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Aims In diabetes mellitus, heart failure with preserved ejection fraction (HFPEF) is a significant comorbidity. No therapy is available that improves cardiovascular outcomes. The aim of this study was to characterize myocardial function and ventricular-arterial coupling in a mouse model of diabetes and to analyse the effect of selective heart rate (HR) reduction by If-inhibition in this HFPEF-model. Methods and results Control mice, diabetic mice (db/db), and db/db mice treated for 4 weeks with the If-inhibitor ivabradine (db/db-Iva) were compared. Aortic distensibility was measured by magnetic resonance imaging. Left ventricular (LV) pressure–volume analysis was performed in isolated working hearts, with biochemical and histological characterization of the cardiac and aortic phenotype. In db/db aortic stiffness and fibrosis were significantly enhanced compared with controls and were prevented by HR reduction in db/db-Iva. Left ventricular end-systolic elastance (Ees) was increased in db/db compared with controls (6.0 ± 1.3 vs. 3.4 ± 1.2 mmHg/µL, P < 0.01), whereas other contractility markers were reduced. Heart rate reduction in db/db-Iva lowered Ees (4.0 ± 1.1 mmHg/µL, P < 0.01), and improved the other contractility parameters. In db/db active relaxation was prolonged and end-diastolic capacitance was lower compared with controls (28 ± 3 vs. 48 ± 8 μL, P < 0.01). These parameters were ameliorated by HR reduction. Neither myocardial fibrosis nor hypertrophy were detected in db/db, whereas titin N2B expression was increased and phosphorylation of phospholamban was reduced both being prevented by HR reduction in db/db-Iva. Conclusion In db/db, a model of HFPEF, selective HR reduction by If-inhibition improved vascular stiffness, LV contractility, and diastolic function. Therefore, If-inhibition might be a therapeutic concept for HFPEF, if confirmed in humans. [ABSTRACT FROM PUBLISHER]

Right ventricular (RV) failure due to chronically abnormal loading is a main determinant of outcome in pulmonary hypertension (PH) and congenital heart disease. However, distinct types of RV loading have been associated with different outcomes. To determine whether the adaptive RV response depends on loading type, we compared hemodynamics, exercise, and hypertrophy in models of pressure overload due to pulmonary artery banding (PAB), pressure overload due to PH, combined pressure and volume overload, and isolated volume load. Ninety-four rats were subjected to either PAB, monocrotaline-induced PH (PH), aortocaval shunt (shunt), or combined monocrotaline and aortocaval shunt (PH shunt). We performed pressure-volume analysis and voluntary exercise measurements at 4 wk. We compared PAB to PH (part I) and PH shunt to either isolated PH or shunt (part II). In part I, enhanced contractility (end-systolic elastance and preload recruitable stroke work) was present in PH and PAB, but strongest in PAB. Frank- Starling mechanism was active in both PAB and PH. In PAB this was accompanied by diastolic dysfunction (increased end-diastolic elastance, relaxation constant), clinical signs of RV failure, and reduced exercise. These distinct responses were not attributable to differences in hypertrophy. In part II, in PH shunt the contractility response was blunted compared with PH, which caused pseudonormalization of parameters. Additional volume overload strongly enhanced hypertrophy in PH. We conclude that different types of loading result in distinct patterns of RV adaptation. This is of importance for the approach to patients with chronically increased RV load and for experimental studies in various types of RV failure. [ABSTRACT FROM AUTHOR]

Aim Right ventricular (RV) failure due to pressure or volume overload is a major risk factor for early mortality in congenital heart disease and pulmonary hypertension, but currently treatments are lacking. We aimed to demonstrate that the phosphodiesterase 5A inhibitor sildenafil can prevent adverse remodelling and improve function in chronic abnormal RV overload, independent from effects on the pulmonary vasculature. Methods and results In rat models of either pressure or volume overload, we performed pressure–volume studies to measure haemodynamic effects and voluntary exercise testing as clinical outcome after 4 weeks of sildenafil (or vehicle) administration. In the pressure-loaded right ventricle, sildenafil enhanced contractility [end-systolic elastance (mmHg/mL) 247 ±68 vs.155 ±71, sildenafil vs. vehicle, P < 0.05], prevented RV dilatation [end-diastolic volume (μL) 733 ±50 vs. 874 ±39, P < 0.05], reduced wall stress [peak wall stress (mmHg) 323 ±46 vs. 492 ±62, P < 0.05], and partially preserved exercise tolerance [running distance (%) –33 ±15 vs. –62 ±12, P < 0.05]. Protein kinase A was not activated by sildenafil and thus did not mediate the observed effects. In contrast, protein kinase G-1 was activated by sildenafil, but hypertrophy was not inhibited. Importantly, sildenafil did not prevent diastolic dysfunction, whereas RV fibrosis appeared to be increased in sildenafil-treated rats. In the volume-loaded right ventricle, sildenafil treatment did not show any beneficial effects. Conclusion We demonstrate sildenafil to have beneficial, afterload-independent effects on the pressure-loaded right ventricle, but not on the volume-loaded right ventricle. These results indicate that sildenafil may offer a specific treatment for the pressure-loaded right ventricle, although persistent diastolic dysfunction and RV fibrosis could be of concern. [ABSTRACT FROM AUTHOR]

Aims Hyperaldosteronism is associated with an increased prevalence of atrial fibrillation (AF). However, it is unclear whether this is the consequence of altered haemodynamics or a direct aldosterone effect. It was the aim of the study to demonstrate load-independent effects of aldosterone on atrial structure and electrophysiology. Methods Osmotic mini-pumps delivering 1.5 µg/h aldosterone were implanted subcutaneously in rats (Aldo). Rats without aldosterone treatment served as controls. After 8 weeks, surface electrocardiogram, the inducibility of AF, and atrial pressures were recorded in vivo. In isolated working hearts, left ventricular function was measured, and conduction in the right atrium (RA) and the left atrium (LA) was mapped epicardially. The atrial effective refractory period (AERP) was determined. Atrial tissue was analysed histologically. Results Neither systolic nor diastolic ventricular function nor atrial pressures were altered in Aldo rats. All Aldo (11/11) showed inducible atrial arrhythmias vs. two of nine controls (P = 0.03). In Aldo, the P-wave duration and the total RA activation time were longer. Prolongation of local conduction times occurred more often in Aldo, whereas the AERP did not differ between both groups. In Aldo, atrial fibroblasts and interstitial collagen were increased, active matrix metalloproteinase 13 was reduced, and atrial myocytes were hypertrophied. The connexin 43 content was unaltered. Conclusions Aldosterone causes a substrate for atrial arrhythmias characterized by atrial fibrosis, myocyte hypertrophy, and conduction disturbances. The described model imputes atrial proarrhythmia directly to aldosterone, since ventricular haemodynamics appeared unaltered in this model. This mechanism may have therapeutical impact for primary and secondary prevention of AF. [ABSTRACT FROM PUBLISHER]

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]

We previously showed that human cardiomyocyte progenitor cells (hCMPCs) injected after myocardial infarction (MI) had differentiated into cardiomyocytes in vivo 3 months after MI. Here, we investigated the short-term (2 weeks) effects of hCMPCs on the infarcted mouse myocardium. MI was induced in immunocompromised (NOD/scid) mice, immediately followed by intramyocardial injection of hCMPCs labelled with enhanced green fluorescent protein (hCMPC group) or vehicle only (control group). Sham-operated mice served as reference. Cardiac performance was measured 2 and 14 days after MI by magnetic resonance imaging at 9.4 T. Left ventricular (LV) pressure-volume measurements were performed at day 15 followed by extensive immunohistological analysis. Animals injected with hCMPCs demonstrated a higher LV ejection fraction, lower LV end-systolic volume and smaller relaxation time constant than control animals 14 days after MI. hCMPCs engrafted in the infarcted myocardium, did not differentiate into cardiomyocytes, but increased vascular density and proliferation rate in the infarcted and border zone area of the hCMPC group. Injected hCMPCs engraft into murine infarcted myocardium where they improve LV systolic function and attenuate the ventricular remodelling process 2 weeks after MI. Since no cardiac differentiation of hCMPCs was evident after 2 weeks, the observed beneficial effects were most likely mediated by paracrine factors, targeting amongst others vascular homeostasis. These results demonstrate that hCMPCs can be applied to repair infarcted myocardium without the need to undergo differentiation into cardiomyocytes. [ABSTRACT FROM AUTHOR]

Aims Surgical ventricular restoration (SVR) aims to normalize left ventricular (LV) volume and shape in patients with ischaemic cardiomyopathy and anterior wall scar. The chronic effects on LV function may depend on alterations in myocardial collagen metabolism. The present study evaluated myocardial collagen synthesis and degradation rates at baseline and at 6 months follow-up after SVR. We hypothesize that the chronic effects of SVR on LV function and clinical outcome depend on alterations in myocardial collagen metabolism. Methods and results Serum levels of aminoterminal propeptides of type I and III collagen (PINP, PIIINP), carboxyterminal telopeptide of type I collagen (ICTP), and tenascin-C (TNC) were measured at baseline and 6 months after SVR in 24 patients. In addition, New York Heart Association (NYHA) functional class, LV volumes and function were evaluated. At follow-up, a significant improvement in NYHA class (from 3.2 ± 0.8 to 1.4 ± 0.6, P< 0.001) and LV ejection fraction (from 28 ± 9 to 35 ± 7%, P< 0.001) was found, whereas E/A ratio tended to increase (from 1.4 ± 1.1 to 1.9 ± 1.1, P= 0.064). Serum levels of PINP, PIIINP, ICTP, and TNC increased significantly (PINP: from 37 ± 15 to 67 ± 26 μg/L, P< 0.001; PIIINP: from 4.9 ± 1.7 to 7.9 ± 4.0 μg/L, P< 0.001; ICTP: from 5.9 ± 3.7 to 10.0 ± 5.3 μg/L, P< 0.001; TNC: from 30 ± 20 to 44 ± 23 μg/L, P= 0.020). At follow-up, an LV ejection fraction <34% and E/A ratio ≥2.0 were significantly associated with increased serum levels of PIIINP and ICTP. Conclusion In patients who underwent SVR, myocardial collagen metabolism was significantly enhanced 6 months after surgery. Serum levels of myocardial collagen turnover biomarkers were related to post-surgical LV systolic and diastolic function. [ABSTRACT FROM AUTHOR]

. (J Cardiovasc Electrophysiol, Vol. 22, pp. 677-683, June 2011) [ABSTRACT FROM AUTHOR]

Background: Surgical ventricular restoration (SVR) improves left ventricular (LV) systolic function by partially restoring the normal geometry of the left ventricle. However, the beneficial effects of this surgical procedure on long-term clinical outcome remain controversial. The present study aimed to evaluate the independent determinants of 2-year morbidity and mortality rates after SVR. Methods: Seventy-nine patients with ischemic heart disease and LV ejection fraction of 0.35 or less were included. All patients underwent SVR and additionally coronary artery bypass grafting or mitral valve surgery if clinically indicated. Clinical and echocardiographic examination was performed before SVR and at 6 months'' follow-up. The primary end point was a composite of all-cause mortality and hospitalizations for heart failure. Results: At 6 months'' follow-up a significant improvement in heart failure symptoms was noted. In addition, LV ejection fraction increased from 0.27 ± 0.07 to 0.36 ± 0.10 (p < 0.001). During a median follow-up of 2.7 years, the primary end point was recorded in 22% of the patients. Baseline New York Heart Association functional class IV and a 6-month follow-up LV end-systolic volume index of at least 60 mL/m2 were independently associated with worse outcome (hazard ratio, 5.4; 95% confidence interval, 1.9 to 15.2; p < 0.001; hazard ratio, 2.7; 95% confidence interval, 1.3 to 5.6; p < 0.001, respectively). Conclusions: Advanced heart failure status at baseline and large residual postsurgery LV end-systolic volume index were independently associated with increased mortality and heart failure hospitalization rates at 2 years'' follow-up after SVR. [Copyright &y& Elsevier]

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]

Background: Restrictive mitral annuloplasty (RMA) is increasingly applied to treat functional mitral regurgitation in heart failure patients. Previous studies indicated beneficial clinical effects with low recurrence rates. However, the underlying pathophysiology is complex and outcome in terms of left ventricular function is not well known. We investigated chronic effects of RMA on ventricular function in relation to clinical outcome. Methods: Heart failure patients (n = 11) with severe mitral regurgitation scheduled for RMA were analyzed at baseline (presurgery) and midterm follow-up by invasive pressure-volume loops, using conductance catheters. Clinical performance was evaluated by New York Heart Association class, quality-of-life-score, and 6-minute hall-walk-test. Results: All patients were alive without recurrence of mitral regurgitation at follow-up (9.4 ± 4.1 months). Clinical parameters improved significantly (all p < 0.05). Global cardiac function, assessed by cardiac output, stroke volume, and stroke work did not change after RMA. Reverse remodeling was demonstrated by decreased end-systolic and end-diastolic volumes (16% and 11%, both p < 0.001). Systolic function improved, evidenced by increased ejection fraction (0.32 ± 0.05 to 0.36 ± 0.07, p = 0.001) and leftward shift of the end-systolic pressure-volume relation (ESV100: 116 ± 43 to 74 ± 26 mL, p < 0.001). Diastolic function, however, demonstrated impairment by increased tau (69 ± 13 to 80 ± 14 ms, p < 0.001) and stiffness constant (0.022 ± 0.022 to 0.031 ± 0.028 mL−1, p = 0.001). Conclusions: Restrictive mitral annuloplasty significantly improved clinical status without recurrence of mitral regurgitation at midterm follow-up in patients with heart failure. Hemodynamic analyses demonstrated significant reverse remodeling with unchanged global function and improved systolic function, but some signs of diastolic impairment. Overall, RMA appears an appropriate therapy for patients with dilated cardiomyopathy and functional mitral regurgitation. [Copyright &y& Elsevier]

We recently developed a rat model of cardiorenal failure that is characterized by severe left ventricular systolic dysfunction (LVSD) and low nitric oxide (NO) production that persisted after temporary low-dose NO synthase inhibition. We hypothesized that LVSD was due to continued low NO availability and might be reversed by supplementing NO. Rats underwent a subtotal nephrectomy and were treated with low-dose NO synthase inhibition with N?-nitro-l-arginine up to week 8. After 3 wk of washout, rats were treated orally with either the long-acting, tolerance-free NO donor molsidomine (Mols) or vehicle (Veh). Cardiac and renal function were measured on weeks 11, 13, and 15. On week 16, LV hemodynamics and pressure-volume relationships were measured invasively, and rats were killed to quantify histological damage. On week 15, blood pressure was mildly reduced and creatinine clearance was increased by Mols (both P < 0.05). Mols treatment improved ejection fraction (53 ± 3% vs. 37 ± 2% in Veh-treated rats, P < 0.001) and stroke volume (324 ± 33 vs. 255 ± 15 μl in Veh-treated rats, P < 0.05). Rats with Mols treatment had lower end-diastolic pressures (8.5 ± 1.1 mmHg) than Veh-treated rats (16.3 ± 3.5 mmHg, P < 0.05) and reduced time constants of relaxation (21.9 ± 1.8 vs. 30.9 ± 3.3 ms, respectively, P < 0.05). The LV end-systolic pressure-volume relationship was shifted to the left in Mols compared with Veh treatment. In summary, in a model of cardiorenal failure with low NO availability, supplementing NO significantly improves cardiac systolic and diastolic function without a major effect on afterload. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the accuracy and reproducibility of aortic pulse wave velocity (PWV) assessment by in-plane velocity-encoded magnetic resonance imaging (MRI). Materials and Methods In 14 patients selected for cardiac catheterization on suspicion of coronary artery disease and 15 healthy volunteers, PWV was assessed with multislice two-directional in-plane velocity-encoded MRI (PWVi.p.) and compared with conventionally assessed PWV from multisite one-directional through-plane velocity-encoded MRI (PWVt.p.). In patients, PWV was also obtained from intraarterially acquired pressure-time curves (PWVpressure), which is considered the gold standard reference method. In volunteers, PWVi.p. and PWVt.p. were obtained in duplicate in the same examination to test reproducibility. Results In patients, PWVi.p. showed stronger correlation and similar variation with PWVpressure than PWVt.p. (Pearson correlation r = 0.75 vs. r = 0.58, and coefficient of variation [COV] = 10% vs. COV = 12%, respectively). In volunteers, repeated PWVi.p. assessment showed stronger correlation and less variation than repeated PWVt.p. (proximal aorta: r = 0.97 and COV = 10% vs. r = 0.69 and COV = 17%; distal aorta: r = 0.94 and COV = 12% vs. r = 0.90 and COV = 16%; total aorta: r = 0.97 and COV = 7% vs. r = 0.90 and COV = 13%). Conclusion PWVi.p. is an improvement over conventional PWVt.p. by showing higher agreement as compared to the gold standard (PWVpressure) and higher reproducibility for repeated MRI assessment. J. Magn. Reson. Imaging 2010;32:1086-1094. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

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]

Aims Strain rate imaging provides direct information on intrinsic myocardial function and may improve the diagnostic of diastolic dysfunction in heart failure with normal ejection fraction (HFNEF). We therefore correlated global strain with pressure–volume (PV) loop analysis and compared it with flow and tissue Doppler measurements. Methods and results Longitudinal two-dimensional strain rate and flow and tissue Doppler (TDI) indices were measured simultaneously and correlated with diastolic indices of PV relationship obtained by a conductance catheter in 21 patients with HFNEF and 12 controls. HFNEF patients showed a reduced global strain rate during isovolumetric relaxation (SRIVR) [0.27 (0.12–0.39) vs. 0.44 (0.29–0.56) s−1, P = 0.028]. Global strain rate during early (SRE) and late (SRL) diastole did not defer from controls. Their ratios with early transmitral flow, E/SRIVR and E/SRE, were both elevated in HFNEF [3.68 (2.57–7.52) vs. 1.73 (1.47–2.37) m, P = 0.007 and 1.13 (0.76–1.36) vs. 0.83 (0.57–1.04) m, P = 0.030]. SRE and SRIVR correlated with left ventricular (LV) relaxation τ (r = 0.40 and 0.47, P < 0.05); E/SRIVR and E/SRE with LV end-diastolic pressure (r = 0.49 and 0.57, P < 0.01) and LV stiffness constant β (r = 0.42 and 0.43, P < 0.01). Neither of the strain rate indices were significantly more accurate than TDI (area under the curve: SRE 0.55, SRIVR 0.70, E′/A′ 0.72, E/SRE 0.75, E/SRIVR 0.80, and E/E′ 0.83). Conclusion Strain rate imaging is accurate in detecting increased LV stiffness in HFNEF, but it is not superior to already established TDI analysis including E/E′ in patients with only mild degree of disease. [ABSTRACT FROM AUTHOR]

The atria play an important role in cardiac performance. We evaluated their function and the atrioventricular interaction in operated patients with tetralogy of Fallot (TOF). Twenty patients who had undergone surgical repair of TOF and seven controls were investigated. Patients had residual pulmonary but no major tricuspid valve insufficiency. Atrial and ventricular strain rates were obtained by echocardiographic speckle tracking. Cine MRI-derived volumetric analysis provided atrial and ventricular time volume and time volume change curves yielding emptying and filling parameters. In addition, at the atrial level, reservoir, conduit and pump function, and cyclic volume change were calculated. At the atrioventricular valve level, tricuspid and mitral annular plane systolic excursion (TAPSE and MAPSE, respectively) were measured by two-dimensional echocardiography. In the patients compared with controls, right ventricular end-diastolic volumes were increased and biventricular ejection fraction was decreased (all P < 0.05). Biventricular measures of early diastolic ventricular filling were at control levels, but in late diastole, right ventricular filling parameters and strain rates were decreased (P < 0.001). The maximal right atrial size was slightly but not significantly diminished, but cyclic volume change was significantly reduced (P < 0.0001). Pump and reservoir function were decreased (P < 0.05), and conduit function was elevated (P < 0.001). The left atrium showed reduced reservoir function and cyclic volume change (P < 0.05). TAPSE and MAPSE were also decreased (P < 0.05). There were statistically significant interdependencies between RV ejection fraction, TAPSE, and right atrial filling and emptying parameters (all P < 0.05). In TOF patients, moderate systolic and diastolic right ventricular dysfunction is associated with clearly impaired right atrial function. The left atrium is affected to a lesser extent. [ABSTRACT FROM AUTHOR]

Aims To test a method to predict the end-diastolic pressure-volume relationship (EDPVR) from a single beat in patients with heart failure. Methods and results Patients (New York Heart Association class III-IV) scheduled for mitral annuloplasty (n=9) or ventricular restoration (n=10) and patients with normal left ventricular function undergoing coronary artery bypass grafting (n=12) were instrumented with pressure-conductance catheters to measure pressure-volume loops before and after surgery. Data obtained during vena cava occlusion provided directly measured EDPVRs. Baseline end-diastolic pressure (Pm) and volume (Vm) were used for single-beat prediction of EDPVRs. Root-mean-squared error (RMSE) between measured and predicted EDPVRs, was 2.79±0.21 mm Hg. Measured versus predicted end-diastolic volumes at pressure levels 5, 10, 15 and 20 mm Hg showed tight correlations (R2=0.69-0.97). Bland-Altman analyses indicated overestimation at 5 mm Hg (bias: pre-surgery 44 ml (95% CI 29 to 58 ml); post-surgery 35 ml (23 to 47 ml)) and underestimation at 20 mm Hg (bias: pre-surgery -57 ml (-80 to -34 ml); post-surgery -13 ml (-20 to -7.0 ml)). End-diastolic volumes were significantly different between groups and between conditions, but these differences were not dependent on the method (ie, measured versus predicted). RMSEs were not different between groups or conditions, nor dependent on Vm or Pm, indicating that EDPVR prediction was equally accurate over a wide volume range. Conclusions Single-beat EDPVRs obtained from hearts spanning a wide range of sizes and conditions accurately predicted directly measured EDPVRs with low RMSE. Single-beat EDPVR indices correlated well with directly measured values, but systematic biases were present at low and high pressures. The single-beat method facilitates less invasive EDPVR estimation, particularly when coupled with emerging non-invasive techniques to measure pressures and volumes. [ABSTRACT FROM AUTHOR]

Aims: We tested the hypothesis that, in heart failure with normal ejection fraction (HFNEF), diastolic dysfunction is accentuated at increasing heart rates, and this contributes to impaired frequency-dependent augmentation of cardiac output. [ABSTRACT FROM PUBLISHER]

Objectives: This study sought to develop and validate a method for the integrated analysis of systolic and diastolic ventricular function. Background: An integrated approach to assess ventricular pump function, myocontractility (end-systolic pressure–volume relationship [ESPVR]), and diastolic compliance (end-diastolic pressure–volume relation [EDPVR]) is of high clinical value. Cardiac magnetic resonance (CMR) is well established for measuring global pump function, and catheterization-combined CMR was previously shown to accurately measure ESPVR, but not yet the EDPVR. Methods: In 8 pigs, the CMR technique was compared with conductance catheter methods (gold standard) for measuring the EDPVR in the left and right ventricle. Measurements were performed at rest and during dobutamine administration. For CMR, the ESPVR was estimated with a single-beat approach by synchronizing invasive ventricular pressures with cine CMR–derived ventricular volumes. The EDPVR was determined during pre-load reduction from additional volume data that were obtained from real-time velocity-encoded CMR pulmonary/aortic blood flow measurements. Pre-load reduction was achieved by transient balloon occlusion of the inferior vena cava. The stiffness coefficient β was calculated by an exponential fit from the EDPVR. After validation in the animal experiments, the EDPVR was assessed in a pilot study of 3 patients with a single ventricle using identical CMR and conductance catheter techniques. Results: Bland-Altman tests showed good agreement between conductance catheter–derived and CMR-derived EDPVR. In both ventricles of the pigs, dobutamine enhanced myocontractility (p < 0.01), increased stroke volume (p < 0.01), and improved diastolic function. The latter was evidenced by shorter early relaxation (p < 0.05), a downward shift of the EDPVR, and a decreased stiffness coefficient β (p < 0.05). In contrast, in the patients, early relaxation was inconspicuous but the EDPVR shifted left-upward and the stiffness constant remained unchanged. The observed changes in diastolic function were not significantly different when measured with conductance catheter and CMR. Conclusions: This novel CMR method provides differential information about diastolic function in conjunction with parameters of systolic contractility and global pump function. [Copyright &y& Elsevier]

Pulmonary arterial hypertension (PAH) is a chronic lung disease that leads to right ventricular (RV) hypertrophy (RVH), remodeling, and failure. We tested treatment with bone marrow-derived mesenchymal stem cells (MSCs) obtained from donor rats with monocrotaline (MCT)-induced PAH to recipient rats with MCT-induced PAH on pulmonary artery pressure, lung pathology, and RV function. This model was chosen to mimic autologous MSC therapy. On day 1, PAH was induced by MCT (60 mg/kg) in 20 female Wistar rats. On day 14, rats were treated with 106 MSCs intravenously (MCT + MSC) or with saline (MCT6O). MSCs were obtained from donor rats with PAH at 28 days after MCT. A control group received saline on days 1 and 14. On day 28, the RV function of recipient rats was assessed, followed by isolation of the lungs and heart. RVH was quantified by the weight ratio of the RV/(left ventricle + interventricular septum). MCT induced an increase of RV peak pressure (from 27 ± 5 to 42 ± 17 mmHg) and RVH (from 0.25 ± 0.04 to 0.47 ± 0.12), depressed the RV ejection fraction (from 56 ± 11 to 43 ± 6%), and increased lung weight (from 0.96 ± 0.15 to 1.66 ± 0.32 g), including thickening of the arteriolar walls and alveolar septa. MSC treatment attenuated PAH (31 ± 4 mmHg) and RVH (0.32 ± 0.07), normalized the RV ejection fraction (52 ± 5%), reduced lung weight (1.16 ± 0.24 g), and inhibited the thickening of the arterioles and alveolar septa. We conclude that the application of MSCs from donor rats with PAH reduces RV pressure overload, RV dysfunction, and lung pathology in recipient rats with PAH. These results suggest that autologous MSC therapy may alleviate cardiac and pulmonary symptoms in PAH patients. [ABSTRACT FROM AUTHOR]

Purpose To validate magnetic resonance imaging (MRI) assessment of aortic pulse wave velocity (PWVMRI) with PWV determined from invasive intra-aortic pressure measurements (PWVINV) and to test the reproducibility of the measurement by MRI. Materials and Methods PWVMRI was compared with PWVINV in 18 nonconsecutive patients scheduled for catheterization for suspected coronary artery disease. Reproducibility of PWVMRI was tested in 10 healthy volunteers who underwent repeated measurement of PWVMRI at a single occasion. Velocity-encoded MRI was performed on all participants to assess PWVMRI in the total aorta (Aototal), the proximal aorta (Aoprox), and the distal aorta (Aodist). Results The results are expressed as mean ± SD, Pearson correlation coefficient (PCC), and intraclass correlation (ICC). Good agreement between PWVMRI and PWVINV was found for Aototal (6.5 ± 1.1 m/s vs. 6.1 ± 0.8 m/s; PCC = 0.53), Aoprox (6.5 ± 1.3 m/s vs. 6.2 ± 1.1 m/s; PCC = 0.69), and for Aodist (6.9 ± 1.1 m/s vs. 6.1 ± 1.0 m/s; PCC = 0.71). Reproducibility of PWVMRI was high for Aototal (4.3 ± 0.5 m/s vs. 4.6 ± 0.7 m/s; ICC = 0.90, P < 0.01), Aoprox (4.3 ± 0.9 m/s vs. 4.7 ± 1.0 m/s; ICC = 0.87, P < 0.01), and Aodist (4.3 ± 0.6 m/s vs. 4.4 ± 0.8 m/s; ICC = 0.92, P < 0.01). Conclusion MRI assessment of aortic pulse wave velocity shows good agreement with invasive pressure measurements and can be determined with high reproducibility. J. Magn. Reson. Imaging 2009;30:521-526. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Simulations are useful to study the heart’s ability to generate flow and the interaction between contractility and loading conditions. The left ventricular pressure–volume (PV) relation has been shown to be nonlinear, but it is unknown whether a linear model is accurate enough for simulations. Six models were fitted to the PV-data measured in five sheep and the estimated parameters were used to simulate PV-loops. Simulated and measured PV-loops were compared with the Akaike information criterion (AIC) and the Hamming distance, a measure for geometric shape similarity. The compared models were: a time-varying elastance model with fixed volume intercept (LinFix); a time-varying elastance model with varying volume intercept (LinFree); a Langewouter’s pressure-dependent elasticity model (Langew); a sigmoidal model (Sigm); a time-varying elastance model with a systolic flow-dependent resistance (Shroff) and a model with a linear systolic and an exponential diastolic relation (Burkh). Overall, the best model is LinFree (lowest AIC), closely followed by Langew. The remaining models rank: Sigm, Shroff, LinFix and Burkh. If only the shape of the PV-loops is important, all models perform nearly identically (Hamming distance between 20 and 23%). For realistic simulation of the instantaneous PV-relation a linear model suffices. [ABSTRACT FROM AUTHOR]

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]

Objective: Myocardial contractility can be described by the relationship between blood-flow velocity in the carotid artery and the left ventricular cross-sectional area. The authors investigated whether critical myocardial ischemia influences the derived contractility index, E′es. Design: A prospective animal study. Setting: A university research laboratory. Participants: Eleven Göttinger minipigs. Interventions: Within the closed-chest model, the authors placed a U-shaped 8-MHz miniature Doppler probe around the left internal carotid artery and inserted a combined pressure-conductance catheter into the left ventricular cavity via the right internal carotid artery. A balloon occlusion catheter was placed into the inferior caval vein from a femoral vein and acquired transthoracic-view echocardiographic images. An active coronary perfusion catheter was positioned in the proximal left circumflex coronary (LCx) artery. The LCx bed was perfused with blood from the contralateral femoral artery by using a high-precision–output roller pump. Measurements and Main Results: Stage analysis during normal perfusion revealed evidence for the following function: E′es = 0.066 + 0.121 Ees (R = 0.96, R 2 = 0.92, and p < 0.0001), which agrees with previously determined equations. Under ischemic conditions, the relationship changed to E′es = 0.048 + 0.196·Ees (R = 0.83, R 2 = 0.69, and p < 0.0001). The limits of precision to detect changes in contractility by E′es increased from 16% to 45%; the bias did not notably deviate from zero. The indexes of mechanical dyssynchrony (mechanical dyssynchrony and internal flow fraction) derived from conductance catheter measurements increased significantly. Conclusion: The ability of E′es to indicate contractility during acute reduced coronary blood flow is limited. [Copyright &y& Elsevier]

The aim of the present study was to determine the long-term effects of percutaneous transluminal septal myocardial ablation (PTSMA) on systolic and diastolic left ventricular (LV) functions in patients with obstructive hypertrophic cardiomyopathy (HC). Ten consecutive patients with symptomatic HC despite optimal medical treatment were referred for PTSMA at our center. LV systolic and diastolic functions were assessed by online LV pressure–volume loops obtained by conductance catheter at baseline and at 6 months after the procedure. At follow-up, the mean gradients at rest and after extrasystole were significantly decreased compared with baseline (88 ± 29 to 21 ± 11 mm Hg and 130 ± 50 to 35 ± 22 mm Hg, respectively, p <0.01 for the 2 comparisons). End-systolic and end-diastolic pressures significantly decreased (p <0.01), whereas end-systolic and end-diastolic LV volumes significantly increased (p <0.01 for the 2 comparisons). Cardiac output and stroke volume were unchanged, as were ejection fraction (p = 0.25) and maximum dP/dt (p = 0.13). The slope of the end-systolic pressure–volume relation was not decreased, indicating a preserved contractility. The relaxation constant time, end-diastolic stiffness, projected volume of the end-diastolic pressure–volume relation at 30 mm Hg, and diastolic stiffness constant showed a significant improvement of active and passive myocardial diastolic properties. In conclusion, PTSMA is an effective method in the treatment of symptomatic patients with HC. At 6-month follow-up, the LV–aortic gradient was decreased and active and passive LV diastolic properties were increased. Myocardial contractility was not decreased and general hemodynamics was maintained. [Copyright &y& Elsevier]

Myocardial hyperplasia is generally considered to occur only during fetal development. However, recent evidence suggests that this type of response may also be triggered by cardiac overload after birth. In congenital heart disease, loading conditions are frequently abnormal, thereby affecting ventricular function. We hypothesized that chronic right ventricular pressure overload imposed on neonatal hearts initiates a hyperplastic response in the right ventricular myocardium. To test this, young lambs (aged 2–3 weeks) underwent adjustable pulmonary artery banding to obtain peak right ventricular pressures equal to left ventricular pressures for 8 weeks. Transmural cardiac tissue samples from the right and left ventricles of five banded and five age-matched control animals were studied. We found that chronic right ventricular pressure overload resulted in a twofold increase in right-to-left ventricle wall thickness ratio. Morphometric right ventricular myocardial tissue analysis revealed no changes in tissue composition between the two groups; nor were right ventricular myocyte dimensions, relative number of binucleated myocytes, or myocardial DNA concentration significantly different from control values. In chronic pressure overloaded right ventricular myocardium, significantly ( P < 0.01) more myocyte nuclei were positive for the proliferation marker proliferating cellular nuclear antigen than in control right ventricular myocardium. Chronic right ventricular pressure overload applied in neonatal sheep hearts results in a significant increase in right ventricular free wall thickness which is primarily the result of a hyperplastic myocardial response. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 X 105 cells in 20 μl, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/scid mice. Sham-operated mice were used as the control (n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 ± 2% vs. 36 ± 2%; P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 ± 3% vs. 16 ± 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 ± 0.3% of injected cells) expressed von Willebrand factor (16.9 ± 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning. [ABSTRACT FROM AUTHOR]

Abstract: Background: Treatment of heart failure by advanced surgical procedures such as ventricular restoration (SVR) and restrictive mitral annuloplasty (RMA) is increasingly applied. We studied clinical efficacy of heart failure surgery in patients with severe heart failure. Methods and Results: Thirty-three patients (New York Heart Association (NYHA) class III/IV, left ventricular ejection fraction ≤35%) were included. Patients with moderate to severe mitral regurgitation underwent RMA (85%) and patients with anteroseptal aneurysm underwent SVR (52%). A combined procedure was performed in 12 patients, and additional coronary artery bypass grafting in 27 patients. Clinical and echocardiographic parameters were assessed at baseline and 6 months after surgery. Operative mortality was 3% (n = 1), in-hospital mortality was 9% (n = 3), and there was no late mortality. All clinical parameters were significantly improved at 6 months'' follow-up (P < .001); NYHA class improved from 3.4 ± 0.5 to 1.5 ± 0.5, Quality-of-life score improved from 44 ± 22 to 16 ± 12, and 6-minute walking distance increased from 248 ± 134 m to 422 ± 113 m. Left ventricular end-diastolic volume decreased from 107 ± 32 to 80 ± 20 mL/m2 (P < .001) and end-systolic volume decreased from 78 ± 32 to 53 ± 15 mL/m2 (P < .001), whereas ejection fraction improved from 29 ± 9 to 35 ± 7% (P < .01). Conclusions: Surgical treatment of severe heart failure by SVR or RMA was associated with 12% mortality at 6 months. Surviving patients showed highly significant functional and clinical improvements. [Copyright &y& Elsevier]

Aims At present, 20–30% of patients do not respond to cardiac resynchronization therapy (CRT). In this study, the relation between the extent of viable myocardium and scar tissue vs. response to CRT was evaluated. In addition, the presence of scar tissue in the left ventricular (LV) lead position was specifically related to response to CRT. [ABSTRACT FROM PUBLISHER]

We characterized hemodynamics and systolic and diastolic right ventricular (RV) function in relation to structural changes in the rat model of monocrotaline (MCT)-induced pulmonary hypertension. Rats were treated with MCT at 30 mg/kg body wt (MCT30, n = 15) and 80 mg/kg body wt (MCT80, n = 16) to induce compensated RV hypertrophy and RV failure, respectively. Saline-treated rats served as control (Cont, n = 13). After 4 wk, a pressure-conductance catheter was introduced into the RV to assess pressure-volume relations. Subsequently, rats were killed, hearts and lungs were rapidly dissected, and RV, left ventricle (LV), and interventricular septum (WS) were weighed and analyzed histochemically. RV-to-(LV + IVS) weight ratio was 0.29 ± 0.05 in Cont, 0.35 ± 0.05 in MCT30, and 0.49 ± 0.10 in MCT80 (P < 0.001 vs. Cont and MCT30) rats, confirming MCT-induced RV hypertrophy. RV ejection fraction was 49 ± 6% in Cont, 40 ± 12% in MCT30 (P < 0.05 vs. Cont), and 26 ± 6% in MCT80 (P < 0.05 vs. Cont and MCT30) rats, hi MCT30 rats, cardiac output was maintained, but RV volumes and filling pressures were significantly increased compared with Cont (all P < 0.05), indicating RV remodeling. In MCT80 rats, RV systolic pressure, volumes, and peak wall stress were further increased, and cardiac output was significantly decreased (all P < 0.05). However, RV end-systolic and end-diastolic stiffness were unchanged, consistent with the absence of interstitial fibrosis. MCT-induced pressure overload was associated with a dose-dependent development of RV hypertrophy. The most pronounced response to MCT was an overload-dependent increase of RV end-systolic and end-diastolic volumes, even under nonfailing conditions. [ABSTRACT FROM AUTHOR]

Background: Surgical ventricular restoration is increasingly applied in patients with ischemic dilated cardiomyopathy. Previous studies show promising results with regard to survival and clinical outcome. However, a comprehensive midterm analysis of this approach on left ventricular (LV) and right ventricular function is not yet available. We investigated biventricular function and clinical status at 6-month follow-up. Methods: We investigated the effects of surgical ventricular restoration on clinical variables, LV volume, right ventricular reverse remodeling, LV dyssynchrony, tricuspid regurgitation, and pulmonary artery pressure in 21 patients with ischemic dilated cardiomyopathy (New York Heart Association class III or IV) who underwent surgical ventricular restoration and coronary artery bypass grafting. Additional surgery included mitral annuloplasty (n = 14) and tricuspid valve annuloplasty (n = 8). Clinical variables (New York Heart Association class, quality-of-life questionnaire, 6-minute hall-walk test) and echocardiographic variables were assessed at baseline and at 6 months. Results: At 6-month follow-up, all clinical variables were significantly improved. Left ventricular ejection fraction improved from 0.27 ± 0.10 to 0.36 ± 0.11 (p < 0.01), LV end-diastolic volume decreased from 248 ± 78 mL to 152 ± 50 mL (p < 0.001), and LV end-systolic volume decreased from 186 ± 77 mL to 101 ± 50 mL (p < 0.001). Left ventricular dyssynchrony decreased from 61 ± 41 ms to 12 ± 12 ms (p < 0.001). Right ventricular annular diameter decreased from 30 ± 7 mm to 27 ± 6 mm, right ventricular short-axis from 30 ± 9 mm to 27 ± 7 mm, and right ventricular long-axis from 90 ± 7 mm to 79 ± 10 mm (all p < 0.05). Finally, significant reductions in severity of tricuspid regurgitation (from 1.3 ± 1.1 to 0.9 ± 0.6; p = 0.001) and pulmonary artery pressure (42 ± 11 mm Hg to 28 ± 10 mm Hg; p = 0.015) were observed. Conclusions: Surgical ventricular restoration resulted in improvement of clinical variables, significant LV volume reduction, and reduced LV dyssynchrony at 6-month follow-up. In addition, right ventricular reverse remodeling was noted with reductions in tricuspid regurgitation and pulmonary artery pressure. [Copyright &y& Elsevier]

Objectives: Surgical ventricular restoration aims at improving cardiac function by normalization of left ventricular shape and size. Recent studies indicate that surgical ventricular restoration is highly effective with an excellent 5-year outcome in patients with ischemic dilated cardiomyopathy. We used pressure-volume analysis to investigate acute changes in systolic and diastolic left ventricular function, mechanical dyssynchrony and efficiency, and wall stress. Methods: In 3 patient groups (total, n = 33), pressure-volume loops were measured by conductance catheter before and after surgery. The main study group consisted of 10 patients with ischemic dilated cardiomyopathy (New York Heart Association class III/IV, left ventricular ejection fraction <30%) who had surgical ventricular restoration and coronary artery bypass grafting. In this group, 7 patients had additional restrictive mitral annuloplasty. To assess potential confounding effects of restrictive mitral annuloplasty and cardiopulmonary bypass, we included a group of 10 patients (New York Heart Association class III/IV, left ventricular ejection fraction <30%) who had isolated restrictive mitral annuloplasty and a group of 13 patients with preserved left ventricular function who had isolated coronary artery bypass grafting. Results: After surgical ventricular restoration, end-diastolic and end-systolic volumes were reduced from 211 ± 54 to 169 ± 34 mL (P = .03) and from 147 ± 41 to 110 ± 59 mL (P = .04), respectively. Left ventricular ejection fraction (from 27% ± 7% to 37% ± 13%, P = .04) and end-systolic elastance (from 1.12 ± 0.71 to 1.57 ± 0.63 mm Hg/mL, P = .03) improved. Peak wall stress (from 358 ± 108 to 244 ± 79 mm Hg, P < .01) and mechanical dyssynchrony (from 26% ± 4% to 19% ± 6%, P < .01) were reduced, whereas mechanical efficiency improved (from 0.34 ± 13 to 0.49 ± 0.14, P = .03). End-diastolic pressure increased (from 13 ± 6 to 20 ± 5 mm Hg, P < .01), whereas the diastolic chamber stiffness constant tended to be increased (from 0.021 ± 0.009 to 0.037 ± 0.021 mL−1, NS). Conclusions: Surgical ventricular restoration achieves normalization of left ventricular volumes and improves systolic function and mechanical efficiency by reducing left ventricular wall stress and mechanical dyssynchrony. [Copyright &y& Elsevier]

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]

We present the case of a patient with severe dyspnea and Raynaud’s phenomenon. We could clarify, using invasive techniques including left ventricular conductance catheterization and coronary ergonovine provocation, that isolated diastolic dysfunction induced by coronary vasospasm were responsible for the symptoms. Systolic function was not affected. Short–term infusions with the prostacyclin analogue iloprost, known to act as a disease–modifying agent in patients suffering from Raynaud’s phenomenon, led to an improvement of cardiac function. Thus, episodes of dyspnea in patients with Raynaud’s phenomenon might be also interpretated as a coronary ischemia equivalent, which may belong to a visceral form of Raynaud’s phenomenon and which are sensitive to iloprost infusions. [ABSTRACT FROM AUTHOR]

Background Glucocorticosteroids (mostly dexamethasone) are widely used to prevent chronic lung disease in premature infants. Neonatal rats treated with dexamethasone have been shown to have reduced cardiac mass and cardiomyocyte hypertrophy, suggesting a lower number of cardiomyocytes at adult age, and a severely reduced life expectancy. In the present study we tested the hypothesis that a lower number of cardiomyocytes in later life is caused by a reduced cardiomyocyte proliferation and/or by early cell death (apoptosis). Methods and results Rat pups received dexamethasone or saline control on day 1, 2 and 3 and were sacrificed at day 0, 2, 4, 7 and 21. The cardiomyocytes of dexamethasone treated pups showed a reduced proliferation as indicated by a lower mitotic index and reduced number of Ki-67 positive cardiomyocytes on day 2 and 4 as compared to day 0 and day 7 and also as compared to the age-matched saline pups. On day 7 and day 21 the mitotic index was not different between groups. From day 2 onward up to day 21 dexamethasone treated pups showed a lower number of cardiomyocytes. The cardiomyocytes showed no signs (<<1%) of apoptosis (Caspase-3 and cleaved-PARP) in any group. Conclusion The temporary suppression of cardiomyocyte hyperplasia found in dexamethasone treated pups eventually leads to a reduced number and hypertrophy of cardiomyocytes during adult life. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) has a beneficial effect on clinical symptoms, exercise capacity, and systolic left ventricular (LV) performance in patients with heart failure. The aim of the current study was to evaluate whether a gender difference exists in response to CRT. Methods: Consecutive patients with end-stage heart failure (New York Heart Association, NYHA, class III–IV), LV ejection fraction (LVEF) ≤35%, QRS duration >120 ms, and left bundle branch block configuration underwent CRT. At baseline and 6 months post-CRT, clinical and echocardiographic parameters were evaluated; follow-up was obtained up to 5 years. The effects of CRT were compared between women and men. Results: The study population comprised 137 men and 36 women (mean age 66 ± 11 years). No differences in baseline characteristics were observed except that nonischemic cardiomyopathy was more frequent in women than men (67% vs 38%, P < 0.05). In all patients, clinical and echocardiographic parameters improved significantly at 6-month follow-up. The magnitude of improvement in different parameters was similar between women and men, e.g., the improvement in NYHA Class was 0.9 ± 0.6 in women and 1.0 ± 0.7 in men (NS) and the increase in LVEF was 8 ± 8% in women as compared to 7 ± 9% in men (NS). The percentage of individual responders was not different between women and men (76% vs 80%, NS) and 2-year survival was comparable for women and men (84% vs 80%, NS). Conclusion: No gender differences were observed in response to CRT and long-term survival after CRT. [ABSTRACT FROM AUTHOR]