Significant Increase In Stroke Volume Research Articles

Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study.

For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes. The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year. Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure. In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490.

Hemodynamic effects of heart rate lowering in patients admitted for acute heart failure: the RedRate-HF Study (Reduction of heart Rate in Heart Failure).

In patients admitted for acute heart failure (HF) indication for drugs which reduce the heart rate (HR) is debated. The multicentre prospective study Reduction of heart Rate in Heart Failure (RedRate-HF) was designed to analyse the hemodynamic effects of an early reduction of HR in acute HF. Hemodynamic parameters were recorded by using the bioimpedance technique, which was shown to be accurate, highly reproducible and sensitive to intra-observer changes. Lowering HR was obtained by ivabradine 5 mg bd, given 48-72 h after admission on the top of optimized treatment. Patients were followed at 24, 48, 72 h after drug assumption and at hospital discharge. Twenty patients of a mean age of 67 ± 15 years, BNP at entry 1348 ± 1198 pg/ml were enrolled. Despite a clinical stabilization, after 48-72 h from admission, HR was persistently >70 bpm. Ivabradine was well tolerated in all patients with a significant increase in RR interval from 747 ± 69 ms at baseline to 948 ± 121 ms at discharge, P < 0.0001. Change in HR was associated with a significant increase in stroke volume (baseline 73 ± 22 vs. 84 ± 19 ml at discharge, P = 0.03), and reduction in left cardiac work index (baseline 3.6 ± 1.2 vs. 3.1 ± 1.1 kg/m2 at discharge, P = 0.04). Other measures of heart work were also significantly affected while cardiac output remained unchanged. The strategy of an early lowering of HR in patients admitted for acute HF on top of usual care is feasible and safe. The HR reduction causes a positive increase in stroke volume and may contribute to saving energy without affecting cardiac output.

854 SODIUM NITROPRUSSIDE IN ACUTE HEART FAILURE: EFFECTS ON LV AFTERLOAD AND VENTRICULO-ARTERIAL COUPLING

Abstract Background Acute heart failure (AHF) with left ventricle (LV) dysfunction is characterized by a condition of afterload mismatch without preload reserve. LV ejection fraction (LVEF) and stroke volume (SV) become thus dependent on the afterload. Owing to its arteriolar vasodilator properties, sodium nitroprusside (SNP) may reduce LV afterload and result particularly beneficial in this setting, improving LV ejection and ventriculo-arterial coupling (VAC). Hypothesis We aimed to assess the effect of SNP on LV afterload (arterial elastance, Ea), LV contractility (end-systolic elastance, Ees) and VAC (Ea/Ees ratio) in AHF patients. Methods Patients with AHF receiving SNP were prospectively enrolled and underwent Ea and Ees estimation with a single-beat echocardiographic method, before and after SNP infusion. The method was described by Chen et al (J Am Coll Cardiol, 2001) and Kelly et al (Circulation, 1992). Echocardiography was analyzed by a physician blinded to the images timing. Results A total of 36 AHF patients [69% male, age 70 (68, 76) years] received SNP infusion and were enrolled. Patients were admitted for acute coronary syndrome (47%) and for worsening heart failure (53%). SNP median dose was low: 0.30 (0.21-0.57) mcg/kg/min. SNP led to a trend to SBP reduction [140 (131-150) vs 158 (140-168) mmHg; p=0.002]. Heart rate did not change: 84 (75, 92) vs 83 (72, 94) bpm; p=0.800. Afterload (Ea) was reduced following SNP infusion: 2.2 (1.9, 2.7) vs 2.8 (2.4, 3.4) mmHg/mL; p&amp;lt;0.001. LV contractility (Ees) was unchanged: 1.3 (0.8, 2.2) vs 1.5 (0.9, 3.4) mmHg/mL; p=0.13. End-diastolic volume did not change: 148 (110, 205) vs 146 (108, 213) mL; p=0.880. These effects led to an increased SV: 56 (47, 67) vs 50 (38, 56) mL; p&amp;lt;0.001; p&amp;lt;0.001 and, subsequently to an increased EF [40 (30, 50) vs 30 (20, 40)%; p&amp;lt;0.001]. The VAC did not significantly change after SNP infusion: 1.5 (0.9-2.8) vs 1.6 (0.9-2.7); p=0.64. Conclusion In this report on consecutive AHF, low-dose SNP did not significantly affect VAC but led to a significant reduction in LV afterload and to a significant increase in SV and LVEF.

ECHOCARDIOGRAPHIC EVALUATION OF LEFT VENTRICULAR REMODELING AFTER VALSARTAN/SACUBITRIL INITIATION IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION

ECHOCARDIOGRAPHIC EVALUATION OF LEFT VENTRICULAR REMODELING AFTER VALSARTAN/SACUBITRIL INITIATION IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION

Mechanisms for blood pressure reduction following isometric exercise training: a systematic review and meta-analysis.

Isometric exercise training (IET) is established as an effective antihypertensive intervention. Despite this, the physiological mechanisms driving blood pressure (BP) reductions following IET are not well understood. Therefore, we aimed to perform the first meta-analysis of the mechanistic changes measured following IET. PubMed, Cochrane library and SPORTDiscus were systematically searched for randomized controlled trials published between January 2000 and December 2021 reporting the effects of IET on resting BP and at least one secondary mechanistic parameter following a short-term intervention (2-12 weeks). Eighteen studies with a pooled sample size of 628 participants were included in the final analysis. IET produced significant reductions in resting systolic and diastolic BP of 9.35 mmHg (95% confidence interval [CI] = -7.80 to -10.89, P < 0.001) and 4.30 mmHg (CI = -3.01 to -5.60, P < 0.001), respectively. Mechanistically, IET produced a statistically significant reduction in resting heart rate (mean difference [MD]: -1.55 bpm, CI = -0.14 to -2.96, P = 0.031) and a significant increase in stroke volume (MD: 6.35 ml, CI = 0.35 to 12.60, P = 0.038), with no significant change in cardiac output. Conversely, total peripheral resistance (TPR) significantly decreased following IET (MD: -100.38 dyne s -1 cm 5 , CI = -14.16 to -186.61, P = 0.023), with significant improvements in the low frequency to high frequency heart rate variability ratio (MD: -0.41, CI = -0.09 to -0.73, P = 0.013) and baroreceptor reflex sensitivity (MD: 7.43 ms/mmHg, P < 0.001). This work demonstrates that a reduction in TPR, potentially mediated through enhanced autonomic vasomotor control, is primarily responsible for BP reductions following IET. Furthermore, this novel analysis suggests wall squat interventions to be the most effective IET mode, with clinically relevant differences in BP reductions compared to handgrip and leg extension IET; although future direct comparative research is required.

Change in Central Cardiovascular Function in Response to Intense Interval Training: A Systematic Review and Meta-analysis.

High-intensity interval training and sprint interval training significantly increase maximal oxygen uptake (V̇O 2max ), which enhances endurance performance and health status. Whether this response is due to increases in central cardiovascular function (cardiac output (CO) and blood volume) or peripheral factors is unknown. This study aimed to conduct a systematic review and meta-analysis to assess the effects of high-intensity interval training and sprint interval training (referred to as intense interval training) on changes in central cardiovascular function. We performed a systematic search of eight databases for studies denoting increases in V̇O 2max in which CO, stroke volume (SV), blood volume, plasma volume, end-diastolic/systolic volume, or hematocrit were measured. Forty-five studies were included in this analysis, comprising 946 men and women of various health status (age and V̇O 2max , 20-76 yr and 13-61 mL·kg -1 ·min -1 ) who performed 6-96 sessions of interval training. Results showed an increase in V̇O 2max with intense interval training that was classified as a large effect ( d = 0.83). SV ( d = 0.69), and CO ( d = 0.49) had moderate effect sizes in response to intense interval training. Of 27 studies in which CO was measured, 77% exhibited significant increases in resting CO or that obtained during exercise. Similarly, 93% of studies revealed significant increases in SV in response to intense interval training. Effect sizes for these outcomes were larger for clinical versus healthy populations. Plasma volume, blood volume, and hematocrit had small effect sizes after training ( d = 0.06-0.14). Increases in V̇O 2max demonstrated with intense interval training are attendant with increases in central O 2 delivery with little contribution from changes in hematocrit, blood volume, or plasma volume.

THE EFFECT OF AN OUTPATIENT EXERCISE REHABILITATION PROGRAM ON HAEMODYNAMICS AND CARDIAC MRI PARAMETERS OF RV FUNCTION IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION

TYPE: Abstract TOPIC: Pulmonary Rehabilitation PURPOSE: To assess the effect of outpatient exercise on haemodynamics and right ventricular function in patients with Pulmonary Arterial Hypertension (PAH), a subgroup of PH. METHODS: Sixteen patients were randomised to either 12 week outpatient multidisciplinary rehabilitation (MDR) or home walking (exercise training, ET). The MDR program consisted of twice weekly (1hr) supervised exercise, and three psychology telehealth consultations. The ET group were instructed to undertake daily walking, aiming for 30mins per day. Primary outcome measures were right ventricular ejection fraction (RVEF), stroke volume (SV) and SV Index (SVI). Secondary outcomes included: haemodynamic measurements on right heart catheterisation (RHC); six minute walk test (6MWT), vital capacity, dominant hand grip strength (DHGS) and health-related quality of life questionnaires (CAMPHOR and DASS-21). Mixed factorial repeated measures analyses of variance (RM-ANOVAs) were used to examine longitudinal outcome data over time. RESULTS: Significant improvements occurred from baseline to week 12 across the cohort as a whole. These include reduction in mean pulmonary artery wedge pressure (p=0.015), significant increase in SV (p=0.025) and SVI (p=0.016), vital capacity (p=-0.05) and DHGS (p=0.032). Symptoms (p=0.04), depression (p=0.011) and anxiety (p=0.043) improved with exercise. There were no significant differences between the groups in the outcomes tested. Patients reported a high level of satisfaction with both programs when interviewed following the intervention. CONCLUSIONS: Outpatient exercise training/multidisciplinary rehabilitation was feasible and safe for patients with PAH. Such a program may induce physiological and psychological benefits and further, larger studies are warranted. CLINICAL IMPLICATIONS: Exercise based rehabilitation has both both physiological and psychological benefits in patients with Pulmonary Hypertension. DISCLOSURE: The ExPAH study was supported by an unrestricted research grant by Janssen (formerly Actelion). All authors had complete research independence for study protocol design, methodology, analysis and reporting of results. KEYWORD: Pulmonary Hypertension

Efficacy of Stroke Volume Variation-guided Fluid Management of Patients undergoing Off-pump Coronary Artery Bypass Grafting: An Observational Comparative Study between Open and Closed Chest

Introduction: Functional haemodynamic monitoring using dynamic parameter such as Stroke Volume Variation (SVV), based on pulse contour analysis, helps in predicting fluid responsiveness in off pump Coronary Artery Bypass Grafting (CABG) surgery. This allows adequate volume replacement to achieve optimal cardiac performance. Aim: To evaluate the efficacy of SVV in predicting volume responsiveness and effect on haemodynamic variable in patients undergoing off pump CABG in both closed and open chest. Materials and Methods: This single-centre, non randomised observational study was conducted at a tertiary medical college and hospital (LokmanyaTilak Municipal Medical College and General Hospital) Mumbai, Maharashtra, India, from December 2016 to December 2018. A total of 34 patients undergoing elective off pump CABG were included. Haemodynamic measurements Stroke Volume (SV), Cardiac Output (CO), Cardiac Index (CI), and SVV, were recorded with the transducer positioned at the level of midaxillary line. If the SVV was equal to or higher than 12, 100 mL fluid aliquot was given to patients. Endpoints for fluid aliquots was increase in CO by 15%, decrease in SVV of less than 12 or an increase Central Venous Pressure (CVP) upto 15 millimeter of mercury (mmHg). Number of times SVV above 12 during the procedure was recorded. SVV was considered as fluid responsive “if there was an increase in SV by 5%”. Statistical analysis was done using Student’s t-test (two tailed, dependent) on continuous parameters. The p-value &lt;0.05, was considered significant. Results: Out of 103 events of rise in SVV, 65 (63.1%) occurred when chest was open and 38 (36.9%) while chest was closed. The SVV-guided fluid response was 76.3% in closed chest and 75.4% in open chest and there was no significant difference. (p-value=0.91). There was a significant increase in SV (p-value&lt;0.01), CO (p-value=0.04), and significant decrease in SVV (p-value&lt;0.01) and heart rate (p-value&lt;0.01) after fluid loading in the responsive group when compared with non responsive group. There was no statistically significant difference between percentage change in SV, CO, CI, SBP, DBP, MAP and CVP between closed and open chest conditions after fluid replacement. Conclusion: SVV is not affected by open or closed chest conditions in mechanically ventilated patients undergoing CABG and can be used as a guide for fluid replacement. Weather open or closed chest conditions, few patients do not respond to fluid replacement when SVV are more than 12 by an increase in SV, cardiac output or CI, the cause of which remains to be determined.

Existing fluid responsiveness studies using the mini-fluid challenge may be misleading: Methodological considerations and simulations.

The mini-fluid challenge (MFC) is a clinical concept of predicting fluid responsiveness by rapidly infusing a small amount of intravenous fluids, typically 100ml, and systematically assessing its haemodynamic effect. The MFC method is meant to predict if a patient will respond to a subsequent, larger fluid challenge, typically another 400ml, with a significant increase in stroke volume. We critically evaluated the general methodology of MFC studies, with statistical considerations, secondary analysis of an existing study and simulations. Secondary analysis of an existing study showed that the MFC could predict the total fluid response (MFC+400ml) with an area under the receiver operator characteristic curve (AUROC) of 0.92, but that the prediction was worse than random for the response to the remaining 400ml (AUROC=0.33). In a null simulation with no response to both the MFC and the subsequent fluid challenge, the commonly used analysis could predict fluid responsiveness with an AUROC of 0.73. Many existing MFC studies are likely overestimating the classification accuracy of the MFC. This should be considered before adopting the MFC into clinical practice. A better study design includes a second, independent measurement of stroke volume after the MFC. This measurement serves as reference for the response to the subsequent fluid challenge.

The role of thyrostatic agents in the treatment of chronic heart failure patients with comorbid coronary artery disease and thyrotoxicosis

Background: Thyroid dysfunction exerts a pronounced effect on the cardiovascular system, and, if comorbid with an existing cardiovascular disorder, may lead to a significant deterioration in the outcome, thus obviating the need for timely diagnosis and therapy optimization.Aim: To evaluate the effect of combination therapy, including thyrostatics, on the clinical symptoms of chronic heart failure (CHF), heart rate variability, NT-proBNP concentration, and structural and functional parameters of the left heart in patients with comorbid coronary artery disease (CAD) and thyrotoxicosis.Materials and methods: This open-label comparative study included 77 patients aged 45–65 years. The study group consisted of 36 patients with thyrotoxicosis, CAD and CHF II–III functional class, whereas the comparison group consisted of 41 patients with thyrotoxicosis without cardiovascular diseases. The patients were assessed clinically at baseline and after 6 months of therapy with addition of a thyrostatic, with tolerance to physical activity, measurements of NT-proBNP levels, 24-hour Holter monitoring, and echocardiography.Results: At 6 months of the combination therapy including a thyrostatic, with stable drug-induced euthyroidism, the patients in the group 1 showed an increase in the distance of a 6-minute walking test (p&lt;0.001) and a decrease in CHF clinical symptoms. The incidence of heart rhythm disorders decreased (supraventricular extra systoles from 31% to 16%, ventricular extra systoles from 21% to 4%, atrial fibrillation from 32% to 23%; p&lt;0.05), with a positive trend for spectral and temporal parameters of heart rate variability. The NT-proBNP level in patients with CAD, CHF and thyrotoxicosis decreased by 42.9% (p=0.001). During euthyrosis, echocardiography in the patients with ischemic CHF and concomitant thyrotoxicosis showed a significant increase in stroke volume (p=0.03), stroke ejection index (p=0.04), left ventricular ejection fraction (p=0.01), a decrease in the value of myocardial stress (p=0.02), and transmitral blood flow parameters (E/A, p&lt;0.05). This indicates an improvement in systolic and diastolic left ventricular function after normalization of thyroid function.Conclusion: The inclusion of thyreostatics to the combination therapy and the achievement of euthyrosis have contributed to increased tolerance to physical activity, reduction of sympathetic activity level of the autonomic nervous system and frequency of heart rhythm disorders, reduced the NT-proBNP levels, improved systolic and diastolic left ventricular function in patients with ischemic CHF and concomitant thyrotoxicosis.

Functional Recovery after Intramyocardial Injection of Adipose-Derived Stromal Cells Assessed by Cardiac Magnetic Resonance Imaging.

Aims A major clinical concern is the continuous increase in the number of patients diagnosed with advanced coronary artery disease, ischemic heart failure, and refractory angina, and one of the most promising treatment options for these conditions is stem cell-based therapy. The aim of this study was to assess the functional improvement following intramyocardial injection of adipose-derived stromal cells, using cardiac magnetic resonance. Methods and Results Thirteen patients with ischemic heart failure, reduced left ventricular ejection fraction, refractory angina, and who have been disqualified from any form of direct revascularization were enrolled in the study with transthoracic autologous adipose-derived stromal cell implantation. All patients underwent cardiac magnetic resonance prior to the procedure and after 12 months of follow-up. A significant increase in stroke volume (83.1 ± 8.5 mL vs 93.8 ± 13.8 mL, p = 0.025) and stroke volume index (43.3 ± 7.6 mL/m2 vs 48.7 ± 9.1 mL/m2, p = 0.019), a statistical trend toward an increase in left ventricle ejection fraction (36.7 ± 13.2 vs 39.7 ± 14.9, p = 0.052), and cardiac output improvement (5.0 ± 0.7 vs 5.5 ± 0.9, p = 0.073) was observed in the patient postprocedure. Enhanced relative regional thickening was noted in the segments with adipose-derived stromal cell implantation. Conclusions Intramyocardial adipose-derived stromal cell implantation is a promising therapeutic option for selected, symptomatic patients with ischemic heart failure, who have preserved myocardial viability despite being unsuitable for direct revascularization.

Contractile Responses of Murine Hearts Subjected to Different Modes of Motor Activity to Traumatic Brain Injury.

For the first time ever, this research studied the response of stroke volume in animals to various modes of motor activity after a traumatic brain injury. The study showed a pronounced decrease in stroke volume (SV) the first day after modeling an open craniocerebral injury in rats of all age groups. At the same time, the smallest SV response to brain injury was observed in immature animals. After modeling a traumatic brain injury, it was found that the implementation of systematic dynamic exercises by animals of pre-senile agedoes not contribute to increase SV; a significant increase in SV after a traumatic brain injury is observed only in immature animals. It was revealed that limiting physical activity and the performance of isometric exercises after a traumatic brain injury restrain a natural increase in SV in immature rat pups and decrease SV in sexually mature and pre-senile animals.

Neuropeptide Y3-36 incorporated into PVAX nanoparticle improves angiogenesis in a murine model of myocardial ischemia

Neuropeptide-Y (NPY) leads to angiogenesis and remodeling of the ischemic myocardium. The objective of this study is to assess the therapeutic potential of NPY in a model of acute myocardial ischemia using a nanoparticles delivery system targeted to tissue with oxidative stress.NPY3-36 was loaded onto copolyoxalate containing vanillyl alcohol (PVAX) using a double emulsification strategy. Adult C57BL/J6 mice (n = 49) were randomly divided into PVAX-NPY3-36 (n = 22), Vehicle (Saline) (n = 16), and Sham (n = 11) groups. The ischemia to left anterior descending artery was induced in PVAX-NPY3-36 or vehicle groups. The tissue was collected at the end of two weeks after assessing the functional and echocardiographic data. There was a significant decrease in infarction size and mortality in PVAX-NPY3-36 group compared to the Vehicle group (P = 0.01 and P = 0.05). On echocardiography, there was significant improvement in contractility and diastolic parameters (P = 0.01). On pressure-volume loop there was significant increase in stroke volume (P = 0.01), cardiac output (P = 0.01) and ventricular stroke work (P = 0.01) in the PVAX-NPY3-36 group. On Western blot analysis, there was a significant increase in pro-angiogenic factors Ang-1, TGF-β, PDGF- β and its receptors and VEGF in the ischemic tissue treated with PVAX-NPY3-36 as compared to Vehicle ischemic tissue (P = 0.01, P = 0.0003, and P < 0.05 respectively).It may be possible to have targeted delivery of labile neurotransmitters NPY3-36 to the ischemic myocardium using nanoparticle PVAX and achieving angiogenesis and significant functional improvement.

Inhibition of Sodium Glucose Cotransporter‐2 Improves Cardiac Efficiency During Regional Myocardial Ischemia Independent of Sodium/Hydrogen Exchanger‐1

Recent clinical outcome studies demonstrate that inhibitors of the type 2 sodium glucose cotransporters (SGLT2i) significantly reduce major adverse cardiovascular events and heart failure outcomes in type 2 diabetes mellitus. The mechanisms underlying these clinical benefits remain to be elucidated. We tested the hypothesis that SGLT2i improves cardiac function and efficiency during acute, regional ischemia/reperfusion injury via inhibition of cardiac sodium/hydrogen exchanger‐1 (NHE‐1). Lean swine (~50 kg) were anesthetized, a thoracotomy was performed, and perivascular flow transducers were placed around the left anterior descending and circumflex coronary arteries. A pressure‐volume catheter was then inserted into the left ventricle. Swine received a 15–30 min (0.05–0.1 mL/min) infusion of vehicle (DMSO), the SGLT2i canagliflozin (30 μM), or the NHE‐1 inhibitor (NHE‐1i) cariporide (1 μM) immediately prior to a 60 min occlusion of the left circumflex artery followed by a 2‐hour reperfusion period. Mean arterial pressure decreased from ~91 ± 3 mmHg at baseline to ~62 ± 3 mmHg following 60 min of myocardial ischemia in control, canagliflozin and cariporide treated swine. Heart rate averaged ~78 beats/min at baseline and throughout the ischemic period, however, SGLT2i significantly increased heart rate during reperfusion compared to control and NHE‐1i treated swine. SGLT2i was associated with a significant increase in left ventricular end diastolic volume (P = 0.02) that corresponded with a significant increase in stroke volume (P = 0.03) and cardiac efficiency (P &lt; 0.001) relative to control animals. End diastolic volume, stroke volume, and efficiency were not significantly affected by ischemia/reperfusion injury in either the control or NHE‐1i treated animals. Additional fluorometric assays of antiport‐deficient Chinese hamster ovary (AP‐1) cells transfected with wild‐type NHE‐1 showed dose‐dependent inhibition of NHE‐1 activity by cariporide (IC50 = 0.11 mM), while canagliflozin had minimal effect on overall activity. This investigation demonstrates that SGLT2i improves cardiac function and efficiency during acute, regional ischemia in healthy swine. However, these data argue against an important role of NHE‐1 inhibition in mediating the beneficial cardiac effects of SGLT2i.Support or Funding InformationEli Lilly and Company

P4604Insights into left ventricular remodelling and clinical outcomes after Wharton's jelly multipotent stem cells transcoronary administration in a pilot cohort of CIRCULATE-AMI Trial (NCT03404063)

Abstract Introduction CIRCULATE-Acute Myocardial Infarction Trial (NCT03404063) is a double-blind controlled trial (RCT) that is randomizing consecutive patients with their first, large AMI (LVEF ≤45% and/or cMRI -infarct size ≥10% of LV) successfully treated by infarct-related artery (IRA) primary percutaneous coronary intervention reperfusion (TIMI ≥2) to transcoronary administration of Wharton Jelly Multipotent Stem Cells (WJMSCs) vs. placebo (2:1), preceded by evaluation of safety, WJMSCs myocardial uptake, and echocardiographic, cMRI and SPECT left ventricular remodelling and hemodynamic changes in pilot study cohort (PSC). Purpose To evaluate LV remodelling and hemodynamic features following WJMSCs transplantation in CIRCULATE-AMI PSC. Methods Ten consecutive patients (age 32–65 years) were administered 30 000 000 WJMSCs via the infarct-related artery at ≈5–7 days after AMI using transradial approach and a coronary-non-occlusive catheter dedicated to cell delivery. Within 3 years of follow up SPECT was performed at baseline and 1 year, echo and cMRI were performed at baseline, 1 year and 3 years. Results 3-year observation (cMRI) shows a significant decrease of median left ventricular mass (LVM) between WJMSCs administration and 1 year 140 g (IQR 128–150) vs. 97 g (95–128), that is sustained at 3 years 93 g (80–119), p&lt;0,001. There were no significant changes of left ventriular end-diastolic volume (LVEDV) in all diagnostic methods: SPECT baseline vs. 1 year (157.1±27.1 ml vs. 174±24 ml); cMRI baseline vs. 1 year vs. 3 years (171.6±17.7 ml vs. 198.2±23.4 ml vs. 181.9±17.6 ml) and Echo (137±13.3 ml vs. 135±2.9 ml vs. 148±21.8 ml), p value &gt;0,05 for all. Furthermore, there was a significant increase in stroke volume measured by SPECT baseline vs. 1 year (53.3±7.6 ml vs. 68.2±5.2ml); cMRI baseline vs. 1 year vs. 3 years (72.7±5.2 ml vs. 96.9±8.1 ml vs. 93.2±7.8 ml) and Echo (64.3±2.9 ml vs. 68.8±4.1 ml vs. 81.9±7.1 ml), p&lt;0,05 for all. By 3 years there was one non-index territory AMI. There were no other adverse events in the study cohort. cMRI Left Ventricular Mass evolution Conclusions Long-term follow up in CIRCULATE-AMI PSC suggests that transcoronary administration of WJMSCs in a recent large AMI in humans might be associated with an inhibition of LV adverse remodelling and a significant hemodynamic improvement. Our currently running randomized double-blind controlled trial will verify LV remodelling evolution in WJMSCs-treated patients. Acknowledgement/Funding K/ZDS/00564 Jagiellonian University Medical College; STRATEGMED 265761 “CIRCULATE” National Centre for Research and Development/Poland

Conversion to and maintenance of sinus rhythm do not yield a significant increase in stroke-volume in HFREF patients, whose heart works on the flat branch of Frank-Starling curve, thereby making the retrieval of the atrial mechanical contribution in this subset a substantially futile choice.

Conversion to and maintenance of sinus rhythm do not yield a significant increase in stroke-volume in HFREF patients, whose heart works on the flat branch of Frank-Starling curve, thereby making the retrieval of the atrial mechanical contribution in this subset a substantially futile choice.

The hemodynamic effects of a central iliac arteriovenous anastomosis at 6months in patients with resistant and uncontrolled hypertension.

A central iliac arteriovenous anastomosis, termed the "coupler" (ROX Medical), results in a significant reduction in blood pressure (BP) in hypertensive patients. This study assessed functional and hemodynamic changes induced by the device. Twenty-one patients with resistant and/or uncontrolled hypertension underwent stress echocardiography and cardiopulmonary exercise testing (CPET) at baseline and 6months post-coupler implantation. End points were selected to best evaluate cardiac function including Doppler stroke volume (SV), septal and lateral E/E', and right ventricular systolic velocity S' (RV S'). CPET VO2 peak demonstrated total cardiopulmonary performance. SV increased from 76.4 SD12.2mL to 92.1 SD22.7mL 6months post-coupler insertion; P=.002. No changes in RV S', septal or lateral E/E', or VO2 peak were observed. Five patients experienced increased diuretic requirement ≥3 times baseline. RV S' fell from 19.0 SD1.87cm/s to 16.80 SD3.43cm/s in these patients (P>.05). A significant increase in SV 6months post-coupler insertion was observed. In patients with increased diuretic requirement, the device was associated with a lower RV S' suggesting occult RV dysfunction as the mechanism of this pre-specified adverse outcome.

Cardiovascular Effects of Sodium Glucose Cotransporter-2 (SGLT-2) Inhibition in the Setting of Ischemia/Reperfusion Injury

Background and Hypothesis: Recent evidence indicates that sodium glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce the incidence of major adverse cardiovascular events in high risk patients. However, the specific effects of SGLT2i on the cardiovascular system remain poorly defined. This study was designed to test the hypothesis that SGLT2i improves cardiac function and mitigates myocardial infarct size following regional myocardial ischemia and reperfusion injury. &#x0D; Experimental Design: Lean domestic swine received placebo (n=6) or canagliflozin (n=6; 300 mg PO) 24 hours prior to and the morning of an experiment. Hemodynamics, left ventricular pressure and volume were measured in open chest, swine at baseline, during a 60 min coronary occlusion, and during a 2-hour reperfusion period. The degree of myocardial infarction was assessed by staining with 1% tetrazolium. &#x0D; Results: At the onset of ischemia, SGLT2i produced a significant parallel increase in both left ventricular end diastolic (85 ± 9 mL to 129 ± 10 mL; P &lt; 0.05) and end systolic volumes (29 ± 8 mL to 78 ± 9 mL; P &lt; 0.01). This increase in ventricular filling was associated with significant increases in stroke volume (P &lt; 0.05) and stroke work (P &lt; 0.05) relative to untreated controls swine during ischemia. SGLT2i decreased infarct size from 9.4 [Symbol] 2.1% in control swine to 3.1 [Symbol] 0.98% in SGLT2i treated swine. &#x0D; Conclusion: SGLT2 inhibitors significantly improve cardiac contractile function and mitigate myocardial infarct size following regional myocardial ischemia and reperfusion injury in domestic swine.

Assessment of left ventricular hemodynamics and systolic function in patients with apical aneurysm after percutaneous ventricular restoration by echocardiography

Objective To evaluate the changes of left ventricular hemodynamics and systolic function in patients with apical aneurysm after percutaneous ventricular restoration(PVR) by echocardiography. Methods Fifty patients with apical aneurysm were divided into PVR group (25 cases) and conservative treatment group(control group, 25 cases). Two-dimensional transthoracic echocardiography(2D-TTE) combined with real-time three-dimensional transesophageal echocardiography(RT-3DTEE) were applied for all the subjects in PVR group on preoperative, one week after operaction, three months after operaction and in control group on initial stage of prevent ventricular remodeling therapy, one week after therapy, three months after therapy to obtain left ventricular end-diastolic diameter(LVEDD), left ventricular end-systolic diameter(LVSDD), left ventricular end-diastolic volume(EDV), end-systolic volume(ESV), left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), body surface area(BSA), stroke volume(SV), stroke volume index(SVI), cardiac output(CO), cardiac output index(CI). Results There were significant differences in all parameters(P 0.05). Compared with preoperative, there was no difference in all parameters in the following one week after operaction(P>0.05), there was significant increase in SV and significant reduce in LVEDD and EDV (P 0.05). For the control group there was no significant difference between initial stage of prevevt ventricular remodeling therapy and in the following one week or three months after operaction. Conclusions PVR has a definite effect on left ventricular hemodynamics and systolic function in patients with apical aneurysm in the short term, while 2D-TTE and RT-3DTEE provides a reliable basis for clinical to evaluate the effect of the PVR. Key words: Echocardiography; Apical aneurysm; Percutaneous ventricular restoration; Ventricular function, left; Hemodynamics

Inhibition of Sodium Glucose Cotransporter‐2 Preserves Cardiac Function during Regional Myocardial Ischemia via a Frank‐Starling Mechanism

Recent evidence indicates that sodium glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce the incidence of major adverse cardiovascular events in high risk patients. However, the specific effects of SGLT2i on the cardiovascular system remain poorly defined. This study tested the hypothesis that SGLT2i improves cardiac function during acute regional myocardial ischemia and reperfusion. Lean domestic swine (~50 kg; control (n = 6), SGLT2i (n = 5)) were randomized to receive either placebo or oral doses of canagliflozin (300 mg) 24 hours prior to and the morning of a terminal experimental procedure. Measurements were obtained in open chest, anesthetized swine at baseline, during a 30 min complete occlusion of the circumflex coronary artery, and during a 2 hour reperfusion period. Blood pressure (85 ± 6 mmHg), heart rate (78 ± 7 beats/min), coronary flow (0.40 ± 0.05 mL/min/g), and myocardial oxygen consumption (43 ± 6 μL O2/min/g) were unaffected by canagliflozin treatment at rest and were not significantly altered by ischemia/reperfusion in either group. At the onset of ischemia, SGLT2i produced a significant parallel increase in both left ventricular end diastolic (85 ± 9 mL to 129 ± 10 mL; P < 0.05) and end systolic volumes (29 ± 8 mL to 78 ± 9 mL; P < 0.01) that was manifest ~30 to 90 sec post coronary artery occlusion. Left ventricular volumes remained elevated throughout the ischemic period and returned to baseline levels following ~30 min of reperfusion. Ventricular volumes remained unchanged in control swine throughout the entire protocol. Canagliflozin-mediated increases in end diastolic volume were directly associated with significant increases in stroke volume (P < 0.05) and stroke work (P < 0.05) relative to untreated controls swine during ischemia. SGLT2i also increased cardiac efficiency (P < 0.05), as defined by stroke work/myocardial oxygen consumption. No differences in myocardial substrate uptake of glucose (P = 0.54) or lactate (P = 0.16) were noted between groups at any experimental time point. These data support the hypothesis that SGLT2i preserves cardiac contractile function during regional myocardial ischemia via activation of a Frank-Starling mechanism and independent of alterations in myocardial substrate selection. Attached figure illustrates control responses (black) and SGLT2i responses (red). Support or Funding Information NIH HL117620 Representative pressure volume loops from control (black) and SGLT2i treated (red) animals under baseline (solid) and ischemic (dashed) conditions are presented in panels A & B. Panels C & D illustrate the rate of change to ventricular volume parameters present in treated (D) but not control (C) animals subsequent to onset of ischemia. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.