1 × 105 plaque forming units of CVB3. After 24 h, mice were treated with colchicine (5 μmol/kg body weight) or phosphate‐buffered saline (PBS) via oral gavage (p.o.). Seven days post infection, cardiac function was haemodynamically characterized via conductance catheter measurements. Blood, the left ventricle (LV) and spleen were harvested for subsequent analyses. In vitro experiments on LV‐derived fibroblasts (FB) and HL‐1 cells were performed to further evaluate the anti‐(fibro)inflammatory and anti‐apoptotic effects of colchicine via gene expression analysis, Sirius Red assay, and flow cytometry. CVB3 + colchicine mice displayed improved LV function compared with CVB3 + PBS mice, paralleled by a 4.7‐fold (P < 0.01) and 1.7‐fold (P < 0.001) reduction in LV CVB3 gene expression and cardiac troponin‐I levels in the serum, respectively. Evaluation of components of the NLRP3 inflammasome revealed an increased percentage of apoptosis‐associated speck‐like protein containing a CARD domain (ASC)‐expressing, caspase‐1‐expressing, and interleukin‐1β‐expressing cells in the myocardium and in the spleen of CVB3 + PBS vs. control mice, which was reduced in CVB3 + colchicine compared with CVB3 + PBS mice. This was accompanied by 1.4‐fold (P < 0.0001), 1.7‐fold (P < 0.0001), and 1.7‐fold (P < 0.0001) lower numbers of cardiac dendritic cells, natural killer cells, and macrophages, respectively, in CVB3 + colchicine compared with CVB3 + PBS mice. A 1.9‐fold (P < 0.05) and 4.6‐fold (P < 0.001) reduced cardiac gene expression of the fibrotic markers, Col1a1 and lysyl oxidase, respectively, was detected in CVB3 + colchicine mice compared with CVB3 + PBS animals, and reflected by a 2.2‐fold (P < 0.05) decreased Collagen I/III protein ratio. Colchicine further reduced Col3a1 mRNA and collagen protein expression in CVB3‐infected FB and lowered apoptosis and viral progeny release in CVB3‐infected HL‐1 cells. In both CVB3 FB and HL‐1 cells, colchicine down‐regulated the NLRP3 inflammasome‐related components ASC, caspase‐1, and IL‐1β.ConclusionsColchicine improves LV function in CVB3‐induced myocarditis, involving a decrease in cardiac and splenic NLRP3 inflammasome activity, without exacerbation of CVB3 load.

A case of middle aortic syndrome in takayasu arteritis with left ventricle dysfunction and heart failure

Left ventricular dysfunction is an uncommon complication of Takayasu arteritis (TA) with a prevalence of about 10%–15%. We report a case of a 27-year-old girl who presented with dyspnea, bipedal edema, loss of weight, and easy fatigability for 3 months. Patient also developed right hemiparesis 3 months ago. Computed tomography of the brain was suggestive of the left temporal infarct, on evaluation she was diagnosed as left ventricle (LV) dysfunction and she was treated for CVA and heart failure. Clinical examination revealed the absence of the left upper limb and bilateral lower limb pulses with right upper limb hypertension. Echocardiography revealed severe LV dysfunction (ejection function ~20%). Computed tomography angiogram and other inflammatory markers confirmed the diagnosis of TA and revealed the presence of coaraction of the thoracic and abdominal aorta. Coaractoplasty was done, and immunosuppressant therapy with oral prednisolone and weekly oral methotrexate was started. On follow-up, patient is asymptomatic with improved LV function. Any patient with LV dysfunction or dilated cardiomyopathy, reversible causes have to be ruled out and TA has to be thought of as a differential diagnosis particularly in young females. Checking of all four limbs pulses and blood pressure is strictly recommended. TA is a systemic vasculopathy that can progress to cause vital organ ischemia. Therefore, early diagnosis and management as well as long-term follow-up is recommended.

IN THE HEART OF IT: A RARE PRESENTATION OF DISSEMINATED CRYPTOCOCCUS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Since the emergence of highly active antiretroviral therapy (HAART), incidence cryptococcosis has fallen. We discuss a rare presentation of disseminated cryptococcosis. CASE PRESENTATION: A previously well 31 year old woman presented with 3 weeks of nausea, vomiting & headache. She was sent to hospital when she developed dizziness & palpitations after a positive HIV test was found on an outpatient visit. Examination revealed diffuse adenopathy. Urine was positive for opiates, cannabinoids & barbiturates. Non-contrast computed tomography head revealed no acute abnormalities, but abdomen/pelvis found abdominal & retroperitoneal lymphadenopathy. On day 2, she developed diaphoresis, cold extremities with HR160bpm, BP89/53mmhg, RR44bpm, SpO289% & T100F. She was intubated & put on vasopressors. She subsequently had 3 PEA cardiac arrests with return of spontaneous circulation after several minutes. Bedside transthoracic echocardiogram (TTE) revealed a severely hypokinetic dilated right ventricle (RV) & underfilled left ventricle (LV). Bedside transesophageal echocardiogram noted hyperdynamic apex, akinetic base & echogenic material within the right pulmonary artery, concerning for a pulmonary embolism. Hemodynamic instability was refractory to thrombolytics & she was placed on veno-arterial ECMO. She was empirically given vancomycin, piperacillin-tazobactam & clindamycin/primaquine. Blood cultures were later positive for yeast, so caspofungin & fluconazole added. Follow-up TTE showed minimal improvement in RV or LV function. On day 3, after 24 hours off sedation, pupils were dilated & brainstem reflexes absent. Apnea test confirmed brain death. After expiration, HIV viral load was found to be 528,000 copies/ml (reference range: not detected), CD4 was <20 cells/mcl (490-1740cells/mcl), & Cryptococcus neoformans was isolated, with titer ≥1:2560 (normal: negative). DISCUSSION: Cryptococcosis is the most common fungal disease in HIV, but its incidence has decreased in the US. Earlier HIV diagnosis & HAART explain this. It most commonly affects the nervous system. Occasionally, blood cultures are positive indicating disseminated disease. We postulate that pulmonary vascular occlusion can occur due to disseminated cryptococcal infection. Cryptococcomas are extremely rare solid tumor-like masses which have been reported to invade the central nervous system & the skin. Our suspicion for this is high given her poor response to TPA & significant fungemia which likely led to right heart failure & cardiovascular collapse. Literature review identified one other such case. More common sequelae include meningitis or pulmonary involvement. Amphotericin B & Flucytosine represent the most potent therapy for severe disease. CONCLUSIONS: Cardiopulmonary collapse from right heart failure with disseminated cryptococcus is extremely rare. Early diagnosis & treatment of HIV remains the most important tool. REFERENCE #1: Bramantono, B., Danial, A., & Hadi, U. (2020). A case of an AIDS patient with Cryptococcus neoformans infection. The Pan African medical journal, 36, 88. https://doi.org/10.11604/pamj.2020.36.88.20406 REFERENCE #2: Gültaşli NZ, Ercan K, Orhun S, Albayrak S. MRI findings of intramedullary spinal cryptococcoma. Diagn Interv Radiol. 2007 Jun;13(2):64-7. PMID: 17562509. REFERENCE #3: Sperry BW, Howard EW, Gitterman S, Panza JA. A case of cryptogenic dyspnea: disseminated cryptococcosis. Am J Med. 2014 Aug;127(8):707-10. doi: 10.1016/j.amjmed.2014.04.007. Epub 2014 Apr 21. PMID: 24769024. DISCLOSURES: No relevant relationships by Janeen Grant-Sittol, source=Web Response No relevant relationships by Lena Makartian, source=Web Response No relevant relationships by Priya Patidar, source=Web Response No relevant relationships by Rani Sittol, source=Web Response

Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

PurposeMyocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation–contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by naltrexone would affect cardiac function and neurohumoral parameters in Wistar rats with volume overload-induced heart failure.MethodsVolume overload in Wistar rats was induced by an aortocaval fistula (ACF). Left ventricular cardiac opioid receptors were identified by immunohistochemistry and their messenger ribonucleic acid (mRNA) as well as their endogenous ligand mRNA quantified by real-time polymerase chain reaction (RT-PCR). Following continuous delivery of either the opioid receptor antagonist naltrexone or vehicle via minipumps (n = 5 rats each), hemodynamic and humoral parameters were assessed 28 days after ACF induction. Sham-operated animals served as controls.ResultsIn ACF rats mu-, delta-, and kappa-opioid receptors colocalized with voltage-gated L-type Ca2+ channels in left ventricular cardiomyocytes. Chronic naltrexone treatment of ACF rats reduced central venous pressure (CVP) and left ventricular end-diastolic pressure (LVEDP), and improved systolic and diastolic left ventricular functions. Concomitantly, rat brain natriuretic peptide (rBNP-45) and angiotensin-2 plasma concentrations which were elevated during ACF were significantly diminished following naltrexone treatment. In parallel, chronic naltrexone significantly reduced mu-, delta-, and kappa-opioid receptor mRNA, while it increased the endogenous opioid peptide mRNA compared to controls.ConclusionOpioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload.

Duchenne muscular dystrophy: preliminary experience with sacubitril-valsartan in patients with asymptomatic left ventricular dysfunction.

Duchenne muscular dystrophy (DMD) is an inherited X-linked recessive neuromuscular disease caused by mutations of the dystrophin gene, leading to early and progressive muscle deterioration and dilated cardiomyopathy. The aim of this investigation was to assess whether treatment with sacubitril/valsartan (S/V) is well tolerated and may have beneficial effects in DMD patients with left ventricle (LV) dysfunction. We administered S/V to 3 DMD patients (19-29 yeard old) with LV ejection fraction <35% at echocardiography but no symptoms of heart failure. All patients were on optimal medical therapy. S/V was initiated at a very low dose of 12/13 mg/die, after withdrawal of angiotensin-converting enzyme inhibitor therapy, and slowly titrated to the dose of 49/51 mg twice daily or the maximally tolerated dose. Clinical and echocardiographic follow-up was performed after 3, 6 and 12 months. At baseline, the LV ejection fraction was 32±1%. A significant improvement of LV ejection fraction was observed at 3 months (44.0±6.0%; p<0.05), which was maintained at 6 (45.7±5.0%) and 12 (43.3±3.2%) months (p<0.05 for both). No relevant side effects were reported throughout the period of the study. Our preliminary data suggest that, in DMD patients with reduced LV ejection fraction, S/V is safe and may improve LV function.

75-OR: Dietary Nitrate and Fecal Transplantation Prevent Cardiac Dysfunction and Attenuate Left Ventricular Mitochondrial Reactive Oxygen Species Emission in High-Fat Diet-Fed Mice

Cardiometabolic diseases are multifactorial conditions involving dysfunction within the left ventricle (LV), adipose tissue (AT), and gut microbiome. Nitrate supplementation has been shown to influence cardiac contractility, mitochondrial function, and microbial populations, effects which require commensal gut bacteria to metabolize nitrate. Therefore, we examined if dietary nitrate and fecal microbial transplant (FMT) from nitrate-fed mice were capable of preventing high fat diet (HFD) induced cardiac abnormalities. Male C57Bl/6N mice were fed a control diet, or HFD (60% fat) in the absence or presence of 4mM sodium nitrate in drinking water for 8 weeks. A further subset of HFD-fed mice were gavaged with feces from HFD+nitrate donors or HFD donors for 3 days at the beginning of week 7, and followed until week 8. Compared to controls, HFD mice presented with ∼25% reduction in end diastolic volume, stroke volume, and cardiac output, in association with an increase in cardiac fibrosis, AT inflammation, and serum lipids. In contrast, dietary nitrate prevented these detrimental effects. The improvement in cardiac function following dietary nitrate was not attributed to changes in LV mitochondrial respiration, however, nitrate prevented the increase in LV mitochondrial reactive oxygen species (ROS) emission associated with HFD. While FMT from HFD+nitrate donors did not influence AT inflammation or cardiac fibrosis, HFD+nitrate FMT decreased serum lipids, LV ROS, and improved cardiac function compared to FMT from HFD-fed donors, without increasing serum nitrate concentrations. Altogether, dietary nitrate prevents the detriments of HFD on cardiac function and LV mitochondrial ROS emission, effects which may not be directly dependent on increasing serum nitrate. Rather, the beneficial effects of nitrate may be linked to changes in the gut microbiome, as FMT from nitrate-fed donors improved LV function. Disclosure H.L. Petrick: None. H. Brunetta: None. A. Kirsh: None. P. Barbeau: None. L.M. Ogilvie: None. J. Simpson: None. J.D. Schertzer: None. G. Holloway: None. Funding Natural Sciences and Engineering Research Council of Canada (400362)

P1573 Late recovery of left ventricular function in patients with non-severe ischemic mitral regurgitation and multivessel disease qualified to cardiosurgery treatment

Abstract Late recovery of left ventricular function in patients with non-severe ischemic mitral regurgitation and multivessel disease qualified to cardiosurgery treatment. Purpose In patients (pts) after myocardial infarction (MI) with chronic left ventricle (LV) dysfunction, the presence and degree of ischemic mitral regurgitation (IMR) are predominantly related to LV remodelling and mitral valvular deformation. The aim of this study was to compare functional recovery (LVFR) as well as reverse remodelling of the left ventricle (LVRR) in pts with non-severe IMR qualified for cardiosurgical treatment - coronary artery bypass grafting alone (CABGa) or CABG with mitral repair (CABGmr in the 12-month follow-up. Materials and methods A total of 100 pts (mean age 64,4 ± 7,9 years) after MI, eligible for CABG, were included in a prospective study. Echo and clinical assessment were performed before and 12-months after surgery. Pts were referred for CABG a(gr.1; n = 74) or CABGmr (gr.2; n = 26) based on clinical assessment, 2D echo at rest and exercise and myocardial viability assessment (low dose dobutamine - dbx). Effective regurgitation orifice area (EROA) was used for quantitative IMR assessment. An increase in EF≥ 5% (ΔEF) from baseline value was considered as LVFR. A decrease in LV end-systolic volume &amp;gt; 15% from baseline value was considered as LVRR. Multivariable logistic regression analysis was used to identify the strongest factors of lack of LVFR and LVRR. Results An LVFR was observed, at late control, in 35 (49%) of pts in the CABGa group and in 11 (48%) of pts in CABGmr group (p = 0,948). LVRR was observed in 41 (56%) of pts in the CABGa group and in 16 (70%) of pts in CABGmr group 12 months follow-up (p = 0,5). In pts with LVFR, there was a lower incidence of at least moderate IMR at follow-up (ΔEF dbx≥5% vs ΔEFdbx &amp;lt; 5%:11% vs 30% pts; p = 0,05). Multivariable logistic regression analysis revealed that in both CABGa and CABGmr group only preoperative age and EF changes during stress echo remained the independent predictors of the lack of LVFR in 12 months follow-up (table 1). Conclusions 1. LVFR and LVRR were reported in most of the pts in both analyzed groups. 2. Preoperative assessment of changes EF during dbx (ΔEFdbx)can be used to identify pts with IMR at increased risk of lack of improvement in LV function and risk of residual IMRin 12-month f-up after surgery. Parameters Odds ratio (OR) Odds ratio (OR) p CABGa vs CABGmr 0,644 0,215 - 1,927 0,432 Age (increase by every 5 years) 1,11 1,039 - 1,879 0,003 ΔEF dbx (increase by every 5%) 0,21 0,096 - 0,46 &amp;lt;0,001 Table 1. Prognostic factors lack improvement in left ventricle function.

Real time 3D-OCT predicts restenosis by identifying geographic miss between overlapping stents after complex multivessel percutaneous coronary intervention

A 78-year-old male patient with a history of cerebrovascular accident and left hemiparesis presented with evolved inferior wall myocardial infarction and preserved left ventricle (LV) function. Coronary angiogram revealed triple-vessel disease. After heart team discussion, he was advised multivessel percutaneous coronary intervention (PCI). He underwent PCI to right coronary artery (2× sirolimus-eluting stent) in the first stage with good result. After 4 weeks, he again presented to the emergency department with acute coronary syndrome (ACS). He underwent imaging-guided left main (LM) bifurcation PCI (mini-crush technique) with 2 ×× everolimus-eluting stent (EES) across LM to left anterior descending artery (LAD) and 2 ×× EES in left circumflex artery (LCX). Real-time three-dimensional optical coherence tomography (3D-OCT) identified 1 mm geographic miss between overlapping stents in heavily calcified LAD. Cine fluoroscopy and intravascular ultrasound (IVUS) did not identify the same. In view of elderly age, already high contrast load, mild renal impairment, and low-risk OCT features, he was managed conservatively. He was doing well until 10 months after PCI, when he presented again to the emergency department with ACS and LV dysfunction. CAG showed critical in-stent restenosis (ISR) at the LAD stent overlap area. Other stents were all patent with mild ISR in LCx. He underwent PCI to LAD with 1 ×× EES. He is in follow-up for the last 1 year without any complaints and improved LV function. The availability of real-time 3D-OCT machines allowed us to easily identify “geographic miss” which is sometimes difficult to detect with cine flouroscopy or IVUS, particularly in heavily calcified vessels. This newer technology adds another dimension to intravascular imaging-guided PCI and has shown great promise particularly in complex and bifurcation PCI.

1036 Prognostic role of left ventricle longitudinal strain for the prediction of survival after surgical ventricular repair

Abstract Background Surgical ventricular repair (SVR) in patients with ischemic cardiomyopathy is aimed to reshape left ventricle (LV) and reduce its volume in order to improve prognosis and quality of life. There are controversies regarding benefit of SVR, especially in patients with severely enlarged LV. Purpose Our purpose was to investigate prognostic value of LV longitudinal strain for survival and for the improvement of LV function after SVR in patients with anteroapical LV aneurysm. Methods 218 pts (2005-2018, mean age 63.6 ± 11.2y, 73.9% males) with anteroapical LV aneurysm due to myocardial infarction underwent SVR combined with coronary bypass grafting (77.5%), mitral valve repair (18.3%) and LV thrombectomy (22.0%). Preoperative strain analysis was done retrospectively for 146 patients. Prognostic value of strain was tested in pts according to the LV end systolic volume index (LVESVI) with the cut-off value of 60ml/m². In 17 pts 1-year follow-up with strain quantification was done. Results During a median follow-up of 3.9 years (IQR: 1.0-6.8 years) there were 68 deaths and 1 patient was lost to follow-up. 30-days survival rate was 93.5% (95%CI: 90.3; 96.9%), 5 year survival – 72.5% (95%CI: 66.0-79.6%). Pts who died were significantly older, with higher proportion of diabetes (DM), peripheral artery disease, renal failure (RF) and atrial fibrillation (AF). Baseline ejection fraction (EF) and global longitudinal strain (GLS) did not differ significantly. Whereas basal longitudinal strain (BLS) was higher (more negative) in pts who survived (-11.4 ± 3% vs. -10.1 ± 4%, p = 0.027). Risk stratification by tertiles revealed that BLS was a significant predictor of survival. The risk of dying was 3 times higher for pts in the lowest tertile compared to those in the highest tertile (HR: 2.94, 95%CI:1.37-6.25, p = 0.013). When adjusted to age, AF, DM, RF, and previous heart surgery, BLS was an independent predictor of death (HR = 1.14, 95%CI:1.03;1.26, p = 0.032). At 1-year follow-up (12.7 ± 5.1 months) there was significant decrease of LV end-diastolic and end-systolic volume indices, from 102.8 ± 24.1 ml/m² to 77.9 ± 24 ml/m² (p &amp;lt; 0.001) and from 67 ± 23.2 ml/m² to 44.3 ± 7.6 ml/m² (p &amp;lt; 0.001), correspondingly, and increase of EF from 36.3 ± 9.4% to 44.4 ± 7.6% (p = 0.001). The mean systolic GLS improved from -6.6 ± 2.6% to -8.7 ± 3.2%, p = 0.008. Among 81 segments with baseline hypokinesia, 44 segments (54.3%) recovered their contractility, 36 segments (44.4%) remained hypokinetic and 1 segment deteriorated to akinesia. Mean systolic strain of segments which showed recovery was -6.6 ± 4.0% compared to -3.8 ± 4.5% with no improvement (p = 0.005). Cut-off value of systolic strain for prediction of recovery was -5.4 % (AUC = 0.69, p = 0.004; PPV = 0.73, NPV = 0.61). Conclusion Our study demonstrates that BLS is an independent predictor of survival after SVR in patients with LV anteroapical aneurysm. Furthermore, higher systolic strain predicts recovery of LV regional function at 1-year after SVR.

1028 Early response to a low- dose acubitril/valsartan (ARNI) therapy among stable symptomatic patients with HFrEF

Abstract Funding Acknowledgements no financial support Background Sacubitril/valsartan (S/V) has shown to improve outcomes, that is related to reverse remodeling of the left ventricle (LV) with improved ejection fraction (LVEF) and mitral regurgitation (MR) during long-term therapy. There are limited data on early effects of S/V treatment with respect to the left ventricle function and echocardiographic evaluation of this phenomenon. Aim of the study was to evaluate the early effect of a starting-dose of S/V administered in patients (pts) with stable symptoms of heart failure on clinical symptoms, laboratory tests and echocardiographic parameters using global longitudinal strain (GLS) as a sensitive parameter detecting improvement of LV function. Methods Twenty pts (mean age 60 years, 2 female), with HFrEF (NYHA class II-III) on optimal medical treatment with ICM (75%) or NICM (35%) were included to low-dose S/V treatment (24/26mg) after excluding contraindications. Clinical and echocardiographic evaluation was performed at baseline and after 30 days. The following parameters have been measured: 6-Minutes Walking Test (6MWT) and Minnesota Living with Heart Failure questionnaire, laboratory results and echocardiographic assessment with speckle tracking technique (STE). Results All pts completed 30 days treatment period without complications and no change to medication. During this period the mean values of RR decreased significantly (SBP 129,4mmHg vs 121,25mmHg and DBP 81,6mmHg vs 79,2mmHg respectively). Other clinical parameters did not change. There were no differences NT-pro BNP and TNT levels (respectively 1726 vs 1930 pg/ml and 26 vs 22 ng/ml). After 30days, the mean 6MWT distance increased by 50m (349,5 vs 401,5m p &amp;lt; 0.01), and a positive response was observed in Minnesota Living with Heart Failure Questionnaire (p &amp;lt; 0.001). Echocardiographic parameters revealed positive remodeling of LV and left atrium (LA). There was a significant improvement in LVEDd (67,9mm vs 64,9mm, p &amp;lt; 0.01), LVESd (61,6mm vs 58,8mm, p &amp;lt; 0.01) and stroke volume (40,5 to 45,8ml, p &amp;lt; 0.01). There was no significant increase in LVEF (30% vs 31,5%, p = 0.052). The diastolic parameters of LV function didn’t change during the study. The LA volumes significantly decreased (110 vs 92ml, p &amp;lt; 0.01) during the treatment period as well as the degree of MR (ERO 0.51 vs 0,37 p &amp;lt; 0.01). Out of several LV deformation parameters, only global longitudinal strain has changed significantly (GLS-6,1% vs -7,0%, p = 0,02). The improvement in symptoms and 6MWT correlated only with global systolic radial (RS) and longitudinal (GLS) strain correlated positively after 30 days treatment. Conclusion:Thirty days treatment with low-dose S/V in stable, symptomatic HFrEF patients leads to symptomatic and clinical improvement which correlates with positive remodeling of the left ventricle and reduces the degree of mitral regurgitation. The GLS is a sensitive indicator of LV function improvement after short time S/V treatment and may be used to assess early response.

P1508The Coronary Arteriogenesis with combined Heparin and Exercise therapy in chronic refractory Angina (CARHEXA) trial: a double-blind randomized placebo-controlled stress echocardiographic study

Abstract Background Coronary collateral circulation exerts protective effects on myocardial ischemia due to coronary artery disease (CAD) and can be promoted by exercise (E) with heparin (H) co-administration. Whether this arteriogenetic effects is accompanied by functional improvement of left ventricle (LV) during stress remains unknown. Purpose To establish the stress-induced functional effects on LV regional and global function of 2-week cycle of H+E in patients with “no-option” CAD. Methods In a prospective, single-center, double-blind, randomized, parallel-group study we recruited 32 “no-option” patients (27 males; mean age of 61±8 years), with stable angina and CTO, refractory to OMT, not suitable for revascularization and with E-induced ischemia. All underwent 2-week cycle of E (2 E test per day, 5 days a week) and were pre-treated with i.v. 0.9% saline or unfractionated H (100 IU/kg up to maximum of 5.000IU, 10 min prior to E). Canadian Class Score (CCS) and 12-lead E-ECG for time-to-1 mm ST-segment depression were assessed at entry and after treatment. LV function was evaluated during treadmill exercise with conventional and advanced imaging indices: Wall Motion Score Index (WMSI); Ejection Fraction (EF); Force (systolic blood pressure/end-systolic volume); Global Longitudinal Strain (GLS). Results Post-treatment exercise-time and CCS improved in both groups. In H+E patients exercise-time improved from 369.8±107.8 sec to 475.3±114.6 sec (p=0.001) while in E patients improved from 384±152.7 sec to 464.8±134.1 sec (p=0.019). CCS score changed in H+E from 2.6±0.7 to 1.9±0.7 (p=0.000), and in E group from 2.4±0.7 to 2.1±0.9 (p=0.046). At peak exercise, H+E was different from E group for EF and GLS (see Table). Effects of H+E on SE parameters H+E p P+E p *H+E vs P+E STRESS Time 0 vs Time 1 Time 0 vs Time 1 Time 0 Time 1 WMSI 1.377 vs 1.279 0.005 1.404 vs 1.376 0.290 0.626 0.255 EF (%) 60.9 vs 64.8 0.016 61.2 vs 57.8 0.284 0.943 0.016 Force (mmHg/mL) 6.36 vs 6.5 0.158 5.82 vs 4.68 0.209 0.760 0.098 GLS (%) −16.96 vs −18.50 0.001 −15.79 vs −15.60 0.380 0.325 0.027 SE = stress echocardiography; H+E = heparin+exercise; P+E = placebo+exercise; Time 0 = before randomization; Time 1 = after 2-week therapy cycle. *p values. Conclusion A 2-week, H+E cycle is associated with improvement in regional and global LV function during exercise, concordantly shown by conventional (WMSI, EF) and advanced (GLS) echocardiographic indices of LV function. This integrates and supplements the classical objective index based on ST-segment depression, unable to localize and quantify the functional consequences of therapy on myocardial ischemia.

Epoxyeicosatrienoic Acid-Based Therapy Attenuates the Progression of Postischemic Heart Failure in Normotensive Sprague-Dawley but Not in Hypertensive Ren-2 Transgenic Rats.

Epoxyeicosatrienoic acids (EETs) and their analogs have been identified as potent antihypertensive compounds with cardio- and renoprotective actions. Here, we examined the effect of EET-A, an orally active EET analog, and c-AUCB, an inhibitor of the EETs degrading enzyme soluble epoxide hydrolase, on the progression of post-myocardial infarction (MI) heart failure (HF) in normotensive Hannover Sprague-Dawley (HanSD) and in heterozygous Ren-2 transgenic rats (TGR) with angiotensin II-dependent hypertension. Adult male rats (12 weeks old) were subjected to 60-min left anterior descending (LAD) coronary artery occlusion or sham (non-MI) operation. Animals were treated with EET-A and c-AUCB (10 and 1 mg/kg/day, respectively) in drinking water, given alone or combined for 5 weeks starting 24 h after MI induction. Left ventricle (LV) function and geometry were assessed by echocardiography before MI and during the progression of HF. At the end of the study, LV function was determined by catheterization and tissue samples were collected. Ischemic mortality due to the incidence of sustained ventricular fibrillation was significantly higher in TGR than in HanSD rats (35.4 and 17.7%, respectively). MI-induced HF markedly increased LV end-diastolic pressure (Ped) and reduced fractional shortening (FS) and the peak rate of pressure development [+(dP/dt)max] in untreated HanSD compared to sham (non-MI) group [Ped: 30.5 ± 3.3 vs. 9.7 ± 1.3 mmHg; FS: 11.1 ± 1.0 vs. 40.8 ± 0.5%; +(dP/dt)max: 3890 ± 291 vs. 5947 ± 309 mmHg/s]. EET-A and c-AUCB, given alone, tended to improve LV function parameters in HanSD rats. Their combination amplified the cardioprotective effect of single therapy and reached significant differences compared to untreated HanSD controls [Ped: 19.4 ± 2.2 mmHg; FS: 14.9 ± 1.0%; +(dP/dt)max: 5278 ± 255 mmHg/s]. In TGR, MI resulted in the impairment of LV function like HanSD rats. All treatments reduced the increased level of albuminuria in TGR compared to untreated MI group, but neither single nor combined EET-based therapy improved LV function. Our results indicate that EET-based therapy attenuates the progression of post-MI HF in HanSD, but not in TGR, even though they exhibited renoprotective action in TGR hypertensive rats.

Effects of prostate cancer and exercise training on left ventricular function and cardiac and skeletal muscle mass

Prostate cancer was found to reduce cardiac and left ventricle (LV) masses in association with diminished exercise capacity in rats. We tested the hypothesis that exercise training will mitigate prostate cancer-induced cardiac and skeletal muscle atrophy and improve LV function versus sedentary tumor-bearing counterparts. Copenhagen rats ( n = 39; ~5 mo old) were randomized into four groups: exercise-trained tumor-bearing (EXTB) or control (EXCON) and sedentary tumor-bearing (SEDTB) or control (SEDCON). Dunning R-3327 prostate cancer cells were injected orthotopically in 19 of the 39 animals. Treadmill exercise training was performed for 60 min/day for ~30 days. Animals underwent echocardiography to examine ventricle dimensions "Pre-" cancer injection or exercise (PRE) and 15 (Post 1) and 32-35 (Post 2) days after cancer cell injection with tissues collected after Post 2. LV TNF-α and IL-6 concentrations were measured post mortem. Cardiac and LV mass of SEDTB animals were lower than all groups ( P < 0.05). Tumor mass was negatively correlated with LV mass in EXTB (-0.75, P < 0.02) and SEDTB animals (-0.72, P < 0.02). EXCON group had higher stroke volume Post 2 assessment compared with both sedentary groups ( P < 0.05) but not EXTB animals. No difference in LV [IL-6] or [TNF-α] was found between the cancer groups. The current investigation demonstrates prostate cancer, independent of anticancer treatment, significantly reduces cardiac mass and LV mass as well as locomotor muscle masses. However, moderate-intensity exercise training can mitigate cardiac and skeletal muscle atrophy with prostate cancer and preserve the cardiac phenotype (i.e., mass and function) to that of the healthy sedentary group. NEW & NOTEWORTHY This study demonstrates the atrophic effects of prostate cancer on cardiac and skeletal muscle mass independent of anticancer treatment(s) that can be mitigated with moderate-intensity exercise. These findings have important implications for potentially improving the quality of life as well as therapeutic outcomes for patients with prostate cancer.

N-acetylcysteine attenuated sepsis-induced cardiac depression: down-regulation of MMP-2 pathway in mice

During sepsis,the inflammatory responses mediate myocardium injury,including LV dysfunction and cardiac pathophysiological changes. To understanding the pathway of sepsis in cardiac depression,we tested the hypothesis that N-acetylcysteine attenuated sepsis-induced cardiac depression through down-regulation of MMP-2 pathway. Adult (4 to 6 months) male Albino-Webster mice,and their weights ranged from 25 to 30 gm,were pre-treated with N-acetylcysteine ip following cecal ligation and puncture (CLP). Left ventricle (LV) function was assessed using a micro-catheter system. MCP-1 and cytokines mediator’s in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). Further,the cardiac MMP2 measured by qRT-PCR and the pathological changes and cells injuries in the myocardium were examined using hematoxylin and eosin staining. CLP mice displayed worse LV function. The exaggerated cardiac depression in CLP mice was associated with higher levels of MCP-1 and cytokines in plasma and myocardium together with greater cardiac levels of cTn-I and MMP2. Neutralization of sepsis by NAC resulted in improved LV function and greater reductions in inflammatory mediators,MMP2 and myocardium injury. Taken together,NAC improved LV function following sepsis through down-regulation of MMP2 and serve as a potential therapeutic in cardiac endotoxemia.

‐LCZ696, the First‐in‐Class Angiotensin Receptor Neprilysin Inhibitor, Improves Vascular Reactivity in Hypertensive Rats in the Setting of Heart Failure ‐

BackgroundLCZ696 combines an angiotensin receptor blocker (ARB) with a neprilysin inhibitor (NEPi). This inhibits RAAS over activity while simultaneously augmenting the natriuretic peptide system. LCZ696 has been shown to improve cardiovascular function in the setting of heart failure, however, its effects on vascular function have not been defined.MethodsMale spontaneously hypertensive rats (SHRs) at 18–20 weeks of age were subjected to 45 minutes of transient LAD coronary artery ligation followed by reperfusion for 8 weeks to induce heart failure with reduced ejection fraction. At 4 weeks post‐reperfusion animals received daily oral therapy of either vehicle (VEH, n=14) or 68 mg/kg LCZ696 (LCZ, n=14). Myocardial infarct size as measured by plasma troponin levels at 4 hours post‐reperfusion were similar between the study groups. After 4 weeks of therapy, thoracic aorta was collected and evaluated for vascular reactivity in a tissue chamber apparatus connected to force transducers. Vasoreactivity was assessed for the endothelium‐dependent vasodilator acetylcholine (ACh, 0.1nM–10mM) and the direct smooth muscle vasodilator sodium nitroprusside (SNP, 0.1nM–10 mM). In addition, we also studied the vasoconstriction response to the endothelial nitric oxide synthase (eNOS) inhibitor N(omega)‐nitro‐L‐arginine methyl ester (L‐NAME, 30mM). Effects on heart function were also determined via 2‐D echocardiography and measurements of left ventricle (LV) pressures.ResultsLCZ improved LV function with a significant reduction in LV end‐diastolic pressure (3.31 ± 0.39 mmHg vs 7.86 ± 1.10mmHg; p&lt;0.01). LCZ also attenuated the decrease in ejection fraction at 8 weeks post reperfusion (−6.1 ± 2.5% vs −14.3 ± 3.6%; p=0.06). LCZ treatment significantly improved vascular reactivity in the dose response relaxation curve for both ACh and SNP. There was a significant improvement in maximal relaxation in response to ACh (76.1 ± 3.6% vs 52.9 ± 3.6%; p&lt;0.0001) as well as ACh EC50 (11.0 ± 4.0 nM vs 97.3 ± 9.8 nM, p&lt;0.0001) suggesting augmented endothelium mediated vasorelaxation. Similar changes were seen in SNP maximal relaxation (90.9 ± 3.5% vs 69.1 ± 5.9%; p&lt;0.01) and SNP EC50 (26.8 ± 4.4nM vs 125.7 ± 13.4nM, p&lt;0.0001) suggesting improvements in vascular smooth muscle function. Lastly, there was an increased contraction in response to administration of L‐NAME following maximal relaxation by ACh suggesting the potential role of nitric oxide in the improvements seen in vascular reactivity (60 ± 6mg vs 40 ± 6mg, p=0.06).ConclusionLCZ696 significantly improved LV function during heart failure in the setting of hypertension with concomitant improvements in vascular reactivity. These improvements in vascular reactivity are likely a result of increased activity of eNOS and increased bioavailability of nitric oxide (NO). Studies are currently underway to evaluate eNOS function and NO levels following LCZ administration in heart failure.

Radiofrequency Renal Denervation Improves Vascular Reactivity in a Rodent Model of Heart Failure

BackgroundWe have previously reported that radiofrequency (RF) renal denervation (RDN) exerts cardioprotective effects in the setting of myocardial ischemia‐reperfusion (MI‐R) injury. The protective actions of RF‐RDN in MI‐R injury are related in part to attenuated oxidative stress and increased nitric oxide (NO) bioavailability. More recently we have demonstrated that RF‐RDN protects the failing heart independent of reductions in blood pressure. The mechanisms by which RF‐RDN affords these benefits have not been fully described, including the effects on vascular function.MethodsMale Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at 20 weeks of age were subjected to 45 minutes of transient LAD coronary artery ligation followed by reperfusion for 12 weeks. Four weeks following reperfusion animals were subjected to either bilateral RF‐RDN or a sham procedure (SHAM) with n=12 in all groups. At 12 weeks after reperfusion, thoracic aorta was harvested and vascular reactivity was evaluated. Vasoactivity was assessed for the endothelium‐dependent vasodilators acetylcholine (ACh, 0.1nM–10mM) and the calcium ionophore A23187 (A23187, 10nM‐1mM). In addition, vascular reactivity to the endothelium‐independent vasodilator sodium nitroprusside (SNP, 0.1nM–10 mM) was investigated. The effects of RF‐RDN therapy on cardiac structure and function were also determined via biweekly 2‐D serial echocardiography.ResultsRF‐RDN significantly improved cardiovascular function as reflected in improved left ventricle (LV) ejection fraction at 12 weeks following reperfusion in both SHRs (46.8 ± 2.4% vs. 30.4 ± 2.5%, p&lt;0.01) and WKYs (50.4 ± 3.0% vs 35.4 ± 2.7%; p&lt;0.05). RF‐RDN treatment significantly improved endothelium mediated vasorelaxation in both hypertensive and normotensive animals as reflected in ACh EC50 (SHR: 98.8 ± 19.2 nM vs. 349.6 ± 25.0 nM, p&lt;0.0001; WKY: 10.03 ± 1.32 nM vs. 44.97 ± 12.03 nM, p&lt;0.01). Similar improvements were seen in smooth muscle mediated vasorelaxation due to SNP (SHR: 29.4 ± 4.2 nM vs. 145.3 ± 14.2 nM, p&lt;0.0001; WKY: 11.68 ± 1.28 nM vs 39.68 ± 7.47 nM, p&lt;0.01). RF‐RDN also improved vasorelaxation to the direct endothelium‐dependent vasodilator, A23187, in hypertensive animals (SHR: 10.8 ± 1.3 nM vs. 23.2 ± 2.7 nM, p&lt;0.001) but not normotensive animals. We did not observe any significant reductions in blood pressure in either the SHR or WKY rats following RF‐RDN at anytime during the experimental protocol.ConclusionRF‐RDN significantly improved LV function in the setting of heart failure independent of blood pressure reductions. Therapy improved vascular function suggesting that the cardiovascular benefits afforded by RF‐RDN may be partially due to improved vascular function. The improved vascular reactivity and cardiac function observed following RF‐RDN may be a result of reduced oxidative stress and increased NO bioavailability. Experiments are currently underway to evaluate this possibility. Our results reveal a novel mechanism related to the beneficial effects of RF‐RDN in heart failure.

Indocyanine Green-001 (ICG-001) Attenuates Wnt/β-catenin-induces Myocardial Injury Following Sepsis.

Objective:To investigate the mechanistic pathway of both indocyanine green (ICG)-001 in attenuated endotoxemia-induced cardiac depression through downregulation cardiac Wnt/ β-catenin cell signaling.Materials and Methods:Adult (4–6 months) male Albino-Webster mice, their weights ranged from 25 to 30 g, were pretreated with ICG-001 i.p., following cecal ligation and puncture (CLP). Left ventricle (LV) function was assessed using a microcatheter system. Monocyte chemoattractant protein-1 (MCP-1) and cytokines mediators in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay. Further, the cardiac Wnt protein measured by quantitative real-time polymerase chain reaction while β-catenin analysis through Western blotting procedure. The pathological changes and cells injury in the myocardium were examined using hematoxylin and eosin staining.Results:CLP mice displayed worse LV function. The exaggerated cardiac depression in CLP mice was associated with higher levels of MCP-1 and cytokines in plasma and myocardium together with greater cardiac levels of cardiac troponin-I and Wnt/β-catenin. Neutralization of sepsis by either ICG-001resulted in improved LV function and reductions in inflammatory mediators.Conclusion:Taken together, these data showed that ICG-001 improved LV function following sepsis through downregulation of Wnt/β-catenin and serve as a potential mechanistic pathway ICG-001 in therapeutic cardiac endotoxemia in animal model.