C Parsai

Toward understanding response to cardiac resynchronization therapy: left ventricular dyssynchrony is only one of multiple mechanisms

AIM To date, most published echocardiographic methods have assessed left ventricular (LV) dyssynchrony (DYS) alone as a predictor for response to cardiac resynchronization therapy (CRT). We hypothesized that the response is instead dictated by multiple correctable factors. METHODS AND RESULTS A total of 161 patients (66 +/- 10 years, EF 24 +/- 6%, QRS > 120 ms) were investigated pre- and post-CRT (median of 6 months). Reduction in NYHA Class >/=1 or LV reverse remodelling (end-systolic volume reduction >/= 10%) defined response. Four different pathological mechanisms were identified. Group1: LVDYS characterized by a pre-ejection septal flash (SF) (87 patients, 54%). Elimination of SF (77 of 87 patients) resulted in reverse remodelling in 100%. Group 2: short-AV delay (21 patients, 13%) resolution (19 of 21 patients) resulted in reverse remodelling in 16 of 19. Group 3: long-AV delay (16 patients, 10%) resolution (14 of 16 patients) resulted in NYHA Class reduction >/=1 in 11 with reverse remodelling in five patients. Group 4: exaggerated LV-RV interaction (15 patients, 9%) reduced post-CRT. All responded clinically with fall in pulmonary artery pressure (P = 0.003) but did not volume respond. Group 5: patients with none of the above correctable mechanisms (22 patients, 14%). None responded to CRT. CONCLUSION CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.

Low-dose dobutamine stress echo to quantify the degree of remodelling after cardiac resynchronization therapy

AIMS Presence of contractile reserve during low-dose dobutamine stress echo (DSE) appears predictive of cardiac resynchronization therapy (CRT) outcome. We hypothesize that changes in left bundle branch block (LBBB)-induced dyssynchronous motion during low-dose DSE could be related to the extent of reverse remodelling. METHODS AND RESULTS Fifty-two patients (69 +/- 2 years, EF: 24 +/- 7%, QRS > 120 ms) were studied pre- and post-CRT (7 +/- 1 months). Reduction in left ventricular end-systolic volume (LVESV) >/=10% defined response. A clinical improvement was sought additionally prior to implant and after CRT (NYHA class reduction >1), increase in 6 min walk test (>10%), and fall in BNP (>/=30%). To identify the presence of septal scar and its impact on our assessment during low-dose DSE, a cardiac magnetic resonance was performed pre-CRT. Presence of an abnormal short-lived septal motion occurring during the isovolumic contraction time [septal flash (SF)] identified LBBB-induced dyssynchrony. Septal flash extent was quantified from M-mode and radial velocity traces. At baseline, 31/52 patients had an SF. In all patients, DSE increased SF. Twenty-nine out of thirty-one patients responded with reverse remodelling post-CRT. The degree of peak low-dose stress SF correlated with the extent of reverse remodelling (R = 0.6, P < 0.0001). Additionally, SF increase correlated with greater fall in BNP post-CRT (R = 0.4, P = 0.01). Among patients with no SF at rest (21/52 patients), low-dose DSE induced an SF and a fall in stroke volume (SV) in five patients who all showed reverse remodelling after CRT. With low-dose DSE, the remaining 16 patients all failed to demonstrate a SF, and all but one patient with additional atrioventricular dyssynchrony were non-responders. CONCLUSION Low-dose DSE increases and unmasks LBBB-induced dyssynchronous motion, easing its detection. The degree of clinical and echocardiographic response correlated with the extent of peak SF seen during low-dose DSE.

How to detect early left atrial remodelling and dysfunction in mild-to-moderate hypertension.

Background and objectives Early changes in left atrial function in hypertension are difficult to assess quantitatively. Measuring atrial reversal flow into the pulmonary veins and regional left atrial deformation parameters assessed by Tissue Doppler-derived strain/rate (S/SR) imaging could provide quantitative assessment of left atrial deformation. We aimed to quantify changes in left atrial volume and deformation and pulmonary flow reversal (PVREVERS) in hypertension to detect subclinical left atrial dysfunction. Design, setting and patients In 74 hypertensive and 34 age-matched normotensive patients (mean age 49 ± 1.4 vs. 44.2 ± 2.1 years) echo studies were performed, including measurements of LAV during reservoir, conduit and pump phases and standard indices reflecting left ventricular filling. S/SR was measured in the lateral left atrial wall. Total deformation (STOTAL) and the contribution to early (SE-index) and late (SA-index) filling were calculated. Results Hypertensive patients had significantly impaired diastolic function and increased left atrial volume during all phases. Only LAVCONDUIT significantly correlated with both ventricular hypertrophy and parameters of diastolic function. Velocity time integral of PVREVERS correlated with blood pressure and LAVCONDUIT. In hypertensive patients STOTAL was significantly higher (54.9 ± 2.6 vs. 45.5 ± 2.7%, P < 0.03) and SE-index was lower (P < 0.0001). This was compensated for by an increased SA-index (P < 0.0001) and SR during atrial contraction (−4.9 ± 0.2 vs. −2.9 ± 0.3 1/s, P < 0.0001). SA-index correlated significantly with blood pressure (R = 0.4; P < 0.0001) and PVREVERS (R = 0.3; P < 0.001). Conclusion Changes in left atrial function due to hypertensive diastolic impairment are best reflected by LAVCONDUIT expansion. Hypertensive atrial dilatation is related to increase in PVREVERS. Left atrial S/SR offers a clinically valuable approach to detecting subclinical atrial dysfunction.

Interventricular interaction as a possible mechanism for the presence of a biphasic systolic velocity profile in normal left ventricular free walls

Background: In normal subjects, systolic longitudinal regional velocity profiles (SVP) (measured both based on pulsed or tissue Doppler) have a non-uniform pattern. SVP from the right ventricle (RV), the septal (Sep) and the inferior wall are similar in shape and tend to be monophasic. Their shape differs markedly from the lateral wall (LW), the posterior wall and the anterior wall, which are biphasic. We studied the hypothesis that the double-peaked SVP in the left ventricular free walls are caused by interventricular interaction. This might have additional implication in understanding the measurements of the timing of SVP maxima in pathology as, for example, used to determine intraventricular dyssynchrony in heart failure. Methods: 38 healthy individuals underwent a standard echo examination and a tissue Doppler study. SVP from the RV, Sep and LW basal segments were acquired in an apical four-chamber view. The amplitude and timing of the peak velocities were measured. If a double peak was present, the amplitude and timing of the dip was calculated. Results: RV and Sep had a single systolic velocity peak, while the LW had two peaks with a clear dip between both peaks. The first peak in the LW was the earliest event in the cycle (119 (19) ms) followed by the peak Sep (123 (20) ms; p = 0.34). Peak RV velocity occurred at the same time as the dip in the LW (200 (30) vs 203 (30) ms, respectively; p = 0.53). Conclusion: Our study suggests that the biphasic SVP in the free walls is probably caused by interventricular interaction. Therefore the timing of maxima on SVP should be used with great caution when looking for intraventricular dyssynchrony as the peaks are influenced by RV function.

The shape of the aortic outflow velocity profile revisited: is there a relation between its asymmetry and ventricular function in coronary artery disease?

AIMS Myocardium contracts in the beginning of ejection causing outflow acceleration, resulting in asymmetric outflow velocity profiles peaking around one-third of ejection and declining when force development declines. This article aimed to demonstrate that decreased contractility in coronary artery disease (CAD) changes outflow timing and profile symmetry. METHODS AND RESULTS Seventy-nine patients undergoing routine full dose dobutamine stress-echo (DSE) were divided into two groups based on resting wall motion and DSE response: DSE negative (DSE(neg)) (35 of 79 patients) and positive (DSE(pos)) (44 of 79 patients) which were compared with 32 healthy volunteers. Aortic CW-Doppler traces at rest were analysed semi-automatically; time-to-peak (T(mod)), ejection-time (ET(mod)), rise-time (t(rise)), and fall-time (t(fall)) were quantified. Asymmetry (asymm) was calculated as the normalized difference of left and right half of the spectrum. Normal curves were triangular, early-peaking, whereas patients showed more rounded shapes and later peaks. T(rise) was longest in DSE(pos). T(fall) was shortest in DSE(pos), followed by controls and DSE(neg). Asymm was lowest in DSE(pos), followed by controls and DSE(neg). Abnormally symmetric profiles (asymm <0.25) were found in none of the controls, 2.9% DSE(neg), and 27.3% DSE(pos). A good correlation was found between assym and ejection fraction (EF) and T(mod)/ET(mod) and EF. Notably, an LV dynamic gradient was induced in 71.4% DSE(neg) and in 18.2% DSE(pos), associated with LV hypertrophy and supernormal (very asymmetric) traces. CONCLUSION Decreased myocardial function results in a more symmetrical outflow, while very asymmetrical traces suggest increased contractility, potentially inducing intra-cavity gradients during DSE. Therefore, including outflow symmetry as a clinical measurement provides additional information on patients with CAD.

An integrated framework for the assessment of cardiac function - Description and illustrated applications

Assessing myocardial function is a difficult task in clinical practice. Routinely, (systolic) cardiac function is mostly quantified based on ejection fraction, a measure of the volume fraction of the left ventricle being ejected with each cardiac cycle. However, this approach has a lot of limitations since normal ejection fraction can occur while there are clearly functional abnormalities, while a reduced value does not say anything about what is wrong with the heart muscle. Recently, echocardiographic strain (-rate) imaging has been introduced, enabling the regional quantification of myocardial deformation. However, local deformation is also influenced by a number of factors and therefore does not necessarily represent local contractile force development. In this paper, we present an integrated framework, describing intrinsic cardiac function in its relationship with the boundary conditions. To illustrate how this framework can be used to study and understand cardiac function, two applications are discussed (regional ischemia and left bundle branch block). These applications are illustrated with simulations of regional deformation profiles.

915 The second regional systolic shortening found in LV lateral wall motion is due to ventricular interaction and should not be used to infer late contraction in this wall when studying LV dysynchrony

Variations in regional systolic velocity profiles (SVP) have been widely used to assess cardiac dyssynchrony. However, regional longitudinal SVP have a non-uniform pattern. SVP in the septum (SEP) and inferior wall are similar being mono-phasic with an early systolic peak. In contrast, SVP in the anterior (ANT) and lateral (LAT) walls differ, being bi-phasic with two systolic peaks. Thus when assessing the timing of delayed contraction in the ANT and LAT walls it is important to know what each peak represents. Ventricular interaction could be responsible for the early deceleration of the first peak in ANT and LAT wall motion and could explain the bi-phasic systolic pattern. We postulated that early cessation of the first systolic motion and appearance of a second shortening motion in the LAT wall may be due either to a combination of cardiac twisting around the long axis of the heart and interaction with right ventricle (RV) contractility rather than local myocardial shortening. As regional strain rates (SR) but not velocities (VEL) reflect myocardial contractile function we investigated the relationship between regional peak systolic SR and SVP in the RV free wall, SEP and LAT wall. Methods: In 23 normals (age 45.5±2) long axis regional SVP and SR were obtained from the basal segments of RV, SEP and LAT. Time to max deceleration of the first peak was measured in the LAT and its relationship to RV peak SVP determined. In addition the time to peak VEL and SR in all walls was calculated. Results: The timing of peak SVP in the RV corresponded to the end of deceleration of the first peak in the LAT SVP (0.199±0.03 vs 0.197±0.03 s. p=NS). There was a consistent and significant difference between the time to peak systolic VEL in LAT vs RV (0.130±0.02 vs 0.199±0.03 s, p<0.001) with the SEP peak systolic VEL in an intermediate position at 0.154±0.03 s (p=NS vs RV and LAT). Systolic SR in all walls had a single peak which occurred in early systole with no significant difference between cardiac walls (0.100±0.02; 0.103±0.02; and 0.105±0.02 s in SEP, LAT and RV respectively). The second systolic peak in the LAT wall was not associated with any measurable deformation on the SR curve. Conclusions: This study showed that the early cessation of the first peak systolic VEL and second VEL peak in the LW wall is due to motion induced by RV contraction and does not represent LV contractile function. Furthermore, first rather second peak in LAT corresponds to peak systolic SR, which reflects true myocardial contraction. Therefore measurement of cardiac synchronization should not be based on SVP but rather on SR profiles.