Cardiac memory in cardiac resynchronization therapy: A vectorcardiographic comparison of biventricular and left ventricular pacing.

INTRODUCTION: "Cardiac memory" (CM) refers to a change in repolarization induced by an altered pathway of activation, manifested after resumption of spontaneous ventricular activation (SVA). AIMS: To investigate for the first time in humans the effects of left ventricular (LV) pacing on CM development through vectorcardiography (VCG). METHODS: We studied 28 patients with heart failure (HF) and left bundle branch block (LBBB) treated with cardiac resynchronization therapy (CRT). Fourteen patients underwent biventricular (BIV) stimulation; the other 14 underwent LV stimulation only. VCG was acquired during SVA at baseline and during AAI and DDD pacing immediately after and 7 and 90 days after the implant. RESULTS: At baseline, in both groups, the QRS and T vectors angles were those specific of LBBB pattern. During DDD pacing, QRS vector angle changed to the right and upward in BIV patients while no significant differences were observed in LV patients. During AAI pacing, T vector angle changed significantly in BIV patients, following the direction of the paced QRS and amplitude significantly increased. In LV patients no significant differences in T vector angles were observed. Only T vector amplitude significantly increased at 7 days (p=0.03) and at 90 days (p=0.008 vs baseline). CONCLUSION: In patients with LBBB, BIV pacing induces cardiac memory development as a significant change in T vector magnitude and angle, while LV pacing doesn't induce significant modifications in QRS and T vector angles and CM is manifested only as a significant T vector amplitude change.

Prognostic value of natriuretic peptides and restrictive filling pattern before surgical ventricular restoration.

OBJECTIVE: Both increased natriuretic peptide levels and restrictive filling pattern (RFP) are important risk predictors in patients with heart failure. The aim of this study was to examine the role of the combined use of natriuretic peptide and RFP for the prognostic stratification of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration in the Biomarker Plus study. METHODS: A total of 186 patients (aged 64 ± 10 years) underwent echocardiographic study and N-terminal pro-B-type natriuretic peptide assay at baseline (before surgical ventricular restoration). Patients were divided into 4 groups depending on baseline diastolic filling pattern (RFP/no RFP) and N-terminal pro-B-type natriuretic peptide level (less than or greater than or equal to the upper tertile value of 2003 ŋg/L). RFP was defined as E/A ratio ≥2. All-cause death or heart failure hospitalizations within 36-month follow-up were analyzed. RESULTS: Despite similar ejection fraction, volumes, and mass, the 4 groups presented distinct clinical and structural pattern of presurgical ventricular restoration ventricular remodeling and significantly different clinical outcome after surgical unloading. During follow-up, 67 patients died or were hospitalized for heart failure (36%). High N-terminal pro-B-type natriuretic peptide levels and RFP, considered individually, were significantly associated with outcome (P < .0001). The combination of both was associated with the highest adjusted hazard of adverse events (hazard ratio, 3.63; 95% CI, 1.73-7.6; P < .0001). CONCLUSIONS: The simultaneous use of 2 markers, 1 biological and 1 echocardiographic, may allow better prognostic stratification and characterization of the distinct structural and clinical phenotypes in a population of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration. This approach could be useful in the decision-making process to guide treatment choices in patients with ischemic cardiomyopathy.

Restrictive filling pattern in ischemic cardiomyopathy: Insights after surgical ventricular restoration.

OBJECTIVE: To examine factors possibly involved in the resolution or persistence of restrictive filling pattern (RFP) after surgical ventricular restoration (SVR) in a series of patients with ischemic cardiomyopathy (ICM) and RFP. METHODS: Echocardiography was performed at baseline (pre-SVR), discharge, and follow-up in 43 patients with ICM and RFP (E/A ratio ≥2). Patients were divided into 2 groups based on E/A ratio at discharge: improved (E/A ratio <2; 22 patients) and unchanged (E/A ratio ≥2; 21 patients). RESULTS: The improved group had a significantly increased mean deceleration time (from 137 ± 22 ms to 194 ± 68 ms; P = .002) and mean A wave velocity (from 43 ± 10 cm/s to 92 ± 37 cm/s; P = .001), and decreased E/e' ratio (from 27.7 ± 9.5 to 19.2 ± 7.8; P = .01) after SVR. The unchanged group did not show any significant variations in diastolic parameters. The only significant differences at baseline between the two groups were thinner left ventricle posterior wall and lower relative wall thickness (RWT) in the unchanged group. RWT was the sole baseline parameter independently associated with persistent RFP. CONCLUSIONS: RFP was reversed after SVR in 22 of our 43 patients with ICM with a response that remained stable over time, associated with improved New York Heart Association class. RWT was the sole baseline echocardiographic parameter significantly associated with the evolution of RFP after SVR.

Improvements in Regional Left Ventricular Function Following Late Percutaneous Coronary Intervention for Anterior Myocardial Infarction.

BACKGROUND: Late revascularization following a myocardial infarction has questionable clinical benefit. METHODS: We studied 13 patients with anterior wall myocardial infarction who underwent percutaneous coronary intervention within 2 weeks of the primary event, by quantitative analysis of 2-dimensional echocardiographic images. Endocardial segmentations of the left ventricular (LV) endocardium from the 4-chamber views were studied over time to establish cumulative wall displacements (CWDs) throughout the cardiac cycle. RESULTS: Left ventricular end-systolic volume decreased to 42 ± 8 mL/body surface area (P = .034) and LV ejection fraction improved to 52% ± 7% (P = .04). Analysis of LV endocardial CWD demonstrated significant improvements in mid-systolic to late-systolic phases in the apical LV segments, from 3.5 ± 0.32 to 5.89 ± 0.43 mm (P = .019). Improvements in CWD were also observed in the late-diastolic phase of the cardiac cycle, from 1.50 ± 0.42 to 1.76 ± 0.52 mm (P = .04). CONCLUSIONS: In our pilot patient cohort, following late establishment of infarct-related artery patency following an anterior wall myocardial infarction, regional improvements were noted in the LV apical segments during systole and late diastole.

Surgical ventricular restoration improves mechanical intraventricular dyssynchrony in ischemic cardiomyopathy.

BACKGROUND: In ischemic cardiomyopathy, dyssynchrony of left ventricular (LV) mechanical contraction produces adverse hemodynamic consequences. This study tests the capacity of geometric rebuilding by surgical ventricular restoration (SVR) to restore a more synchronous contractile pattern after a mechanical, rather than electrical, intervention. METHODS AND RESULTS: A prospective study of the global and regional components of dyssynchrony was conducted in 30 patients (58+/-8 years of age) undergoing SVR at the Cardiothoracic Center of Monaco. The protocol used simultaneous measurements of ventricular volumes and pressure to construct pressure/volume (P/V) and pressure/length (P/L) loops. Angiograms were done before and after SVR to study a 600-ms cycle during atrial pacing at 100 bpm. Mean QRS duration was similar, at 100+/-17 ms preoperatively and 114+/-28 ms postoperatively (NS). Preoperative LV contraction was highly asynchronous, because P/V loops showed abnormal isometric phases with a right shifting. Endocardial time motion was either early or delayed at the end-systolic phase so that P/L loops were markedly abnormal in size, shape, and orientation. Postoperatively, SVR resulted in leftward shifting of P/V loops and increased area; endocardial time motion and P/L loops almost normalized to allow a better contribution of single regions to global ejection. The hemodynamic consequences of SVR were improved ejection fraction (30+/-13% to 45+/-12%; P=0.001); reduced end-diastolic and end-systolic volume index (202+/-76 to 122+/-48 and 144+/-69 to 69+/-40 mL/m(2); P=0.001); more rapid peak filling rate (1.75+/-0.7 to 2.32+/-0.7 EDV/s; P=0.0001); peak ejection rate (1.7+/-0.7 to 2.6+/-0.9 Sv/s; P=0.0002), and mechanical efficiency (0.56+/-0.15 to 0.65+/-0.18; P=0.04). CONCLUSIONS: SVR produces a mechanical intraventricular resynchronization that improves LV performance.

Mitral effective regurgitant orifice area versus left ventricular ejection fraction as prognostic indicators in patients with dilated cardiomyopathy and heart failure.

BACKGROUND: This study aimed at investigating the relative powers of the quantitative evaluation of functional mitral regurgitation (FMR) and ejection fraction (EF) in predicting the clinical changes and prognosis of dilated cardiomyopathy (DCM) with severe systolic dysfunction. METHODS: A total of 81 patients with DCM, EF < 0.40 and at least mild FMR were prospectively evaluated during a mean follow-up of 24 +/- 7 months. Twenty cardiac deaths were recorded. At the time of enrolment all patients underwent echocardiographic evaluation of the effective regurgitant orifice area (ERO), EF, left atrial area, and tenting area. In 42/81 patients, the data obtained at enrolment were compared to those measured at a mean follow-up of 10 +/- 2 months. A multivariate analysis was performed to determine the best predictor of NYHA class and mortality. RESULTS: There was a correlation between the NYHA class and the ERO (chi2 = 26.1, p = 0.0001) but not with EF (chi2 = 4.3, p = 0.22) and at multivariate analysis, the ERO was found to be the main determinant of the NYHA class (r = 0.64, standard error 0.6, p = 0.0001). The NYHA class remained unchanged or improved in 28/42 (67%) and deteriorated in 14/42 (33%) patients. In the first group, the ERO increased from 22.3 +/- 10 to 30.2 +/- 16.4 mm2 (p = 0.05) and the tenting area from 5.8 +/- 1.8 to 6.8 +/- 1.8 cm2 (p = 0.001); in the second group, the ERO increased from 25.1 +/- 5.6 to 39.0 +/- 14.5 mm2 (p = 0.04) and the tenting area from 5.9 +/- 2.1 to 7.6 +/- 1.8 cm2 (p = 0.0001), in both groups without significant changes in EF. The mortality was 8.1% in patients with an ERO < 21 mm2, 30.3% in patients with an ERO of 21-30 mm2, and 50% in those with an ERO > 30 mm2. The EF was similar in the three subgroups. At Cox multivariate analysis the best predictors of mortality were the ERO (chi2 = 13.83, p = 0.0001), EF (chi2 = 5.48, p = 0.019), and left atrial area (chi2 = 4.52, p = 0.04). CONCLUSIONS: FMR in DCM well correlated with the clinical status of the patients and its worsening was suggestive of progression of the disease. The ERO was found to be the best predictor of the NYHA class and mortality.

Characterization of dysfunctional remote myocardium in left ventricular anterior aneurysms and improvements following surgical ventricular restoration using cardiac magnetic resonance imaging: preliminary results.

OBJECTIVES: In patients with previous myocardial infarction, the remote uninfarcted regions, although contractile, demonstrate dysfunctional wall kinetics because of increased afterload, which improves after surgical ventricular restoration (SVR). We characterized left ventricular (LV) mean myocardial velocity (MMV) through an analysis of endocardial motion and wall thickening (WT) over the cardiac cycle using standard cardiac magnetic resonance (cMR). METHODS: LV endocardial motion and WT from cMR data in 7 heart failure (HF) patients with postinfarction antero apical aneurysm were compared against normal controls to establish a baseline for the mean myocardial velocity during phases of the cardiac cycle. The HF patients' MMV and WT curves were compared with post-SVR data. RESULTS: Global MMV showed significant postoperative improvements in the ejection phase of systole and the early filling phase of diastole. The aneurysmal wall was dyskinetic in both systole and diastole. The remote myocardium preoperatively had a delayed peak velocity during the ejection phase of systole and diminished velocity during early filling in diastole. After SVR, the remote myocardium had an increased MMV with an earlier peaking during the ejection phase and slightly improved early diastolic velocity. WT increased cumulatively during systole and decreased during diastole with improved end-systolic and end-diastolic wall thickness after SVR. The end-systolic wall thickness showed a significant correlation with left ventricular ejection fraction (r(2) = 0.89, P = 0.001) and stroke volume (r(2) = 0.80, P = 0.02). The MMV had a significant correlation with WT over the phases of the cardiac cycle (r(2) = 0.953, P ≤ 0.0001). CONCLUSIONS: In patients with chronic ischaemic heart disease with LV aneurysms/large areas of scar, improvements in the remote myocardial MMV and WT underline LV systolic function improvements after SVR. The persistence of myocardial WT in early diastole is the likely mechanism for incomplete or absence of relief of LV diastolic dysfunction by SVR.

Cardiac memory in humans: vectocardiographic quantification in cardiac resynchronization therapy.

BACKGROUND: "Cardiac memory" (CM) refers to a change in repolarization induced by an altered pathway of activation. The effects of biventricular pacing on CM induction have not been investigated. OBJECTIVE: To investigate the development of CM during cardiac resynchronization therapy (CRT) through vectorcardiography (VCG). METHODS: Eleven patients undergoing CRT were enrolled. VCG was acquired during spontaneous ventricular activation at baseline and during AAI and DDD pacing immediately after and 7, 14, 21 and 60 days after the implantation. RESULTS: At 1-week follow-up, during AAI pacing T vector angles significantly changed (azimuth 23 ± 19°; p = 0.002; elevation 23 ± 27°; p = 0.019) and magnitude significantly increased (baseline 1.13 ± 0.69 mV; 7 days: 1.77 ± 1.27 mV; p = 0.026). T angle changes remained stable throughout the follow-up period while a further significant increase in magnitude was observed at 60 days (2.21 ± 1.50 mV; p = 0.01 vs. baseline and p = 0.04 vs. 7 days). Paced T vector magnitude at implant (2.24 ± 1.25 mV) decreased significantly at 7 days (1.64 ± 1.26 mV; p = 0.030) with a further significant decrease at 60 days (1.40 ± 1.18 mV; p = 0.003 vs. baseline; p = 0.02 vs. 7 days). CONCLUSION: CRT induces a significant change in T vector magnitude, azimuth, and elevation after resumption of spontaneous ventricular activation after 7 days from implantation. While further changes in T vector angle were not observed, after 2 months of CRT a significant decrease of paced T vector magnitude and a significant increase of spontaneous T vector magnitude were observed.

Impact of surgical ventricular reconstruction on stroke volume in patients with ischemic cardiomyopathy.

OBJECTIVE: Left ventricular end-diastolic volume is decreased and ejection fraction is increased after surgical ventricular reconstruction; however, the impact on left ventricular stroke volume is not well established. METHODS: We analyzed 248 consecutive patients who underwent surgical ventricular reconstruction at a single center. There were 14 perioperative deaths (5.6%). The 234 surviving patients had pre- and postsurgical ventricular reconstruction echocardiographic measurement of end-diastolic volume, end-systolic volume, and stroke volume, each indexed to body size and ejection fraction. A total of 120 patients had echocardiography data at follow-up (median 8 months). RESULTS: Overall, surgical ventricular reconstruction resulted in reductions in end-diastolic volume index (-30% ± 18%) and end-systolic volume index (-37% ± 20%), and increases in ejection fraction (21% ± 18% relative increase). However, stroke volume index decreased from 35 ± 8 mL/m(2) preoperatively to 28 ± 7 mL/m(2) early postoperatively (a 17% ± 24% relative reduction, P < .0001); 165 patients (71%) exhibited a decrease and 69 patients (29%) exhibited an increase or no change in stroke volume index after surgical ventricular reconstruction. Stroke volume index reduction was strictly related to end-diastolic volume reduction. Patients who initially had a stroke volume index decrease showed recovery, so that at the time of chronic follow-up there was no significant difference between the groups. Notably, 4-year survival was approximately 85% and did not differ between patients with an increase or decrease in stroke volume index (P = .383). CONCLUSIONS: Although surgical ventricular reconstruction uniformly results in an impressive decrease in end-diastolic volume index and increase in ejection fraction, seemingly indicating beneficial remodeling and improved pump function, systolic volume index, which more directly indexes cardiac pump function, frequently decreases after surgical ventricular reconstruction. Further study is needed to identify baseline characteristics that predict those patients in whom cardiac performance is enhanced by surgical ventricular reconstruction and to clarify whether there is a beneficial impact on exercise tolerance and cardiac output at peak exercise.

Left ventricular shape and function in primary coronary angioplasty.

OBJECTIVES: To evaluate the effects of primary coronary angioplasty (PCA) on regional left ventricular (LV) contractile dysfunction and deformation, and on global remodeling. METHODS: In 99 consecutive patients (81 males, aged 61+/-11 years) who underwent successful PCA of left anterior descending (LAD) and right coronary (RCA) arteries for treatment of first myocardial infarction and completed a hemodynamic follow-up at 1 and 6 months, LV eccentricity and circularity indexes, centreline wall motion and regional curvature were analyzed. Asynergy and akinesia were defined as centreline impairment -1 standard deviation) at 6 months was used to categorize the outcome as improved. RESULTS: Systolic deformation and impairment of regional LV function soon after LAD and RCA occlusion closely resembled those of the chronic myocardial infarction. PCA improved regional contractility in all patients, due to early salvage of the epicardial injured myocardium, and at least in two fifths of patients the injury area magnitude reduced by improvement of the ischemic boundaries of the infarct. Irrespective of either persistently impaired or normalized regional contractility, LV shape remained abnormal. In contract to the persistence of local deformation, global remodeling was observed in patients categorized as the highest end-diastolic volume quartile at presentation who had greater myocardial damage. CONCLUSION: Regional contractility impairment induced by acute myocardial infarction can be reverted by PCA, but systolic shape deformation persists over time.

Rate stabilization by right ventricular apex or His bundle pacing in patients with atrial fibrillation.

AIMS: In patients with atrial fibrillation right ventricular pacing can block antegrade conduction at pacing intervals longer than the shortest spontaneous R-R interval, causing the stabilization of ventricular rhythm. In this study the effects of pacing at two sites were compared in order to evaluate the role of conduction times in determining the stabilization of ventricular rhythm. METHODS: In eight patients with permanent atrial fibrillation, the ventricular rate was recorded before and during pacing at the right ventricular apex and the His bundle with different cycle lengths. RESULTS: In all patients, we obtained a reduction in spontaneous QRS complexes with respect to those anticipated at pacing rates slightly above the spontaneous mean rate, and the ventricular rhythm stabilized at pacing intervals longer than the spontaneous shortest R-R intervals. Between pacing sites we did not observe any difference in the reduction in spontaneous beats and the cycle stabilizing the rhythm. Moreover, simulation of the interaction between antegrade and retrograde impulses in a computer model confirmed that results obtained by pacing at the His bundle cannot be readily explained as a consequence of conduction delays. CONCLUSION: This study suggests that the lag introduced by the His-Purkinje conduction cannot explain, as proposed, the stabilization of ventricular rhythm observed in patients with atrial fibrillation and right ventricular pacing.

A perspective on atrioventricular delay optimization in patients with a dual chamber pacemaker.

Atrioventricular delay (AVD) is critical in patients with DDD pacemakers (PM). Echo/Doppler evaluation of AVD providing the longest left ventricular filling time (FT) or the highest cardiac output (CO) is used for AVD optimization. Recently myocardial performance index (MPI) has been shown to improve by optimizing AVD. The aim was to compare the CO, FT, MPI derived optimal AVD, and to analyze systolic and diastolic performance at every optimal AVD. Twenty-five patients, 16 men 68 +/- 11 years, ejection fraction >or= 50%, with a DDD PM for third-degree AV block, without other major cardiomyopathies, underwent echo/Doppler AVD optimization. CO, FT, and MPI derived optimal AVDs were identified as the AVDs providing the highest CO, the longest FT, and the minimum MPI, respectively. Isovolumic contraction and relaxation time (ICT, IRT), ejection time (ET), ICT/ET, and IRT/ET ratios were also evaluated at every optimal AVD. CO, FT, and MPI derived optimal AVDs were significantly different (148 +/- 36 ms, 116 +/- 34 ms, and 127 +/- 33 ms, respectively). ICT/ET was similar at CO, FT, and MPI derived optimal AVD (0.22 +/- 0.10, 0.23 +/- 0.11, and 0.21 +/- 0.10, respectively). IRT/ET ratio was similar at FT and MPI derived optimal AVDs (0.34 +/- 0.15 and 0.33 +/- 0.15, respectively) and significantly shorter (P < 0.02) than at CO derived optimal AVD (0.40 +/- 0.15). Different methods indicate different optimal AVDs. However analysis of systolic and diastolic performance shows that different AVDs result in similar systolic or diastolic performance. At MPI optimized AVD, a high CO combined with the most advantageous conditions of both isovolumic contraction and relaxation phases is achieved.