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Electrical Impact of the Left Ventricular Pacing Site in CRT Introduction Recent studies have demonstrated that left ventricular (LV) pacing site is a critical parameter in optimizing cardiac resynchronization therapy (CRT). The present study evaluates the effect of pacing from different LV locations on QRS duration (QRSd) and their relationship to acute hemodynamic response in congestive heart failure patients. Methods and Results Thirty-five patients with nonischemic dilated cardiomyopathy and left bundle branch block referred for CRT device implantation were studied. Eleven predetermined LV pacing sites were systematically assessed in random order: epicardial: coronary sinus (CS); endocardial: basal and mid-cavity (septal, anterior, lateral, and inferior), apex, and the endocardial site facing the CS pacing site. For each patient QRSd and +dP/dtmax during baseline (AAI) and DDD LV pacing at 2 atrioventricular delays were compared. Response to CRT was significantly better in patients with wider baseline QRSd (≥150 milliseconds). Hemodynamic response was inversely correlated to increase of QRSd during LV pacing (short atrioventricular [AV] delay: r = 0.44, P < 0.001; long AV delay: r = 0.59, P < 0.001). Compared to baseline, LV pacing at the site of shortest QRSd significantly improved +dP/dtmax (+18 ± 25%, P < 0.001) but was not superior to other conventional strategy (lateral wall, CS pacing, and echo-guided) and was inferior to a hemodynamically guided strategy. Conclusions In our study, we have demonstrated that changes of QRSd during LV pacing correlated with acute hemodynamic response and that LV pacing location was a primary determinant of paced QRSd. Although QRSd did not predict the maximum hemodynamic response, our results confirm the link between electrical activation and hemodynamic response of the LV during CRT. [ABSTRACT FROM AUTHOR]

Rationale: Severe increase in right ventricular pressure can compromise left ventricular (LV) function because of impaired interventricular interaction and aggravate the symptoms. Objectives: To elucidate how nonsevere idiopathic pulmonary arterial hypertension (IPAH) influences LV function because of impaired interventricular interaction. Methods: Invasive pressure-volume (PV) loop analysis obtained by conductance catheterization was performed at rest and during atrial pacing in patients with mild IPAH (n = 10) compared with patients with isolated LV diastolic dysfunction (DD) (n = 10) and control subjects without heart failure symptoms (n = 9). Measurements and Main Results: Patients with nonsevere IPAH (pulmonary artery pressure mean 29 ± 5 mm Hg) and patients with DD showed preserved systolic (ejection fraction 63 ± 12% and 62 ± 9%) and impaired LV diastolic function at rest (LV stiffness 0.027 ± 0.012 ml(-1) and 0.029 ± 0.014 ml(-1)). During pacing at 120 per minute patients with IPAH and DD decreased their stroke volume (-25% and -30%; P < 0.05) and failed to increase cardiac output significantly. Opposite to patients with DD and control subjects, temporary preload reduction during inferior vena cava occlusion initially induced an expansion of LV end-diastolic volume in IPAH (+7%; P < 0.05), whereas end-diastolic pressure continuously dropped. This resulted in an initial downward shift to the right of the PV loop indicating better LV filling, which was associated with a temporary improvement of cardiac output (+11%; P < 0.05) in the patients with IPAH, but not in patients with DD and control subjects. Conclusions: Mild idiopathic pulmonary arterial pressure impairs LV diastolic compliance even in the absence of the intrinsic LV disease and contributes to the reduced cardiac performance at stress. [ABSTRACT FROM AUTHOR]

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Objectives: Previous studies demonstrated beneficial short-term effects of surgical ventricular restoration on mechanical dyssynchrony and left ventricular function and improved midterm and long-term clinical parameters. However, long-term effects on systolic and diastolic left ventricular function are still largely unknown. Methods: We studied 9 patients with ischemic dilated cardiomyopathy who underwent surgical ventricular restoration with additional restrictive mitral annuloplasty and/or coronary artery bypass grafting. Invasive hemodynamic measurements by conductance catheter (pressure–volume loops) were obtained before and 6 months after surgery. In addition, New York Heart Association classification, quality-of-life score, and 6-minute hall-walk test were assessed. Results: At 6 months'' follow-up, all patients were alive and clinically in improved condition: New York Heart Association class from 3.3 ± 0.5 to 1.4 ± 0.7, quality-of-life score from 46 ± 22 to 15 ± 15, and 6-minute hall-walk test from 302 ± 123 to 444 ± 78 m (all P < .01). Hemodynamic data showed improved cardiac output (4.8 ± 1.4 to 5.6 ± 1.1 L/min), stroke work (6.5 ± 1.9 to 7.1 ± 1.4 mm Hg · L; P = .05), and left ventricular ejection fraction (36% ± 10% to 46% ± 10%; P < .001). Left ventricular surgical remodeling was sustained at 6 months: end-diastolic volume decreased from 246 ± 70 to 180 ± 48 mL and end-systolic volume from 173 ± 77 to 103 ± 40 mL (both P < .001). Left ventricular dyssynchrony decreased from 29% ± 6% to 26% ± 3% (P < .001) and ineffective internal flow fraction decreased from 58% ± 30% to 42% ± 18% (P < .005). Early relaxation (Tau, minimal rate of pressure change) was unchanged, but diastolic stiffness constant increased from 0.012 ± 0.003 to 0.023 ± 0.007 mL−1 (P < .001). Conclusions: Surgical ventricular restoration with additional restrictive mitral annuloplasty and/or coronary artery bypass grafting leads to sustained left ventricular volume reduction at 6 months'' follow-up. We observed improved systolic function and unchanged early diastolic function but impaired passive diastolic properties. Clinical improvement, supported by decreased New York Heart Association class, improved quality-of-life score, and improved 6-minute hall-walk test may be related to improved systolic function, reduced mechanical dyssynchrony, and reduced wall stress. [Copyright &y& Elsevier]

Objective: Doppler echocardiography, including tissue Doppler imaging, is widely applied to assess diastolic left ventricular function using early transmitral flow velocity combined with mitral annular velocity as a noninvasive estimate of left ventricular filling pressures. However, the accuracy of early transmitral flow velocity/mitral annular velocity in patients with heart failure, particularly after extensive cardiac surgery, is debated. Global diastolic strain rate during isovolumic relaxation obtained with 2-dimensional speckle-tracking analysis was recently proposed as an alternative approach to estimate left ventricular filling pressures. Methods: We analyzed diastolic function in patients with heart failure after surgical ventricular restoration and/or restrictive mitral annuloplasty. Echocardiography, including tissue Doppler imaging and speckle-tracking analysis, was performed to determine early transmitral flow velocity/atrial transmitral flow velocity, isovolumetric relaxation time, deceleration time, early transmitral flow velocity/mean mitral annular velocity, strain rate during isovolumic relaxation, and early transmitral flow velocity/strain rate during isovolumic relaxation. These noninvasive indices were correlated with relaxation time constant Tau, peak rate of pressure decline, and left ventricular end-diastolic pressure obtained in the catheterization room using high-fidelity pressure catheters. Results: Twenty-three patients were analyzed 6 months after restrictive mitral annuloplasty (n = 8), surgical ventricular restoration (n = 4), or a combined procedure (n = 11). The strongest correlation with invasive indices, in particular left ventricular end-diastolic pressure, was found for strain rate during isovolumic relaxation (r = −0.76, P < .001). Early transmitral flow velocity/mean mitral annular velocity did not correlate significantly with any of the invasive indices. Strain rate during isovolumic relaxation (cutoff value < 0.38 s−1) accurately predicted left ventricular end-diastolic pressure of 16 mm Hg or more with 100% sensitivity and 93% specificity. Conclusions: In a group of patients with heart failure who were investigated 6 months after cardiac surgery, early transmitral flow velocity/mean mitral annular velocity correlated poorly with invasively obtained diastolic indexes. Global strain rate during isovolumic relaxation, however, correlated well with left ventricular end-diastolic pressure and peak rate of pressure decline. Our data suggest that global strain rate during isovolumic relaxation is a promising noninvasive index to assess left ventricular filling pressures in patients with heart failure after extensive cardiac surgery, including restrictive mitral annuloplasty and surgical ventricular restoration. [Copyright &y& Elsevier]

The time-varying elastance concept provides a comprehensive description of the intrinsic mechanical properties of the left ventricle that are assumed to be load independent. Based on pressure-volume measurements obtained with combined pressure conductance catheterization in six open-chest anesthetized sheep, we show that the time to reach end systole (defined as maximal elastance) is progressively prolonged for increasing ventricle pressures, which challenges the original (load-independent) time-varying elastance concept. Therefore, we developed a method that takes into account load dependency by normalization of time course of the four cardiac phases (isovolumic contraction, ejection, isovolumic relaxation, filling) individually. With this normalization, isophase lines are obtained that connect points in pressure-volume loops of different beats at the same relative time in each of the four cardiac phases, instead of isochrones that share points at the same time in a cardiac cycle. The results demonstrate that pressure curves can be predicted with higher accuracy, if elastance curves are estimated using isophase lines instead of using isochrones [root-mean- square error (RMSE): 3.8 ± 1.0 vs. 14.0 ± 7.4 mmHg (P < 0.001), and variance accounted for (VAF): 94.8 ± 1.3 vs. 78.6 ± 14.8% (P < 0.001)1. Similar results were found when the intercept volume was assumed to be time varying [RMSE: 1.7 ± 0.3 vs. 13.4 ± 7.4 mmHg (P < 0.001), and VAF: 97.4 ± 0.5 vs. 81.8 ± 15.5% (P < 0.001)]. In conclusion, phase-dependent time normalization reduces cardiac load dependency of timing and increases accuracy in estimating time-varying elastance. [ABSTRACT FROM AUTHOR]

Dexamethasone is clinically applied in preterm infants to treat or prevent chronic lung disease. However, concern has emerged about adverse side effects. The cardiovascular short-term side effects of neonatal dexamethasone treatment are well documented, but long-term consequences are unknown. Previous studies showed suppressed mitosis during dexamethasone treatment, leading to reduced ventricular weight, depressed systolic function, and compensatory dilatation in prepubertal rats. In addition, recent data indicated a reduced life expectancy. Therefore, we investigated the long-term effects of neonatal dexamethasone treatment on cardiovascular function. Neonatal rats were treated with dexamethasone or received saline. Cardiac function was determined in 8-, 50-, and 80-wk-old animals, representing young adult, middle-aged, and elderly stages. A pressure-conductance catheter was introduced into the left ventricle to measure pressure-volume loops. Subsequently, the hearts were collected for histological examination. Our results showed reduced ventricular and body weights in dexamethasone-treated rats at 8 and 80 wk, but not at 50 wk. Cardiac output and diastolic function were unchanged, but systolic function was depressed at 50 and 80 wk, evidenced by reduced ejection fractions and rightward shifts of the end-systolic pressure-volume relationships. We concluded that previously demonstrated early adverse effects of neonatal dexamethasone treatment are transient but that reduced ventricular weight and systolic dysfunction become manifest again in elderly rats. Presumably, cellular hypertrophy initially compensates for the dexamethasone treatment-induced lower number of cardiomyocytes, but this mechanism falls short at a later stage, leading to systolic dysfunction. If applicable to humans, cardiac screening of a relatively large patient group to enable secondary prevention may be indicated. [ABSTRACT FROM AUTHOR]

Background Conductance catheter in vivo ventricular volume measurements during lung ventilation may provide important information on left ventricular (LV) function. Breathing potentially may alter parallel conductance ( Vc), complicating interpretation of the conductance-derived volume signals. The effects of controlled positive pressure lung inflation (PPLI) on measured parallel conductance with dual-field conductance volumetry were investigated. Methods Eight anaesthetized pigs were instrumented with an LV dual-field conductance volumetry catheter. Vc was measured repeatedly, using the hypertonic saline injection method, at three different levels of lung insufflation: continuous positive airway pressure (PPLI) 0, 5, and 10 cmH2O. Results Vcs measured at PPLI 0, 5 and 10 cmH2O were 70·9 ± 4·8, 70·7 ± 5·5 and 70·5 ± 5·9 ml, respectively. The corresponding uncalibrated end-diastolic volumes (EDVu) were 115·5 ± 7·1, 117·0 ± 7·5 and 117·5 ± 7·7 ml, respectively. Mean coefficients of variance for Vc and EDVu at all three PPLI levels were 3·8% and 1·25%, respectively. Discussion Several levels of PPLI demonstrated no systematic change in parallel conductance for LV dual-field conductance volume signal. We concluded that lung inflation at these levels does not generate changes in Vc. [ABSTRACT FROM AUTHOR]

Objective: In this study, the relationship VfAR, which was obtained from carotid blood-flow velocity (Vf) and the cross-sectional area (A) of the left ventricle, was used to assess changes in left ventricular (LV) systolic performance as indicated by the LV pressure-volume relationship (PVR) and end-systolic LV elastance (Ees). Background: The relationship of maximum systolic Vf as a surrogate for LV pressure and end-systolic LV area as a surrogate for end-systolic LV volume may allow for the estimation of LV elastance and ejection properties. Methods: In 25 pigs, internal carotid Vf was recorded by using continuous-wave Doppler mode. Echocardiographic measurements of A were continuously performed with an automated border detection system and combined with data for Vf to display VfAR as a series of loop diagrams. These were shifted during acute preload reduction, and an index E′es was calculated by applying the time varying elastance concept to end-systolic VfAR. Simultaneously, Ees was acquired by conductance catheter and micromanometer techniques. Comparisons of E′es and Ees were made at various contractility levels obtained by the administration of dobutamine, 5 μg/kg/min, and esmolol, 40 to 60 mg, and at various cardiac load levels, obtained by a fluid bolus infusion or administration of a vasoconstrictor. Results: Highly linear elastance curves (r ≥ 0.85, p < 0.0001) were derived from both end-systolic VfAR and PVR. Correlation of E′es and Ees revealed an almost linear function: E′es = 0.052 + 0.11 Ees (r = 0.98, p < 0.0001). Administration of dobutamine increased Ees from 5.8 ± 3.04 mmHg/mL to 10.1 ± 4.19 mmHg/mL (p < 0.05), and E′es from 0.68 ± 0.288 cm2/min/mL to 1.24 ± 0.458 cm2/min/mL (p < 0.05). After administration of esmolol, Ees and E′es both dropped significantly by 3.7 ± 2.4 mmHg/mL and 0.44 ± 0.15 cm2/min/mL, respectively. No load dependency of E′es was seen. Bland-Altman analysis revealed that the change in E′es, which is required to predict a significant change in Ees, should exceed +16.9% or −13.1% of the preceding value. Conclusion: Application of the time-varying elastance concept on the relation of Vf and LV area allows for the determination of an index E′es that may be used to estimate Ees. [Copyright &y& Elsevier]

Abstract: Background: The cardiac troponin T I79N mutation, linked to familial hypertrophic cardiomyopathy, carries a high risk of sudden cardiac death even in the absence of significant cardiac hypertrophy. The pathology underlying this mechanism has not yet been identified. Aims: To study the underlying mechanism of this phenomenon we characterized the left ventricular (LV) performance of transgenic mice carrying the human troponin T mutation I79N under basal and isoproterenol-induced stress conditions. Methods and results: LV function was analyzed by recording pressure–volume loops using a microconductance catheter. Despite a hypercontractile systolic function under basal conditions TnT-I79N mice showed a diastolic dysfunction indicated by an increase in end-diastolic pressure–volume relationship (EDPVR), a load-independent factor of LV stiffness (0.06±0.01 vs. 0.02±0.01; P <0.05), when compared to mice expressing human wild-type troponin T (TnT-WT). TnT-I79N mutants developed severe diastolic heart failure and cardiac sudden death under isoproterenol stress. This was prevented after pretreatment with the L-type Ca2+ channel inhibitor diltiazem. Conclusions: Diastolic dysfunction due to increased LV stiffness in TnT-I79N mice leads to severe primary diastolic heart failure and finally to cardiac sudden death, which can be prevented by diltiazem. [Copyright &y& Elsevier]

Objective: To test the feasibility of the transcardiac conductance (TCC) method for continuous, on-line measurement of absolute left ventricular (LV) volume and to validate the method by comparison with biplane angiography.Design and Setting: Prospective clinical feasibility and validation study in a cardiac catheterization laboratory in a university hospital.Patients and Interventions: Ten patients scheduled for electrophysiological studies ( n=5), percutaneous transluminal coronary angioplasty ( n=3), and left- and right-sided cardiac catheterization ( n=2) were enrolled in the feasibility study. Twenty patients scheduled for diagnostic left- and right-sided cardiac catheterization were included in the validation study. The latter were studied at baseline and during right atrial pacing 30 beats/min above baseline.Measurements and Results: In the feasibility study satisfactory ventricular volume signals were obtained by TCC in eight of ten patients. In the validation study calibration factors (alpha and V(p)) for TCC were obtained by thermodilution and hypertonic saline dilution, to yield absolute LV volume. Results indicate a good linear correlation with angiographic volume ( R(2)=0.78) with an intercept of 10+/-15 ml, not significantly different from 0 and slope of 1.17+/-0.16. Mean calibration factors alpha and V(p) were 0.017+/-0.002 (interpatient variability 0.018) and 75.1+/-0.4 ml (interpatient variability 35.4 ml), respectively.Conclusions: The TCC method provides on-line and continuous LV volume signals in patients in a relatively noninvasive way. Calibration yields absolute LV volumes with a good linear correlation in comparison to biplane LV angiography. TCC appears to be a promising methodology for monitoring absolute LV volume in the ICU. [ABSTRACT FROM AUTHOR]

The trans-cardiac conductance (TCC) method provides on-line left ventricular (LV) volume signals by determining the electrical conductance of blood in the LV by means of central venous and epithoracic electrodes. Conductive structures outside the LV blood pool cause a "parallel conductance" offset term (V[sup p]) that can be determined by bolus injections of hypertonic saline in the pulmonary artery (V[sup p, sub saline]), which cause a transient increase in blood conductivity. This study in anesthetized sheep evaluates the accuracy of the saline calibration method and the variabilities of V[sup p] between animals, between hemodynamic conditions and during the cardiac cycle, The conventional intra-cardiac conductance catheter method was used to obtain independent estimates of V[sup p] by the zero-volume method (V[sup p, sub zero volume]). Mean baseline V[sup p, saline] and V[sup p, sub zero volume] were 104 ± 6 ml and 106 ± 6 ml, respectively. Bland-Altman analysis showed a small nonsignificant bias (-2.5 ml) and narrow limits of agreement (4.6 ml). V[sup p] was not significantly different between hemodynamic conditions (baseline, dobutamine, volume load, propranolol), but had a substantial in-teranimal variability (IAV) (38%). Average variations during the cardiac cycle were <10% of mean V[sup p]. We conclude that the saline method can be applied to determine V[sup p] for TCC. IAV is substantial, so that V[sup p] must be determined in each animal, but within-animal variability is relatively small. [ABSTRACT FROM AUTHOR]

Presents a study which determined the accuracy of parallel conductance of the left ventricular blood volume by the hypertonic saline method. Methodology; Results; Discussion.

Background: The size of the remnant left ventricle (LV) may influence right ventricular function and thus long-term outcome in palliated hypoplastic left heart syndrome (HLHS). We therefore sought to assess the impact of the size of the hypoplastic LV on intrinsic RV function in HLHS patients after Fontan surgery. Methods: Fifty-seven HLHS patients were studied 2.5 (range: 0.8-12.6) years after Fontan-type palliation with the pressure-volume conductance system. The patient cohort was divided into two groups according to the median LV area index (group 1: LV area index≤1.33cm2/m2, n=29; group 2: LV area index>1.33cm2/m2, n=28). Results: The slopes of the end systolic elastance (Ees) and the preload recruitable stroke work relation (Mw) were not different between group 1 and 2 (Ees: 2.70±1.92 vs. 3.68±2.68mmHg/ml; Mw: 52.75±14.98 vs. 51.09±16.63mmHg x ml; P =NS for all). Furthermore, the systolic responses to dobutamine were not statistically different between groups. However, the slope of the end diastolic stiffness (Eed) was higher in group 2 and catecholaminergic stimulation resulted in a decrease in Eed in group 2 (group 1: 0.40±0.26 vs. 0.52±0.45; group 2: 0.68±0.44 vs. 0.47±0.38mmHg/ml, P <0.01). Furthermore Eed was lowest in patients with mitral atresia/aortic atresia, the anatomic subgroup with the smallest LV remnant. Conclusions: Intrinsic systolic RV function is not affected by the size of the hypoplastic LV in survivors of surgical palliation of HLHS. Diastolic stiffness, however, was higher in patients with a larger LV remnant. [ABSTRACT FROM AUTHOR]

Abstract: Pulmonary hypertension induces right ventricular (RV) overload, which is transmitted to cardiomyocytes via integrins that activate intracellular messengers, including focal adhesion kinase (FAK) and neuronal nitric oxide synthase (NOS1). We investigated whether RV hypertrophy (RVH) and RV failure (RVF) were associated with activation of FAK, NOS1, and matrix metalloproteinases (MMPs). Rats were treated without (RVC) or with a low dose of monocrotaline (30mg/kg) to induce RVH, and with a high dose (80mg/kg) to induce RVF. After ≈30 days, RV function was determined using a combined pressure-conductance catheter. After sacrifice, FAK, NOS1, their phosphorylated forms (FAK-P and NOS1-P), MMP-2, and MMP-9 were quantified in RV myocardium by immunohistochemistry. In RVH and RVF, RV weight/ body weight increased by 36% and 109%, whereas RV ejection fraction decreased by 23% and 57% compared to RVC, respectively. FAK-P and FAK-P/FAK were highest in RVH (2.87±0.12 and 2.52±0.23 fold compared to RVC, respectively) and slightly elevated in RVF (1.76±0.17 and 1.15±0.13 fold compared to RVC, respectively). NOS1-P and NOS1-P/NOS1 were increased in RVH (1.63±0.12 and 3.06±0.80 fold compared to RVC, respectively) and RVF (2.16±0.03 and 3.30±0.38 fold compared to RVC, respectively). MMP-2 was highest in RVH and intermediate in RVF (3.50±0.12 and 1.84±0.22 fold compared to RVC, respectively). MMP-9 was elevated in RVH and RVF (2.39±0.35 and 2.92±0.68 fold compared to RVC, respectively). Activation of FAK in RVH points to an integrin-dependent hypertrophic response of the myocardium. Activation of NOS1 in failing RV suggests a role of excessive NO in the development of failure and activation of MMPs leading to ventricular remodeling. [Copyright &y& Elsevier]

Objectives: The results from the recent Targeted Temperature Management trial raised the question whether cooling or merely the avoidance of fever mediates better neurologic outcome in resuscitated patients. As temperature per se is a major determinant of cardiac function, we characterized the effects of hyperthermia (40.5°C), normothermia (38.0°C), and mild hypothermia (33.0°C) on left ventricular contractile function in healthy pigs and compared them with dobutamine infusion.Design: Animal study.Setting: Large animal facility, Medical University of Graz, Graz, Austria.Subjects: Nine anesthetized and mechanically ventilated closed-chest Landrace pigs (67 ± 2 kg).Interventions: Core body temperature was controlled using an intravascular device. At each temperature step, IV dobutamine was titrated to double maximum left ventricular dP/dt (1.8 ± 0.1 µg/kg/min at normothermia). Left ventricular pressure-volume relationships were assessed during short aortic occlusions. Left ventricular contractility was assessed by the calculated left ventricular end-systolic volume at an end-systolic left ventricular pressure of 100 mm Hg.Measurements and Main Results: Heart rate (98 ± 4 vs 89 ± 4 vs 65 ± 2 beats/min; all p < 0.05) and cardiac output (6.7 ± 0.3 vs 6.1 ± 0.3 vs 4.4 ± 0.2 L/min) decreased with cooling from hyperthermia to normothermia and mild hypothermia, whereas left ventricular contractility increased (left ventricular end-systolic volume at a pressure of 100 mm Hg: 74 ± 5 mL at hyperthermia, 52 ± 4 mL at normothermia, and 41 ± 3 mL at mild hypothermia; all p < 0.05). The effect of cooling on left ventricular end-systolic volume at a pressure of 100 mm Hg (hyperthermia to normothermia: -28% ± 3% and normothermia to mild hypothermia: -20% ± 5%) was of comparable effect size as dobutamine at a given temperature (hyperthermia: -28% ± 4%, normothermia: -27% ± 6%, and mild hypothermia: -27% ± 9%).Conclusions: Cooling from hyperthermia to normothermia and from normothermia to mild hypothermia increased left ventricular contractility to a similar degree as a significant dose of dobutamine in the normal porcine heart. These data indicate that cooling can reduce the need for positive inotropes and that lower rather than higher temperatures are appropriate for the resuscitated failing heart. [ABSTRACT FROM AUTHOR]

Abstract: Background: Mild hypothermia (MH) decreases infarct size and mortality in experimental reperfused myocardial infarction, but may potentiate ischaemia-induced left ventricular (LV) diastolic dysfunction. Methods: In anaesthetized pigs (70±2kg), polystyrol microspheres (45μm) were infused repeatedly into the left circumflex artery until cardiac power output decreased >40%. Then, pigs were assigned to normothermia (NT, 38.0°C, n =8) or MH (33.0°C, n =8, intravascular cooling) and followed for 6h (CME 6h). *p <0.05 vs baseline, †p <0.05 vs NT. Results: In NT, cardiac output (CO) decreased from 6.2±0.3 to 3.4±0.2*l/min, and heart rate increased from 89±4 to 101±6*bpm. LV end-diastolic volume fell from 139±8 to 64±4ml*, while LV ejection fraction remained constant (49±1 vs 53±4%). The corresponding end-diastolic pressure–volume relationship was progressively shifted leftwards, reflecting severe LV diastolic dysfunction. In MH, CO fell to a similar degree. Spontaneous bradycardia compensated for slowed LV relaxation, and the leftward shift of the end-diastolic pressure–volume relationship was less pronounced during MH. MH increased systemic vascular resistance, such that mean aortic pressure remained higher in MH vs NT (69±2† vs 54±4mmHg). Mixed venous oxygen saturation at CME 6h was higher in MH than in NT (59±4† vs 42±2%) due to lowered systemic oxygen demand during cooling. Conclusion: We conclude that (i) an acute loss of end-diastolic LV compliance is a major component of acute cardiac pump failure during experimental myocardial infarction, and that (ii) MH does not potentiate this diastolic LV failure, but stabilizes haemodynamics and improves systemic oxygen supply/demand imbalance by reducing demand. [Copyright &y& Elsevier]

Objectives: We sought to evaluate the role of exercise-related changes in left ventricular (LV) relaxation and of LV contractile function and vasculoventricular coupling (VVC) in the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and to assess myocardial energetic status in these patients. Background: To date, no studies have investigated exercise-related changes in LV relaxation and VVC as well as in vivo myocardial energetic status in patients with HFpEF. Methods: We studied 37 patients with HFpEF and 20 control subjects. The VVC and time to peak LV filling (nTTPF, a measure of LV active relaxation) were assessed while patients were at rest and during exercise by the use of radionuclide ventriculography. Cardiac energetic status (creatine phosphate/adenosine triphosphate ratio) was assessed by the use of 31P magnetic resonance spectroscopy at 3-T. Results: When patients were at rest, nTTPF and VVC were similar in patients with HFpEF and control subjects. The cardiac creatine phosphate/adenosine triphosphate ratio was reduced in patients with HFpEF versus control subjects (1.57 ± 0.52 vs. 2.14 ± 0.63; p = 0.003), indicating reduced energy reserves. Peak maximal oxygen uptake and the increase in heart rate during maximal exercise were lower in patients with HFpEF versus control subjects (19 ± 4 ml/kg/min vs. 36 ± 8 ml/kg/min, p < 0.001, and 52 ± 16 beats/min vs. 81 ± 14 beats/min, p < 0.001). The relative changes in stroke volume and cardiac output during submaximal exercise were lower in patients with HFpEF versus control subjects (ratio exercise/rest: 0.99 ± 0.34 vs. 1.25 ± 0.47, p = 0.04, and 1.36 ± 0.45 vs. 2.13 ± 0.72, p < 0.001). The nTTPF decreased during exercise in control subjects but increased in patients with HFpEF (−0.03 ± 12 s vs. +0.07 ± 0.11 s; p = 0.005). The VVC decreased on exercise in control subjects but was unchanged in patients with HFpEF (−0.01 ± 0.15 vs. −0.25 ± 0.19; p < 0.001). Conclusions: Patients with HFpEF have reduced cardiac energetic reserve that may underlie marked dynamic slowing of LV active relaxation and abnormal VVC during exercise. [Copyright &y& Elsevier]

Abstract: Objective: Recent studies indicate that normothermic cardiopulmonary bypass (CPB) with intermittent antegrade warm blood cardioplegia (IAWBC) may have metabolic and clinical advantages, but limited data exist on its effects on myocardial function. Therefore, we investigated the acute effects of this approach on systolic and diastolic left ventricular function and on chronotropic responses. Methods: In 10 patients undergoing isolated CABG we obtained on-line left ventricular pressure-volume loops using the conductance catheter before and after normothermic CPB with IAWBC. Steady state and load-independent indices of left ventricular function derived from pressure-volume relations were obtained during right atrial pacing (80–100–120beats/min) to determine baseline systolic and diastolic function and chronotropic responses. Results: The mean time of CPB was 105±36min (median 103, range 60–167min) with a mean aortic cross-clamp time of 75±27min (median 69, range 43–129min). Baseline (80beats/min) end-systolic elastance (E ES) did not change after CPB (1.22±0.53 to 1.12±0.28mmHg/ml, P>0.2), while the diastolic chamber stiffness constant (k ED) significantly increased (0.014±0.005 to 0.040±0.007ml−1, P=0.018) and relaxation time constant (τ) significantly decreased (61±3 to 49±2ms, P=0.004). Before CPB, incremental atrial pacing had no significant effects on E ES and τ but significant negative effects on k ED (0.014±0.005 to 0.045±0.012ml−1, P=0.013). After CPB, atrial pacing had significant positive effects on E ES, τ and k ED (E ES: 1.12±0.28 to 2.60±1.54mmHg/ml, P=0.021; τ: 49±2 to 45±2ms, P=0.009; k ED: 0.040±0.007 to 0.026±0.005mmHg, P=0.010), indicating improved systolic and diastolic chronotropic responses. Conclusion: On-pump normothermic CABG with IAWBC preserved systolic function, increased diastolic stiffness, and improved systolic and diastolic chronotropic responses. Normalization of the chronotropic responses post-CPB is likely due to effects of successful revascularization and subsequent relief of ischemia. [Copyright &y& Elsevier]