Rate Of Left Ventricular Pressure Rise Research Articles

Comparison of acute hemodynamic effect of prioritizing ventricular resynchronization vs left ventricular filling during optimization of cardiac resynchronization therapy

BackgroundTargeting maximal ventricular resynchronization, with the shortest QRS duration (QRSd), is commonly implemented after cardiac resynchronization therapy (CRT). ObjectiveThe purpose of this study was to compare optimization of ventricular resynchronization with optimization of left ventricular (LV) filling during CRT by measuring their acute hemodynamic effects. MethodsPatients with standard CRT indications, recruited from 2 centers, underwent biventricular pacing (BVP) and left bundle branch pacing (LBBP). We performed a within-patient comparison of acute hemodynamic response of systolic blood pressure (SBP) at the atrioventricular delay (AVD) with the shortest QRSd against the AVD with the most efficient LV filling. In a validation substudy, we also performed electrical assessment using QRS area (QRSa) and hemodynamic assessment with the maximum rate of LV pressure rise (dP/dtmax). ResultsThirty patients (age 65 ± 10 years; 53% male) were recruited. The AVD producing maximal ventricular resynchronization was associated with a significantly shorter QRSd (difference 15 ± 12 ms for BVP and 18 ± 13 ms for LBBP, both P <.01) and a significantly smaller improvement in SBP (difference −3 ± 4 mm Hg for BVP and −2 ± 2 mm Hg for LBBP, both P <.01) compared with the AVD that optimized filling. Similar findings were observed in the substudy, with a significantly smaller improvement in dP/dtmax assessed with QRSd and QRSa (difference −9% ± 7% and −6% ± 4% during BVP, and −5% ± 6% and −3% ± 3% during LBBP, all P <.01). ConclusionTargeting the maximal ventricular resynchronization results in suboptimal acute hemodynamic performance with both BVP and LBBP as CRT. These findings support prioritizing LV filling when programming AVD for CRT.

Prognostic implications of invasive hemodynamics during cardiac resynchronization therapy: Stroke work outperforms dP/dtmax

Invasive measurements of left ventricular (LV) hemodynamic performance can evaluate acute response to cardiac resynchronization therapy (CRT). The study sought to determine which metric, maximum rate of LV pressure rise (LV dP/dtmax) or LV stroke work (LVSW), is more strongly associated with long-term prognosis. CRT patients were prospectively included from 3 academic centers. Invasive pressure-volume loop measurements during implantation were performed, and LV dP/dtmax and LVSW were determined at baseline and during biventricular pacing (BVP) as well as their relative increase (%Δ). Hazard ratios (HRs) for the primary outcome of 8-year all-cause mortality were derived using Cox proportional hazards. The secondary endpoint was echocardiographic response, defined as 6-month LV end-systolic volume reduction ≥15%. Paired data from 82 patients were analyzed (67% male; age 66 ± 9 years; QRS duration 158 ± 22 ms, median survival time 72 months). Survival was better when LVSW during BVP was ≥4400 mL∙mm Hg (HR 0.21, 95% CI 0.08-0.58, P < .003) or when ΔLVSW% was ≥10% (HR 0.22, 95% CI 0.08-0.65, P=.006). In multivariate analysis, following direct comparison of continuous measures of acute ΔLV dP/dtmax% and ΔLVSW%, only ΔLVSW% remained associated with the primary endpoint (HR 0.982 per percentage point, P = .028). In contrast to LV dP/dtmax (all P > .05), significant associations with echocardiographic response were found for stroke work during BVP (area under the receiver-operating characteristic curve 0.745, P = .001) and ΔLVSW% (area under the receiver-operating characteristic curve 0.803, P < .001). Stroke work, but not LV dP/dtmax, is consistently associated with long-term prognosis and response after CRT. Our results therefore favor the use of stroke work as the hemodynamic parameter to predict long-term outcome after CRT.

Heart sound–derived systolic time intervals for atrioventricular delay optimization in cardiac resynchronization therapy

Phonocardiography (PCG) can be used to determine systolic time intervals (STIs) from ventricular pacing spike to the first heart sound (VS1) and from the first to the second heart sound (S1S2). The purpose of this study was to investigate the relations between STIs and hemodynamics during atrioventricular (AV) delay optimization of biventricular pacing (BiVP) in animals and patients. Five pigs with AV block underwent BiVP, while PCG was collected from an epicardial accelerometer. In 21 patients undergoing cardiac resynchronization therapy device implantation, PCG was recorded with a pulse generator-embedded microphone. Optimal AV delays derived from shortest VS1 and longest S1S2 were compared with AV delays derived from highest left ventricular pressure (LVP), maximal rate of rise in LVP, and stroke work. In pigs, VS1 and S1S2 predicted the AV delays with optimal hemodynamics (highest LVP, maximal rate of rise in LVP, and stroke work) by a median error of 2-28 ms, resulting in a median loss of <2% of pump function. In patients, VS1 and S1S2 predicted the optimal AV delay by errors of 32.5 and 37.5 ms, respectively, resulting in 0.2%-0.9% lower LVP and stroke work, which were reduced to 21 and 24 ms in 8 patients with a full-capture AV delay of >180 ms. During BiVP with varying AV delays, close relations exist between PCG-derived STIs and hemodynamic parameters. AV delays advised by PCG-derived STIs cause only a minimal loss of pump function compared with those based on invasive hemodynamic measurements. ClinicalTrials.gov Identifier: NCT01832493.

Coronary microembolization sheep model by adjusting the number of microspheres based on coronary blood flow.

A heart failure (HF) model using coronary microembolization in large animals is indispensable for medical research. However, the heterogeneity of myocardial response to microembolization is a limitation. We hypothesized that adjusting the number of injected microspheres according to coronary blood flow could stabilize the severity of HF. This study aimed to evaluate the effect of microsphere injection based on the left coronary artery blood flow in an animal model. Microembolization was induced by injecting different numbers of microspheres (polystyrene, diameter: 90 μm) into the left descending coronary artery of the two groups of sheep (400 and 600 times coronary blood flow [ml/min]). Hemodynamic parameters, the pressure-volume loop of the left ventricle, and echocardiography findings were examined at 0.5, 1.5, 3.5, and 6.5 h after microembolization. End-diastolic pressure and normalized heart rate increased over time, and were significantly higher in 600 × coronary blood flow group than those in 400 × coronary blood flow group (p=0.04 and p < 0.01, respectively). The maximum rate of left-ventricular pressure rise and normalized stroke volume decreased over time, and were significantly lower in 600 × coronary blood flow group than those in 400 × coronary blood flow group (p < 0.01 and p < 0.01, respectively). The number of microspheres per coronary blood flow was significantly correlated with the decrease in stroke volume and the maximum rate of left ventricular pressure rise in 6.5 h (r=0.74, p=0.01 and r=0.71, p=0.02, respectively). Adjusting the number of injected microspheres based on the coronary blood flow enabled the creation of HF models with different degrees of severity.

Protective Effect of Hydrogen Sulphide in Cardioplegia on Global Myocardium Ischemia‐reperfusion Injury

ObjectiveThe endogenous gaseous transmitter hydrogen sulfide (H2S) is an important regulator of the cardiovascular system and is reported to have cardioprotective activity against ischemia/reperfusion (I/R) injury. We investigated the cardioprotective effect of H2S added in cardioplegia against I/R injury in global cardioplegic arrest.MethodsIsolated Wistar rat hearts were perfused in Langendorff apparatus and underwent 30 min perfusion, 120 min cold ischemia, and 90 min reperfusion. The rats were randomly divided into 5 groups: Control group, ischemic and reperfusion (I/R), St. Thomas cardioplegia (St. Thomas +I/R), St. Thomas plus H2S donor NaHS (NaHS+St.Thomas+I/R), St.Thomas plus NaHS and glibenclamide (an antagonist of KATP channel; NaHS+Glib+St.Thomas+I/R). The following indices were compared among the groups: the change of left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), heart rate, heart rhythm, and coronary blood flow. The difference in left ventricular developed pressure (LVDP), the maximum left ventricular pressure rise rate (+dp/dtmax), and the maximum left ventricular pressure drop rate (‐dp/dtmax) were also compared. Western blot was used to detect the changes of related myocardial enzymes among different groups.ResultsNaHS+St.Thomas+I/R treatment significantly improved cardiac function (LVSP, LVDP, +dp/dtmax and ‐dp/dtmax) compared to other groups (p&lt;0.05), although no significant differences on coronary flow and heart rate were observed. After reperfusion, the frequency of ventricular arrhythmia in I/R group and St.Thomas+I/R group was significantly higher than that in NaHS+St.Thomas+I/R group. Further, the expression of cardiac Troponin T, troponin I, and creatine kinase in the NaHS+St.Thomas+I/R group was significantly lower than that in other groups (p&lt;0.05).ConclusionCardioplegia containing H2S confers significant protection against global I/R injury during cold cardioplegic arrest. This effect is associated with opening of the myocardial KATP channels. Therefore, H2S may be a useful adjunct to cardioplegic solutions in heart surgery.

Sphingosine-1-phosphate induces myocyte autophagy after myocardial infarction through mTOR inhibition

Sphingosine-1-phosphate (S1P)/S1P receptor 1 signaling exerts cardioprotective effects including inhibition of myocyte apoptosis. However, little is known about the effect of S1P treatment on myocyte autophagy after myocardial infarction (MI). In the present study, we tested the hypothesis that S1P induces myocyte autophagy through inhibition of the mammalian target of rapamycin (mTOR), leading to improvement of left ventricular (LV) function after MI. Sprague–Dawley rats underwent MI or sham operation. The animals were randomized to receive S1P (50 μg/kg/day, i.p.) or placebo for one week. H9C2 cardiomyocytes cultured in serum- and glucose-deficient medium were treated with or without S1P for 3 h. MI rats exhibited an increase in LV end-diastolic dimension (EDD) and decreases in LV fractional shortening (FS) and the maximal rate of LV pressure rise (+dP/dt). S1P treatment attenuated the increase in LV EDD and decreases in LV FS and +dP/dt. In the MI placebo group, the LC3 II/I ratio, a marker of autophagy, was increased, and increased further by S1P treatment. S1P also enhanced the autophagy-related proteins Atg4b and Atg5 after MI. Similarly, in cultured cardiomyocytes, autophagy was increased under glucose and serum deprivation, and increased further by S1P treatment. The effect of S1P on myocyte autophagy was associated with mTOR inhibition after MI or in cultured cardiomyocytes under glucose and serum deprivation. S1P treatment prevents LV remodeling, enhances myocyte autophagy and inhibits mTOR activity after MI. These findings suggest that S1P treatment induces myocyte autophagy through mTOR inhibition, leading to the attenuation of LV dysfunction after MI.

The crosstalk of HDAC3, microRNA-18a and ADRB3 in the progression of heart failure

BackgroundHeart failure (HF) is a clinical syndrome characterized by left ventricular dysfunction or elevated intracardiac pressures. Research supports that microRNAs (miRs) participate in HF by regulating targeted genes. Hence, the current study set out to study the role of HDAC3-medaited miR-18a in HF by targeting ADRB3.MethodsFirstly, HF mouse models were established by ligation of the left coronary artery at the lower edge of the left atrial appendage, and HF cell models were generated in the cardiomyocytes, followed by ectopic expression and silencing experiments. Numerous parameters including left ventricular posterior wall dimension (LVPWD), interventricular septal dimension (IVSD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LEVDP), heart rate (HR), left ventricular pressure rise rate (+ dp/dt) and left ventricular pressure drop rate (-dp/dt) were measured in the mice. In addition, apoptosis in the mice was detected by means of TUNEL staining, while RT-qPCR and Western blot analysis were performed to detect miR-18a, HDAC3, ADRB3, cMyb, MMP-9, Collagen 1 and TGF-β1 expression patterns. Dual luciferase reporter assay validated the targeting relationship between ADRB3 and miR-18a. Cardiomyocyte apoptosis was determined by means of flow cytometry.ResultsHDAC3 and ADRB3 were up-regulated and miR-18a was down-regulated in HF mice and cardiomyocytes. In addition, HDAC3 could reduce the miR-18a expression, and ADRB3 was negatively-targeted by miR-18a. After down-regulation of HDAC3 or ADRB3 or over-expression of miR-18a, IVSD, LVEDD, LVESD and LEVDP were found to be decreased but LVPWD, LVEF, LVFS, LVSP, + dp/dt, and −dp/dt were all increased in the HF mice, whereas fibrosis, hypertrophy and apoptosis of HF cardiomyocytes were declined.ConclusionCollectively, our findings indicate that HDAC3 silencing confers protection against HF by inhibiting miR-18a-targeted ADRB3.

Acute recoordination rather than functional hemodynamic improvement determines reverse remodelling by cardiac resynchronisation therapy

Purpose: Cardiac resynchronisation therapy (CRT) improves left ventricular (LV) function acutely, with further improvements and reverse remodelling during chronic CRT. The current study investigated the relation between acute improvement of LV systolic function, acute mechanical recoordination, and long-term reverse remodelling after CRT. Methods: In 35 patients, LV speckle tracking longitudinal strain, LV volumes & ejection fraction (LVEF) were assessed by echocardiography before, acutely within three days, and 6 months after CRT. A subgroup of 25 patients underwent invasive assessment of the maximal rate of LV pressure rise (dP/dtmax,) during CRT-implantation. The acute change in dP/dtmax, LVEF, systolic discoordination (internal stretch fraction [ISF] and LV systolic rebound stretch [SRSlv]) and systolic dyssynchrony (standard deviation of peak strain times [2DS-SD18]) was studied, and their association with long-term reverse remodelling were determined. Results: CRT induced acute and ongoing recoordination (ISF from 45 ± 18 to 27 ± 11 and 23 ± 12%, p < 0.001; SRS from 2.27 ± 1.33 to 0.74 ± 0.50 and 0.71 ± 0.43%, p < 0.001) and improved LV function (dP/dtmax 668 ± 185 vs. 817 ± 198 mmHg/s, p < 0.001; stroke volume 46 ± 15 vs. 54 ± 20 and 52 ± 16 ml; LVEF 19 ± 7 vs. 23 ± 8 and 27 ± 10%, p < 0.001). Acute recoordination related to reverse remodelling (r = 0.601 and r = 0.765 for ISF & SRSlv, respectively, p < 0.001). Acute functional improvements of LV systolic function however, neither related to reverse remodelling nor to the extent of acute recoordination. Conclusion: Long-term reverse remodelling after CRT is likely determined by (acute) recoordination rather than by acute hemodynamic improvements. Discoordination may therefore be a more important CRT-substrate that can be assessed and, acutely restored.

Sub-clinical Detection of Left Ventricular Myocardial Dysfunction in Valvular Heart Diseases: A State-of-the-Art Review in a Speckle Tracking Echocardiography and Myocardial Performance

Purpose of the state-of-the-art review: Left ventricular (LV) global longitudinal strain (GLS) is recently recognized as a more sensitive measure of LV myocardial systolic function compared with LV ejection fraction (LVEF). In addition, left ventricular GLS , myocardial performance index (MPI) and maximum rate of LV pressure rise during isovolumetric contraction (LV dP/dtmax) are more reproducible than traditional assessment of LV systolic function by two dimensional echocardiography (2DE) LVEF. These underutilized techniques can detect preclinical myocardial dysfunction in patients who are at risk of LV failure in valvular-induced heart disease . Current guidelines for diagnosis and treatment of valvular heart disease (VHD) include LVEF as one of the parameters to take into consideration in the clinical decision-making. However, a large body of evidence has shown that left ventricular GLS, MPI and LV dP/dtmax have been classically considered as a sensitive marker of LV contractility and inotropic state. In turn GLS and myocardial performance may be a better prognosticator than LVEF in aortic and mitral valve heart diseases. This timely state-of-the-art review, appraised the evidence and role of GLS, MPI and dP/dT as clinical tools in patients with aortic and mitral valve disease. Recent findings: Left ventricular GLS has been shown to be prognostic in low-flow, low-gradient severe aortic stenosis with preserved LVEF. The role of left ventricular GLS, Tei index (MPI) and maximum rate of LV pressure rise (LV dP/dtmax) in patients with aortic regurgitation and mitral valve diseases (regurgitation and stenosis) is less well established. Summary: Echocardiography is considered the primary non-invasive imaging tool for valvular heart disease assessment and the cornerstone method in diagnosing and evaluating the morphology and severity of aortic and mitral valve diseases. Currently, diagnostic-cardiac catheterization is no more recommended except in very rare cases when echocardiographic image quality is suboptimal, non-diagnostic and when the results of 2DE are discrepant with clinical data. Once clinical decision-making is based on the 2DE and three dimensional echocardiographic in assessment of the severity of mitral and aortic valve diseases, it is crucial that standards should be adopted to maintain accuracy and consistency across echocardiographic laboratories. This illustrative review article assesses left ventricular systolic function (LVEF) employing two and/or three dimensional echocardiography in comparison to GLS, MPI and LV dP/dtmax, especially applied for aortic valve (AV) and mitral valve (MV) diseases. It is noteworthy that this document only provides echocardiographic standards rather than making recommendations for clinical management. Conclusion: It is concluded that GLS, MPI and maximum rate of LV pressure rise during isovolumetric contraction (LV dP/dtmax) are recommended and more so, they should be increasingly used to identify subclinical LV myocardial dysfunction in patients with mitral and aortic valve heart diseases, to identify optimal timing for surgery and prognosticate outcomes after surgery

New Insight in the Assessment of Left Ventricular Function in Paradoxical Low Flow Aortic Stenosis Patients with Normal Left Ventricular Ejection Fraction: A Mini-Review

Paradoxical valvular aortic stenosis (VAS) is a challenging area of clinical cardiology for the practitioners. It involves a small aortic valve area, low flow rate and mean pressure gradient although there is normal left ventricular ejection fraction. The aim of this study was to assess left ventricular (LV) dysfunction in a symptomatic severe aortic valve stenosis which is of crucial importance in identifying patients at risk of heart failure, postoperative complications and increased mortality. There are new insights which are involved in assessment of LV myocardial function including global longitudinal strain (GLS) by two-dimensional speckle tracking echocardiography (2D STE), myocardial performance index (MPI) and maximum rate of LV pressure rise (+dP/dt) during isovolumetric contraction time of the LV. This information can provide both diagnostic and prognostic information in addition to standard echocardiographic and clinical parameters. However, a profound understanding of the complex interaction between loading conditions, chamber geometry and contractility is necessary for the correct interpretation of myocardial deformation in order to draw appropriate conclusions in patients with aortic valve disease. This mini review is related to new and novel insights into the assessment of left ventricular function (LVF) in paradoxical low flow aortic stenosis patients with normal left ventricular ejection fraction (LVEF).

Left ventricular end-systolic volume is a more sensitive marker of acute response to cardiac resynchronization therapy than contractility indices: insights from an experimental study.

There are conflicting data and no consensus on how to measure acute response to cardiac resynchronization therapy (CRT). This study investigates, which contractility indices are best markers of acute CRT response. In eight anaesthetized dogs with left bundle branch block, we measured left ventricular (LV) pressure by micromanometer and end-diastolic volume (EDV) and end-systolic volume (ESV) by sonomicrometry. Systolic function was measured as LV ejection fraction (EF), peak rate of LV pressure rise (LV dP/dtmax) and as a gold standard of contractility, LV end-systolic elastance (Ees), and volume axis intercept (V0) calculated from end-systolic pressure-volume relations (ESPVR). Responses to CRT were compared with inotropic stimulation by dobutamine. Both CRT and dobutamine caused reduction in ESV (P < 0.01) and increase in LV dP/dtmax (P < 0.05). Both interventions shifted the ESPVR upwards indicating increased contractility, but CRT which reduced V0 (P < 0.01), caused no change in Ees. Dobutamine markedly increased Ees, which is the typical response to inotropic stimulation. Preload (EDV) was decreased (P < 0.01) by CRT, and there was no change in EF. When adjusting for the reduction in preload, CRT increased EF (P = 0.02) and caused a more marked increase in LV dP/dtmax (P < 0.01). Increased contractility by CRT could not be identified by Ees, which is a widely used reference method for contractility. Furthermore, reduction in preload by CRT attenuated improvement in contractility indices such as EF and LV dP/dtmax. These results suggest that changes in LV volume may be more sensitive markers of acute CRT response than conventional contractility indices.

Antioxidant N-acetylcysteine inhibits maladaptive myocyte autophagy in pressure overload induced cardiac remodeling in rats

Increased oxidative stress and myocyte autophagy co-exist in cardiac remodeling. However, it is unclear whether oxidative stress mediates maladaptive myocyte autophagy in pathological ventricular remodeling. In this study, we tested the hypothesis that antioxidants prevent maladaptive myocyte autophagy in pressure overload-induced left ventricular (LV) remodeling. Sprague–Dawley rats underwent abdominal aortic constriction (AAC) or sham operation. The animals were randomized to receive an antioxidant N-acetylcysteine (NAC), an autophagy inhibitor 3-methyladenine (3-MA) or placebo treatment for 2 weeks. We measured LV structure and function by echocardiography and hemodynamics, myocyte autophagy and oxidative stress assessed by 8-hydroxy-2-deoxyguanosine (8-OHdG). AAC rats exhibited increased LV hypertrophy assessed by LV wall thickness and myocyte cross-sectional area. NAC prevented LV hypertrophy in AAC rats. There were no significant differences in LV fractional shortening, end-diastolic dimension and the maximal rate of LV pressure rise among the groups. AAC rats showed an increase in myocardial 8-OHdG that was prevented by NAC. The expression of LC3 II protein, a marker of autophagy, was increased at 2 weeks after AAC. Immunohistochemical scores further confirmed the increase in LC3 expression in AAC rats. The expression of autophagic proteins Beclin1 and Atg12 and ERK activity were also increased in AAC rats. NAC prevented the increases in LC3 II protein, LC3 scores, Beclin1, Atg12 and ERK activity in AAC rats. Inhibition of autophagy by 3-MA prevented LV hypertrophy after pressure overload. These findings suggest that antioxidants may be of value to prevent pressure overload-induced cardiac remodeling through inhibition of maladaptive myocyte autophagy.

OPTIMIZATION OF ACUTE RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY WITH A QUADRIPOLAR LV LEAD: SHOULD WE USE THE PRESSURE DERIVATE DP/DTMAX OR STROKE WORK DERIVED FROM PRESSURE-VOLUME LOOPS?

Hemodynamic optimization of Cardiac Resynchronization Therapy (CRT) with quadripolar left ventricular (LV) leads can increase CRT benefits. Most often the maximum rate of LV pressure rise (dP/dtmax) is used but stroke work (SW) incorporates both pressure and volume changes. Previously we showed SW

Angiotensin Type 2 Receptor Stimulation Ameliorates Left Ventricular Fibrosis and Dysfunction via Regulation of Tissue Inhibitor of Matrix Metalloproteinase 1/Matrix Metalloproteinase 9 Axis and Transforming Growth Factor β1 in the Rat Heart

Left ventricular (LV) remodeling is the main reason for the development of progressive cardiac dysfunction after myocardial infarction (MI). This study investigated whether stimulation of the angiotensin type 2 receptor is able to ameliorate post-MI cardiac remodeling and what the underlying mechanisms may be. MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with the angiotensin type 2 receptor agonist compound 21 (0.03 mg/kg) was started 6 hours post-MI and continued for 6 weeks. Hemodynamic parameters were measured by echocardiography and intracardiac catheter. Effects on proteolysis were studied in heart tissue and primary cardiac fibroblasts. Compound 21 significantly improved systolic and diastolic functions, resulting in improved ejection fraction (71.2±4.7% versus 53.4±7.0%; P<0.001), fractional shortening (P<0.05), LV internal dimension in systole (P<0.05), LV end-diastolic pressure (16.9±1.2 versus 22.1±1.4 mm Hg; P<0.05), ratio of early (E) to late (A) ventricular filling velocities, and maximum and minimum rate of LV pressure rise (P<0.05). Compound 21 improved arterial stiffness parameters and reduced collagen content in peri-infarct myocardium. Tissue inhibitor of matrix metalloproteinase 1 was strongly upregulated, whereas matrix metalloproteinases 2 and 9 and transforming growth factor β1 were diminished in LV of treated animals. In cardiac fibroblasts, compound 21 initially induced tissue inhibitor of matrix metalloproteinase 1 expression followed by attenuated matrix metalloproteinase 9 and transforming growth factor β1 secretion. In conclusion, angiotensin type 2 receptor stimulation improves cardiac function and prevents cardiac remodeling in the late stage after MI, suggesting that angiotensin type 2 receptor agonists may be considered a future pharmacological approach for the improvement of post-MI cardiac dysfunction.

Assessment of left ventricular function by pulse wave analysis in critically ill patients

Left ventricular (LV) performance is often quantified by echocardiography in critically ill patients. Pulse wave analysis (PWA) systems can also monitor cardiac function but in a continuous fashion. We compared echocardiographic and PWA-derived indices of LV function. We enrolled 70 critically ill patients equipped with invasive arterial pressure monitoring who required echocardiography. We simultaneously assessed LV ejection fraction (LVEF), the rate of LV pressure rise during systole (dP/dt MAX) obtained with echocardiography (EC-dP/dt MAX), the ratio of effective arterial elastance to LV end-systolic elastance (E a/E es) determined by echocardiography, the dP/dt MAX estimated from the arterial pressure waveform (AP-dP/dt MAX) and the cardiac cycle efficiency (CCE) using PWA. Mean LVEF was 53 ± 18 % and CCE 0.16 ± 0.26. CCE was correlated linearly with LVEF (r = 0.88, 95 % CI 0.81 to 0.92, P < 0.001), and the dP/dt MAX values from the two techniques were linearly correlated (r = 0.93, 95 % CI 0.87 to 0.96, P < 0.001). There was minimal bias between the techniques for measurement of dP/dt MAX (23.7 mmHg/ms; 95 % CI -23.6 to 71.0). E a/E es and CCE were inversely correlated (r = -0.81, 95 % CI -0.88 to -0.71, P < 0.001). A CCE value of <0.07 predicted LVEF <40 % with a sensitivity of 0.93 and a specificity of 0.96 (AUC 0.98, 95 % CI 0.90 to 1.0, P < 0.001). A CCE value of >0.12 predicted LVEF ≥50 % with a sensitivity of 0.96 and a specificity of 0.82 (AUC 0.94, 95 % CI 0.87 to 1.0, P < 0.001). A CCE value <0.12 predicted E a/E es ≥1.3 with a sensitivity of 0.93 and a specificity of 0.89 (AUC 0.94, 95 % CI 0.83 to 1.0, P < 0.001). PWA-derived variables provide relevant information on cardiac contractility and performance in critically ill patients. PWA provides an easy method for online hemodynamic evaluation in critically ill patients.

Effects of ivabradine on heart rate and left ventricular function in healthy cats and cats with hypertrophic cardiomyopathy

To evaluate the effects of the pacemaker funny current (I(f)) inhibitor ivabradine on heart rate (HR), left ventricular (LV) systolic and diastolic function, and left atrial performance in healthy cats and cats with hypertrophic cardiomyopathy (HCM). 6 healthy cats and 6 cats with subclinical HCM. Anesthetized cats underwent cardiac catheterization and were studied over a range of hemodynamic states induced by treatment with esmolol (200 to 400 μg/kg/min, IV), esmolol and dobutamine (5 μg/kg/min, IV), ivabradine (0.3 mg/kg, IV), and ivabradine and dobutamine. Left ventricular systolic and diastolic function, cardiac output, and left atrial function were studied via catheter-based methods and echocardiography. Treatment with ivabradine resulted in a significant reduction of HR, rate-pressure product, and LV contractile function and a significant increase in LV end-diastolic pressure, LV end-diastolic wall stress, and LV relaxation time constant (tau) in cats with HCM. Concurrent administration of ivabradine and dobutamine resulted in a significant increase of LV contractility and lusitropy, with blunted chronotropic effects of the catecholamine. Left atrial performance was not significantly altered by ivabradine in cats with HCM. Regression analysis revealed an association between maximum rate of LV pressure rise and tau in cats with HCM. Ivabradine had significant effects on several cardiovascular variables in anesthetized cats with HCM. Studies in awake cats with HCM are needed to clinically validate these findings.

Therapeutic effects of neuregulin-1 in diabetic cardiomyopathy rats

BackgroundDiabetic cardiomyopathy (DCM) is a disorder of the heart muscle in people with diabetes, which is characterized by both systolic and diastolic dysfunction. The effective treatment strategy for DCM has not been developed.MethodsRats were divided into 3 groups with different treatment. The control group was only injected with citrate buffer (n = 8). The diabetes group and diabetes treated group were injected with streptozotocin to induce diabetes. After success of diabetes induction, the rats with diabetes were treated with (diabetes treated group, n = 8) or without (diabetes group, n = 8) recombinant human Neuregulin-1 (rhNRG-1). All studies were carried out 16 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate the cardiac function. Apoptotic cells were determined by TUNEL staining. Left ventricular (LV) sections were stained with Masson to investigate myocardial collagen contents. Related gene expressions were analyzed by quantitative real-time PCR (qRT-PCR).ResultsDiabetes impaired cardiac function manifested by reduced LV systolic pressure (LVSP), maximum rate of LV pressure rise and fall (+dp/dt max and -dp/dt max) and increased LV end-diastolic pressure (LVEDP). The rhNRG-1 treatment could significantly alleviate these symptoms and improve heart function. More TUNEL staining positive cells were observed in the diabetic group than that in the control group, and the rhNRG-1 treatment decreased apoptotic cells number. Furthermore, qRT-PCR assay demonstrated that rhNRG-1 treatment could decrease the expression of bax and caspase-3 and increase that of bcl-2. Collagen volume fraction was higher in the diabetic group than in the control group. Fibrotic and fibrotic related mRNA (type I and type III collagen) levels in the myocardium were significantly reduced by administration of rhNRG-1.ConclusionrhNRG-1 could significantly improve the heart function and reverse the cardiac remodeling of DCM rats with chronic heart failure. These results support the clinical possibility of applying rhNRG-1 as an optional therapeutic strategy for DCM treatment in the future.

Can optimization of pacing settings compensate for a non-optimal left ventricular pacing site?

Optimal left ventricular (LV) lead position improves the response to cardiac resynchronization therapy (CRT). However, in some patients it is not possible to position the LV lead at an optimal pacing site. The aim of this study was to determine whether optimization of the pacing settings atrioventricular delay (AVD) and interventricular delay (VVD) can compensate for a non-optimal LV pacing site. In 16 patients with heart failure [New York Heart Association class III (13) or IV (3), median QRS duration of 172 ms and median LV ejection fraction of 20%] the acute haemodynamic effect of biventricular pacing was assessed at > or =2 pacing sites by the increase in maximum rate of LV pressure rise (%dP/dt(max)). At each site the AVD and VVD were optimized. Biventricular pacing with nominal settings at a non-optimal LV pacing site improved dP/dt(max) by 12.8% (-0.5 to 23.2%). This could be further improved by 6.5 percentage points (1.2-13.9) by optimization of pacing settings (P = 0.001) and by 9.9 percentage points (3.7-13.3, P = 0.004) by optimization of pacing site. Optimization of the LV pacing site and pacing settings together improved %dP/dt(max) by 16.2 per cent points (10.0-21.8, P < 0.001). Optimization of the AVD and VVD can partly compensate for a non-optimal LV pacing site. However, a combination of an optimal LV pacing site and optimized pacing settings gives the best acute haemodynamic response.

Loss of Bradykinin Signaling Does Not Accelerate the Development of Cardiac Dysfunction in Type 1 Diabetic Akita Mice

Bradykinin signaling has been proposed to play either protective or deleterious roles in the development of cardiac dysfunction in response to various pathological stimuli. To further define the role of bradykinin signaling in the diabetic heart, we examined cardiac function in mice with genetic ablation of both bradykinin B1 and B2 receptors (B1RB2R(-/-)) in the context of the Akita model of insulin-deficient type 1 diabetes (Ins2(Akita/+)). In 5-month-old diabetic and nondiabetic, wild-type and B1RB2R(-/-) mice, in vivo cardiac contractile function was determined by left-ventricular (LV) catheterization and echocardiography. Reactive oxygen species levels were measured by 2'-7'-dichlorofluorescein diacetate fluorescence. Mitochondrial function and ATP synthesis were determined in saponin-permeabilized cardiac fibers. LV systolic pressure and the peak rate of LV pressure rise and decline were decreased with diabetes but did not deteriorate further with loss of bradykinin signaling. Wall thinning and reduced ejection fractions in Akita mouse hearts were partially attenuated by B1RB2R deficiency, although other parameters of LV function were unaffected. Loss of bradykinin signaling did not increase fibrosis in Ins2(Akita/+) diabetic mouse hearts. Mitochondrial dysfunction was not exacerbated by B1RB2R deficiency, nor was there any additional increase in tissue levels of reactive oxygen species. Thus, loss of bradykinin B2 receptor signaling does not abrogate the previously reported beneficial effect of inhibition of B1 receptor signaling. In conclusion, complete loss of bradykinin expression does not worsen cardiac function or increase myocardial fibrosis in diabetes.

Opioid receptor agonist reduces myocardial ischemic injury when administered during early phase of myocardial ischemia

Aim of the study Postresuscitation myocardial dysfunction is one of the leading causes of early death after initial success of resuscitation, the mechanisms of postresuscitation myocardial dysfunction remain controversial. We hypothesize that ischemia injury, rather than reperfusion injury is the major cause of postresuscitation myocardial dysfunction. We proposed to investigate the separate effects of ischemia and reperfusion injury on postresuscitation myocardial dysfunction. Methods Thirty-three Langendorff-perfused isolated rat hearts were subjected to 15 min of global ischemia followed by 120 min of reperfusion. Pentazocine was utilized as a myocardial protective agent, either before ischemia or during reperfusion. All hearts were randomized into 3 groups: (1) “ischemia protection”, in which pentazocine was infused 10 min prior to global ischemia, (2) “reperfusion protection”, in which pentazocine was infused during 2 h of reperfusion and (3) “control”, with no pentazocine infusion. Left ventricular (LV) functions were measured by the maximal rate of LV pressure rise (d P/d t max) and decline (−d P/d t max), the maximal LV diastolic pressure (LVDP). The incidences of postischemic arrhythmias were measured. Results When pentazocine was administered before onset of ischemia, the LV systolic and diastolic functions were significantly greater, and the postischemic arrhythmias were significantly less in comparison to those with reperfusion protection ( p < 0.05) and the control group ( p < 0.05). Conclusions In this model, the severity of postischemic myocardial dysfunction was less when the heart was protected during ischemia. Ischemia injury may therefore be the major cause of postresuscitation myocardial dysfunction.