Identification of responders to cardiac resynchronization therapy by contractile reserve during stress echocardiography

Aims The identification of responders to cardiac resynchronization therapy (CRT) remains a challenge. We assessed the role of dyssynchrony (DYS) and contractile reserve (CR) in identifying CRT responders. Methods and results Sixty-nine patients (55% with ischaemic aetiology) referred for CRT (ejection fraction 35%, New York Heart Association III, and QRS duration 120 ms) underwent baseline evaluation of DYS and dobutamine stress-echo [up to 40 mg/kg/min: CR was defined as a wall motion score index (WMSI) variation 0.20]. CRT responders were identified by clinical and/or echocardiographic [end-systolic volume (ESV) decrease 15%] follow-up criteria. During a median follow-up of 11 months, 46 patients (66%) were classified as clinical responders. Reverse remodelling was found in 34 of the 59 patients (58%) with echocardiographic follow-up. CR was present in 78% of clinical responders (P ? 0.001) and in 69% with reverse remodelling (P ? 0.005). DYS was equally present in the two groups. Reverse remodelling was correlated with rest-stress changes in ESV (r ? 0.439, P ? 0.003) and in WMSI (r ? 0.450, P ? 0.001), but not with DYS. CR (OR ? 6.2, 95% CI ? 1.4-27.6, P ? 0.015) was the best predictor of response to CRT. Conclusion Patients with CR show a favourable clinical and reverse LV remodelling response to CRT. This finding shifts the focus from electrical (dyssynchrony) to the myocardial substrate of functional response

CRT in Patients with Heart Failure: Time Course of Perfusion and Wall Motion Changes

In patients treated with CRT no data relative to the relationship between regional wall motion and perfusion and reverse remodelling of the left ventricle at short and medium term followup were available. To this aim, 36 heart failure patients were studied by G-SPECT before (T0), within 2 months (T1) and 6 months (T2) after CRT. A clinical followup was completed for 36 months. In 30/36 patients there was an improvement of NYHA Class at T1 that persisted at T2. G-SPECT showed significant improvement of perfusion at T1 in 92% of patients without further changes at T2. A reduction of LV volumes, an increase of EF and an improvement of regional wall motion and thickening were observed at T1 versus baseline, with only minor changes at T2. Moreover, baseline extension of perfusion defects was scarcely correlated with improvement after CRT. Finally, end diastolic volume, perfusion defect and diabetes mellitus were independent predictors of survival. The main effects of CRT on regional myocardial perfusion and wall motion are obtained within 2 months. Volume overload modulates recovery of ventricular function independently of reperfusion and, with extension of perfusion abnormalities and diabetes were independent predictors of survival during followup

Identification of responders to CRT by stress echo: no contractile reserve, no party

Background: Cardiac resynchronization therapy (CRT) is increasingly used, but the identification of "responders" remains challenging. Aim: to assess the value of inotropic reserve during pharmacological echo stress to identify responders. Materials and methods: We enrolled 32 patients (age 69?9 years; 9 females) referred to CRT, all with LV ejection fraction (LVEF) ≤35n %, NYHA ≥IIb and QRS duration ≥130 milliseconds. Twenty-two patients showed echocardiographic criteria for dyssynchrony (at least one of M-mode, Tissue Doppler, or live 3D echo criteria). All patients underwent pharmacological stress echo (dobutamine, up to 40 mcg/Kg/min in 29, dipyridamole 0.84 mg/kg 10 min, in 3). Patients were considered with contractile response if variation of WMSI (from 1=normal, to 4=dyskinetic, 17 segment model of left ventricle) stress-rest (delta WMSI) was ≥0.20. "Responders" to CRT were defined at 6 months follow-up as survivors with NYHA class improvement ≥1 grade and without new hospital admission for acute heart failure. Results: In the follow-up (median=20 months), 16 patients were responders to CRT (Group I) and 16 non-responders (Group II). Responders showed a wider QRS (I=162?25 vs. II=142 ?27 msec; p .044) and a greater delta WMSI (I=0.34?0.25 vs. II= 0.15?0.18; p=.021). At individual patient analysis, inotropic reserve was more often associated with a favourable clinical outcome (see figure) whereas dyssynchrony criteria by echocardiography were equally present in the two groups (I=12/16 vs. II=10/16, p=ns). In the follow-up there were 5 deaths, all in group II. Conclusion: Patients with contractile reserve during stress echo show a favourable clinical response to CRT. This parameter shifts the focus from electrical (dyssynchrony) to the myocardial substrate of functional response: no muscle, no party

Adrenomedullin plasma levels as predictors of left ventricular reverse remodelling in patients treated with cardiac resynchronization therapy

Purpose: Adrenomedullin (ADM), a potent natriuretic and vasorelaxing peptide, has been isolated from human pheochromocytoma cells and from cardiovascular tissue. Increase in ADM plasma levels in congestive heart failure (CHF) patients (pts) is due to many cardiac and systemic factors and in particular to the greater plasma volume and to the activation of sympathetic nervous system. Aim of this study was to assess the role of plasma ADM levels in CHF pts treated by cardiac resynchronization therapy (CRT). Methods: 42 pts, mean age 70 years, 27 males, NYHA Class III-IV CHF underwent CRT. Cause of CHF were idiopathic dilated cardiomyopathy in 27 pts, post ischemic in 15; all pts were in sinus rhythm and with complete left bundle branch block (QRS duration 138?8 msec). A complete echoDoppler exam, blood samples for brain natriuretic peptide (BNP) and ADM were obtained within 2 days before implantation. Results: At 18?6 months follow-up, >1 NYHA Class improvement was observed in 31/42 pts. However, a >10% reduction in end-systolic dimensions (ESD): -18.2?2.3% was reported in 16 pts (Group I); in the remaining 26 pts ESD change was almost negligible: -1.5?3.2% (Group II). The two groups were comparable for age, sex, cause of LV dysfunction, ongoing therapy, QRS duration at baseline, pre implantation ESD (60.6?1.8 vs 59.9?1.9 mm - Group I vs II), LVEF% (24.3?1.2 vs 25.4?1.3%) and BNP (545?80 vs 494?89 pg/ml). Significantly higher pre implantation ADM levels were present in Group I than in Group II (25.8?2.4 pmol/l vs. 17.1?1.6, p = 0.005). Conclusions: Significantly higher ADM levels indicate a subgroup of pts in whom significant reverse remodelling can be observed after CRT. Since AM is also produced in cardiac myocytes, lower ADM values before CRT could suggest the presence of more severe myocardial damage which may impair LV reverse remodelling even in the setting of clinically successful resynchronization

Subthreshold bipolar atrial stimulation affects the discharge rate of the sinus node: an animal study

Aim of this study was to verify whether the electrical field generated inside the right atrium by sub-threshold electrical impulses (impulses unable to induce cells activation) may condition the discharge rate of the sinus node cells. An electrophysiological study was performed on seven young farm pigs before and after denervation. After general anesthesia, pigs were stimulated with impulses delivered at constant rate by a bipolar catheter positioned inside the right atrium. The amplitude of the stimulus was set to avoid atrial capture. A 10-minute atrial stimulation was performed at a rate above and below the spontaneous heart rate, both before and after denervation. Three animals showed a conditioning of the sinus rhythm, observed as phase synchronization. The different response, or even the no response, of animals to stimulation could be due to different factors, concerning biological, pharmacological and "geometric" conditions. The important result remains that a perturbation of the sinus rhythm can be induced by a very low electrical field, as the one generated by the activity of artificial pacemakers, and it could help explaining the onset of rhythm disturbances in paced patients

SYNCHRONIZATION INDUCED BY PACED ATRIAL SUBTHRESHOLD STIMULATION ON THE SINUS NODE ACTIVITY IN ANIMAL EXPERIMENT

Synchronization is the well-known phenomenon that indicates adjustment of frequencies of weakly interacting self-sustained periodic oscillators [1]. Besides the physics environment, synchronization is often encountered even in physiological systems exhibiting oscillatory behaviour. Above all others, the heart, the biological oscillator par excellence, has been object of a number of investigations. At the cellular level interesting experiments were carried out on spontaneously beating aggregates of cardiac cells from embryonic chicken heart stimulated with single impulse or impulses of different amplitudes and frequencies [2]. These experiments evidenced the interaction between stimuli and cardiac cells activity in terms of phase resetting (single stimulus) and synchronization (train of impulses). Aim of this study was to verify whether the electrical field generated inside the right atrium by subthreshold electrical impulses (impulses unable to induce cells activation) may condition the discharge rate of the sinus node cell

Myocardial structural, perfusion and metabolic correlates of left bundle branch block mechanical derangement in patient with dilated cardiomyopathy

Background-Left bundle branch block (LBBB) influences upon regional left ventricular (LV) structure, perfusion and metabolism were not thoroughly investigated in dilated cardiomyopathy (DCM) patients. Methods and Results-Eleven DCM patients with LBBB (69?11 years, LV ejection fraction[EF]: 35?8%) and 7 DMC patients without LBBB (58?9 years, LV EF: 37?10%) were studied by cardiac magnetic resonance (CMR) and positron emission tomography (PET). Left ventricle was divided in 3 regions: septum, adjacent (anterior-inferior) and lateral. Regional midwall circumferential strain, maximum shortening (&#1013;peak) and strain rate were obtained from tagged CMR. Systolic stretch index (SSI) was calculated as positive strain rate (stretching) divided by total strain rate. Myocardial metabolic rate of glucose (MMRG), resting and hyperemic myocardial blood flow (MBF) were quantitated using 2-[18F]fluoro-2-deoxyglucose and [13N]ammonia PET, respectively. Conversely from non LBBB patients, LBBB patients showed highly inhomogeneous systolic deformation pattern which changed gradually moving from discoordinate [(SSI: 0.485 (0.284)] and poorly contracting (&#1013;peak: -1.14?0.96%) septum to coordinate [SSI: 0.002 (0.168)] and strongly contracting (&#1013;peak: -13.63?2.58%) lateral region (both P<0.0001). This pattern was closely matched to MMRG distribution disclosing lowest, intermediate and highest values respectively in the septum, adjacent and lateral regions (P<0.0001). Septal-to-lateral thickness ratio was lower in LBBB than non LBBB patients (P=0.03). In both groups, LV distribution of resting and hyperemic MBF and MBF reserve did not differ significantly. Conclusions-In DCM patients, the extensive LV contraction abnormalities induced by LBBB caused regional myocardial metabolic and structural remodeling without consistent changes in blood flows.-

Livelli plasmatici di adrenomedullina come indicatori di prognosi dopo terapia di resincronizzazione cardiaca

The cardiac resynchronization therapy (CRT), based on correction of electro-mechanical dyssynchrony by biventricular pacing in patientswith severe chronicHF unresponsive to optimalmedical treatment and left ventricular conduction disturbances, has been developed. The determination of plasma adrenomedullin (ADM) levels before implantation could provide important additional information to reduce the high percentage (30%) of patients not responding to treatment despite the use of increasingly sophisticatedmethods for selecting candidates. The case described illustrates the importance of basal ADM plasma levels in predicting the clinical and functional improvement after treatment with CRT