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Objectives: The purpose of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in heart failure patients with narrow QRS complex (<120 ms) and evidence of left ventricular (LV) dyssynchrony on tissue Doppler imaging (TDI)., Background: Cardiac resynchronization therapy is beneficial in selected heart failure patients with wide QRS complex (> or =120 ms). Patients with narrow QRS complex are currently not eligible for CRT, and the potential effects of CRT are not well studied., Methods: Thirty-three consecutive patients with narrow QRS complex and 33 consecutive patients with wide QRS complex (control group) were prospectively included. All patients needed to have LV dyssynchrony > or =65 ms on TDI, New York Heart Association (NYHA) functional class III/IV heart failure, and LV ejection fraction < or =35%., Results: Baseline characteristics, particularly LV dyssynchrony, were comparable between patients with narrow and wide QRS complex (110 +/- 8 ms vs. 175 +/- 22 ms; p = NS). No significant relationship was observed between baseline QRS duration and LV dyssynchrony (r = 0.21; p = NS). The improvement in clinical symptoms and LV reverse remodeling was comparable between patients with narrow and wide QRS complex (mean NYHA functional class reduction 0.9 +/- 0.6 vs. 1.1 +/- 0.6 [p = NS] and mean LV end-systolic volume reduction 39 +/- 34 ml vs. 44 +/- 46 ml [p = NS])., Conclusions: Cardiac resynchronization therapy appears to be beneficial in patients with narrow QRS complex and severe LV dyssynchrony on TDI, with similar improvement in symptoms and comparable LV reverse remodeling to patients with wide QRS complex. The current results need confirmation in larger patient cohorts.

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]

Human mesenchymal stem cells (hMSCs) have only a limited differentiation potential toward cardiomyocytes. Forced expression of the cardiomyogenic transcription factor myocardin may stimulate hMSCs to acquire a cardiomyogenic phenotype, thereby improving their possible therapeutic potential. hMSCs were transduced with green fluorescent protein (GFP) and myocardin (hMSCmyoc) or GFP and empty vector (hMSC). After coronary ligation in immune-compromised NOD/scid mice, hMSCmyoc (n = 10), hMSC (n = 10), or medium only (n = 12) was injected into the infarct area. Sham-operated mice (n = 12) were used to determine baseline characteristics. Left ventricular (LV) volumes and ejection fraction (EF) were serially (days 2 and 14) assessed using 9.4-T magnetic resonance imaging. LV pressure-volume measurements were performed at day 15, followed by histological evaluation. At day 2, no differences in infarct size, LV volumes, or EF were observed among the myocardial infarction groups. At day 14, left ventricular ejection fraction in both cell-treated groups was preserved compared with the nontreated group; in addition, hMSCmyoc injection also reduced LV volumes compared with medium injection (p < .05). Furthermore, pressure-volume measurements revealed a significantly better LV function after hMSCmyoc injection compared with hMSC treatment. Immunohistochemistry at day 15 demonstrated that the engraftment rate was higher in the hMSCmyoc group compared with the hMSC group (p < .05). Furthermore, these cells expressed a number of cardiomyocyte-specific markers not observed in the hMSC group. After myocardial infarction, injection of hMSCmyoc improved LV function and limited LV remodeling, effects not observed after injection of hMSC. Furthermore, forced myocardin expression improved engraftment and induced a cardiomyocyte-like phenotype hMSC differentiation. [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]

Background: Coronary angiography is considered the gold standard in evaluating vein graft disease; however, angiography does not allow assessment of hemodynamic consequences of lesions. In this study hemodynamic consequences of significant stenoses in vein grafts were evaluated by Doppler velocity assessment, and results were compared with single photon emission computed tomography (SPECT) perfusion imaging.Methods and Results: Angiography was performed in 58 patients after coronary artery bypass grafting because of recurrent chest pain. During the procedure, Doppler velocity measurements were acquired before and after administration of adenosine. Of 58 patients (with 78 vein grafts), 20 patients (with 24 vein grafts) underwent SPECT perfusion imaging. Grafts were divided into those with nonsignificant percent diameter stenosis (< 50%) (n = 49) and those with significant percent diameter stenosis (> or =50%) (n = 29). When a cutoff value for coronary flow velocity reserve (CFVR) of 1.8 was applied, modest agreement (69%, kappa = 0.25, P < .05) between CFVR and angiography was shown. Agreement between SPECT and angiography was also modest (63%, kappa = 0.28, P = not significant). SPECT and CFVR provided comparable information in 20 of 24 grafts with available SPECT, illustrating good agreement (83%, kappa = 0.61, P = .001).Conclusions: Significant stenoses in vein grafts require further exploration to assess their hemodynamic significance. The Doppler velocity results agreed better with SPECT perfusion imaging than with percent diameter stenosis in the evaluation of vein graft function. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the relationship between right atrial (RA) reservoir and conduit function and to determine how hemodynamic changes influence this relationship and its impact on cardiac output. In 11 open-chest sheep, RA reservoir and conduit function were quantified as RA inflow with the tricuspid valve closed versus open. respectively. Conduit function was separated into early (before A wave) and late (after A wave) components. The effects of inotropic stimulation, partial pulmonary artery occlusion, and pericardiotomy were tested. At baseline with the pericardium intact, reservoir function accounted for 0.56 (SD 0.13) of RA inflow, early conduit for 0.29 (SD 0.07), and late conduit (during RA contraction) for 0.16 (SD 0.11). Inotropic stimulation decreased conduit function and increased reservoir function, but these effects did not reach statistical significance. With partial pulmonary artery occlusion, early conduit function fell to 0.20 (SD 0.11) (P < 0.04), and the conduit-to-reservoir ratio decreased by 41% (P < 0.03). Similarly, after pericardiotomy, early conduit function fell to 0.14 (SD 0.09) (P < 0.004), reservoir function increased to 0.72 (SD 0.08) (P < 0.04), and, consequently, the early conduit-to-reservoir ratio decreased by 63% (P < 0.006). Cardiac output was inversely related to the conduit-to-reservoir ratio (r = 0.39, P < 0.001). This study demonstrated that the right atrium adjusts its ability to act more as a reservoir than a conduit in a dynamic manner. The RA conduit-to-reservoir ratio was directly related to the right ventricular pressure-RA pressure gradient at the time of maximum RA volume, with increased ventricular pressures favoring conduit function, but it was inversely related to cardiac output, with an increase in the reservoir contribution favoring improved cardiac output. [ABSTRACT FROM AUTHOR]

MOLHOEK, S.G., et al.: QRS Duration and Shortening to Predict Clinical Response to Cardiac Resynchronization Therapy in Patients with End-Stage Heart Failure. Despite current selection criteria (NYHA Class III–IV, LVEF < 35%, QRS > 120 ms with LBBB), 30% of patients do not benefit from cardiac resynchronization therapy (CRT). The use of QRS duration as selection criteria for CRT has not been evaluated systematically yet. Accordingly, the value of QRS duration at baseline (and reduction in QRS duration after CRT) to predict responders was studied. Patients were evaluated at baseline and after 6 months of CRT for NYHA Class, quality of life score, and 6-minute walk test. QRS duration was evaluated before, directly after implantation, and after 6 months of CRT. Sixty-one patients were included; 45 (74%) patients were classified as responders (improvement of NYHA Class, 6-minute walking distance and quality of life score) and 16 (26%) as nonresponders. QRS duration at baseline was similar between the two groups: 179 ± 30 ms versus 171 ± 32 ms, NS. Directly after implantation, QRS duration was reduced from 179 ± 30 ms to 150 ± 26 ms (P < 0.01) in responders; nonresponders did not exhibit this reduction (171 ± 32 ms vs 160 ± 26 ms, NS). After 6 months of CRT, QRS shortening was only observed in responders (from 179 ± 30 ms to 159 ± 25 ms, P < 0.01). ROC curve analysis showed that a reduction in QRS duration > 10 ms had a high sensitivity (73%) with low specificity (44%); conversely, a > 50 ms reduction in QRS duration was highly specific (88%) but not sensitive (18%) to predict response to CRT. No optimal cutoff value could be defined. QRS duration at baseline is not predictive for response to CRT; responders exhibit a significant reduction in QRS duration after CRT, but individual response varies highly, not allowing adequate selection of responders. (PACE 2004; 27:308–313) [ABSTRACT FROM AUTHOR]

Quantification of left ventricular mechanical dyssynchrony by conductance catheter in heart failure patients. Am J Physiol Heart Circ Physiol 286: H723–H730, 2004. First published October 9, 2003; 10.1152/ajpheart.00555. 2003.—Mechanical dyssynchrony is an important codeterminant of cardiac dysfunction in heart failure. Treatment, either medical, surgical, or by pacing, may improve cardiac function partly by improving mechanical synchrony. Consequently, the quantification of ventricular mechanical (dys)synchrony may have important diagnostic and prognostic value and may help to determine optimal therapy. Therefore, we introduced new indexes to quantify temporal and spatial aspects of mechanical dyssynchrony derived from online segmental conductance catheter signals obtained during diagnostic cardiac catheterization. To test the feasibility and usefulness of our approach, we determined cardiac function and left ventricular mechanical dyssynchrony by the conductance catheter in heart failure patients with intraventricular conduction delay (n = 12) and in patients with coronary artery disease (n = 6) and relatively preserved left ventricular function. The heart failure patients showed depressed systolic and diastolic function. However, the most marked hemodynamic differences between the groups were found for mechanical dyssynchrony, indicating a high sensitivity and specificity of the new indexes. Comparison of conductance catheter-derived indexes with septal-to-lateral dyssynchrony derived by tissue-Doppler velocity imaging showed highly significant correlations. The proposed indexes provide additional, new, and quantitative information on temporal and spatial aspects of mechanical dyssynchrony. They may refine diagnosis of cardiac dysfunction and evaluation of interventions, and ultimately help to select optimal therapy. [ABSTRACT FROM AUTHOR]

Background Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in systolic heart failure patients. Conflicting data exist on the interaction of RV function and left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). This prospective monocentric trial was set up to assess the predictive value of baseline RV function and corresponding RV-pulmonary artery (PA) coupling on LV reverse remodeling after CRT. Methods 110 patients with a CRT indication were prospectively enrolled. RV function and RV-PA interaction were analyzed at baseline using echocardiographic and invasive pressure-volume loop catheter approach. The primary endpoint was reverse LV remodeling (CRT-responder) defined as a reduction in LV end-systolic volume of ≥15% at 6 months. Results Responders had higher RV-PA coupling ratios (single-beat end-systolic elastance/PA elastance: Ees/Ea) at baseline, which corresponded to smaller RVs with better ejection fraction and lower afterload. After multivariate adjustment, the baseline Ees/Ea remained an independent predictor for LV response (OR 14.0 [1.5–130.8], p  = 0.021). Normal coupling (Ees/Ea ≥ 1) was associated with higher responder rates (RR) (86%). Progressive uncoupling was associated with lower LV-RR (Ees/Ea ≤ 1–0.5: 57%, and Ees/Ea < 0.5: 32%, p  < 0.001), corresponded with higher degrees of LV impairment and severity of mitral regurgitation, and was independently associated with an adverse outcome. Conclusions A higher baseline RV-PA coupling, reflecting a lower degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with an improved LV-reverse remodeling and is independently associated with better prognosis. The value of RV-PA ratio as potential guide for CRT patient selection warrants further investigation. Clinical Trial Registration – URL: http://www.drks.de . Unique Identifier: DRKS00011133. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) is beneficial in selected patients with moderate to severe heart failure (New York Heart Association [NYHA] classes III to IV). Patients with mildly symptomatic heart failure (NYHA class II) are currently not eligible for CRT and the potential beneficial effects in these patients have not been well studied. Fifty consecutive patients in NYHA class II heart failure and 50 consecutive patients in NYHA classes III to IV (control group) were prospectively included. All patients had left ventricular (LV) ejection fraction ≤35% and QRS duration >120 ms. The effects of CRT in NYHA class II patients were compared with the results obtained in both groups. The severity of baseline LV dyssynchrony (assessed with color-coded tissue Doppler imaging) was comparable between patients in NYHA class II versus those in NYHA classes III to IV (83 ± 49 vs 96 ± 51 ms, p = NS); resynchronization was achieved in all patients. NYHA class II patients showed a significant improvement in LV ejection fraction (from 25 ± 7% to 33 ± 10%, p <0.001) and reduction in LV end-systolic volume (from 168 ± 55 to 132 ± 51 ml, p <0.001) after CRT, similar to patients in NYHA classes III to IV. In addition, only 8% of NYHA class II patients had progression of heart failure symptoms. In conclusion, CRT had comparable effects in patients in NYHA class II and in NYHA classes III to IV heart failure in terms of LV resynchronization, improvement in LV ejection fraction, and LV reverse remodeling. [Copyright &y& Elsevier]

The effect of long-term cardiac resynchronization therapy (CRT) was evaluated in 32 patients with heart failure (HF) and diabetes mellitus (DM) compared with 65 patients with HF and no DM. Clinical parameters were obtained before and after 6 months of CRT. Long-term follow-up was performed &#60;2 years after implantation. [Copyright &y& Elsevier]

We evaluated whether long-term cardiac resynchronization therapy affects the inducibility of ventricular tachyarrhythmias in relation to reverse remodeling in cardiac arrest survivors with either ischemic or idiopathic dilated cardiomyopathy. Clinical, electrophysiologic, and echocardiographic data of 18 patients were obtained before and after 6 months of cardiac resynchronization. [Copyright &y& Elsevier]

Cardiac resynchronization therapy (CRT) is a new therapeutic option for patients who have drug-refractory end-stage heart failure. Much information has been obtained from patients who have sinus rhythm, but the use of CRT in patients who have chronic atrial fibrillation (AF) has not been studied extensively. Accordingly, we evaluated the clinical response and long-term survival rate of CRT in patients who had heart failure and chronic AF, and the results were compared with those in patients who had sinus rhythm and who underwent CRT. Sixty patients who had end-stage heart failure (30 had sinus rhythm and 30 had chronic AF), New York Heart Association classes III to IV, left ventricular ejection fraction &#60;35%, QRS interval >120 ms, and a left bundle branch block received a biventricular pacemaker. New York Heart Association class, Minnesota Quality of Life score, and 6-minute walking distance were evaluated at baseline and after 6 months of CRT. Long-term follow-up was ≤2 years. New York Heart Association class, Minnesota Quality of Life score, and 6-minute walking distance improved significantly in the 2 groups after 6 months of CRT. The number of nonresponders was greater among patients who had AF. Nevertheless, the long-term survival rate was comparable between patients who had sinus rhythm and those who had AF. Patients who had AF demonstrated comparable benefit from CRT as those who had sinus rhythm. [Copyright &y& Elsevier]

This study was designed to predict the response and prognosis after cardiac resynchronization therapy (CRT) in patients with end-stage heart failure (HF).Cardiac resynchronization therapy improves HF symptoms, exercise capacity, and left ventricular (LV) function. Because not all patients respond, preimplantation identification of responders is needed. In the present study, response to CRT was predicted by the presence of LV dyssynchrony assessed by tissue Doppler imaging. Moreover, the prognostic value of LV dyssynchrony in patients undergoing CRT was assessed.Eighty-five patients with end-stage HF, QRS duration >120 ms, and left bundle-branch block were evaluated by tissue Doppler imaging before CRT. At baseline and six months follow-up, New York Heart Association functional class, quality of life and 6-min walking distance, LV volumes, and LV ejection fraction were determined. Events (death, hospitalization for decompensated HF) were obtained during one-year follow-up.Responders (74%) and nonresponders (26%) had comparable baseline characteristics, except for a larger dyssynchrony in responders (87 ± 49 ms vs. 35 ± 20 ms, p < 0.01). Receiver-operator characteristic curve analysis demonstrated that an optimal cutoff value of 65 ms for LV dyssynchrony yielded a sensitivity and specificity of 80% to predict clinical improvement and of 92% to predict LV reverse remodeling. Patients with dyssynchrony ≥65 ms had an excellent prognosis (6% event rate) after CRT as compared with a 50% event rate in patients with dyssynchrony <65 ms (p < 0.001).Patients with LV dyssynchrony ≥65 ms respond to CRT and have an excellent prognosis after CRT. [Copyright &y& Elsevier]

In the present study, the effects of cardiac resynchronization therapy (CRT) in elderly patients were evaluated. The study included 170 consecutive patients whose clinical and echocardiographic improvements were evaluated after 6 months of follow-up. Survival was evaluated up to 2 years. The effects of CRT in elderly patients (age ≥70 years) were compared with those in younger patients (age &#60;70 years). [Copyright &y& Elsevier]

Cardiac resynchronization therapy (CRT) is considered a major advance in the treatment of patients with heart failure. The presence of left ventricular (LV) dyssynchrony seems mandatory for a positive response to CRT. Currently, only patients with wide QRS complexes are considered for CRT, although patients with narrow QRS complexes may also have LV dyssynchrony. In the present study, the incidence of LV dyssynchrony was prospectively evaluated in 64 patients with heart failure and narrow QRS complexes using tissue Doppler imaging. [Copyright &y& Elsevier]