Conductance Catheter Research Articles

Early detection of left ventricular failure in right ventricular congenital heart diseases

BackgroundEarly detection of left ventricular (LV) failure is crucial to improve prognosis of patients with right ventricular (RV) overload. ObjectivesWe aim to assess whether LV function is precociously affected in 2 surgical porcine models of moderate (Fallot repaired) and severe RV dysfunction (progressive pulmonary hypertension HP) at in vivo and in vitro levels. MethodsThree animals of each surgical group were compared with 6 controls/Sham. 4 months after surgeries, LV function was evaluated using echocardiography/strain compared with conductance catheter. At cellular level using isolated cardiomyocytes, calcium transients amplitude with relaxation time associated and sarcomere shortening were recorded using Ionoptix system. T-tubules network integrity (DI-4-ANEPPS) and colocalization (Immunofluorescence) between main Excitation/Contraction (EC) actors (Ca2+v1.2-Ryr) were analyzed. Contractile reserve was evaluated by adrenergic stimulation in-vivo and in-vitro (Dobutamine-isoproterenol). ResultsDespite RV dysfunctions in both groups, LV present hemodynamic impairment only in HP group (Longitudinal strain 9 versus 18%. Conductance catether with dobutamin: Elastance arterial 7.7 versus 1.32, SV 14 versus 75ml and tau (relaxation) 49 versus 27, P<0.05). In cardiomyocytes, we observe decrease of Ca2+ transient amplitude and cardiomyocytes contraction, acceleration of Ca2+ relaxation time, T-tubule network desorganisation and Cav1.2/Ryr decoupling (Fig. 1).In vivo and in vitro, adrenergic stimulations increase dysfunction. ConclusionIn vitro experiments pointed early abnormalities in LV EC particularly after adrenergic stimulation. A better understanding of cellular alterations could lead to survival improvement.

Electrical cardiometry and detection of left ventricular failure in right ventricular heart diseases

Early and easy to do detection of left ventricular (LV) failure is crucial to improve following and outcomes of patients with right ventricular (RV) overload in congenital heart diseases. Electrical cardiometry (Osypka medical) is easy handling, even in medical office or in pre-hospital condition, and can provide cardiac output, and a new contractility index (ICON) supposed to be independent from load conditions. ICON have never been previously challenged to our knowledge. We aim to compare ICON with the only contractility parameter independent from load conditions: the elastance slope (Emax). Using porcine models of Fallot repaired and pulmonary hypertension (PH), we assess LV function using conductance catheter and electrical cardiometry devices over 4 months after surgery. We measured ICON, Emax, Contractile reserve (ΔEmax) and VIC (respiratory variations of ICON) at basal state and after adrenergic stimulation (Dobutamine). Three animals of each group were compared with 6 controls. Non parametric correlation (spearman) hightlights at basal state a non significant and low correlation between ICON and Emax and ΔEmax ( r = 0.5). However after Dobutamine, correlation is important and strong with r = 0.98 between ICON/Emax (0.05) and 0.89 between VIC/Emax. We did not find strong correlation between ΔEmax and VIC or ΔICON. These results obtain on a small in vivo/animal cohort highlight than electrical cardiometry device could be a useful and easy handling (4 skin patchs) tool for LV failure and loss of contractility early screening, specially after adrenergic stimulation and stress conditions. It could provide precious help in patients following.

Interventricular dyssynchrony during continuous-flow left ventricular assist device support: observation using the conductance method.

The purpose of this study was to observe and clarify the interventricular dysscynchrony caused by continuous-flow left ventricular assist device (CF-LVAD) support using the conductance method. During CF-LVAD support, the systolic phase of the left ventricle (LV) becomes shorter than that of the right ventricle (RV). Accordingly, timing of the systole and diastole during the cardiac cycle is not synchronous between the LV and RV. In this study, we evaluated this phenomenon in a normal heart model using the adult goat (n = 5, body weight 44.5 ± 2.9kg). A centrifugal LVAD was implanted under general anesthesia. We inserted the conductance catheter into the RV and LV to obtain the pressure-volume relationship of the two ventricles simultaneously. We defined the dyssynchronous status as the sign (plus or minus) of the LV volume-change opposite to that of RV volume-change. Dyssynchronous phase of the cardiac cycle was observed in 5.6 ± 0.65% of hearts under LVAD pump-off and 25.3 ± 3.3% under LVAD full bypass, respectively (p < 0.05). To the best of our knowledge, this is the first experimental report clarifying interventricular dyssynchrony during CF-LVAD support using the conductance method. Quantification of this phenomenon under various support conditions and assessment of influences on the right ventricular function will be studied in future studies.

Quantification of interventricular dyssynchrony during continuous-flow left ventricular assist device support.

Under continuous-flow left ventricular assist device (CF-LVAD) support, the ventricular volume change and cardiac cycle between the left ventricle (LV) and right ventricle (RV) become dyssynchronous due to the shortening of the LV systole. The purpose of this study was to quantify interventricular dyssynchrony based on different CF-LVAD support conditions and assess its relationship with LV unloading. In this study, we evaluated seven goats (body weight 44.5 ± 6.5kg) with normal hearts. A centrifugal LVAD was implanted under general anesthesia. We inserted the conductance catheters into the left ventricle (LV) and right ventricle (RV) to assess the volume signal simultaneously. We defined the interventricular dyssynchrony as a signal (increase or decrease) of LV volume (LVV) change opposite to that of RV volume (RVV) (i.e., (dLVV/dt) × (dRVV/dt) < 0). The duration of interventricular dyssynchrony (DYS) was reported as the percentage of time that a heart was in a dyssynchronous state within a cardiac cycle. The mean DYS of normal hearts, hearts with LVAD clamp and hearts supported by LVADs with a bypass rate of 50%, 75% and 100% were 5.6 ± 1.6%, 8.7 ± 2.4%, 8.6 ± 2.8%, 15.1 ± 5.1%, and 25.6 ± 8.0%, respectively. Furthermore, the DYS was found to be associated with the degree of LV stroke volume reduction caused by LV unloading. These findings may be useful for understanding interventricular interactions and physiology during CF-LVAD support. Influences on the right ventricular function and heart failure models warrant further study.

Cannula Tip With Integrated Volume Sensor for Rotary Blood Pump Control: Early-Stage Development.

The lack of direct measurement of left ventricular unloading is a significant impediment to the development of an automatic speed control system for continuous-flow left ventricular assist devices (cf-LVADs). We have developed an inlet cannula tip for cf-LVADs with integrated electrodes for volume sensing based on conductance. Four platinum-iridium ring electrodes were installed into grooves on a cannula body constructed from polyetheretherketone (PEEK). A sinusoidal current excitation waveform (250 μA pk-pk, 50 kHz) was applied across one pair of electrodes, and the conductance-dependent voltage was sensed across the second pair of electrodes. The conductance catheter was tested in an acute ovine model (n = 3) in conjunction with the HeartMate II rotary blood pump to provide circulatory support and unload the ventricle. Echocardiography was used to measure ventricular size during pump support for verification for the conductance measurements. The conductance measurements correlated linearly with the echocardiography dimension measurements more than the full range of pump support from minimum support to suction. This cannula tip will enable the development of automatic control systems to optimize pump support based on a real-time measurement of ventricular size.

Magnetic resonance hyperpolarization imaging detects early myocardial dysfunction in a porcine model of right ventricular heart failure.

AimsEarly detection of heart failure is important for timely treatment. During the development of heart failure, adaptive intracellular metabolic processes that evolve prior to macro-anatomic remodelling, could provide an early signal of impending failure. We hypothesized that metabolic imaging with hyperpolarized magnetic resonance would detect the early development of heart failure before conventional echocardiography could reveal cardiac dysfunction.Methods and resultsFive 8.5 kg piglets were subjected to pulmonary banding and subsequently examined by [1-13C]pyruvate hyperpolarization, conventional magnetic resonance imaging, echocardiography, and blood testing, every 4 weeks for 16 weeks. They were compared with a weight matched, healthy control group. Conductance catheter examination at the end of the study showed impaired right ventricular systolic function along with compromised left ventricular diastolic function. After 16 weeks, we saw a significant decrease in the conversion ratio of pyruvate/bicarbonate in the left ventricle from 0.13 (0.04) in controls to 0.07 (0.02) in animals with pulmonary banding, along with a significant increase in the lactate/bicarbonate ratio to 3.47 (1.57) compared with 1.34 (0.81) in controls. N-terminal pro-hormone of brain natriuretic peptide was increased by more than 300%, while cardiac index was reduced to 2.8 (0.95) L/min/m2 compared with 3.9 (0.95) in controls. Echocardiography revealed no changes.ConclusionHyperpolarization detected a shift towards anaerobic metabolism in early stages of right ventricular dysfunction, as evident by an increased lactate/bicarbonate ratio. Dysfunction was confirmed with conductance catheter assessment, but could not be detected by echocardiography. Hyperpolarization has a promising future in clinical assessment of heart failure in both acquired and congenital heart disease.

Antifibrotic Effect of (−)‐Epicatechin in a Rodent Model of Early Stage HFpEF

BackgroundThe prevalence of heart failure with preserved ejection fraction (HFpEF) continues to increase and no effective therapies have been identified. Two‐thirds of HFpEF patients are post‐menopausal women with hypertension and/or metabolic syndrome, key factors of cardiac fibrosis. The goals of this study were: 1) to develop a rat model that displays cardiac features of HFpEF in humans evaluated using a comprehensive panel of physiological endpoints and, 2) to characterize the antifibrotic potential of the cacao flavanol (−)‐epicatechin (Epi) which we have demonstrated to exert such activity in an animal model of muscular dystrophy.Methodsusing a model integrating the roles of aging, estrogen depletion and metabolic syndrome on promoting diastolic dysfunction and myocardial fibrosis. Female, 18‐month‐old, Fischer 344 rats were allocated into an ovariectomy (OVX), ovariectomy+epi (OVE), ovariectomy+fructose (OVF) and ovariectomy+fructose+epi (OFE) (n=8–11/group). Left ventricular (LV) function was monitored monthly by echocardiography. At 22 months of age, in vivo studies included LV hemodynamics using pressure‐volume (PV) loops obtained with a conductance catheter, as well as ex‐vivo passive LV PV curves and epicardial strains in diastole arrested hearts. Histological measures and collagen area fraction were obtained. Subgroups of animals received vehicle (water) or Epi (1 mg/kg/day) by gavage for 1 month (from 21 to 22 months of age).Resultsall aged groups exhibited high systolic blood pressure while OVF animals showed increased body weight. Echocardiographic assessment was not able to detect mayor morphometric changes between groups with treatment and their vehicle counterpart, but there is evidence of time‐dependent changes in cardiac morphometry. The intraventricular analysis showed increased Tau, decreased Stroke Volume index, and changes in aortic pressures at both diastole and systole. (−)‐Epi treatment revealed differences pressure and heart rate, fructose animals showed changes on systolic function and aortic pressures (p&lt;0.05 vs OVF). Intraventricular measures did not change between treated and vehicle groups maintaining a normal ejection fraction (EF) (&gt;50%). Passive PV curves showed no differences between treated and vehicle groups. Regional strain analysis revealed no differences for circumferential strain (E11), but showed differences in longitudinal strain (E22) for OVE vs OVX (p&lt;0.05). Histological analysis indicated increasing levels of perivascular and interstitial fibrosis at both endo‐ and epicardium (p&lt;0.05). Differences were present between OVF and OFE groups in base and septum sections (p&lt;0.05) for collagen content.ConclusionThis aging female rat model appears to mimic many of the features in female HFpEF patients. OVX appears to compromise cardiac output while not affecting EF. Although preliminary, results suggest that Epi, which has been tested in humans with other conditions, may deserve consideration as an antifibrotic agent in the setting of diseases such as HFpEF.Support or Funding InformationDepartment of Defense PR150090This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Brainstem pre‐sympathetic neurons contribute to irregular breathing patterns in volume overload heart failure

Chronic heart failure (CHF) is characterized by sympathoexcitation and a high prevalence of breathing disorders. It has been shown that rostral ventrolateral medulla catecholaminergic neurons (RVLM‐C1) contributes to sympathetic outflow regulation in CHF and that RVLM‐C1 neurons are hyperactivated in experimental CHF. Recently, it has been shown that acute activation of RVLM‐C1 neurons also stimulates breathing in healthy rodents. However, there is no evidence showing the contribution of RVLM‐C1 neurons, if any, on breathing disorders in CHF. Therefore, we aimed to determine the role of RVLM‐C1 neurons on disordered breathing in CHF. Sprague‐Dawley rats underwent volume overload to induce CHF. Stereotaxic bilateral injections of anti‐dopamine β‐hydroxylase‐saporin toxin (DβH–SAP: 5ng/150nl) were used to selectively eliminate RVLM‐C1 neurons. Whole‐body plethysmography, blood pressure radiotelemetry and pression‐volume conductance catheter were used to study breathing stability, chemoreflex function, cardiac autonomic control, respiratory‐cardiovascular coupling (RCC) and cardiac function. Depletion of RVLM‐C1 neurons (~70%) in CHF rats (CHF+Veh vs. CHF+DβH+SAP, respectively) restored regular breathing pattern (Breathing irregularity score: 25.5 ± 3.0 vs. 11.9 ± 1.2 %; p&lt;0.05), decreased apnea/hypopnea incidence (11.0 ± 0.9 vs. 6.5 ± 0.8 events/hr; p&lt;0.05) and improves cardiac autonomic control as evidenced by a decrease in the low/high frequency component of spectral analysis of heart rate variability (HRV) (LF/HFHRV 2.7 ± 0.3 vs. 1.5 ± 0.1; p&lt;0.05). In addition, CHF rats displayed active expiration compared to Sham rats, evidenced by the increase in the early/late expiration ratio (E2/E1: 0.51 ± 0.02 vs. 1.07 ± 0.07 Sham+Veh vs. CHF+Veh, p&lt;0.05) and DβH–SAP toxin treatment decrease active expiration in CHF rats (E2/E1: 1.07 ± 0.07 vs. 0.81 ± 0.01 ml, CHF+Veh vs. CHF+DβH‐SAP; p&lt;0.05). Accordingly, DβH–SAP toxin treatment eliminate RCC in CHF rats (Coherencepeak: 0.74 ± 0.04 vs. 0.59 ± 0.05, CHF+Veh vs. HF+DβH–SAP; p&lt;0.05). In addition, the deleterious effects of central chemoreflex activation on diastolic cardiac function and cardiac autonomic control were blunted after RVLM‐C1 neuron ablation (EDPVR: 0.023 ± 0.008 vs. 0.005 ± 0.001 mmHg/μl; LF/HFHRV 2.19 ± 0.15 vs. 1.09 ± 0.23; CHF+Veh+Hypercapnia vs. CHF+DβH‐SAP+ Hypercapnia; p&lt;0.05). No changes in central chemoreflex drive and/or in the number of central chemoreceptor neurons (from the retrotrapezoid nucleus) were found in CHF+DβH‐SAP rats compared to CHF+Veh treated rats. Our results showed that RVLM‐C1 neurons play a critical role in the maintenance of altered breathing patterns in CHF rats and highlighted their contribution to the worsening of cardiac function during central chemoreflex activation.Support or Funding InformationFondecyt 1180172; The basal Center of Excellence in Aging and Regeneration (AFB 170005)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Glucagon-Like Peptide-1–Mediated Cardioprotection Does Not Reduce Right Ventricular Stunning and Cumulative Ischemic Dysfunction After Coronary Balloon Occlusion

Stunning and cumulative ischemic dysfunction occur in the left ventricle with coronary balloon occlusion. Glucagon-like peptide (GLP)-1 protects the left ventricle against this dysfunction. This study used a conductance catheter method to evaluate whether the right ventricle (RV) developed similar dysfunction during right coronary artery balloon occlusion and whether GLP-1 was protective. In this study, the RV underwent significant stunning and cumulative ischemic dysfunction with right coronary artery balloon occlusion. However,GLP-1 did not protect the RV against this dysfunction when infused after balloon occlusion.

Ectopic Cardiogenic Transcription Factor Expression Augments the Anti‐fibrogenic Activity of Administered Cardiac Mesenchymal Stromal Cells in a Model of Chronic Ischemic Cardiomyopathy

Preclinical studies suggest that donor cell cardiomyogenic lineage commitment may be an important determinant of the efficacy of cardiac mesenchymal stromal cell (CMC) therapy; however, to what extent myogenic commitment influences CMC cardiac reparative capacity, as well as the underlying mechanisms by which they promote cardiac functional recovery remains poorly defined. In the current study we examine the consequences of enhanced cardiomyogenic lineage commitment on CMC cardiac reparative capacity in vivo and paracrine signaling potency in vitro, via ectopic expression of core cardiogenic transcription factors GMT (GMT: GATA4, MEF2C, and TBX5). Rat CMCs transduced with a tricistronic lentiviral construct harboring GMT coding sequences, or green fluorescent protein (GFP) control, were intramyocardially delivered in a rat model of chronic ischemic cardiomyopathy 30 days after a reperfused myocardial infarction. Indices of cardiac function were assessed by echocardiography and left ventricular (LV) Millar conductance catheterization 35 days after treatment. Infarct size and myocardial collagen deposition were enumerated in coronal‐dissected, cardiac tissue sections by Masson's trichrome or picrosirius red staining, respectively. Cytokine array analyses and in vitro cardiac fibroblast activation assays were performed using conditioned medium (CoMed) derived from either GMT or GFP CMCs, to respectively assess cardiotrophic factor secretion and anti‐fibrogenic paracrine signaling potential. Compared to GFP controls, GMT CMCs exhibited superior ability to attenuate LV systolic dysfunction and myocardial fibrosis in vivo. Proteome cytokine array analyses of CoMed revealed enhanced expression of cytokines with GMT CMCs that function in pathways that regulate matrix remodeling and collagen catabolism. Further, CoMed harvested from GMT CMCs more robustly inhibited Col1A1 synthesis in TGFβ1 activated cardiac fibroblast assays in vitro, compared to that of GFP CMCs. These results provide direct evidence that CMC myogenic lineage commitment biases cardiac repair and, further, that enhanced anti‐fibrogenic paracrine signaling potency may underlie, in part, their improved therapeutic utility.Support or Funding InformationNational Institutes of Health Grant R01 HL141081This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

New Insights into Right Ventricular Function among Patients with Left Ventricular Assist Devices Using High Fidelity Conductance Catheters to Generate Real Time Pressure Volume Loops

Purpose Determine the impact of continuous-flow (CF) left ventricular devices (LVADs) on resting and exertional right ventricular (RV) performance. Methods Eight LVAD patients (all male, 57±8yrs) with normal resting RV function completed invasive hemodynamic assessment during submaximal (mild and moderate, defined by rate of perceived exertion score of 7-9, and 11-13, respectively), and peak exercise on an upright cycle ergometer, and up- and downward pump speed adjustments under supine resting conditions. Results were compared with 7 healthy controls (HC, five males, 37±10yrs). Results Compared to HC, CF-LVAD patients had a lower cardiac output (Qc), oxygen uptake (VO2), and heart rate (HR) at submaximal and peak exercise. Analysis of RV PV loops during exercise testing (Figure 1A-B, and Table 1) shows that RV contractility (Starling contractile Index and DP/DT) was greater, and RV relaxation (-DP/DT), was less than HC during all exercise stages. Among CF-LVAD patients, peak Qc was lower, and DP/DT was similar to, values observed among HC at mild exercise (ie, a similar workload). Changes in pump speed were not associated with any significant change in RV contractility, relaxation, RV end-diastolic pressure, or myocardial energetics (Figure 1C). Conclusion RV function among CF-LVAD patients is characterized by reduced metrics of contractility and relaxation and lower cardiac output compared to healthy individuals exercising at similar workloads. Up- and downward changes in pump speed had minimal impact on resting RV performance.

Cardiac Magnetic Resonance Imaging-Based Right Ventricular Strain Analysis for Assessment of Coupling and Diastolic Function in Pulmonary Hypertension

ObjectivesThis study sought to compare cardiac magnetic resonance (CMR) imaging-derived right ventricular (RV) strain and invasively measured pressure-volume loop-derived RV contractility, stiffness, and afterload and RV-arterial coupling in pulmonary hypertension (PH). BackgroundIn chronic RV pressure overload, RV-arterial uncoupling is considered the driving cause of RV maladaptation and eventual RV failure. The pathophysiological and clinical value of CMR-derived RV strain relative to that of invasive pressure-volume loop-derived measurements in PH remains incompletely understood. MethodsIn 38 patients with PH, global RV CMR strain was measured within 24 h of diagnostic right heart catheterization and conductance (pressure-volume) catheterization. Associations were evaluated by correlation, multivariate logistic binary regression, and receiver operating characteristic analyses. ResultsLong-axis RV longitudinal and radial strain and short-axis RV radial and circumferential strain were −18.0 ± 7.0%, 28.9% [interquartile range (IQR): 17.4% to 46.6%]; 15.6 ± 6.2%; and −9.8 ± 3.5%, respectively. RV-arterial coupling (end-systolic [Eds]/arterial elastance [Ea]) was 0.76 (IQR: 0.47 to 1.07). Peak RV strain correlated with Ees/Ea, afterload (Ea), RV diastolic dysfunction (Tau), and stiffness (end-diastolic elastance [Eed]) but not with contractility (Ees). In multivariate analysis, long-axis RV radial strain was associated with RV-arterial uncoupling (Ees/Ea: <0.805; odds ratio [OR]: 5.50; 95% confidence interval [CI]: 1.50 to 20.18), whereas long-axis RV longitudinal strain was associated with increased RV diastolic stiffness (Eed: ≥0.124 mm Hg/ml; OR: 1.23; 95% CI: 1.10 to 1.51). The long-axis RV longitudinal strain-to-RV end-diastolic volume/body surface area ratio strongly predicted RV diastolic stiffness (area under receiver operating characteristic curve: 0.908). ConclusionsIn chronic RV overload, CMR-determined RV strain is associated with RV-arterial uncoupling and RV end-diastolic stiffness and represents a promising noninvasive alternative to current invasive methods for assessment of RV-arterial coupling and end-diastolic stiffness in patients with PH. (Right Ventricular Haemodynamic Evaluation and Response to Treatment [Rightheart I]; NCT03403868)

Right Ventricular Function After Pulmonary Artery Banding: Adaptive Processes Assessed by CMR and Conductance Catheter Measurements in Sheep.

This experimental study describes the adaptive processes of the right ventricular (RV) myocardium after pulmonary artery banding (PAB) evaluated by cine cardiac magnetic resonance (CMR), phase-contrast CMR (PC-CMR), and conductance catheter. Seven sheep were subjected to CMR 3months after PAB. Conductance catheter measurements were performed before and 3months after PAB. Four nonoperated, healthy, age-matched animals served as controls. Higher RV masses (p < 0.01), elevated RV end-systolic volumes (p < 0.05), and lower RV ejection fraction (p < 0.01) were observed in the operated group. The time-to-peak pulmonary artery flow was longer in the banding group (p < 0.01). RV maximal pressure and RV end-diastolic pressure correlated with the time-to-peak flow in the pulmonary artery (r = - 0.70 and - 0.69, respectively). In summary, PAB caused RV hypertrophy, increased myocardial contractility, and decreased RV-EF and cardiac output. The time-to-peak pulmonary artery flow correlated with RV pressures.

Effects of pulmonary artery banding in doxorubicin-induced left ventricular cardiomyopathy

ObjectiveCentral pulmonary banding has been proposed as a novel alternative for the treatment of left ventricular dilated cardiomyopathy in children. We sought to investigate the effects of central pulmonary banding in an experimental model of doxorubicin-induced left ventricular dilated cardiomyopathy. MethodsFour-month-old sheep (n = 28) were treated with intermittent intracoronary injections of doxorubicin (0.75 mg/kg/dose) into the left main coronary artery. A total dose of up to 2.15 mg/kg of doxorubicin was administered until signs of left ventricular dilation with functional impairment occurred by transthoracic echocardiography evaluation. Animals that survived were treated with surgical central pulmonary banding through a left anterior thoracotomy or sham surgery. Transthoracic echocardiography and pressure-volume loop measurements were used to compare left ventricular function preoperatively and 3 months later. Macroscopic and microscopic histologic examinations followed after hearts were harvested. ResultsNine animals from the central pulmonary banding group and 8 animals from the sham group survived and were included in the final analysis. Both groups showed similar inflammation and fibrosis upon histologic examination consistent with the toxic myocardial effects of doxorubicin. There were no differences in the echocardiographic measurements before central pulmonary banding or sham operation. Baseline measurements before the central pulmonary banding/sham operation were considered as 100%. The central pulmonary banding group had better left ventricular ejection fraction (102.5% ± 21.6% vs 76.7% ± 11.7%, P = .01), with a tendency for smaller left ventricular end-diastolic (101.2% ± 7.4% vs 120.4% ± 10.8%, P = .18) and significantly smaller end-systolic (100.3% ± 12.9% vs 116.5 ± 9.6%, P = .02) diameter of the left ventricle in comparison with the sham animals at 3 months. The end-systolic volume (101.4% ± 31.6% vs 143.4% ± 28.6%, P = .02) was significantly lower in the central pulmonary banding group 3 months postoperatively. Fractional shortening in the long axis (118.5% ± 21.5% vs 85.2% ± 22.8%, P = .016) and short axis (122.5% ± 18% vs 80.9% ± 13.6%, P = .0005) revealed significantly higher values in the central pulmonary banding group. In the conductance catheter measurements, no significant differences were seen between the groups for the parameters of systolic and diastolic function. ConclusionsCentral pulmonary artery banding in the setting of experimental toxic left ventricular dilated cardiomyopathy improved left ventricular echocardiographic function and dimensions.

Electrical Conductance Device for Stent Sizing.

The minimum stent area (MSA) has been clinically established as a significant predictor of restenosis, thrombosis, and ischemia using intra-vascular ultrasound (IVUS). Unfortunately, IVUS measurements are far from routine because of significant cost of IVUS, the training required, the subjectivity of image interpretation and the time added to the procedure. The objective of this study is to verify the accuracy of a conductance catheter for stent sizing. Here, we introduce an easy and entirely objective device and method for real time determination of MSA. A 10 kHz, 35 μA rms current is passed through the external electrodes of an intravascular catheter while the conductance is measured across a separate set of electrodes. Both phantom and ex vivo validations of metal stent sizing in five porcine carotid arteries were confirmed. The accuracy of the measurements were found to be excellent in phantoms (root mean square, rms, of 3.4% of actual value) and in ex-vivo vessels (rms = 3.2% of measured value). An offset of conductance occurs when a conductive metal stent (e.g., bare metal stent) is deployed in the vessel, while the slope remains the same. This offset is absent in the case of drug eluting stent where the metal is coated (i.e., insulated) or non-metal bioresorbable stent. The present device makes easy, accurate and reproducible measurements of the size of stented blood vessels within 3.2% rms error. This device provides an alternative method to sizing of stent (i.e., MSA) in real-time without subjective interpretation and with less cost than IVUS.

Left ventricular vortex and intraventricular pressure difference in dogs under various loading conditions.

Restrictions on the conventional evaluation of diastolic function have been recognized, especially under various loading conditions. Recently, new noninvasive ventricular vortex indexes have been introduced and are expected to reflect the cardiac function. Physiologically, there is a hypothesis that the intraventricular pressure difference (IVPD) is related to the formation of vortexes. IVPD and vortex indexes were simultaneously measured, and the relationship between the two was investigated. To verify the possibility of diastolic vorticity as an index of diastolic relaxation, a correlation between diastolic vorticity and the load dependency of vorticity [time constant (τ)] was examined. Six healthy dogs were studied using transthoracic echocardiography, pressure, and a conductance catheter. Vorticity was analyzed using vector flow mapping (VFM). IVPD was determined using Euler's equation with color M-mode Doppler images. Data were obtained at baseline, at balloon dilatation in the thoracic aorta to alter afterload, at hydroxyethyl starch infusion to alter preload, and at milrinone administration to alter ventricular relaxation. Peak vorticity at early diastole (E-Vor) and IVPD of the midventricle (MIVPD) decreased under pressure loading, were unchanged under volume loading, and increased during milrinone administration. In multivariate analysis, the independent predictors of τ were global longitudinal strain, strain rate at early diastole, and E-Vor. MIVPD was strongly correlated with E-Vor ( r = 0.84). VFM-derived peak E vorticity was strongly related to IVPD, especially MIVPD, under various loading conditions. Both of these novel indexes are promising as reliable indexes of ventricular relaxation, independent from preload. NEW & NOTEWORTHY We showed the close relationship of vortex and intraventricular pressure difference and showed that both of them can become new markers of the left ventricular relaxation property. Our present study creates a paradigm for future studies in the field of intraventircular flow physiology and clinical diastology.

Impella CP or VA-ECMO in profound cardiogenic shock: left ventricular unloading and organ perfusion in a large animal model.

The aim of this study was to evaluate the Impella CP over veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and their impact on left ventricular unloading and end-organ perfusion. Cardiogenic shock (CS) was induced by injecting microspheres into the left coronary artery in fourteen adult female swine. Impella CP or VA-ECMO was initiated in the presence of CS and evaluated after 60 minutes. Left ventricular pressure-volume area (PVA, total mechanical work) was obtained from a conductance catheter. Results are presented as mean (95% confidence interval) and the rank-sum test was used to assess differences between devices. Compared to the CS state, PVA was unaffected by Impella CP and increased on VA-ECMO (from 2,548 [2,193; 2,904] mmHg x mL during CS to 5,775 [4,451; 7,099], between device p-value=0.02). Arterial lactate increased during CS and decreased on support with no difference between devices. Renal venous oxygen saturation decreased during CS and increased on support with no difference between devices. Cerebral venous oxygen saturation increased to 33% [25, 40] on Impella CP and to 69% [49, 89] on VA-ECMO, p=0.04. In this porcine model of profound CS, Impella CP unloaded the left ventricle compared to VA-ECMO. Both devices improved end-organ perfusion, with a tendency towards higher venous oxygen saturations on VA-ECMO.

Immediate Reduction in Left Ventricular Wall Stress Post Transcatheter Aortic Valve Replacement

Background: Patients with aortic stenosis (AS) may have other competing comorbidities to account for their symptoms. Left ventricular wall stress (LVWS) is increased in patients with severe AS and is likely to be an indicator of AS severity, however the immediate effects of transcatheter aortic valve replacement (TAVR) have not been documented. We assessed acute changes in LVWS post TAVR. Methods: Six patients (median age 82 years (IQR 81.8–84)) undergoing TAVR for severe, symptomatic AS (median AV V max: 4.1 m/s (3.8–4.4), AVA 0.7 cm2 (0.68–0.85)) underwent MRI within 24 hours prior to TAVR. CMR-derived volumes were integrated with invasive haemodynamic data obtained using conductance catheters, to construct pressure-volume (PV) loops immediately before and after valve implantation. Pressures obtained on PV-loops were used to derive regional end-systolic (ES) and end-diastolic (ED) LVWS pre- and post-intervention (for 7 contiguous SAX planes). Results: TAVR was associated with a significant reduction in average ES-LVWS (7.8 to 5.7 × 103 N/m2, p = 0.046). There was a non-significant trend to suggest a reduction in median LV-ESP (133 mmHg pre, 129 mmHg post, p = 0.6), LV-EDP (15 mmHg pre, 13 mmHg post, p = 0.46) as well as a trend to suggest a reduction in maximum regional ES-LVWS (9.8 to 9.2 × 103 N/m2, p = 0.5) and minimum regional ES-LVWS (5.6 to 4.9 × 103 N/m2, p = 0.46). In contrast there was no significant change in ED-LVWS following TAVR (average ED-LVWS 2.3 to 2.3, p = 0.46, maximum ED-LVWS 2.6–2.8 × 103 N/m2, p = 0.46). Conclusion: In patients with severe, symptomatic AS, TAVR is associated with an immediate reduction in end-systolic wall stress, however end-diastolic wall stress is unchanged.

Reliability of effective arterial elastance using peripheral arterial pressure as surrogate for left ventricular end-systolic pressure.

To compare the effective arterial elastance (Ea) obtained from the arterial pressure with Ea calculated from left-ventricular (LV) pressure-volume analysis. Experimental study. LV pressure-volume data was obtained with a conductance catheter and arterial pressures were measured via a fluid-filled catheter placed in the proximal aorta, femoral and radial arteries. Ea was calculated as LV end-systolic pressure (ESP)/stroke volume (SV). Experimental protocol consisted sequentially changing afterload (phenylephrine/nitroprusside), preload (bleeding/fluid), and contractility (esmolol/dobutamine). 90% of systolic pressure (Eaao_SYS, Eafem_SYS, Earad_SYS), mean arterial pressure (Eaao_MAP, Eafem_MAP, Earad_MAP), and dicrotic notch pressure (Eaao_DIC, Eafem_DIC, Earad_DIC) were used as surrogates for LV ESP. SV was calculated from the LV pressure-volume data. When Ea was compared with estimations based on 90% SAP, the relationship was r2 = 0.95, 0.94 and 0.92; and the bias and limits of agreement (LOA): - 0.01 ± 0.12, - 0.09 ± 0.12, - 0.05 ± 0.15mmHg ml-1, for Eaao_SYS, Eafem_SYS and Earad_SYS, respectively. For estimates using dicrotic notch, the relationship was r2 = 0.94, 0.95 and 0.94 for Eaao_DIC, Eafem_DIC and Earad_DIC, respectively; with a bias and LOA: 0.05 ± 0.11, 0.06 ± 0.12, 0.10 ± 0.12mmHg ml-1, respectively. When Ea was compared with estimates using MAP, the relationship was r2 = 0.95, 0.96 and 0.95 for Eaao_MAP, Eafem_MAP and Earad_MAP, respectively; with a bias and LOA: 0.05 ± 0.11, 0.06 ± 0.11, 0.06 ± 0.11mmHg ml-1, respectively. LV ESP can be estimated from the arterial pressure. Provided that the SV measurement is reliable, the ratio MAP/SV provides a robust Ea surrogate over a wide range of hemodynamic conditions and is interchangeably in any peripheral artery, so it should be recommended as an arterial estimate of Ea in further research.

Performance comparison of ventricular and arterial dP/dtmax for assessing left ventricular systolic function during different experimental loading and contractile conditions

BackgroundMaximal left ventricular (LV) pressure rise (LV dP/dtmax), a classical marker of LV systolic function, requires LV catheterization, thus surrogate arterial pressure waveform measures have been proposed. We compared LV and arterial (femoral and radial) dP/dtmax to the slope of the LV end-systolic pressure-volume relationship (Ees), a load-independent measure of LV contractility, to determine the interactions between dP/dtmax and Ees as loading and LV contractility varied.MethodsWe measured LV pressure-volume data using a conductance catheter and femoral and radial arterial pressures using a fluid-filled catheter in 10 anesthetized pigs. Ees was calculated as the slope of the end-systolic pressure-volume relationship during a transient inferior vena cava occlusion. Afterload was assessed by the effective arterial elastance. The experimental protocol consisted of sequentially changing afterload (phenylephrine/nitroprusside), preload (bleeding/fluid bolus), and contractility (esmolol/dobutamine). A linear-mixed analysis was used to assess the contribution of cardiac (Ees, end-diastolic volume, effective arterial elastance, heart rate, preload-dependency) and arterial factors (total vascular resistance and arterial compliance) to LV and arterial dP/dtmax.ResultsBoth LV and arterial dP/dtmax allowed the tracking of Ees changes, especially during afterload and contractility changes, although arterial dP/dtmax was lower compared to LV dP/dtmax (bias 732 ± 539 mmHg⋅s− 1 for femoral dP/dtmax, and 625 ± 501 mmHg⋅s− 1 for radial dP/dtmax). Changes in cardiac contractility (Ees) were the main determinant of LV and arterial dP/dtmax changes.ConclusionAlthough arterial dP/dtmax is a complex function of central and peripheral arterial factors, radial and particularly femoral dP/dtmax allowed reasonably good tracking of LV contractility changes as loading and inotropic conditions varied.