Improvement In Left Ventricular Performance Research Articles

Abstract 12821: Progressive Improvement in Left Ventricular Performance Associated With Progressive Regional Dyssynchrony

Background : We have shown that non-excitatory epicardial stimulation (NES) increases measures of cardiac function mediated by local release of norepinephrine. In this further investigation we determined whether NES is accompanied by improved indices of left ventricular (LV) performance, reflected in PV loops and timing of aortic valve opening and closing. Methods : Anesthetized pigs (n=6) were instrumented with a LV high-fidelity pressure/volume conductance transducer, thoracic aortic pressure transducer, left atrial (LA)/ LV epicardial electrodes, and sonomicrometer segment length (SL) gauges placed proximal (lateral base) and distal (posterior mid LV) to the LV stimulation site. During constant LA pacing, LV pulses (0.8ms, 2-3x threshold volts) were applied during the absolute refractory period for 3 minutes (3x), before and after β-receptor blockade (BB, metoprolol). Data were analyzed at baseline, and at an estimated 30%, 60% and 100% of developed ventricular dyssynchrony (DVD) contraction pattern. Results: Consistent with earlier findings, NES resulted in an early shortening and relaxation pattern of the proximal SL manifest as an 80% decrease in the LVP vs. SL loop area in the absence of change in the remote segment. This was accompanied by an increase in peak systolic pressure and LV dP/dt max. Although NES did not change the area of the LVP vs. LV volume loop (stroke work) or alter the interval from LV electrical activation (R wave) to the onset of LV pressure increase, aortic valve opening occurred up to 14.1 ± 2.8 ms earlier (p <0.01) compared to baseline. The duration of an open aortic valve slightly increased (6.0 ± 3.9 ms) whereas ejection duration from valve opening to peak Pao decreased 18.2 ± 3.0 ms (p < 0.01). Conclusion : These findings demonstrate that NES elicits a local contractile dysynchrony resulting in an enhanced cardiac inotropic state characterized by more rapid global LV contraction with earlier aortic valve opening with no change in stroke work.

Alterations in ACE and ACE2 Activities and Cardiomyocyte Signaling Underlie Improved Myocardial Function in a Rat Model of Repeated Remote Ischemic Conditioning.

Post-ischemic left ventricular (LV) remodeling and its hypothetical prevention by repeated remote ischemic conditioning (rRIC) in male Sprague–Dawley rats were studied. Myocardial infarction (MI) was evoked by permanent ligation of the left anterior descending coronary artery (LAD), and myocardial characteristics were tested in the infarcted anterior and non-infarcted inferior LV regions four and/or six weeks later. rRIC was induced by three cycles of five-minute-long unilateral hind limb ischemia and five minutes of reperfusion on a daily basis for a period of two weeks starting four weeks after LAD occlusion. Sham operated animals served as controls. Echocardiographic examinations and invasive hemodynamic measurements revealed distinct changes in LV systolic function between four and six weeks after MI induction in the absence of rRIC (i.e., LV ejection fraction (LVEF) decreased from 52.8 ± 2.1% to 50 ± 1.6%, mean ± SEM, p < 0.05) and in the presence of rRIC (i.e., LVEF increased from 48.2 ± 4.8% to 55.2 ± 4.1%, p < 0.05). Angiotensin-converting enzyme (ACE) activity was about five times higher in the anterior LV wall at six weeks than that in sham animals. Angiotensin-converting enzyme 2 (ACE2) activity roughly doubled in post-ischemic LVs. These increases in ACE and ACE2 activities were effectively mitigated by rRIC. Ca2+-sensitivities of force production (pCa50) of LV permeabilized cardiomyocytes were increased at six weeks after MI induction together with hypophosphorylation of 1) cardiac troponin I (cTnI) in both LV regions, and 2) cardiac myosin-binding protein C (cMyBP-C) in the anterior wall. rRIC normalized pCa50, cTnI and cMyBP-C phosphorylations. Taken together, post-ischemic LV remodeling involves region-specific alterations in ACE and ACE2 activities together with changes in cardiomyocyte myofilament protein phosphorylation and function. rRIC has the potential to prevent these alterations and to improve LV performance following MI.

Is it possible to expect left ventricular ejection fraction improvement in patients with known advanced heart diseases in the case of right atrial flutter treated by ablation?

Atrial flutter (AFL)-related tachycardia-induced cardiomyopathy (TICM) is a treatable cause of heart failure (HF). This study aims to explore the effect of AFL ablation on left ventricular (LV) function in right AFL patients with or without advanced heart diseases. Between January 2013 and December 2019, 149 patients underwent ablation for persistent AFL. Among them, 60 patients with persistent right atrial (RA) flutter had symptomatic HF and elevated natriuretic peptide levels. Group 1 consisted of 35 patients without advanced heart diseases, and group 2 consisted of 25 patients with prior history of ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM) or surgery for valvular heart disease (VHD). Follow-up echocardiography was performed 6months later. Improvement of LV performance was defined as LV ejection fraction (EF) increase ≥50% of baseline EF without clinical HF symptoms or LVEF recovery to ≥60%. Group 2 had larger LV end-diastolic volume (LVEDV) and LV end-systolic volume than group 1. At follow-up, group 2 had larger LV end-systolic volume than group 1. Group 1 had more increase in LVEF than group 2 (21.7±15.2% vs 4.1±13.2%; P<.001). A receiver operating characteristic curve was constructed to determine the discrimination threshold of baseline LVEDV (137mL) in the overall study group for improvement of LV performance after ablation (P=.005). Successful ablation for right AFL could achieve more reversal of LV dysfunction in patients without advanced heart diseases. Pre-ablation LVEDV≥137mL was associated with no improvement of LV performance after ablation.

The role of cardiac magnetic resonance imaging in the detection and monitoring of cardiotoxicity in patients with breast cancer after treatment: a comprehensive review.

The use of chemotherapy medicines for breast cancer (BC) has been associated with an increased risk of cardiotoxicity. In recent years, there have been growing interests regarding the application of cardiovascular magnetic resonance (CMR) imaging, a safe and noninvasive modality, with the potential to identify subtle morphological and functional changes in the myocardium. In this investigation, we aimed to review the performance of various CMR methods in diagnosing cardiotoxicity in BC, induced by chemotherapy or radiotherapy. For this purpose, we reviewed the literature available in PubMed, MEDLINE, Cochrane, Google Scholar, and Scopus databases. Our literature review showed that CMR is a valuable modality for identifying and predicting subclinical cardiotoxicity induced by chemotherapy. The novel T1, T2, and extracellular volume mapping techniques may provide critical information about cardiotoxicity, in addition to other CMR features such as functional and structural changes. However, further research is needed to verify the exact role of these methods in identifying cardiotoxicity and patient management. Since multiple studies have reported the improvement of left ventricular performance following the termination of chemotherapy regimens, CMR remains an essential imaging tool for the prediction of cardiotoxicity and, consequently, decreases the mortality rate of BC due to heart failure.

Protective Effects of Statin and Angiotensin Receptor Blocker in a Rat Model of Doxorubicin- and Trastuzumab-Induced Cardiomyopathy

Chemotherapy has led to improved survival in patients with breast cancer; however, it is associated with an increased risk of cardiac dysfunction and heart failure. We investigated the protective effects of rosuvastatin and candesartan, alone and in combination, in a doxorubicin- and trastuzumab-induced rat model of cardiomyopathy. Forty-two rats were allocated into six groups (G1-G6): G1, control; G2, doxorubicin only; G3, doxorubicin +trastuzumab; G4, doxorubicin+trastuzumab+rosuvastatin; G5, doxorubicin+trastuzumab+candesartan; and G6, doxorubicin+trastuzumab+rosuvastatin+candesartan. Doxorubicin and trastuzumab were sequentially administered for 28days. Left ventricular end-systolic dimension and longitudinal strain (LS) were assessed via echocardiography. Left ventricular (LV) performance was evaluated using a microcatheter in the LV apex on day 28. Blood for biomarker analysis was collected from the inferior vena cava before sacrifice. Doxorubicin in combination with trastuzumab increased the LV end-systolic dimension but worsened LS compared with the control group (all P<.05). The level of C-reactive protein was lower in the rosuvastatin treatment group (P=.007) than in the controls but not in the candesartan treatment group. Both rosuvastatin and candesartan attenuated the increase in glutathione. Candesartan treatment improved+dP/dt (P=.011), whereas rosuvastatin did not. In the combination treatment group, the worsening of LS was significantly attenuated compared with that in either the rosuvastatin or candesartan group (all P<.05). In a rat model of doxorubicin- and trastuzumab-induced cardiomyopathy, rosuvastatin alleviated systemic inflammation, while candesartan improved LV performance. Combination therapy with rosuvastatin and candesartan demonstrated additional preventive effects on myocardial strain. The protective mechanisms of rosuvastatin and candesartan appear to be different but complementary in chemotherapy-induced cardiomyopathy.

MitraClip and left ventricular reverse remodelling: a strain imaging study.

AimsThe purpose of this study is to identify echocardiography predictors of clinical response and reverse left ventricular (LV) remodelling in patients with functional mitral regurgitation (FMR) treated with MitraClip.Method and resultsWe retrospectively analysed 86 high surgical risk patients with severe FMR; of those, 58 were implanted a MitraClip, and 28 received medical treatment and served as controls. At baseline and at 1‐year follow‐up, we performed clinical and echocardiography evaluation to assess global longitudinal strain (GLS) and myocardial work [global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE)]. Mitral regurgitation was significantly reduced after MitraClip implantation (3.7 ± 0.4 vs. 1.7 ± 0.8, P < 0.001), and the procedure was associated with improvement in brain natriuretic peptide levels (980 ± 1027 vs. 420 ± 338 pg/mL, P < 0.001), New York Heart Association class status (3.2 ± 0.55 vs. 2.0 ± 0.6, P < 0.001), 6‐min walking test (233 ± 154 vs. 286 ± 114 m, P = 0.01) at follow‐up and reduction of left ventricle end‐systolic (LVESV) and left ventricle end‐diastolic volumes (LVEDV) (152 ± 68 vs. 136 ± 43 mL, P = 0.004 & 219 ± 74 vs. 193 ± 66 mL, P = 0.001, respectively). MitraClip procedure was associated with improvement of LV performance and significant increase of GWI (607 ± 282 vs. 650 ± 260 mmHg%, P = 0.045) and GCW (854 ± 288 vs. 949 ± 325 mmHg%, P < 0.001). Baseline ejection fraction (EF), GLS, GWI, GCW, and effective regurgitant orifice area were the variables that were associated with reduction of LVEDV 1 year after intervention (P < 0.05 for all) and baseline GCW of the LV was the only variable associated with reduction of LVESV (P = 0.002). Receiver operating characteristic curve analysis identified that a GLS cut‐off value of −8.65% (AUC 0.815, P = 0.007) was associated with a 20% reduction of the LVEDV with a sensitivity and specificity of 72% and 70%, respectively, and that a GCW cut‐off value of 846 mmHg% (AUC 0.759, P = 0.007) was associated with a 10% reduction of LVESV with sensitivity and specificity 79% and 74%, respectively.ConclusionsMitral valve repair with MitraClip has positive clinical and echocardiographic impact in patients with FMR 1 year after implantation. Preserved GLS and GCW values appear to be associated with LV reverse remodelling post intervention.

The altered expression of autophagy-related genes participates in heart failure: NRBP2 and CALCOCO2 are associated with left ventricular dysfunction parameters in human dilated cardiomyopathy.

This study aimed to analyze changes in the expression of autophagy- and phagocytosis-related genes in patients with dilated cardiomyopathy (DCM), especially in relation to left ventricular (LV) dysfunction. Furthermore, transmission electron microscopy of the diseased tissue was carried out to investigate if the gene expression changes are translated into ultrastructural alterations. LV tissue samples from patients with DCM (n = 13) and from controls (CNT; n = 10) were analyzed by RNA-sequencing, whereupon the altered expression (P < 0.05) of 13 autophagy- and 3 phagocytosis-related genes was observed. The expression changes of the autophagy-related genes NRBP2 and CALCOCO2 were associated with cardiac dysfunction and remodeling (P < 0.05). The affected patients had a higher activity of these degradation processes, as evidenced by the greater number of autophagic structures in the DCM tissue (P < 0.001). Differences in the ultrastructural distribution were also found between the DCM and CNT tissues. These results show that in patients with DCM, the altered expression of NRBP2 and CALCOCO2 is related to LV dysfunction and remodeling. Clarification of the molecular mechanisms of cardiac autophagy would help in the future development of therapies to improve LV performance.

Long-Term Hemodynamic Improvement after Transcatheter Mitral Valve Repair

Correction of mitral regurgitation (MR) alters the load on the left ventricle. There are few data on the long-term hemodynamic adaptations of the cardiovascular system after transcatheter mitral valve repair (TMVR). The aim of this study was to determine a comprehensive hemodynamic status using noninvasive pressure-volume analysis. Pressure-volume parameters were calculated from echocardiography with simultaneous arm-cuff blood pressure measurements at baseline before TMVR and 12months after TMVR. Eighty-eight consecutive patients undergoing edge-to-edge mitral clip implantation because of grade 3+or 4+, symptomatic (79.5% in New York Heart Association functional class≥III) MR were prospectively enrolled. The mean left ventricular (LV) ejection fraction was 42±14%. Sixty-seven percent of the patients had secondary MR. Twelve months after TMVR, 17.7% of patients had died, and 19.0% were rehospitalized because of decompensated heart failure. MR grade was ≤2+in 90% of surviving patients, and 77% were in New York Heart Association functional class≤II. LV end-diastolic volume index decreased from 87±38 to 77±40mL/m2 (P<.0001), end-systolic volume index changed from 54±34 to 50±36mL/m2 (P=.018), hence total stroke volume index was reduced (from 34±11 to 28±7ml/m2, P<.0001). Ejection fraction and global longitudinal peak systolic strain remained unchanged. Increased forward ejection fraction (30±14% vs 41±20%, P<.0001), cardiac index (from 1.7±0.4 to 1.9±0.5mL/min/m2, P=.003), and peak power index (214±114 vs 280±149mm Hg/sec, P=.0001) as well as similar end-systolic elastance at reduced LV volumes indicated improved LV performance. Cardiac efficiency, measured as cardiac index relative to myocardial energy, was improved (0.012±0.008 vs 0.019±0.010mm Hg-1, P=.002). Logistic regression analysis revealed baseline values of total ejection fraction and diastolic pulmonary pressure gradient as predictors of clinical improvement (odds ratios, 1.076 [P=.009] and 0.812 [P=.015], respectively) after TMVR. One year after TMVR, patients showed reverse remodeling and improved LV performance that was associated with improved symptom status. This hemodynamic improvement supports TMVR as long-term effective therapy for patients with symptomatic MR.

Association between High Endocardial Unipolar Voltage and Improved Left Ventricular Function in Patients with Ischemic Cardiomyopathy.

We know that endocardial mapping reports left ventricular electrical activity (voltage) and that these data can predict outcomes in patients undergoing traditional revascularization. Because the mapping data from experimental models have also been linked with myocardial viability, we hypothesized an association between increased unipolar voltage in patients undergoing intramyocardial injections and their subsequent improvement in left ventricular performance. For this exploratory analysis, we evaluated 86 patients with left ventricular dysfunction, heart-failure symptoms, possible angina, and no revascularization options, who were undergoing endocardial mapping. Fifty-seven patients received bone marrow mononuclear cell (BMC) injections and 29 patients received cell-free injections of a placebo. The average mapping site voltage was 9.7 ± 2 mV, and sites with voltage of ≥6.9 mV were engaged by needle and injected (with BMC or placebo). For all patients, at 6 months, left ventricular ejection fraction (LVEF) improved, and after covariate adjustment this improvement was best predicted by injection-site voltage. For every 2-mV increase in baseline voltage, we detected a 1.3 increase in absolute LVEF units for all patients (P=0.038). Multiple linear regression analyses confirmed that voltage and the CD34(+) count present in bone marrow (but not treatment assignment) were associated with improved LVEF (P=0.03 and P=0.014, respectively). In an exploratory analysis, higher endocardial voltage and bone marrow CD34(+) levels were associated with improved left ventricular function among ischemic cardiomyopathy patients. Intramyocardial needle injections, possibly through stimulation of angiogenesis, might serve as a future therapy in patients with reduced left ventricular function and warrants investigation.

Decrease of the Pericardial Fat around the Heart has a Positive Correlation with Improvement of Left Ventricular Performance

Objective: The objective of the study was to evaluate the effect of an eight week period of very low calorie diet (VLCD) on left ventricular performance and on the amount of pericardial adipose tissue around the heart in obese people without heart disease. This is an extension of the study “Cardiac systolic and diastolic function can be improved over a short period of time in obese patients without heart disease by the very low calorie diet” with the same authors and study group, being currently under evaluation for publication in this Journal. Methods: Fifty-seven obese patients (41 women, 16 men, mean age 48.0±12.0 years, mean BMI 46.1±7.2g/m2) were assigned to a VLCD enriched with vegetables for eight weeks. Transthoracic echocardiography was performed before and after the diet period. Left ventricular size, ejection fraction, myocardial performance index and thickness of pericardial adipose tissue were measured. Results: During the diet period the BMI decreased from 46.1±7.2 kg/m2 to 41.7±6.4 kg/m2 (p<0.0001). The left ventricular performance index decreased from 0.41±0.07 to 0.37±0.07 (p<0.0001) showing significant systolic and diastolic improvement in the performance of left ventricle. The thickness of pericardial fat decreased from 2.2±1.6 mm to 1.4±1.3 mm (p<0.0001). The improvement of the left ventricular myocardial performance index correlated positively with the decrease of pericardial fat (r=0.46, p<0.001). Conclusion: Changing the diet for only eight weeks time caused significant reduction in BMI as well as in the amount of pericardial fat and significant improvement in the systolic and diastolic performance of the left ventricle in obese persons. There was a positive correlation between the improvement on left ventricular performance and the decrease of pericardial fat.

Early feasibility evaluation of thoracoscopically assisted transcatheter ventricular reconstruction in an experimental model of ischaemic heart failure with left anteroapical aneurysm.

To test the feasibility of a thoracoscopically assisted, off-pump, transcatheter ventricular reconstruction (TCVR) approach in an ovine model of left ventricular (LV) anteroapical aneurysm. Myocardial infarction (MI) was induced by coil occlusion of the middle left anterior descending artery and diagonals. Two months after MI creation, TCVR was performed via a minimal thoracotomy in eight sheep. Under endoscopic and fluoroscopic guidance, trans-interventricular septal puncture was performed from the LV epicardial scar. A guidewire was externalised via a snare placed in the right ventricle from the external jugular vein. An internal anchor was inserted over the wire and positioned on the right ventricular septum and an external anchor was deployed on the LV anterior epicardium. Serial pairs of anchors were placed and plicated together to exclude the scar completely. Immediately after TCVR, echocardiography showed LV end-systolic volume decreased from pre-procedure 58.8±16.6 ml to 25.1±7.6 ml (p<0.01) and the ejection fraction increased from 32.0±7.3% to 52.0±7.5% (p<0.01). LV twist significantly improved (3.83±2.21 vs. pre-procedure -0.41±0.94, p=0.01) and the global peak-systolic longitudinal strain increased from -5.64% to -10.77% (p<0.05). TCVR using minimally invasive access techniques on the off-pump beating heart is feasible and resulted in significant improvement in LV performance.

Pre-treatment with glucagon-like Peptide-1 protects against ischemic left ventricular dysfunction and stunning without a detected difference in myocardial substrate utilization.

This study sought to determine whether pre-treatment with intravenous glucagon-like peptide-1 (GLP-1)(7-36) amide could alter myocardial glucose use and protect the heart against ischemic left ventricular (LV) dysfunction during percutaneous coronary intervention. GLP-1 has been shown to have favorable cardioprotective effects, but its mechanisms of action remain unclear. Twenty patients with preserved LV function and single-vessel left anterior descending coronary artery disease undergoing elective percutaneous coronary intervention were studied. A conductance catheter was placed into the LV, and pressure-volume loops were recorded at baseline, during 1-min low-pressure balloon occlusion (BO), and at 30-min recovery. Patients were randomized to receive an infusion of either GLP-1(7-36) amide at 1.2 pmol/kg/min or saline immediately after baseline measurements. Simultaneous coronary artery and coronary sinus blood sampling was performed at baseline and after BO to assess transmyocardial glucose concentration gradients. BO caused both ischemic LV dysfunction and stunning in the control group but not in the GLP-1 group. Compared with control subjects, the GLP-1 group had a smaller reduction in LV performance during BO (delta dP/dTmax, -4.3 vs. -19.0%, p = 0.02; delta stroke volume, -7.8 vs. -26.4%, p = 0.05), and improved LV performance at 30-min recovery. There was no difference in transmyocardial glucose concentration gradients between the 2 groups. Pre-treatment with GLP-1(7-36) amide protects the heart against ischemic LV dysfunction and improves the recovery of function during reperfusion. This occurs without a detected change in myocardial glucose extraction and may indicate a mechanism of action independent of an effect on cardiac substrate use. (Effect of Glucgon-Like-Peptide-1 [GLP-1] on Left Ventricular Function During Percutaneous Coronary Intervention [PCI]; ISRCTN77442023).

Similar improvement of left ventricular performance after valve replacement for aortic stenosis with small aortic annuli among three different implantation techniques

Background We evaluated the effects of three implantation techniques (everting mattress, non-everting mattress, and simple interrupt techniques) for aortic valve replacement in severe aortic stenosis with small aortic annulus on left ventricular performance and function.

Continuously adjusting CRT therapy: clinical impact of adaptive cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is a well-established therapy to reduce morbidity and mortality in patients with moderate and severe symptomatic congestive heart failure. Left ventricular (LV) pacing that fuses with intrinsic right ventricular (RV) conduction results in similar or even better cardiac performance compared to biventricular (Biv) pacing. Optimal programming of the atrio-ventricular (AV) and inter-ventricular (VV) delays is crucial to improve LV performance since suboptimal programming of AV and VV delays affect LV filling as well as cardiac output. CRT optimization using echocardiogram is resource-dependent and time consuming. Adaptive CRT (aCRT) algorithm provides a dynamic, automatic, ambulatory adjustment of CRT pacing configuration (Biv or LV pacing) and optimization of AV and VV delays. aCRT algorithm is safe and efficacious for CRT-indicated patients without permanent atrial fibrillation. It has been shown to improve CRT response and reduce morbidity and mortality for patients with normal AV conduction.

Preserved Left Ventricular Performance In Spontaneously Hypertensive Rats Following Preload And Afterload Challenges

Hypertension‐induced left ventricular (LV) hypertrophy is an independent risk factor for heart failure. We studied LV performance and myocardial nitric oxide (NO) signaling and reactive oxygen species (ROS) in 6‐month‐old SHRs and age‐matched Wistar‐Kyoto rats (WKY) subjected to preload and afterload challenges. Under basal conditions, LV nNOS, but not eNOS, expression and nitrite/nitrate (NOx) were higher in SHR than in WKY rats. SHRs also exhibited higher LV weight, LV developed pressure (LVDP), LV end‐systolic pressure (LVESP), rate of rise (LV dp/dtmax) and fall (LV dp/dtmin) in LV pressure. In the acute volume overload model (dextrose infusion), SHRs showed significantly smaller reductions in LV dp/dtmax and LVDP and greater increases in LVEDP and isovolumic relaxation constant (Tau, τ), compared with WKY rats, suggesting enhanced systolic and depressed diastolic functions in SHRs. We also report improved LV performance in SHRs during pressure overload (phenylephrine infusion) as reflected by the increases in LVDP, LVESP, LV dp/dtmin, and LV dp/dtmax. LV ROS was increased by the two overload challenges in WKY, but not SHR, rats. The results suggest that despite evidence of early LV hypertrophy, the ability of the SHR to curtail myocardial oxidative stress may accounts, at least partly, for the preservation of the left ventricular performance during pressure or volume overload challenge in SHRs.

Acute Hemodynamic Effect of Left Ventricular Endocardial Pacing in Cardiac Resynchronization Therapy

Background— During cardiac resynchronization therapy (CRT) device implantation, the pacing lead is usually positioned in the coronary sinus (CS) to stimulate the left ventricular (LV) epicardium. Transvenous LV endocardial pacing via transseptal puncture has been proposed as an alternative method. In the present study, we evaluated the acute hemodynamic effects of CRT through LV endocardial pacing in heart failure patients by analyzing LV pressure–volume relationships. Methods and Results— LV pressure and volume data were determined via conductance catheter during CRT device implantation in 10 patients. In addition to the standard epicardial CS pacing, the following endocardial LV sites were systematically assessed: the site transmural to the CS lead, the LV apex, the septal midwall, the basal lateral free wall, and the midlateral free wall. Four atrioventricular delays were tested. There was a significant improvement of systolic function with CRT in all LV pacing configurations, whereas no differences in systolic or diastolic function were detected between LV epicardial and endocardial transmural sites. The optimal pacing site varied among patients but was rarely related to relatively longer activation delays, as assessed by analyzing endocardial electric activation maps. Nonetheless, positioning the pacing lead at the optimal endocardial LV site in each patient significantly improved LV performance in comparison with conventional CS site stimulation (stroke volume, 83 [79–112] mL versus 73 [62–89] mL; P =0.034). Conclusions— Pacing at the optimal individual LV endocardial site yields enhanced LV performance in comparison with conventional CS site stimulation. Endocardial LV pacing might constitute an alternative approach to CRT, when CS pacing is not viable.

The Incremental Value of Valvuloarterial Impedance in Evaluating the Results of Transcatheter Aortic Valve Implantation in Symptomatic Aortic Stenosis

Valvuloarterial impedance (Z(va)) can estimate the global hemodynamic load on the left ventricle in patients with severe aortic stenosis better than the standard indexes, as shown in previous studies. In fact, Z(va) can estimate global left ventricular hemodynamic load as the sum of valvular and vascular loads. The aim of this study was to evaluate the acute improvement of left ventricular performance in patients with symptomatic aortic stenosis after transcatheter aortic valve implantation (TAVI) using Z(va). One hundred two consecutive patients who underwent TAVI were submitted to transthoracic echocardiography immediately before and after aortic valve implantation, together with invasive hemodynamic measurements. After TAVI, immediate reductions in the transaortic peak pressure gradient (P < .0001) and mean pressure gradient (P < .0001) and a concomitant increase in aortic valve area (P < .0001) were seen on echocardiography. Left ventricular ejection fraction significantly increased immediately after TAVI in all patients (from 48.9 ± 10.3% to 52.1 ± 11.1%, P < .0001). Regarding global left ventricular hemodynamic load, acute and significant reductions in end-systolic meridional wall stress (from 82.7 ± 42.6 to 57.8 ± 30.1 kdyne · cm(-2), P < .0001) and in Z(va) (from 6.81 ± 2.51 to 5.38 ± 2.13 mm Hg · mL(-1) · m(-2), P < .0001) were observed. Furthermore, patients who died at 6-month follow-up had higher baseline Z(va) values compared with those who were alive at 6-month follow-up (8.13 ± 3.08 vs 6.41 ± 2.12 mm Hg · mL(-1) · m(-2), P < .004). TAVI is characterized by an immediate enhancement of global left ventricular hemodynamic performance, as demonstrated by an acute Z(va) improvement, even in patients with low baseline ejection fractions.

Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra

Myocardial function is impaired in rheumatoid arthritis (RA). Inhibition of interleukin (IL)-1 activity reduces experimental myocardial infarction by limiting apoptosis. We investigated whether a) soluble apoptotic markers are related with impaired left ventricular (LV) performance and b) treatment with anakinra, an IL-1 receptor antagonist, reduces apoptotic markers leading to improved LV performance in RA. We studied 46 RA patients. In an acute, double-blind cross-over trial, 23 patients were randomised to a single injection of anakinra or placebo and after 48 hours (h) to the alternative treatment. In a chronic trial, 23 patients who received anakinra for 30 days were compared with 23 patients who received prednisolone. At baseline, 3 h and 30 days after treatment, we measured circulating IL-1β, tumour necrosis factor (TNF)-α, Fas, Fas-ligand and caspase-9 to assess apoptosis. At baseline and 30 days after treatment, we assessed LV longitudinal strain, strain rate and E/Em ratio using 2D-speckle tracking and tissue Doppler echocardiography. At baseline, increased apoptotic markers were related with reduced LongSRS and increased E/Em (p<0.05). After 3 h and 30 days of anakinra, there was a reduction in Fas (median 481 vs. 364 vs. 301 pg/ml), Fas-ligand (median 289 vs. 221 vs. 190 pg/ml), caspase-9 (median 1.90 vs. 1.40 vs. 1.07 ng/ml), TNF-α and IL-1β (p<0.05 for all comparisons). E/Em, LongS and LongSRS were improved after anakinra (p<0.01) and their percent changes were related with the corresponding changes of Fas and caspase-9 (p<0.05). No changes of the examined parameters were observed after prednisolone. In conclusion, inhibition of IL-1 activity by anakinra reduces apoptotic markers leading to improved LV performance in RA.

Hyperinsulinemia improves ischemic LV function in insulin resistant subjects

BackgroundGlucose is a more efficient substrate for ATP production than free fatty acid (FFA). Insulin resistance (IR) results in higher FFA concentrations and impaired myocardial glucose use, potentially worsening ischemia. We hypothesized that metabolic manipulation with a hyperinsulinemic euglycemic clamp (HEC) would affect a greater improvement in left ventricular (LV) performance during dobutamine stress echo (DSE) in subjects with IR.Methods24 subjects with normal LV function and coronary disease (CAD) awaiting revascularization underwent 2 DSEs. Prior to one DSEs they underwent an HEC, where a primed infusion of insulin (rate 43 mU/m 2/min) was co-administered with 20% dextrose at variable rates to maintain euglycemia. At steady-state the DSE was performed and images of the LV were acquired with tissue Doppler at each stage for offline analysis. Segmental peak systolic velocities (Vs) were recorded, as well as LV ejection fraction (EF). Subjects were then divided into two groups based on their insulin sensitivity during the HEC.ResultsHEC changed the metabolic environment, suppressing FFAs and thereby increasing glucose use. This resulted in improved LV performance at peak stress, measured by EF (IS group mean difference 5.3 (95% CI 2.5-8) %, p = 0.002; IR group mean difference 8.7 (95% CI 5.8-11.6) %, p < 0.0001) and peak V s in ischemic segments (IS group mean improvement 0.7(95% CI 0.07-1.58) cm/s, p = 0.07; IR group mean improvement 1.0 (95% CI 0.54-1.5) cm/s, p < 0.0001) , that was greater in the subjects with IR.ConclusionsIncreased myocardial glucose use induced by HEC improves LV function under stress in subjects with CAD and IR. Cardiac metabolic manipulation in subjects with IR is a promising target for future therapy.

Echocardiographic Effects of Changing Atrioventricular Delay in Cardiac Resynchronization Therapy Based on Displacement

In studies showing benefits of cardiac resynchronization therapy (CRT), individual atrioventricular (AV) delays have been optimized using echocardiography. However, the method for AV delay optimization remains controversial. In 100 consecutive patients with CRT device implantation, AV delay was optimized using echocardiography. The optimal AV delay was determined by changing the interval in 20-ms increments while measuring displacement in 6 basal left ventricular segments (averaged and reported as left ventricular displacement [D(LV)]) and other echocardiographic measures. A single optimal AV delay existed for each patient, and the associated highest D(LV) corresponded with the maximal velocity-time integral (VTI) in the left ventricular outflow tract (VTI(LVOT)) and the E/e' ratio. Significant increases in D(LV) and the VTI(LVOT) from before to after implantation with standard settings and from standard to optimal AV delay by displacement were found. Diastolic filling time corresponded poorly with D(LV) and the VTI(LVOT). Individual optimal AV delay programming provides significant improvement in left ventricular performance and hemodynamics. Displacement analysis and the VTI(LVOT) are interchangeable, whereas diastolic filling time cannot be recommended.