Preserved Ventricular Function Research Articles

Pulmonary artery banding in infants and young children with end-stage left ventricular dilated cardiomyopathy-Cohort Study.

Dilated cardiomyopathy (DCM) is the most common cardiomyopathy and 40-50% patients may die or need heart transplant in 5 years after diagnosis. Although heart transplantation being the most effective life-saving option of end-stage DCM, scarcity of donors and series of complications prevent many patients from receiving timely treatment. Pulmonary artery banding (PAB) is recently described as an alternative strategy for end-stage DCM, with low left ventricular function (LVEF) but preserved right ventricular function, may potentially restore heart function and delay the need for heart transplantation, but current clinical evidence is still insufficient. On the other hand, the medication treatment of DCM in pediatric patients is mostly based on the experience of adults. It remains unclear whether PAB combing medication treatment could benefit infants and young children patients. The aim of this study was to assess the short-term efficacy of PAB combined with medication therapy in infants and young children with end stage DCM, comparing with medication therapy alone. This is a retrospective analysis of 18 consecutive pediatric patients aged ranging from 1 month to 44 months old who diagnosed with end-stage DCM (LVEF30%) with preserved right ventricular function between 2019 and 2023 in our hospital. All patients had been treated with conventional medications for two months. Then they were divided in two groups: PAB surgery group (6/18), and non-surgery group (12/18). Regardless of whether surgery was performed, both groups continued to receive medication treatment. Recovery of ventricular function was primary endpoints. Secondary endpoints included 180-day mortality and severe heart failure (LVEF≤30%). We found there were no differences in age, weight, height, BMI, renal function, liver function, pulmonary hypertension, tricuspid valve regurgitation, mitral valve regurgitation and genetic abnormalities between those with and without PAB surgery. Comparing with non-surgery group, 5 patients in surgery group regain the normal cardiac ejection fraction (LVEF≥50%) (5/6, 83.3% vs. 4/12, 33.3%, P=0.131). A total of 3 patients had sudden death in non-surgery group, and there was no death in surgery group (P=0.180). 5 patients (5/12, 41.7%) still remain the low heart failure (LVEF≤40%) after 6 months of enrollment only given medical therapy, and none of patients present with LVEF≤40% in PAB surgery group (0/6, 0% vs. 8/12, 67.7%, P=0.034). Pulmonary artery banding is safe and effective in infants and young children with end-stage DCM with preserved right ventricular function. Combined with conventional heart failure medication therapy, it may provide short-term benefits post-operatively, decrease the cardiogenic shock, and act as a bridge to recovery and potentially reduce the need for heart transplantation. Long-term effects remain further observation, and larger randomized controlled trials would be more persuasive in validating its efficacy.

Abstract P3075: Neutrophil Secreted Chitinase 3-like-1 Antagonizes Macrophage Reparative Polarization And Contributes To Ventricular Dysfunction After Myocardial Infarction

Clinical studies show that chitinase 3-like-1 (CHI3L1) is a biomarker and predictor of all-cause mortality in heart failure. Studies from our lab demonstrated that CHI3L1 is elevated in hearts post-MI, and CHI3L1 deficiency in mice results in preserved ventricular structure and function post-MI. Furthermore, we found that CHI3L1 is secreted from activated neutrophils but has no effect on neutrophil recruitment in hearts after MI. The goal of the current study was to elucidate mechanisms whereby CHI3L1 contributes to exacerbated cardiac dysfunction after MI. Post-MI neutrophil recruitment is followed by the sequential programming of macrophages to pro-inflammatory or pro-reparative phenotypes. We sought to determine the impact of neutrophil-secreted CHI3L1 on macrophage polarization. Activated neutrophils isolated from Chil1 +/+ and Chil1 -/- mice were co-cultured with bone marrow-derived macrophages. We found that macrophages directly co-cultured with Chil1 -/- but not Chil1 +/+ neutrophils showed upregulation of the pro-reparative markers, Chil4 and Arg1 (n=5/group, p<0.05). Additionally, direct co-culture of Chil1 -/- neutrophils and macrophages showed trends towards downregulation of the pro-inflammatory polarization markers, Il1b and Tnfa relative to macrophages co-cultured with Chil +/+ neutrophils. These data suggest that neutrophil-derived CHI3L1 may antagonize signaling to polarize macrophages towards a pro-reparative phenotype that may explain delayed scar formation and exacerbated ventricular dysfunction after MI. Future efforts will elucidate the signaling role of CHI3L1 associated with neutrophil extracellular traps (NETs) on macrophage function.

Preoperative higher right ventricular stroke work index increases the risk of de novo aortic insufficiency after continuous-flow left ventricular assist device implantation

During continuous-flow left ventricular assist device (CF-LVAD) support, hemodynamic shear stress causes a burden on aortic valve (AV) leaflets, leading to de novo aortic insufficiency (AI). This study investigated the influence of preoperative hemodynamic parameters on de novo AI in CF-LVAD recipients. We reviewed 125 patients who underwent CF-LVAD implantation without concomitant AV surgery between 2005 and 2018. De novo AI was defined as moderate or severe AI in those with none or trivial preoperative AI. During mean 30 ± 16 months of CF-LVAD support, de novo AI-free rate was 86% and 67% at 1 and 2 years, respectively. Multivariable analysis showed that higher right ventricular stroke work index (RVSWI) (hazard ratio, 1.12 /g/m2/beat; 95% confidence interval, 1.00–1.20; p = 0.047) and trivial grade AI (hazard ratio, 2.8; 95% confidence interval, 1.2–6.4; p = 0.020) were independent preoperative risk factors for de novo AI. The longitudinal analysis using generalized mixed effects model showed that higher RVSWI was associated with continuous AV closure after LVAD implantation (Odd ratio, 1.20/g/m2/beat; 95% confidence interval, 1.00–1.43 /g/m2/beat; p = 0.047). Right heart catheterization revealed that preoperative RVSWI was positively correlated with postoperative pump flow index in patients with continuously closed AV (r = 0.44, p = 0.04, n = 22). Preoperative higher RVSWI was a significant risk factor for de novo AI following CF-LVAD implantation. In patients with preserved right ventricular function, postoperative higher pump flow may affect AI development via hemodynamic stress on the AV.

Comparison between different methods used for tricuspid valve repair for functional tricuspid regurge

Background: Severe functional tricuspid regurgitation represents an important unmet need in clinical cardiology given its prevalence, adverse prognostic impact and symptom burden. Surgical tricuspid valve annuloplasty remains the treatment of choice for the majority of patients, especially if the operative risk is acceptable and preserved right ventricular function is present. However, several trans-catheter techniques are currently in bench and early clinical testing to provide alternative treatment options for patients with a very high surgical risk. The aim of this study was to compare between different methods used for tricuspid valve repair for functional tricuspid regurge. Summary: Ring annuloplasty for secondary severe functional tricuspid regurge is significantly better than Devega procedure in mid-term outcome, regarding residual regurge and right ventricular remodeling. Although both procedure are equally effective in early postoperative period.

MiR Profile of Chronic Right Ventricular Pacing: a Pilot Study in Children with Congenital Complete Atrioventricular Block

Chronic ventricular pacing can lead to pacing-induced cardiomyopathy (PICM). Clinical data alone is insufficient to predict who will develop PICM. Our study aimed to evaluate the circulating miR profile associated with chronic right ventricular pacing in children with congenital complete AV block (CCAVB) and to identify candidate miRs for longitudinal monitoring. Clinical data and blood were collected from chronically paced children (N = 9) and compared with non-paced controls (N = 13). miR microarrays from the buffy coat revealed 488 differentially regulated miRs between groups. Pathway analysis predicted both adaptive and maladaptive miR signaling associated with chronic pacing despite preserved ventricular function. Greater profibrotic signaling (miRs-92a, 130, 27, 29) and sodium and calcium channel dysregulation (let-7) were seen in those paced > 10 years with the most dyregulation seen in a patient with sudden death vs. those paced < 10 years. These miRs may help to identify early adverse remodeling in this population.Graphical abstract

Pulmonary artery acceleration time accuracy for systolic pulmonary artery pressure estimation in critically ill patients

BackgroundEstimation of pulmonary pressures is of key importance in acute cardiovascular and respiratory failure. Pulmonary artery acceleration time (PAAT) has emerged as reliable parameter for the estimation of systolic pulmonary artery pressure (sPAP) in cardiological population with preserved right ventricular function. We sought to find whether PAAT correlates with sPAP in critically ill patients with and without right ventricular (RV) systolic dysfunction.MethodsObservational study. We measured sPAP using continuous-wave Doppler analysis of tricuspid regurgitation velocity peak method and we assessed the validity of PAAT in estimating sPAP in patients admitted to adult intensive care unit (ICU) for acute cardiovascular and respiratory failure.ResultsWe enrolled 236 patients admitted to cardiothoracic ICU for cardiovascular and respiratory failure (respectively: 129, 54.7% and 107, 45.3%). 114 (48.3%) had preserved RV systolic function (defined as TAPSE ≥ 17 mm), whilst 122 (51.7%) had RV systolic impairment (defined as TAPSE < 17 mm). A weak inverse correlation between PAAT and sPAP (ρ–0.189, p 0.0035) was observed in overall population, which was confirmed in those with preserved RV systolic PAAT and sPAP (ρ–0.361, p 0.0001). In patients with impaired RV systolic function no statistically significant correlation between PAAT and sPAP was demonstrated (p 0.2737). Adjusting PAAT values for log10, heart rate and RV ejection time did not modify the abovementioned correlations.ConclusionsPAAT measurement to derive sPAP is not reliable in cardiothoracic critically ill patients, particularly in the coexistence of RV systolic impairment.

Vieussens' Arterial Ring

The Vieussens' artery is an anastomotic communication between the conus branch of the right coronary artery and the left anterior descending (LAD). Vieussens' ring is so named because it circles around the great vessels in the form of a partial ring. The course of the artery can be best understood in 2 orthogonal views. In the left oblique view, the artery appears coursing upward to the left. In the right oblique view, it courses anteriorly across the right ventricular outflow tract. The clinical significance of Vieussens' arterial ring lies in it being a major source of collateral blood flow to an occluded LAD. The presence of this large collateral may explain preserved ventricular function in our patient, despite severe triple-vessel disease.

Right heart chambers geometry and function in patients with the atrial and the ventricular phenotypes of functional tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction — Atrial functional tricuspid regurgitation (A-FTR) is a recently defined phenotype of FTR associated with persistent/permanent atrial fibrillation. Differently from the classical ventricular form of FTR (V-FTR), patients with A-FTR might present with severely dilated right atrium (RA) and tricuspid annulus (TA), and with preserved right ventricular (RV) size and systolic function. However, the geometry and function of the RV, RA and TA in patients with A-FTR and V-FTR remain to be systematically evaluated. Purpose — Accordingly, we sought to: i. study the geometry and function of the RV, RA and TA in A-FTR by two- and three-dimensional transthoracic echocardiography; and ii. compare them with those found in V-FTR. Methods — We prospectively analysed 113 (44 men, age 68 ± 18 years) FTR patients (A-FTR = 55 and V-FTR = 58) that were compared to two groups of age- and sex-matched controls to develop the respective Z-scores. Results — The severity of FTR, and the degree of TA dilation were similar in A-FTR and V-FTR patients. The Z-scores of RV size were significantly larger, and those of RV function were significantly lower in V-FTR than in A-FTR (p &amp;lt; 0.001 for all). The RA was significantly enlarged in both A-FTR and V-FTR compared to controls (p &amp;lt; 0.001, Z-scores &amp;gt; 2), with similar RA maximal volumes (RAVmax) between A-FTR and V-FTR (p = 0.2). Whereas, the RA minimal volumes (RAVmin) were significantly larger in A-FTR than in V-FTR (p = 0.001). Conclusion — Despite similar degrees of FTR, RAVmax and TA size, A-FTR patients show larger RAVmin than V-FTR patients. Conversely, V-FTR patients show dilated, more elliptic and dysfunctional RV than A-FTR patients. Abstract Figure. A-FTR versus V-FTR Abstract Figure. Remodelling patterns in A-FTR and V-FTR

Inclusion of echocardiographic measure of right ventricular function in the non-invasive French pulmonary arterial hypertension risk stratification method

Although preserved right ventricular (RV) function is consistently associated with better survival in pulmonary arterial hypertension (PAH), the French risk assessment method has not yet considered echocardiographic criteria of RV function. In the present study, we tested the value of tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography for non-invasive PAH risk assessment. We retrospectively studied a cohort of 306 incident PAH patients treated in two French expert centers who underwent follow-up TAPSE measurement from echocardiographic apical 4-chamber view in addition to previously validated invasive and non-invasive risk stratification variables. The primary composite outcome was 3-year lung transplantation free survival after follow-up assessment. At re-evaluation, 66% of patients were in NYHA functional class I-II and mean pulmonary arterial pressure, cardiac index, N-Terminal pro brain natriuretic peptide (NTproBNP), and 6-minute walk distance (6MWD) were 40 ± 16 mmHg, 3.5 ± 1.1 L/min/m 2 , 270 [interquartile range (IQR) 896] ng/L and 401 (IQR 213) meters, respectively. The primary outcome occurred in 58 (19%) patients. In multivariable Cox regression analysis, NYHA functional class I-II ( P = 0.02), NTproBNP < 300 ng/L or BNP < 50 ng/L ( P = 0.02), 6MWD > 440 m ( P = 0.049) and TAPSE≥17 mm ( P = 0.02) were associated with lung transplantation free survival. TAPSE provided similar information over 6MWD when both were used alternatively to stratify PAH patients at low risk (log-rank < 0.001); Harrell's c-index 0.73 ( Fig. 1 ). Three dichotomized low-risk criteria (TAPSE, 6MWD and NTproBNP or BNP plasma levels) allow non-invasive risk assessment in PAH.

319 Right heart chambers geometry and function in patients with the atrial and the ventricular phenotypes of functional tricuspid regurgitation

Abstract Aims Atrial functional tricuspid regurgitation (A-FTR) is a recently defined phenotype of FTR associated with persistent/permanent atrial fibrillation. Differently from the classical ventricular form of FTR (V-FTR), patients with A-FTR might present with severely dilated right atrium (RA) and tricuspid annulus (TA), and with preserved right ventricular (RV) size and systolic function. However, the geometry and function of the RV, RA, and TA in patients with A-FTR and V-FTR remain to be systematically evaluated. Accordingly, we sought to: (i) study the geometry and function of the RV, RA, and TA in A-FTR by two- and three-dimensional transthoracic echocardiography and (ii) compare them with those found in V-FTR. Methods and results We prospectively analysed 113 (44 men, age 68 ± 18 years) FTR patients (A-FTR = 55 and V-FTR = 58) that were compared to two groups of age- and sex-matched controls to develop the respective Z-scores. Severity of FTR was similar in A-FTR and V-FTR patients. Z-scores of RV size were significantly larger, and those of RV function were significantly lower in V-FTR than in A-FTR (P &amp;lt; 0.001 for all). The RA was significantly enlarged in both A-FTR and V-FTR compared to controls (P &amp;lt; 0.001, Z-scores &amp;gt; 2), with similar RA maximal volume (RAVmax) between A-FTR and V-FTR (P = 0.2). Whereas, the RA minimal volumes (RAVmin) were significantly larger in A-FTR than in V-FTR (P = 0.001). Conclusions Despite similar degrees of FTR, and RAVmax size, A-FTR patients show a larger RAVmin, and smaller TA areas than V-FTR patients. Conversely, V-FTR patients show dilated, more elliptic, and dysfunctional RV than A-FTR patients.

Unmasking right ventricular-arterial uncoupling during fluid challenge in pulmonary hypertension

Patients with pulmonary hypertension (PH) frequently show preserved right ventricular (RV) function at rest. However, volume challenge may uncover pending RV dysfunction. We aimed to assess the physiological and prognostic impact of RV-pulmonary arterial (RV-PA) uncoupling during volume challenge in patients with precapillary PH. We prospectively assessed 32 patients with PH (pulmonary arterial hypertension, n=27; inoperable chronic thromboembolic disease, n=5) and 4 controls using invasive pressure-volume (PV) catheterization. PV loops were recorded during preload reduction (balloon occlusion of inferior vena cava; baseline) and acute volume loading (200ml saline in 20s). Contractility (multi-beat end-systolic elastance [Ees]), arterial elastance (Ea), and RV-PA coupling (Ees/Ea) were obtained at baseline and at maximum volume loading (MVL). Median [interquartile range] time to MVL was 19 [18-22] s. Ees/Ea significantly declined from baseline (0.89 [0.69-1.23]) to MVL (0.16 [0.12-0.34]; p<0.001) in patients with PH but remained stable in controls (baseline: 1.08 [0.94-1.80]; MVL: 1.01 [0.80-2.49]; p=0.715). The same pattern was observed for Ees, while Ea remained unchanged. The percent decline of RV-PA coupling (ΔEes/Ea) during fluid challenge was significantly associated with pulmonary resting hemodynamics, RV ejection fraction (RVEF), and RV end-diastolic volume. Kaplan-Meier analysis revealed that patients with PH who had a smaller ΔEes/Ea (<-65%) had a significantly better prognosis (log-rank p=0.0389). In multivariate Cox regression analysis, clinical worsening was predicted by ΔEes/Ea (hazard ratio: 0.96 [95% confidence interval: 0.93-1.00]) and RVEF (hazard ratio: 0.95 [95% confidence interval: 0.92-0.98]). Assessment of PV loops during fluid challenge uncovers exhausted RV coupling reserve with severely reduced contractility in PH. RV-PA uncoupling during volume challenge can be predicted by pulmonary resting hemodynamics and RVEF. RV-PA uncoupling during fluid challenge and RVEF (as a noninvasive correlate) are predictors of clinical worsening. URL: https://www.clinicaltrials.gov. Unique identifier: NCT03403868 (January 19, 2018).

Complications After Heart Transplantation According to the Type of Pretransplant Circulatory/Ventricular Support

The purpose of the study was to analyze postcardiac transplant complications in patients who received transplants with short-term mechanical ventricular assist devices and to compare complications according to the type of device. Ambispective and consecutive study of urgent heart transplants from 2015 to 2019. Pediatric transplants, retransplants, and combined transplants were excluded. A total of 45 patients were analyzed in 4 groups: (1) venoarterial extracorporeal membrane oxygenation (ECMO) implanted <10 days before heart transplant (HTx) (n=17); (2) ECMO implanted for more than 10 days (n=8); (3) Levitronix Centrimag implanted in INTERMACS 2 to 3 patients (n=13); and (4) Levitronix Centrimag implanted in INTERMACS 2 patients (n=7). ECMO assistance was in INTERMACS 2 and severe right ventricular dysfunction. Levitronix Centrimag was implanted in patients with preserved right ventricular function. Primary graft failure associated with the need for ECMO was more frequent in patients with ECMO than with Levitronix (P < .05). When comparing the 2 groups with ECMO, an implant more than 10 days before HTx was associated, after transplant, with a longer stay in the critical care unit (P=.02), higher mortality (P=.03), and an increase in complications in general. When comparing the 2 groups with Levitronix, all the parameters studied were much better when the Levitronix was implanted in INTERMACS 2-3 (P < .05). On the other hand, all cases of deep vein thrombosis and pulmonary thromboembolism occurred in patients who were assisted with ECMO. HTx with mechanical assist devices is associated with significant complications. ECMO produces more complications than the Levitronix Centrimag, although they are related to the days of implantation. The best group are patients implanted with a Levitronix in INTERMACS 2-3.

Cardiac Magnetic Resonance Depiction of Different Morphological Appearances of Becker Cardiomyopathy in Siblings

Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutation of the dystrophin gene. Cardiac involvement in BMD is frequent and represents the foremost cause of mortality. Two male siblings with severe left ventricular (LV) dysfunction and presence of deletion in the dystrophin gene underwent cardiac magnetic resonance (CMR) imaging, which revealed typical but varying imaging findings. The CMR revealed dilated left ventricle with severe global hypokinesis with preserved right ventricular (RV) function. Few patchy areas of septal edema were seen with typical epicardial enhancement along the LV lateral wall and the RV side of septum in one sibling. Both the siblings revealed an elevated myocardial native T1 values. CMR has the potential to detect cardiac involvement early by identifying and quantifying fibrosis, before wall motion abnormalities set in and determine prognosis in patients with muscular dystrophy and BMD carriers.

Impact of tricuspid valve insufficiency on the performance of left ventricular assist devices

ObjectiveTo evaluate the impact of severe tricuspid valve insufficiency (TVI) at the time of left ventricular assist device (LVAD) implantation on the hemodynamic and LVAD parameters in an acute ovine model. MethodsStable heart failure (HF) was induced in 10 ovines through the application of 3 ± 1 coronary ligations. Once stable HF was obtained (after 15 ± 5 days), the animals were supported with an LVAD. Hemodynamic data and pump parameters were obtained and compared in 2 settings; first with LVAD in place after weaning from the cardiopulmonary bypass machine (no TVI condition) and second following the induction of severe TVI through resection of the tricuspid valve (TVI condition). ResultsThere were no statistically significant differences in the hemodynamic and pump parameters between TVI condition and no TVI conditions except for lower cardiac output in the TVI condition (2 [1.38-2.8] L/min vs 3.2 [1.55-3.7] L/min, P = .027) and the expected greater central venous pressure in the TVI condition (26 [24-31] mm Hg vs 15 [13-25] mm Hg, P = .020). A median pump flow of 2.8 (2.45-3.75) L/min versus 2.9 (2.75-3.8) L/min in the TVI condition and no TVI condition was documented (P = .160). ConclusionsResults from this acute animal study suggest that severe TVI in HF with preserved right ventricular function does not have significant impact on the LVAD pump parameters. The observed reduction in cardiac output may warrant further investigations, especially under loading conditions.

Flow profile characteristics in Fontan circulation are associated with the single ventricle dilation and function: principal component analysis study.

The Fontan circulation is characterized as a nonpulsatile flow propagation without a pressure-generating ventricle. However, flow through the Fontan circulation still exhibits oscillatory waves as a result of pressure changes generated by the systemic single ventricle. Identification of discrete flow patterns through the Fontan circuit may be important to understand single ventricle performance. Ninety-seven patients with Fontan circulation underwent phase-contrast MRI of the right pulmonary artery, yielding subject-specific flow waveforms. Principal component (PC) analysis was performed on preprocessed flow waveforms. Principal components were then correlated with standard MRI indices of function, volume, and aortopulmonary collateral flow. The first principal component (PC) described systolic versus diastolic-dominant flow through the Fontan circulation, accounting for 31.3% of the variance in all waveforms. The first PC correlated with end-diastolic volume (R = 0.34, P = 0.001), and end-systolic volume (R = 0.30, P = 0.003), cardiac index (R = 0.51, P < 0.001), and the amount of aortopulmonary collateral flow (R = 0.25, P = 0.027)-lower ventricular volumes and a smaller volume of collateral flow-were associated with diastolic-dominant cavopulmonary flow. The second PC accounted for 19.5% of variance and described late diastolic acceleration versus deceleration and correlated with ejection fraction-diastolic deceleration was associated with higher ejection fraction. Principal components describing the diastolic flow variations in pulmonary arteries are related to the single ventricle function and volumes. Particularly, diastolic-dominant flow without late acceleration appears to be related to preserved ventricular volume and function, respectively.NEW & NOTEWORTHY The exact physiological significance of flow oscillations of phasic and temporal flow variations in Fontan circulation is unknown. With the use of principal component analysis, we discovered that flow variations in the right pulmonary artery of Fontan patients are related to the single ventricle function and volumes. Particularly, diastolic-dominant flow without late acceleration appears to be related to more ideal ventricular volume and systolic function, respectively.

Pulmonary Artery Banding for Children With Dilated Cardiomyopathy: US Experience.

Pulmonary artery band placement is a recently described therapeutic strategy for dilated cardiomyopathy with preserved right ventricular function, originally reported from Germany.1 We present the results of the multicenter retrospective study of pulmonary artery band experience in the United States, with comparison to the German experience. Five centers contributed a total 14 patients (median age 5 months, interquartile range 3.5-10). Mechanical ventilation was required in 9/12 (75%) patients and inotropes were used in 13/14 (93%) patients preoperatively. Ultimately, 4 (29%) patients experienced cardiac recovery, 8 (57%) were bridged to cardiac transplantation (6 with ventricular assist device placement), and 2 (14%) died. Although both the US and Germany series demonstrated high prevalence of achieving patients' individual target (either cardiac recovery or transplant), the mode of success was different (recovery rate: <1/3 in the United States and >2/3 in Germany). Lower recovery rate may be a reflection of sicker preoperative status, and thereby a more advanced stage of heart failure (preoperative intubation: >2/3 in the United States vs <1/3 in Germany). Further studies would be warranted to gain more insight into patient selection as well as optimal timing for the intervention.

Interaction of α Carboxyl Terminus 1 Peptide With the Connexin 43 Carboxyl Terminus Preserves Left Ventricular Function After Ischemia-Reperfusion Injury.

Backgroundα Carboxyl terminus 1 (αCT1) is a 25–amino acid therapeutic peptide incorporating the zonula occludens‐1 (ZO‐1)–binding domain of connexin 43 (Cx43) that is currently in phase 3 clinical testing on chronic wounds. In mice, we reported that αCT1 reduced arrhythmias after cardiac injury, accompanied by increases in protein kinase Cε phosphorylation of Cx43 at serine 368. Herein, we characterize detailed molecular mode of action of αCT1 in mitigating cardiac ischemia‐reperfusion injury.Methods and ResultsTo study αCT1‐mediated increases in phosphorylation of Cx43 at serine 368, we undertook mass spectrometry of protein kinase Cε phosphorylation assay reactants. This indicated potential interaction between negatively charged residues in the αCT1 Asp‐Asp‐Leu‐Glu‐Iso sequence and lysines (Lys345, Lys346) in an α‐helical sequence (helix 2) within the Cx43‐CT. In silico modeling provided further support for this interaction, indicating that αCT1 may interact with both Cx43 and ZO‐1. Using surface plasmon resonance, thermal shift, and phosphorylation assays, we characterized a series of αCT1 variants, identifying peptides that interacted with either ZO‐1–postsynaptic density‐95/disks large/zonula occludens‐1 2 or Cx43‐CT, but with limited or no ability to bind both molecules. Only peptides competent to interact with Cx43‐CT, but not ZO‐1–postsynaptic density‐95/disks large/zonula occludens‐1 2 alone, prompted increased pS368 phosphorylation. Moreover, in an ex vivo mouse model of ischemia‐reperfusion injury, preischemic infusion only with those peptides competent to bind Cx43 preserved ventricular function after ischemia‐reperfusion. Interestingly, a short 9–amino acid variant of αCT1 (αCT11) demonstrated potent cardioprotective effects when infused either before or after ischemic injury.ConclusionsInteraction of αCT1 with the Cx43, but not ZO‐1, is correlated with cardioprotection. Pharmacophores targeting Cx43‐CT could provide a translational approach to preserving heart function after ischemic injury.

Mean velocity of the pulmonary artery estimated by cardiac magnetic resonance as an early prognostic predictor in heart failure

Background and objectiveTo identify early, non-invasive prognostic indicators in heart failure (HF), with and without associated pulmonary hypertension, by means of cardiac magnetic resonance, and oxidative stress and anti-inflammatory biomarkers such as Trolox™ (antioxidant status) and IL-10 (anti-inflammatory cytokine). Patients and methodsWe prospectively included 70 patients admitted for new-onset HF. During index admission, mean velocity of the pulmonary artery (mvPA) was measured, and blood Trolox™ and IL-10 determined. The study sample was divided in two groups according to the optimal cut-off value for event prediction calculated by the ROC curve (mvPA=8cm/s), considering HF-readmission and all-cause mortality as the primary combined event. ResultsDuring a median follow-up of 290 days, 16 events occurred. In patients with preserved right ventricular (RV) function, mvPA ≤8cm/s was associated with a higher incidence of events during follow-up, Kaplan–Meier survival analysis (log rank 6.01, p=0.014). MvPA did not add prognostic value when RV dysfunction was already established. Trolox™ concentration was lower in patients with mvPA ≤8cm/s. Higher IL-10 expression was associated with a lower incidence of cardiovascular events during follow-up. ConclusionIn HF patients, mvPA ≤8cm/s predicts a higher rate of cardiovascular events. Specifically, mvPA identifies a higher risk population among patients with preserved RV function, thus confirming its role as an early prognostic indicator. Lower Trolox™ concentration in the worse prognosis group concurs with previous studies on oxidative stress in pulmonary hypertension. Higher IL-10 concentration among patients free of cardiovascular events could be a reflection of its anti-inflammatory and thus protective role in HF.

CEST MRI reveals a correlation between visceral fat mass and reduced myocardial creatine in obese individuals despite preserved ventricular structure and function.

Systolic cardiac function is typically preserved in obese adults, potentially masking underlying declines in cardiomyocyte metabolism that may contribute to heart failure. We used chemical exchange saturation transfer (CEST) MRI, a sensitive method for measurement of myocardial creatine, to examine whether myocardial creatine levels correlate with cardiac structure, contractile function, or visceral fat mass in obese adults. In this study, obese (body mass index, BMI>30, n=20) and healthy (BMI<25, n=11) adults were examined with dual-energy x-ray absorptiometry to quantify fat masses. Cine MRI and myocardial tagging were performed at 1.5T to measure ventricular structure and global function. CEST imaging with offsets in the range of ±10 parts per million (ppm) were performed in one mid-ventricular slice, where creatine CEST contrast was calculated at 1.8ppm following field homogeneity correction. Ventricular structure, global function (ejection fraction 69.4±4.3% healthy versus 69.6±9.3% obese, NS), and circumferential strain (-17.0±2.3% healthy versus -16.5±1.5% obese, NS) and strain rate were preserved in obese adults. However, creatine CEST contrast was significantly reduced in obese adults (6.8±1.3% healthy versus 4.1±2.7% obese, p=0.001). Creatine CEST contrast was inversely correlated with total body fat% (ρ=-0.45, p=0.011), visceral fat mass (ρ=-0.58, p=0.001), and septal wall thickness (ρ=-0.44, p=0.013), but uncorrelated to ventricular function or contractile function. In conclusion, creatine CEST-MRI reveals a strong correlation between heightened body and visceral fat masses and reduced myocardial metabolic function that is independent of ventricular structure and global function in obese adults.

Impact of Severe Tricuspid Valve Insufficiency on the Performance of the Left Ventricular Assist Devices. Acute and Chronic Animal Studies

Purpose Up to 50% of the left ventricular device (LVAD) candidates present with moderate -severe tricuspid valve insufficiency (TVI) at the time of LVAD implantation . The exact strategy weather to perform a TV repair (TVR) or not in these patients is not well investigated. We aimed to evaluate the impact of severe iatrogenic TVI at the time of LVAD implantation on the hemodynamic and LVAD parameters in an acute and chroic ovine model. Methods Chronic stabile heart failure (HF) was induced in 10 ovines (mean weight 61±7 kg) through the application of several coronary ligations. Once stabile HF was obtained (after 15 ± 5 days), animals were brought back to the operating room and supported with HeartWare LVAD (HeartWare Inc., Framingham, MA). Hemodynamic data (mean arterial pressure (MAP),pulmonary artery pressure, central venous pressure (CVP), cardiac output (CO) and heart rate) as well as pump flow, speed and power consumption were obtained in two settings; first with LVAD in place after weaning from cardiopulmonary bypass (CPB) machine (no TVI setting) and second following reinitiating the CPB and induction of severe TRI through resection of the tricuspid valve (TVI setting). Hemodynamic and pump parameters were compared between these two settings without changing the pump speed. Results The total CPB time was 101 ± 22 min and the total LVAD support time was 41 ± 20min. There were no statistical significant differences in the hemodynamic and pump parameters between TVI setting and no TVI conditions except for expected higher CVP in the TVI setting(27±6 mmHg vs. 18±8 mmHg, p=0.013) and higher CO in the TVI setting (2.4 ±1.5 L/ min vs. 3.2± 1.0 L/ min, p = 0.011). At average pump speed of 2300 ± 87 rpm in the TVI and 2322 ± 130rpm in the no TVI setting, the mean pump flow in the TVI and no TVI setting were 3.3 ± 2.1L/min and 3.3 ± 1.0 L/ min respectively (p=0.895). Meanwhile, a MAP of 70 ± 9 mmHg and 69 ±14 mmHg in the TVI and no TVI setting was measured respectively (p= 0.779). Based on these results, two additional chronic animal studies were successively performed. Conclusion This study of severe iatrogenic TVI in chronic HF animals with preserved right ventricular function (RVF) showed no significant differences in the pump performance between TVI setting and no TVI condition. This finding may questions the necessity of TVR by preserved RVF at the time of LVAD implantation.