Myocardial collagen metabolism in failing hearts before and during cardiac resynchronization therapy

BACKGROUND: In patients with heart failure cardiac resynchronization therapy (CRT) leads to reverse ventricular remodelling. AIM: To evaluate whether myocardial collagen metabolism in patients with heart failure is implicated in adverse ventricular remodelling and response to CRT. METHODS: Collagen synthesis and degradation were assessed from the concentrations of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP) and carboxyterminal telopeptide of type I collagen (ICTP), respectively, in serum of 64 patients with heart failure before and after 6 months of CRT. Forty-six patients (72%) showed a > 10% reduction in LV end-systolic volume at follow-up and were classified as responders to CRT, the other 18 patients (28%) were classified as non-responders. RESULTS: Responders demonstrated a mean (+/-SEM) increase of serum PINP and PIIINP during follow-up, from 32.9+/-2.2 to 46.7+/-4.0 microg/L (p < 0.001) and from 4.59+/-0.24 to 5.13+/-0.36 microg/L (p < 0.05), respectively. In non-responders, serum PINP and PIIINP remained unchanged during follow-up. At baseline, responders had significantly lower serum PINP than non-responders (32.9+/-2.2 vs. 41.8+/-4.3 microg/L; p < 0.05). ICTP levels of responders at baseline tended to be higher than in non-responders (3.54+/-0.56 vs. 2.08+/-0.37 microg/L, p = ns), and in both groups ICTP levels did not change upon CRT. CONCLUSION: Reverse LV remodelling following CRT is associated with increased collagen synthesis rate in the first 6 months of follow-up.     

Cardiac resynchronization therapy increases plasma levels of the endogenous inotrope apelin

BACKGROUND: Cardiac resynchronization therapy (CRT) has been introduced to treat drug refractory chronic heart failure (CHF). Apelin, the endogenous ligand of the APJ receptor, is under evaluation for its potential role in human CHF pathophysiology. This study aims to assess whether biventricular pacing affects plasma apelin levels in patients with severe CHF. METHODS AND RESULTS: Fourteen patients (9 men, 5 women, mean age 68+/-13 years) undergoing biventricular pace-maker/ICD implantation were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma apelin and NT-proBNP levels. The evaluation was repeated 48 h and 9+/-2 months after device implantation to assess the acute and chronic effects of CRT on apelin and NT-proBNP levels. Eight healthy age- and sex-matched subjects served as controls. In CHF patients, baseline apelin levels were reduced and NT-proBNP increased compared to control subjects (apelin: 0.47+/-0.2 vs. 0.97+/-0.3 ng/mL, p<0.001; NT-proBNP: 2007+/-114 vs. 229+/-72 pmol/L, p<0.001). Short-term evaluation did not reveal any effect of CRT on apelin or NT-proBNP levels. By contrast, at 9+/-2 months follow-up, CRT responders showed left ventricular reverse remodelling and an increase in ejection fraction, together with a significant increase in plasma apelin levels (0.99+/-0.1 vs. 0.47+/-0.2 ng/mL, p<0.001) and decrease in NT-proBNP (938+/-591 vs. 2007+/-114 pmol/L, p<0.05). CONCLUSIONS: Long-term CRT increases plasma levels of the endogenous inotrope apelin in patients with CHF.     

Differential change in left ventricular mass and regional wall thickness after cardiac resynchronization therapy for heart failure.

AIMS: LV reverse remodelling has been shown to be a favourable response after cardiac resynchronization therapy (CRT) in many clinical trials. This study investigated whether left ventricular (LV) reverse remodelling after CRT has any structural benefit, which include the improvement of LV mass or regional wall thickness. METHODS AND RESULTS: Fifty patients (66 +/- 11 years) receiving CRT were followed up for at least 3 months. Echocardiography with tissue Doppler imaging was performed serially before and at day 1 and 3 months after CRT. Although LV end-systolic volume (LVESV) was decreased at day 1 after CRT (141 +/- 74 vs. 129 +/- 71 cm(3), P < 0.001), further LV reverse remodelling was observed at 3 months (110 +/- 67 cm(3), P < 0.001 vs. day 1). LV ejection fraction increased at day 1 (26.5 +/- 9.3 vs. 28.5 +/- 9.1%, P < 0.005) and was further improved at 3 months (34.2 +/- 10.5%, P < 0.001 vs. day 1). However, reduction of LV mass (231 +/- 67 vs. 213 +/- 59 g, P < 0.001) and regional wall thickness was only observed at 3 months, but not at day 1. The improvement of LV mass correlated with the change in LVESV (r = 0.66, P < 0.001) and the baseline systolic asynchrony index (Ts-SD) (r = -0.52, P < 0.001). LV mass was only decreased significantly in responders of LV reverse remodelling (245 +/- 66 vs. 207 +/- 61 g, P < 0.001), but increased in non-responders (209 +/- 64 vs. 223 +/- 56 g, P = 0.02). Responders had significant decrease in thickness of all the four walls for -6 to -11% (all P < or =0.02), whereas non-responders had increased thickness in septal and lateral walls for +11% (both P < 0.05). CONCLUSION: The acute reduction in LV volume after CRT is mediated by haemodynamic and geometric benefits without actual changes in LV mass. However, at 3-month follow-up, reduction in LV mass and regional wall thickness was demonstrated, which represents structural reverse remodelling. Such benefit was only observed in volumetric responders but was worsened in non-responders.     

Impact of left ventricular lead position in cardiac resynchronization therapy on left ventricular remodelling. A circumferential strain analysis based on 2D echocardiography.

Aims: To assess if myocardial deformation imaging allows definition of an optimal left ventricular (LV) lead position with improved effectiveness of cardiac resynchronization therapy (CRT) on LV reverse remodelling. METHODS: Circumferential strain imaging based on tracking of acoustic markers within 2D echo images (GE Ultrasound) was performed in 47 heart failure patients (59 +/- 9 years, 28 men) at baseline, one day postoperatively, 3 and 10 months after initiation of CRT. Myocardial deformation imaging was used to determine(1) the segment with latest peak negative systolic circumferential strain prior to CRT, and(2) the segment with maximal temporal difference of peak strain before-to-on CRT as the segment with greatest benefit of CRT and assumed LV lead position. Anatomic LV lead position was determined by fluoroscopy. Optimal LV lead position was defined as concordance or immediate neighbouring of the segment with latest systolic strain prior to CRT and segment with assumed LV lead position. RESULTS: Agreement of assumed LV lead position based on strain analysis and LV lead position defined by fluoroscopy were high (kappa = 0.847). At 10 month follow-up, there was greater increase of EF (12 +/- 3 vs. 7 +/- 4%, P < 0.001), greater decrease of left ventricular end-diastolic volume (LVEDV) (23 +/- 8 vs. 13 +/- 7 mL, P < 0.001) and left ventricular end-systolic volume (LVESV) (42 +/- 10 vs. 27 +/- 8 mL, P < 0.001), and greater increase of VO(2)max (2.8 +/- 0.8 vs. 1.9 +/- 1.0 mL/kg/min, P = 0.035) in the optimal (n = 28 patients) compared to the non-optimal LV lead position group (n = 19 patients). The distance between segment with latest systolic strain prior to CRT and segment with assumed LV lead position was the only independent predictor of DeltaLVEDV and DeltaLVESV at 10 month follow-up (R(2) = 0.2175, P = 0.0197) and (R(2) = 0.3774, P = 0.0054), respectively. CONCLUSION: Detailed analysis of the myocardial contraction sequence using circumferential strain imaging allows determination of the LV lead position in CRT. Optimal LV lead position in CRT defined by circumferential strain analysis results in greater improvement in LV function and more LV reverse remodelling than non-optimal LV lead position.     

Predictive parameters of left ventricular reverse remodeling in response to cardiac resynchronization therapy in patients with severe congestive heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) is useful for the treatment of severe congestive heart failure. Unfortunately up to 30% of patients could be non-responders. The aim of our study was to find parameters to predict responsiveness to CRT. METHODS: Fifteen patients (9 males, 6 females, mean age 67.3 +/- 7.8 years, range 52-83 years) with dilated cardiomyopathy, NYHA functional class III-IV, left ventricular (LV) ejection fraction < 35% and QRS > or = 110 ms, underwent CRT. All the patients had echocardiographic evidence of systolic dys-synchrony. RESULTS: One patient died of electromechanical dissociation. The remaining 14 patients maintained biventricular stimulation at 6 months; mean QRS width decreased from 156 to 132 ms (p < 0.001). Ten patients (71%) were considered responders because of a reduction in LV end-systolic volume > 15%. In non-responders (4 patients, 29%) LV end-systolic volume was stable in 3 patients and increased in 1. LV ejection fraction significantly increased only in responders (p < 0.001). Responders had more severe pre-pacing dyssynchrony than non-responders (p < 0.001). Inter- (p = 0.002) and intraventricular dyssynchrony (p = 0.003) did significantly reduce after CRT only in responders. On multiple regression analysis there were two independent predictors of reverse remodeling after pacing: the baseline mitral QS-tricuspid QS (QSm-QSt) time (B = -1.7, p = 0.005) and the intraventricular dyssynchrony index (B = -1.55, p = 0.007). Pre-implant QSm-QSt of 38 ms correctly identified the two groups: responders had a value > 38 ms and non-responders < 38 ms. The pre-implant intraventricular dyssynchrony index of 28 ms was the cut-off value: responders had an index > 28 ms, non-responders < 28 ms. CONCLUSIONS: In the literature a tissue Doppler imaging index of intraventricular dyssynchrony evaluated before implantation is used to select responders to CRT. In our work we studied interventricular and intraventricular dyssynchrony, and both the QSm-QSt time and the standard deviation of the 12 LV segment QS time were correctly able to identify responders.     

Importance of contractile reserve for CRT.

AIMS: To assess whether response to cardiac resynchronization therapy (CRT) is related to myocardial viability in the paced left ventricular (LV) region, evaluated by contractile reserve (CR). Non-response to CRT may partly be due to inefficient pacing by the LV lead located in a fibrotic area. METHODS AND RESULTS: Nineteen patients (64 +/- 13 years, 14 men, 9 ischaemic) with severe heart failure (EF = 27 +/- 8%, QRS = 154 +/- 25 ms) were included in the week after device implantation. Stroke volume (SV) and LV dyssynchrony (by Tissue Doppler Imaging) were successively assessed with CRT on and CRT off. Afterwards, CRT device was maintained off during dobutamine infusion to assess CR in the LV-pacing region. LV end-systolic volume (ESV) was assessed after 6 months to quantify reverse remodelling. CR in the paced LV region (n = 10, 5/9 ischaemic and 5/10 non-ischaemic) was correlated to a reduction in LV dyssynchrony under CRT (120 +/- 76 vs. 78 +/- 64 ms, P = 0.02). Conversely, LV dyssynchrony was unchanged (161 +/- 100 vs. 163 +/- 80 ms) without CR. In desynchronized patients (>65 ms, n = 15), increase in SV under CRT and changes in ESV at 6 months were +22 and -18%, respectively, when CR was present and 0% and +9%, respectively, when absent. CONCLUSION: Acute haemodynamic response and reverse remodelling under CRT require viability in the target region of LV lead.     

心脏再同步治疗术中测试腔内心电图参数的临床意义

目的 探讨心脏再同步治疗（CRT）术中测定腔内心电图参数,尤其是左心室激动延迟时间是否可以预测心力衰竭患者左心室逆重构发生.方法 2009年1月至2013年1月37例完全性左束支阻滞患者在天津市胸科医院心内科植入CRT,术中测试窦性心律自身传导情况下右心室-左心室导线的激动时间差（△t）,测试右心室导线起搏到左心室导线感知时间（RVp-LV）及左心室导线起搏到右心室导线感知时间（LVp-RV）.随访观察1年,比较术前、术后心脏结构变化,以左心室舒张末期容积减小15％或射血分数提高5％为标准分为CRT应答组和无应答组.结果 左心室逆重构的发生与术中测试腔内心电图△t、RVp-LV、LVp-RV等参数均无明显关系,△t与术前QRS时限有关,RVp-LV、LVp-RV在左心室舒张末期内径（LVEDD） ＞75 mm的患者中长于LVEDD≤75 mm的患者（P＜0.05）.左心室导线植入在左心室基底部、中段、心尖部的患者发生左心室逆重构的比例分别为71.4％、90.4％、12.5％,差异有统计学意义（P＜0.05）,3个部位的△t、RVp-LV、LVp-RV差异无统计学意义.结论 术中测定腔内心电图相关参数不能预测CRT是否应答,左心室导线位置仍是决定CRT疗效的关键因素.     

Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study.

AIM: To describe temporal profiles of plasma matrix metalloproteinases (MMP-2 and MMP-9), and their relationship with echocardiographic (Echo) parameters of left ventricular (LV) function and remodelling, after acute myocardial infarction (AMI) in man. METHODS AND RESULTS: Plasma MMP-2 and MMP-9 were assayed at intervals (0-12, 12-24, 24-48, 48-72, 72-96, and > 96 h) in 91 patients with AMI (ST-elevation/non-ST-elevation 77/24; 73% male; 40% anterior site) and on a single occasion in 172 age- and sex-matched control subjects with stable coronary artery disease. Echo assessment of LV volumes, LV ejection fraction (LVEF), and wall motion index score were assessed before discharge and at follow-up (median 176, range 138-262 days) for patients and on a single occassion in controls. Plasma MMP-2 was similar at all times after AMI, elevated when compared with control (P = 0.005-0.001) and unrelated to LV function or volume during index admission or at follow-up. Maximal MMP-9 was seen at 0-12 h and was elevated when compared with control (P = 0.002) followed by fall to a plateau. Both maximal and plateau MMP-9 concentration correlated with white blood cell (WBC, P = 0.023 to < 0.001) and neutrophil count (P = 0.014 to < 0.001). Maximal MMP-9 had independent predictive value for lower LVEF (P = 0.004) during admission and for greater change in LV end-diastolic volume between admission and follow-up (R = 0.3, P = 0.016). In contrast, higher plateau levels of MMP-9 were associated with relative preservation of LV function (increasing LVEF, P = 0.002; decreasing WMIS, P = 0.009) and less change in end-systolic volume and end-diastolic volumes after discharge (P = 0.001 and 0.024, respectively). CONCLUSION: Both MMP-9 and MMP-2 are elevated following AMI. The biphasic profile of plasma MMP-9 is related to LV remodelling and function following AMI in man. Higher early levels of MMP-9 associate with the extent of LV remodelling and circulating WBC levels. In contrast, higher plateau levels later after AMI are associated with relative preservation of LV function. Temporal profile, rather than absolute magnitude, of MMP-9 activity appears to be important for LV remodelling after AMI.     

Burden of atrial fibrillation after cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) may diminish atrial fibrillation (AF) burden in patients with chronic heart failure (HF). Each of 27 patients without permanent AF in whom CRT implantation was unsuccessful was paired with 2 active CRT patients-1 responder and 1 nonresponder-based on age, gender, cause of HF, and history of paroxysmal AF. Device-documented high atrial rates and mode-switching episodes were tabulated during a median follow-up of 386 days. CRT responders had significantly improved left ventricular (LV) ejection fraction and New York Heart Association functional class compared with nonresponders and controls. Left atrial dimension change was similar among the groups (+0.03 +/- 0.92 cm controls; -0.18 +/- 0.80 cm responders; -0.11 +/- 1.01 cm nonresponders) despite a significant reduction in mitral regurgitation in responders compared with nonresponders. There was no significant difference in AF burden between controls and patients who underewent CRT when indexed over time. Median AF-free follow-up was significantly longer in patients who underwent CRT without a history of AF (log-rank p = 0.04), but no differences were seen in the overall cohorts. In conclusion, despite inducing LV reverse remodeling and clinical improvement, CRT does not appear to decrease AF burden in responders compared with nonresponders or matched controls in whom CRT implantation failed. CRT may, however, delay onset of new AF.     

Utility of a new left ventricular asynchrony index as a predictor of reverse remodelling after cardiac resynchronization therapy.

AIMS: The majority of tissue Doppler indexes proposed to predict left ventricular (LV) reverse remodelling in cardiac resynchronization therapy (CRT) reflects LV asynchrony as assessed in ejection phase. We evaluated the predictive value of a new strain-imaging parameter reflecting the total amount of time spent by 12 LV segments in contracting after aortic valve closure. METHODS AND RESULTS: Fifty-nine patients who fulfilled current treatment recommendations were studied before and 6 months after CRT. Time to tissue Doppler systolic peak velocity (Ts) and time exceeding aortic closure (ExcT) in strain curves were measured in 12 LV segments. Ts standard deviation (Ts-SD) and sum of ExcT of overall 12 LV segments (oExcT) were analysed. After 6 months, responders were defined according to > or =15% LV end-systolic volume reduction. Responders (47%) when compared with non-responders (53%) had significantly higher baseline Ts-SD and oExcT values. Receiver operating characteristic (ROC) curve analysis demonstrated that an optimal cutoff value of 760 ms for oExcT yielded 93.5% sensitivity and 82.8% specificity. For Ts-SD at the cutoff of 32 ms, 82% sensitivity and 39% specificity were obtained. Area under ROC was significantly larger for oExcT than for Ts-SD. CONCLUSION: o-ExcT is able to predict LV reverse remodelling after CRT.     

Echocardiographic evaluation of patients with severe heart failure and impairment of intraventricular conduction following cardiac resynchronisation therapy

BACKGROUND: Echocardiographic examination is essential for clinical assessment of patients after cardiac resynchronisation therapy (CRT). AIM: To assess the benefit of CRT in patients with end-stage heart failure at long-term follow-up. METHODS: 28 patients with end-stage heart failure, NYHA class >or= III (>or= II in patients with indications for implantable cardioverter defibrillator and echocardiographic signs of ventricular mechanical systolic dyssynchrony), left ventricular ejection fraction (LVEF) <35%, QRS duration >120 ms and left bundle branch block morphology received a biventricular device. Standard colour Doppler echocardiography examination was performed at baseline, and then every 6 months, up to 2 years. Parameters of systolic and diastolic LV function, mitral insufficiency and right ventricular (RV) pressure were evaluated. RESULTS: Following CRT, a statistically significant improvement of LV dimensions (p<0.05), and LVEF (p<0.001) was recorded. CRT also resulted in a mitral regurgitation decrement (p<0.01). Interventricular mechanical delay was shortened (p=0.0005). After 2 years, non-significant worsening of LV dimensions was observed. At long-term follow-up CRT did not result in LV volume, left atrium, RV dimension or RV pressure reduction. CONCLUSIONS:CRT is associated with reverse remodelling of the LV at mid-term follow-up.     

Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy

OBJECTIVES: This study was designed to predict the response and prognosis after cardiac resynchronization therapy (CRT) in patients with end-stage heart failure (HF). BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Patients with LV dyssynchrony >/=65 ms respond to CRT and have an excellent prognosis after CRT.     

Reverse of left ventricular volumetric and structural remodeling in heart failure patients treated with cardiac resynchronization therapy

Patients with heart failure and mechanical dyssynchrony suffer a progressive increase in left ventricular (LV) mass and asymmetrical regional hypertrophy with eventual poor prognosis. The present study sought to investigate whether cardiac resynchronization therapy (CRT) could reverse these abnormalities. The study included 66 consecutive heart failure patients who received CRT. All patients underwent serial evaluation before, 3 months after, and 12 months after CRT. At 12 months after CRT, 50 patients (76%) were echocardiographic volumetric responders, defined as a >15% reduction in LV end-systolic volume. LV end-systolic volume was decreased from 214 +/- 97 ml to 179 +/- 88 ml at 3 months and was further decreased to 158 +/- 86 ml at 12 months after CRT (all p <0.01). LV ejection fraction was improved from 18% +/- 4% to 28% +/- 7% (p <0.001) at 3 months without further change at 12 months after CRT. LV mass was reduced from 242 +/- 52 g to 222 +/- 45 g at 3 months and was further reduced to 206 +/- 50 g at 12 months after CRT (all p <0.01). Improvement of LV geometry was seen as improvements of the end-diastolic (1.64 +/- 0.14 vs 1.77 +/- 0.17, p <0.001) and the end-systolic (1.63 +/- 0.14 vs 1.99 +/- 0.22, p <0.001) sphericity indexes, respectively, at 3 months, without further significant changes at 12 months after CRT. Volumetric responders had a reduction in LV mass from 240 +/- 50 to 210 +/- 38 at 3 months, and LV mass was further reduced to 186 +/- 37 g at 12 months after CRT (all p <0.01). In contrast, nonresponders had a progressive increase in LV mass from 248 +/- 59 g to 258 +/- 54 g at 3 months, and LV mass was further increased to 269 +/- 60 g at 12 months after CRT (all p <0.05). Likewise, only in volumetric responders, regression of the asymmetric hypertrophy of the lateral wall was noted. In conclusion, CRT results in not only volumetric improvement but also in true reverse LV structural remodeling, evidenced by progressive reduction in LV mass and restoration of regional wall symmetry.     

Relation of response to cardiac resynchronization therapy to left ventricular reverse remodeling

Cardiac resynchronization therapy (CRT) reverses left ventricular (LV) remodeling in patients with congestive heart failure. However, the mechanisms leading to the clinical response to CRT remain unclear. The aim of this study was to analyze whether patients who improve clinically have greater LV reverse remodeling than nonresponders after a 12-month follow-up period. The sample comprised 64 consecutive patients with heart failure, complete left bundle branch block, and LV ejection fractions (EFs) < or =35% who were treated with CRT. Doppler echocardiographic scans were taken just before and immediately after the implantation of the pacemakers and at 6- and 12-month follow-up examinations. LV diameters, volumes, and EFs were compared. Responders were defined as those patients who were alive without cardiac transplantation and with > or =10% improvement in the 6-minute walking test after 1 year of follow-up. There were no clinical differences at baseline between responders and nonresponders. At 6- and 12-month follow-up, LV dimensions decreased significantly in responders but did not change in nonresponders. Furthermore, LVEFs improved only in responders. In conclusion, patients who clinically respond to CRT have greater LV reverse remodeling than nonresponders after 6 and 12 months of follow-up. The effect of CRT on LV remodeling may explain, at least in part, the clinical benefit of this therapy.     

NT-proBNP response to dobutamine stress echocardiography predicts left ventricular contractile reserve in dilated cardiomyopathy

BACKGROUND: Brain natriuretic peptide (BNP) and left ventricular (LV) inotropic reserve are major prognostic indexes in heart failure (HF). AIMS: To investigate the relationship between N-terminal-proBNP (NT-proBNP) changes in response to dobutamine stress echocardiography (DSE) and the LV inotropic reserve, in HF patients with dilated cardiomyopathy (DC). METHODS: We studied 41 patients with DC, LVEF 31.6+/-7.7%, NYHA class II-III and 15 controls. Plasma NT-proBNP levels were measured before and 60 min after three 5-min stages of dobutamine (5 to 15 microg/kg/min). RESULTS: Based on NT-proBNP changes in response to dobutamine, patients were categorized into two groups: In Group A circulating NT-proBNP levels fell (-16.6+/-7.8%), and in Group B they increased (8.4+/-9.1%). Group A had a marked improvement in WMSI compared to Group B (32.1+/-9.7% vs. 18.8+/-15.9%, p<0.001). Multivariate analysis showed that NT-proBNP changes were an independent predictor of LV inotropic reserve (b= -0.55, p<0.001). A reduction of 21.3% in plasma NT-proBNP levels in response to dobutamine predicted an improvement in WMSI of >25% with a sensitivity of 100% and a specificity of 92.3%. CONCLUSIONS: NT-proBNP changes in response to dobutamine reflect improvement in LV contractility and constitute an independent predictor of LV inotropic reserve in patients with DC.     

Left ventricular dyssynchrony predicts right ventricular remodeling after cardiac resynchronization therapy.

OBJECTIVES: The purpose of this research was to evaluate right ventricular (RV) remodeling after six months of cardiac resynchronization therapy (CRT). BACKGROUND: Cardiac resynchronization therapy is beneficial in patients with end-stage heart failure. The effect of CRT on RV size is currently unknown. Accordingly, the effects of CRT on RV size, severity of tricuspid regurgitation, and pulmonary artery pressure were evaluated. METHODS: Fifty-six consecutive patients with end-stage heart failure (52% ischemic cardiomyopathy), left ventricular (LV) ejection fraction (EF) < or =35%, QRS duration >120 ms, and left bundle branch block were included. Clinical parameters, LV volumes, LVEF, LV dyssynchrony, and RV chamber size were assessed at baseline and after six months of CRT; LV dyssynchrony was assessed using tissue Doppler imaging. RESULTS: Clinical parameters improved significantly; LV dyssynchrony was acutely reduced after CRT and remained unchanged at six-month follow-up. Left ventricular EF improved significantly from 19 +/- 6% to 26 +/- 8% (p < 0.001), and LV end-diastolic volume decreased from 257 +/- 98 ml to 227 +/- 86 ml (p < 0.001). Right ventricular annulus decreased significantly from 37 +/- 9 mm to 32 +/- 10 mm, RV short-axis from 29 +/- 11 mm to 26 +/- 7 mm, and RV long-axis from 89 +/- 11 mm to 82 +/- 10 mm (all p < 0.001). Left ventricular and RV reverse remodeling were only observed in patients with substantial LV dyssynchrony at baseline. Finally, significant reductions in severity of tricuspid regurgitation and pulmonary artery pressure were observed. CONCLUSIONS: Cardiac resynchronization therapy results in significant reverse LV and RV remodeling after six months of CRT in patients with LV dyssynchrony. Moreover, CRT leads to a reduction of the severity of tricuspid regurgitation and a decrease in pulmonary artery pressure.     

Baseline Doppler parameters are useful predictors of chronic left ventricular reduction in size by cardiac resynchronization therapy.

AIMS: The identification of responders to cardiac resynchronization therapy (CRT) in patients with left ventricular (LV) dysfunction and left bundle branch block (LBBB) remains difficult. We aimed to define the predictive value of conventional Doppler parameters. METHODS AND RESULTS: In 73 patients (65 +/- 9 years, 51 male, 36 ischaemic, 37 non-ischaemic cardiomyopathy, QRS 167 +/- 31 ms, LVEF 23 +/- 6%) with LBBB, a CRT device was implanted. LV pre-ejection interval (PEI), interventricular mechanical delay (IVMD), LV filling time (FT), and myocardial performance index (MPI) were assessed at baseline and on optimized CRT. Left ventricular end-diastolic diameter (EDD) was obtained at baseline and after 10.6 +/- 6.7 months. end-diastolic diameter diminished from 66.3 +/- 8.1 to 59.9 +/- 9.6 mm (P < 0.001). Initial LVPEI (r = 0.41, P < 0.001), baseline IVMD (r = 0.34, P = 0.003), acute LVPEI shortening (r = 0.33, P = 0.006), and baseline LVEDD (r = 0.32, P = 0.007) correlated with LVEDD reduction. An LVPEI > or =140 ms had a 82% accuracy to predict long-term LVEDD reduction (sensitivity 86%, specificity 67%, positive and negative predictive values 91 and 56%, respectively). Multivariate analysis solely revealed baseline LVPEI as predictor of LVEDD reduction. FT and MPI correlated only with their respective improvements. CONCLUSION: Left ventricular pre-ejection interval and IVMD predict favourable LV remodelling on CRT. The additional application of tissue Doppler parameters may further increase specificity and negative predictive value.     

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

AIMS: To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. METHODS: Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. RESULTS: At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). CONCLUSIONS: Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.     

Early and late effects of cardiac resynchronization therapy on exercise-induced mitral regurgitation: relationship with left ventricular dyssynchrony, remodelling and cardiopulmonary performance.

AIMS: Exercise-induced mitral regurgitation (MR) bears a poor prognosis in patients with congestive heart failure (CHF). Cardiac resynchronization therapy (CRT) is associated with improved clinical outcome but its effects on exercise-induced MR remain undetermined. We investigated serial changes in functional MR in relation to left ventricular (LV) remodelling and cardiopulmonary performance after CRT. METHODS AND RESULTS: Twenty-eight patients with CHF (LV ejection fraction 25 +/- 7%), broad QRS complex (171 +/- 27 ms), and at least mild MR [effective regurgitant orifice (ERO) 0.25 +/- 0.12 cm2] were studied with quantitative exercise echocardiography and cardiopulmonary exercise testing prior, within 1 week, and 3 months after CRT. Early after CRT, a decrease in LV dyssynchrony (from 54 +/- 21 to 19 +/- 7 ms, P < 0.001) and in MR at rest (ERO from 0.25 +/- 0.12 to 0.20 +/- 0.10 cm2, P = 0.047) was observed. However, no change in exercise-induced increase in MR was observed (ERO from 0.34 +/- 0.12 to 0.31 +/- 0.16 cm2, NS). Three months after CRT, a decrease in the mitral valve tenting area (from 3.3 +/- 1.2 to 2.0 +/- 0.6 cm2, P < 0.001) and an increase in LV sphericity index (from 1.5 +/- 0.3 to 1.8 +/- 0.5, P < 0.001) were paralleled by an attenuation of exercise-induced MR (ERO 0.19 +/- 0.06 cm(2), P = 0.001 vs. prior CRT). This was associated with an increase in LV ejection fraction (from 25 +/- 7 to 35 +/- 9%, P < 0.001), peak oxygen uptake (from 11.7 +/- 2.4 to 13.7 +/- 3.8 mL/kg/min, P = 0.001), and a decrease in Nt-pro-BNP (from 2777 +/- 1681 to 1963 +/- 1361 pg/mL, P = 0.067). CONCLUSION: CRT is associated with acute decrease in resting MR but does not immediately attenuate exercise-induced MR. In contrast, only late, CRT-induced reversed LV remodelling and reduced mitral apparatus deformation are associated with a reduction in both resting and exercise-induced MR and with an improvement in cardiopulmonary performance.     

Mechanism of improvement in mitral regurgitation after cardiac resynchronization therapy.

AIMS: The aim of the current study was to evaluate the relationship between the presence of left ventricular (LV) dyssynchrony at baseline and acute vs. late improvement in mitral regurgitation (MR) after cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Sixty eight patients consecutive (LV ejection fraction 23 +/- 8%) with at least moderate MR (>or=grade 2+) were included. Echocardiography was performed at baseline, 1 day after CRT initiation and at 6 months follow-up. Speckle tracking radial strain was used to assess LV dyssynchrony at baseline. The majority of patients improved in MR after CRT, with 43% improving immediately after CRT, and 20% improving late (after 6 months) after CRT. Early and late responders had similar extent of LV dyssynchrony (209 +/- 115 ms vs. 190 +/- 118 ms, P = NS); however, the site of latest activation in early responders was mostly inferior or posterior (adjacent to the posterior papillary muscle), whereas the lateral wall was the latest activated segment in late responders. CONCLUSION: Current data suggest that the presence of baseline LV dyssynchrony is related to improvement in MR after CRT. LV dyssynchrony involving the posterior papillary muscle may lead to an immediate reduction in MR, whereas LV dyssynchrony in the lateral wall resulted in late response to CRT.