Direct haemodynamic effects of pulmonary arteriovenous malformation embolisation

Background

Transcatheter embolisation is widely used to close pulmonary arteriovenous malformations (PAVMs) in patients with hereditary haemorrhagic telangiectasia (HHT). Data on the direct cardiovascular haemodynamic changes induced by this treatment are scarce.

Objectives

We investigated the direct haemodynamic effects of transcatheter embolisation of PAVMs, using non-invasive finger pressure measurements.

Methods

During the procedure, blood pressure, heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and delta pressure/delta time (dP/dt) were continuously monitored using a Finometer®. Potential changes in these haemodynamic parameters were calculated from the pressure registrations using Modelflow® methodology. Absolute and relative changes were calculated and compared using the paired sample t-test.

Results

The present study includes 29 HHT patients (mean age 39?±?15 years, 11 men) who underwent transcatheter embolotherapy of PAVMs. The total number of embolisations was 72 (mean per patient 2.5). Directly after PAVM closure, SV and CO decreased significantly by ?11.9 % (p?=?0.01) and ?9.5 % (p?=?0.01) respectively, without a significant change in HR (1.8 %). Mean arterial blood pressure increased by 4.1 % (p?=?0.02), while the TPR and dP/dt did not increase significantly (5.8 % and 0.2 %, respectively).

Conclusions

Significant haemodynamic changes occur directly after transcatheter embolisation of PAVMs, amongst which a decrease in stroke volume and cardiac output are most important.     

The role of exercise echocardiography in the management of mitral valve disease

Purpose

Exercise echocardiography can assess the dynamic component of mitral valve (MV) disease and may therefore be helpful for the clinical decision-making by the heart team. The purpose of this study is to determine the role of exercise echocardiography in the management of disproportionately symptomatic or otherwise atypical patients with mitral regurgitation (MR) and stenosis (MS) in clinical practice.

Methods

Data of 14 MR and 14 MS patients, including echocardiograms at rest, were presented retrospectively to an experienced heart team to determine treatment strategy. Subsequently, exercise echo data were provided whereupon once again the treatment strategy was determined. This resulted in: value of exercise echo by means of 1) alteration or 2) confirmation of treatment strategy or 3) no additional value.

Results

During exercise the echocardiographic severity of MV disease increased in 9 (64 %) MR and 8 (57 %) MS patients. Based upon alteration or confirmation of the treatment strategy, the value of exercise echocardiography in the management of MR and MS was 86 % and 57 %, respectively.

Conclusion

This study showed that physical exercise echo can have an important role in the clinical decision-making of challenging patients with MV disease. Exercise echocardiography had additional value to the treatment strategy in 71 % of these patients.     

Exercise training programs in Dutch cardiac rehabilitation centres

Purpose

To assess methods for determination of exercise intensity, and to investigate practice variation with respect to the contents, volume and intensity of exercise training programs in Dutch cardiac rehabilitation (CR) centres.

Methods

A paper questionnaire was sent to all Dutch CR centres, consisting of 85 questions for patients with an acute coronary syndrome (ACS) or after coronary revascularisation (Group 1) and for patients with chronic heart failure (CHF, Group 2).

Results

CR professionals from 45 centres completed the questionnaires (58 %). Symptom-limited exercise testing was used to determine exercise capacity in 76 % and 64 % of the CR centres in group 1 and group 2, respectively; in these centres, a percentage of the maximum heart rate was the most frequently used exercise parameter (65 % and 56 %, respectively). All CR centres applied aerobic training and the majority applied strength training (64 % in group 1 and 92 % in group 2, respectively). There was a considerable variation in training intensity for both aerobic and strength training, as well as in training volume (1–20 h and 1–18 h respectively).

Conclusion

Among Dutch CR centres, considerable variation exists in methods for determination of exercise intensity. In addition, there is no uniformity in training volume and intensity.     

Echocardiographic markers of dyssynchrony as predictors of super-response to cardiac resynchronisation therapy – a pilot study

Background

Some patients with congestive heart failure have greater improvement of cardiac remodelling after cardiac resynchronisation therapy (CRT) and they are identified as super-responders (SRs). It remains unclear if echocardiographic markers of dyssynchrony could accuratelly predict super-response to CRT. The aim of this study is to evaluate potential echocardiographic predictors associated with super-response to CRT.

Methods

Fifthy nine CRT patients (mean age 52.9?±?9.0 years, 88% men) with congestive heart failure (54% ischaemic and 46% non-ischaemic aetiology) II-IV NYHA functional class were enrolled. To assess mechanical dyssynchrony we evaluated interventricular mechanical delay, the maximum delay between peak systolic velocities of the septal and posterior walls of left ventricle, duration of left ventricular pre-ejection period (LVPEP), left ventricular and interventricular dyssynchrony by tissue Doppler imaging and systolic dyssynchrony index by 3D echocardiography. After six months the patients were assessed for response and classified as SRs (reduction in left ventricular end-systolic volume (LVESV) ≥30%, n?=?20) and non-SRs (reduction in LVESV <?30%, n?=?39) and baseline data were analyzed to identify the predictors.

Results

Both groups demonstrated significant improvement in NYHA functional class, increase in left ventricular ejection fraction and reduction in LVESV. All parameters of mechanical dyssynchrony at baseline were significantly higher in SR group. Multiple logistic regression analysis showed that LVPEP (HR 1.031; 95% CI 1.007–1.055; p?=?0.011) was an independent predictor for CRT super-response. In ROC curve analysis LVPEP with a cut-off value of 147 ms demonstrated 73.7% sensitivity and 75% specificity (AUC?=?0.753; p?=?0.002) for the prediction of super-response to CRT.

Conclusion

Greater mechanical dyssynchrony is associated with super-response to CRT in patients with congestive heart failure. It is probable that an LVPEP >?147 ms can be used as independent predictor of super-response.

     

Shortening of atrioventricular delay at increased atrial paced heart rates improves diastolic filling and functional class in patients with biventricular pacing

Background

Use of rate adaptive atrioventricular (AV) delay remains controversial in patients with biventricular (Biv) pacing. We hypothesized that a shortened AV delay would provide optimal diastolic filling by allowing separation of early and late diastolic filling at increased heart rate (HR) in these patients.

Methods

34 patients (75 ± 11 yrs, 24 M, LVEF 34 ± 12%) with Biv and atrial pacing had optimal AV delay determined at baseline HR by Doppler echocardiography. Atrial pacing rate was then increased in 10 bpm increments to a maximum of 90 bpm. At each atrial pacing HR, optimal AV delay was determined by changing AV delay until best E and A wave separation was seen on mitral inflow pulsed wave (PW) Doppler (defined as increased atrial duration from baseline or prior pacemaker setting with minimal atrial truncation). Left ventricular (LV) systolic ejection time and velocity time integral (VTI) at fixed and optimal AV delay was also tested in 13 patients. Rate adaptive AV delay was then programmed according to the optimal AV delay at the highest HR tested and patients were followed for 1 month to assess change in NYHA class and Quality of Life Score as assessed by Minnesota Living with Heart Failure Questionnaire.

Results

81 AV delays were evaluated at different atrial pacing rates. Optimal AV delay decreased as atrial paced HR increased (201 ms at 60 bpm, 187 ms at 70 bpm, 146 ms at 80 bpm and 123 ms at 90 bpm (ANOVA F-statistic = 15, p = 0.0010). Diastolic filling time (P < 0.001 vs. fixed AV delay), mitral inflow VTI (p < 0.05 vs fixed AV delay) and systolic ejection time (p < 0.02 vs. fixed AV delay) improved by 14%, 5% and 4% respectively at optimal versus fixed AV delay at the same HR. NYHA improved from 2.6 ± 0.7 at baseline to 1.7 ± 0.8 (p < 0.01) 1 month post optimization. Physical component of Quality of Life Score improved from 32 ± 17 at baseline to 25 ± 12 (p < 0.05) at follow up.

Conclusions

Increased heart rate by atrial pacing in patients with Biv pacing causes compromise in diastolic filling time which can be improved by AV delay shortening. Aggressive AV delay shortening was required at heart rates in physiologic range to achieve optimal diastolic filling and was associated with an increase in LV ejection time during optimization. Functional class improved at 1 month post optimization using aggressive AV delay shortening algorithm derived from echo-guidance at the time of Biv pacemaker optimization.     

Diastolic time – frequency relation in the stress echo lab: filling timing and flow at different heart rates

 

A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration.

Aims

1- To assess the feasibility and extra-value of operator-independent, force sensor-based, diastolic time recording during stress.

Methods

We enrolled 161 patients referred for stress echocardiography (exercise 115, dipyridamole 40, pacing 6 patients). The sensor was fastened in the precordial region by a standard ECG electrode. The acceleration signal was converted into digital and recorded together with ECG signal. Both systolic and diastolic times were acquired continuously during stress and were displayed by plotting times vs. heart rate. Diastolic filling rate was calculated as echo-measured mitral filling volume/sensor-monitored diastolic time.

Results

Diastolic time decreased during stress more markedly than systolic time. At peak stress 62 of the 161 pts showed reversal of the systolic/diastolic ratio with the duration of systole longer than diastole. In the exercise group, at 100 bpm HR, systolic/diastolic time ratio was lower in the 17 controls (0.74 ± 0.12) than in patients (0.86 ± 0.10, p < 0.05 vs. controls). Diastolic filling rate increased from 101 ± 36 (rest) to 219 ± 92 ml/m²* s^-1 at peak stress (p < 0.5 vs. rest).

Conclusion

Cardiological systolic and diastolic duration can be monitored during stress by using an acceleration force sensor. Simultaneous calculation of stroke volume allows monitoring diastolic filling rate. Stress-induced "systolic-diastolic mismatch" can be easily quantified and is associated to several cardiac diseases, possibly expanding the spectrum of information obtainable during stress.     

Compliance of a cobalt chromium coronary stent alloy – the COVIS trial

Aim

Female cardiac transplant recipients' aerobic capacity is 60% lower than sex and age-predicted values. The effect of exercise training on restoring the impaired aerobic endurance and muscle strength in female cardiac transplant recipients is not known. This study examined the effect that aerobic and strength training have on improving aerobic endurance and muscle strength in female cardiac transplant recipients.

Methods

20 female cardiac transplant recipients (51 ± 11 years) participated in this investigation. The subjects performed a baseline six-minute walk test and a leg-press strength test when they were discharged following cardiac transplantation. The subjects then participated in a 12-week exercise program consisting of aerobic and lower extremity strength training. Baseline assessments were repeated following completion of the exercise intervention.

Results

At baseline, the cardiac transplant recipients' aerobic endurance was 50% lower than age-matched predicted values. The training program resulted in a significant increase in aerobic endurance (pre-training: 322 ± 104 m vs. post-training: 501 ± 99 m, p < 0.05) and leg-press strength (pre-training: 48 ± 16 kg. vs. post-training: 78 ± 27 kg, p < 0.05).

Conclusion

Aerobic and strength training are effective interventions that can partially restore the impaired aerobic endurance and strength found in female cardiac transplant recipients.     

Visualisation of coronary venous anatomy by computed tomography angiography prior to cardiac resynchronisation therapy implantation

Background

The purpose of this study was to illustrate the additive value of computed tomography angiography (CTA) for visualisation of the coronary venous anatomy prior to cardiac resynchronisation therapy (CRT) implantation.

Methods

Eighteen patients planned for CRT implantation were prospectively included. A specific CTA protocol designed for visualisation of the coronary veins was carried out on a third-generation dual-source CT platform. Coronary veins were semi-automatically segmented to construct a 3D model. CTA-derived coronary venous anatomy was compared with intra-procedural fluoroscopic angiography (FA) in right and left anterior oblique views.

Results

Coronary venous CTA was successfully performed in all 18 patients. CRT implantation and FA were performed in 15 patients. A total of 62 veins were visualised; the number of veins per patient was 3.8 (range: 2–5). Eighty-five per cent (53/62) of the veins were visualised on both CTA and FA, while 10% (6/62) were visualised on CTA only, and 5% (3/62) on FA only. Twenty-two veins were present on the lateral or inferolateral wall; of these, 95% (21/22) were visualised by CTA. A left-sided implantation was performed in 13 patients, while a right-sided implantation was performed in the remaining 2 patients because of a persistent left-sided superior vena cava with no left innominate vein on CTA.

Conclusion

Imaging of the coronary veins by CTA using a designated protocol is technically feasible and facilitates the CRT implantation approach, potentially improving the outcome.

     

Latent pulmonary hypertension in atrial septal defect: Dynamic stress echocardiography reveals unapparent pulmonary hypertension and confirms rapid normalisation after ASD closure

Objective

Closure of atrial septal defects (ASD) prevents pulmonary hypertension, right heart failure and thromboembolic stroke. The exact timing for ASD closure is controversial.

Methods

In a prospective study to address the question whether unapparent pulmonary hypertension can be revealed prior to right ventricular (RV) remodelling, patients were investigated before and 6, 12, and 24 months after ASD closure using exercise stress echocardiography (ESE) and ergospirometry (n?=?24).

Results

At rest, RV systolic pressure (RVSP) was normal in 58.8 %, slightly elevated in 26.5 %, and moderately elevated in 11.8 %. One patient showed severe pulmonary hypertension. During ESE, all patients with normal RVSP at rest exhibited an increase (25.7?±?1.2 mmHg vs. 45.3?±?2.3 mmHg, p?<?0.001). After closure the RVSP was lower, both at rest and ESE. RV diameters decreased too. Tricuspid annulus plane systolic excursion (TAPSE) at rest remained lower after closure (24.0?±?0.9 vs. 22.0?±?0.9 mm, p?<?0.05). TAPSE in ESE was elevated, and stayed stable after closure (30.1?±?1.8 mm vs. 29.3?±?1.6 mm). Before closure, RV systolic tissue velocities (s^a) at rest were normal and decreased after closure (14.0?±?1.0 cm/s vs. 11.5?±?0.7 (6 month) vs. 10.6?±?0.5 cm/s (12 month), p?<?0.05). During ESE, s^a velocity was similar before and after closure (23.0?±?1.3 cm/s vs. 23.3?±?1.9 cm/s). Maximal oxygen uptake (VO₂/kg) did not differ between baseline and follow-ups.

Conclusion

Latent pulmonary hypertension may become apparent in ESE. ASD closure leads to a significant reduction in this stress-induced pulmonary hypertension and to a decrease in the right heart diameters indicating reverse RV remodelling. RV functional parameters at rest did not improve. The VO₂/kg did not change after ASD closure.     

Lung ultrasound: a new tool for the cardiologist

Background

We have previously reported strain dyssynchrony index assessed by two-dimensional speckle tracking strain, and a marker of both dyssynchrony and residual myocardial contractility, can predict response to cardiac resynchronization therapy (CRT). A newly developed three-dimensional (3-D) speckle tracking system can quantify endocardial area change ratio (area strain), which coupled with the factors of both longitudinal and circumferential strain, from all 16 standard left ventricular (LV) segments using complete 3-D pyramidal datasets. Our objective was to test the hypothesis that strain dyssynchrony index using area tracking (ASDI) can quantify dyssynchrony and predict response to CRT.

Methods

We studied 14 heart failure patients with ejection fraction of 27 ± 7% (all≤35%) and QRS duration of 172 ± 30 ms (all≥120 ms) who underwent CRT. Echocardiography was performed before and 6-month after CRT. ASDI was calculated as the average difference between peak and end-systolic area strain of LV endocardium obtained from 3-D speckle tracking imaging using 16 segments. Conventional dyssynchrony measures were assessed by interventricular mechanical delay, Yu Index, and two-dimensional radial dyssynchrony by speckle-tracking strain. Response was defined as a ≥15% decrease in LV end-systolic volume 6-month after CRT.

Results

ASDI ≥ 3.8% was the best predictor of response to CRT with a sensitivity of 78%, specificity of 100% and area under the curve (AUC) of 0.93 (p < 0.001). Two-dimensional radial dyssynchrony determined by speckle-tracking strain was also predictive of response to CRT with an AUC of 0.82 (p < 0.005). Interestingly, ASDI ≥ 3.8% was associated with the highest incidence of echocardiographic improvement after CRT with a response rate of 100% (7/7), and baseline ASDI correlated with reduction of LV end-systolic volume following CRT (r = 0.80, p < 0.001).

Conclusions

ASDI can predict responders and LV reverse remodeling following CRT. This novel index using the 3-D speckle tracking system, which shows circumferential and longitudinal LV dyssynchrony and residual endocardial contractility, may thus have clinical significance for CRT patients.     

Ontogeny of hypoxic modulation of cardiac performance and its allometry in the African clawed frog Xenopus laevis

The ontogeny of cardiac hypoxic responses, and how such responses may be modified by rearing environment, are poorly understood in amphibians. In this study, cardiac performance was investigated in Xenopus laevis from 2 to 25 days post-fertilization (dpf). Larvae were reared under either normoxia or moderate hypoxia (PO₂ = 110 mmHg), and each population was assessed in both normoxia and acute hypoxia. Heart rate (f _h ) of normoxic-reared larvae exhibited an early increase from 77 ± 1 beats min^?1 at 2 dpf to 153 ± 1 beats min^?1 at 4 dpf, followed by gradual decreases to 123 ± 3 beats min^?1 at 25 dpf. Stroke volume (SV), 6 ± 1 nl, and cardiac output (CO), 0.8 ± 0.1 μl min^?1, at 5 dpf both increased by more than 40-fold to 25 dpf with rapid larval growth (~30-fold increase in body mass). When exposed to acute hypoxia, normoxic-reared larvae increased f _h and CO between 5 and 25 dpf. Increased SV in acute hypoxia, produced by increased end-diastolic volume (EDV), only occurred before 10 dpf. Hypoxic-reared larvae showed decreased acute hypoxic responses of EDV, SV and CO at 7 and 10 dpf. Over the period of 2–25 dpf, cardiac scaling with mass showed scaling coefficients of ?0.04 (f _h ), 1.23 (SV) and 1.19 (CO), contrary to the cardiac scaling relationships described in birds and mammals. In addition, f _h scaling in hypoxic-reared larvae was altered to a shallower slope of ?0.01. Collectively, these results indicate that acute cardiac hypoxic responses develop before 5 dpf. Chronic hypoxia at a moderate level can not only modulate this cardiac reflex, but also changes cardiac scaling relationship with mass.     

Comparison of strain parameters in dyssynchronous heart failure between speckle tracking echocardiography vendor systems

Background

Although mechanical dyssynchrony parameters derived by speckle tracking echocardiography (STE) may predict response to cardiac resynchronization therapy (CRT), comparability of parameters derived with different STE vendors is unknown.

Methods

In the MARC study, echocardiographic images of heart failure patients obtained before CRT implantation were prospectively analysed with vendor specific STE software (GE EchoPac and Philips QLAB) and vendor-independent software (TomTec 2DCPA). Response was defined as change in left ventricular (LV) end-systolic volume between examination before and six-months after CRT implantation. Basic longitudinal strain and mechanical dyssynchrony parameters (septal to lateral wall delay (SL-delay), septal systolic rebound stretch (SRSsept), and systolic stretch index (SSI)) were obtained from either separate septal and lateral walls, or total LV apical four chamber. Septal strain patterns were categorized in three types. The coefficient of variation and intra-class correlation coefficient (ICC) were analysed. Dyssynchrony parameters were associated with CRT response using univariate regression analysis and C-statistics.

Results

Two-hundred eleven patients were analysed. GE-cohort (n = 123): age 68 years (interquartile range (IQR): 61–73), 67% male, QRS-duration 177 ms (IQR: 160–192), LV ejection fraction: 26 ± 7%. Philips-cohort (n = 88): age 67 years (IQR: 59–74), 60% male, QRS-duration: 179 ms (IQR: 166–193), LV ejection fraction: 27 ± 8. LV derived peak strain was comparable in the GE- (GE: -7.3 ± 3.1%, TomTec: ?6.4 ± 2.8%, ICC: 0.723) and Philips-cohort (Philips: ?7.7 ± 2.7%, TomTec: ?7.7 ± 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs. TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC’s of SRSsept and SSI were higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs. QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was low (Cohen’s kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal strain patterns, SRSsept and SSI were associated with changes in LV end-systolic volume for all vendors. SRSsept and SSI had relative varying C-statistic values (range: 0.530–0.705) and different cut-off values between vendors.

Conclusions

Although global longitudinal strain analysis showed fair comparability, assessment of dyssynchrony parameters was vendor specific and not applicable outside the context of the implemented platform. While the standardization taskforce took an important step for global peak strain, further standardization of STE is still warranted.

     

Ventriculo-atrial gradient due to first degree atrio-ventricular block: a case report

Background

Isolated, asymptomatic first degree AV block with narrow QRS has not prognostic significance and is not usually treated with pacemaker implantation. In some cases, yet, loss of AV synchrony because of a marked prolongation of the PR interval may cause important hemodynamic alterations, with subsequent symptoms of heart failure. Indeed, AV synchrony is crucial when atrial systole, the "atrial kick", contributes in a major way to left ventricular filling, as in case of reduced left ventricular compliance because of aging or concomitant structural heart disease.

Case presentation

We performed a trans-septal left atrium catheterization aimed at evaluating the entity of a mitral valve stenosis in a 72-year-old woman with a marked first-degree AV block, a known moderate aortic stenosis and NYHA class III symptoms of functional deterioration. We occurred in a deep alteration in cardiac hemodynamics consisting in an end-diastolic ventriculo-atrial gradient without any evidence of mitral stenosis. The patient had a substantial improvement in echocardiographic parameters and in her symptoms of heart failure after permanent pacemaker implantation with physiological AV delay.

Conclusion

We conclude that if a marked first degree AV block is associated to instrumental signs or symptoms of heart failure, the restoration of an optimal AV synchrony, achieved with dual-chamber pacing, may represent a reasonable therapeutic option leading to a consequent clinical improvement.     

Left cardiac sympathetic denervation in the Netherlands for the treatment of inherited arrhythmia syndromes

Introduction

Treating therapy-resistant patients with inherited arrhythmia syndromes can be difficult and left cardiac sympathetic denervation (LCSD) might be a viable alternative treatment option. We provide an overview of the indications and outcomes of LCSD in patients with inherited arrhythmia syndromes in the only tertiary referral centre in the Netherlands where LCSD is conducted in these patients.

Methods

This was a retrospective study, including all patients with inherited arrhythmia syndromes who underwent LCSD in our institution between 2005 and 2013. LCSD involved ablation of the lower part of the left stellate ganglion and the first four thoracic ganglia.

Results

Seventeen patients, 12 long-QT syndrome (LQTS) patients (71 %) and 5 catecholaminergic polymorphic ventricular tachycardia (CPVT) patients (29 %), underwent LCSD. Most patients (94 %) were referred because of therapy-refractory cardiac events. In 87 % the annual cardiac event rate decreased. However, after 2 years the probability of complete cardiac event-free survival was 59 % in LQTS and 60 % in CPVT patients. Two patients (12 %) had major non-reversible LCSD-related complications: one patient suffered from a Harlequin face post-procedure and one severely affected LQT8 patient died the day after LCSD due to complications secondary to an arrhythmic storm during the procedure.

Conclusion

LSCD for inherited arrhythmia syndromes, which is applied on a relatively small scale in the Netherlands, reduced the cardiac event rate in 87 % of the high-risk patients who had therapy-refractory cardiac events, while the rate of major complications was low. Therefore, LSCD seems a viable treatment for patients with inherited arrhythmia syndromes without other options for therapy.     

Acute beneficial hemodynamic effects of a novel 3D-echocardiographic optimization protocol in cardiac resynchronization therapy

Background

Post-implantation therapies to optimize cardiac resynchronization therapy (CRT) focus on adjustments of the atrio-ventricular (AV) delay and ventricular-to-ventricular (VV) interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized optimization of device based AV delays and VV intervals compared to empiric programming.

Methods

25 recipients of CRT (male: 56%, mean age: 67 years) were included in this study. Ejection fraction (EF), the primary outcome parameter, and left ventricular (LV) dimensions were evaluated by 3DE before CRT (baseline), after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming) and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI) was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI), calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation), and the VV interval with the lowest SDI was programmed (individualized optimization).

Results

EF increased from baseline 23±7% to 30±8 (p<0.001) after AV delay optimization and to 32±8% (p<0.05) after individualized optimization with an associated decrease of end-systolic volume from a baseline of 138±60 ml to 115±42 ml (p<0.001). Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3±5.5% to 6.1±2.6% (p<0.001).

Conclusions

Compared with empiric programming of biventricular pacemakers, individualized echocardiographic optimization with the integration of 3-dimensional indices into the optimization protocol acutely improved LV systolic function and decreased ESV and can be used to select the optimal AV delay and VV interval in CRT.     

Pilot study using 3D–longitudinal strain computation in a multi-parametric approach for best selecting responders to cardiac resynchronization therapy

Background

Almost all attempts to improve patient selection for cardiac resynchronization therapy (CRT) using echo-derived indices have failed so far. We sought to assess: the performance of homemade software for the automatic quantification of integral 3D regional longitudinal strain curves exploring left ventricular (LV) mechanics and the potential value of this tool to predict CRT response.

Methods

Forty-eight heart failure patients in sinus rhythm, referred for CRT-implantation (mean age: 65 years; LV-ejection fraction: 26%; QRS-duration: 160 milliseconds) were prospectively explored. Thirty-four patients (71%) had positive responses, defined as an LV end-systolic volume decrease ≥15% at 6-months. 3D–longitudinal strain curves were exported for analysis using custom-made algorithms. The integrals of the longitudinal strain signals (I _L,peak) were automatically measured and calculated for all 17 LV-segments.

Results

The standard deviation of longitudinal strain peak (SDI _L,peak ) for all 17 LV-segments was greater in CRT responders than non-responders (1.18% s^?1 [0.96; 1.35] versus 0.83% s^?1 [0.55; 0.99], p = 0.007). The optimal cut-off value of SDI _L,peak to predict response was 1.037%.s^?1. In the 18-patients without septal flash, SDI _L,peak was significantly higher in the CRT-responders.

Conclusions

This new automatic software for analyzing 3D longitudinal strain curves is avoiding previous limitations of imaging techniques for assessing dyssynchrony and then its value will have to be tested in a large group of patients.

     

A simplified study of trans-mitral Doppler patterns

Background

Electrical fusion between left ventricular pacing and spontaneous right ventricular activation is considered the key to resynchronisation in sinus rhythm patients treated with single-site left ventricular pacing.

Aim

Use of QRS morphology to optimize device programming in patients with heart failure (HF), sinus rhythm (SR), left bundle branch block (LBBB), treated with single-site left ventricular pacing.

Methods and Results

We defined the "fusion band" (FB) as the range of AV intervals within which surface ECG showed an intermediate morphology between the native LBBB and the fully paced right bundle branch block patterns. Twenty-four patients were enrolled. Echo-derived parameters were collected in the FB and compared with the basal LBBB condition. Velocity time integral and ejection time did not improve significantly. Diastolic filling time, ejection fraction and myocardial performance index showed a statistically significant improvement in the FB. Interventricular delay and mitral regurgitation progressively and significantly decreased as AV delay shortened in the FB. The tissue Doppler asynchrony index (Ts-SD-12-ejection) showed a non significant decreasing trend in the FB. The indications provided by the tested parameters were mostly concordant in that part of the FB corresponding to the shortest AV intervals.

Conclusion

Using ECG criteria based on the FB may constitute an attractive option for a safe, simple and rapid optimization of resynchronization therapy in patients with HF, SR and LBBB.     

The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative <Emphasis Type="Italic">FBN1</Emphasis> mutations

Background

Mild biventricular dysfunction is often present in patients with Marfan syndrome. Losartan has been shown to reduce aortic dilatation in patients with Marfan syndrome. This study assesses the effect of losartan on ventricular volume and function in genetically classified subgroups of asymptomatic Marfan patients without significant valvular regurgitation.

Methods

In this predefined substudy of the COMPARE study, Marfan patients were classified based on the effect of their FBN1 mutation on fibrillin-1 protein, categorised as haploinsufficient or dominant negative. Patients were randomised to a daily dose of losartan 100 mg or no additional treatment. Ventricular volumes and function were measured by magnetic resonance imaging at baseline and after 3 years of follow-up.

Results

Changes in biventricular dimensions were assessed in 163 Marfan patients (48?% female; mean age 38 ± 13 years). In patients with a haploinsufficient FBN1 mutation (n = 43), losartan therapy (n = 19) increased both biventricular end diastolic volume (EDV) and stroke volume (SV) when compared with no additional losartan (n = 24): left ventricular EDV: 9 ± 26 ml vs. ?8 ± 24 ml, p = 0.035 and right ventricular EDV 12 ± 23 ml vs. ?18 ± 24 ml; p < 0.001 and for left ventricle SV: 6 ± 16 ml vs. ?8 ± 17 ml; p = 0.009 and right ventricle SV: 8 ± 16 ml vs. ?7 ± 19 ml; p = 0.009, respectively. No effect was observed in patients with a dominant negative FBN1 mutation (n = 92), or without an FBN1 mutation (n = 28).

Conclusion

Losartan therapy in haploinsufficient Marfan patients increases biventricular end diastolic volume and stroke volume, furthermore, losartan also appears to ameliorate biventricular filling properties.

     

Plasma and lymphocyte Hsp72 responses to exercise in athletes with prior exertional heat illness

We investigated the effect of exercise in the heat on both intracellular and extracellular Hsp72 in athletes with a prior history of exertional heat illness (EHI). Two groups of runners, one consisting of athletes who had a previous history of EHI, and a control group (CON) of similar age (29.7 ± 1.2 and 29.1 ± 2 years CON vs. EHI) and fitness [maximal oxygen consumption $(\dot V{{\text{O}}_2}\hbox{max} )$ 65.7 ± 2 and 64.5 ± 3 ml kg^?1 min^?1 CON vs. EHI] were recruited. Seven subjects in each group ran on a treadmill for 1 h at 72 % $\dot V{{\text{O}}_2}\hbox{max}$ in warm conditions (30 °C, 40 % RH) reaching rectal temperatures of ~39.3 (CON) and ~39.2 °C (EHI). Blood was collected every 10 min during exercise and plasma was analysed for extracellular Hsp72. Intracellular Hsp72 levels were measured in both monocytes and lymphocytes before and immediately after the 60-min run, and then after 1 h recovery at an ambient temperature of 24 °C. Plasma Hsp72 increased from 1.18 ± 0.14 and 0.86 ± 0.08 ng/ml (CON vs. EHI) at rest to 4.56 ± 0.63 and 4.04 ± 0.45 ng/ml (CON vs. EHI, respectively) at the end of exercise (p < 0.001), with no difference between groups. Lymphocyte Hsp72 was lower in the EHI group at 60 min of exercise (p < 0.05), while monocyte Hsp72 was not different between groups. The results of the present study suggest that the plasma Hsp72 response to exercise in athletes with a prior history of EHI remained similar to that of the CON group, while the lymphocyte Hsp72 response was reduced.     

Electrocardiographic patterns in biventricular pacing delivered by second-generation cardiac resynchronization devices

Background

With increasing use of cardiac resynchronization therapy (CRT), treating physicians should be familiar with different electrocardiographic (ECG) patterns of left ventricular (LV) lead and biventricular (BiV) pacing. However, there are a few publications on ECG patterns during BiV pacing.