Anoop Shetty

Invasive Acute Hemodynamic Response to Guide Left Ventricular Lead Implantation Predicts Chronic Remodeling in Patients Undergoing Cardiac Resynchronization Therapy

OBJECTIVES We evaluated the relationship between acute hemodynamic response (AHR) and reverse remodeling (RR) in cardiac resynchronization therapy (CRT). BACKGROUND CRT reduces mortality and morbidity in heart failure patients; however, up to 30% of patients do not derive symptomatic benefit. Higher proportions do not remodel. Multicenter trials have shown echocardiographic techniques are poor at improving response rates. We hypothesized the degree of AHR at implant can predict which patients remodel. METHODS Thirty-three patients undergoing CRT (21 dilated and 12 ischemic cardiomyopathy) were studied. Left ventricular (LV) volumes were assessed before and after CRT. The AHR (maximum rate of left ventricular pressure [LV-dP/dt(max)]) was assessed at implant with a pressure wire in the LV cavity. Largest percentage rise in LV-dP/dt(max) from baseline (atrial antibradycardia pacing or right ventricular pacing with atrial fibrillation) to dual-chamber pacing (DDD)-LV was used to determine optimal coronary sinus LV lead position. Reverse remodeling was defined as reduction in LV end systolic volume ≥15% at 6 months. RESULTS The LV-dP/dt(max) increased significantly from baseline (801 ± 194 mm Hg/s to 924 ± 203 mm Hg/s, p < 0.001) with DDD-LV pacing for the optimal LV lead position. The LV end systolic volume decreased from 186 ± 68 ml to 157 ± 68 ml (p < 0.001). Eighteen (56%) patients exhibited RR. There was a significant relationship between percentage rise in LV-dP/dt(max) and RR for DDD-LV pacing (p < 0.001). A similar relationship for AHR and RR in dilated cardiomyopathy and ischemic cardiomyopathy (p = 0.01 and p = 0.006) was seen. CONCLUSIONS Acute hemodynamic response to LV pacing is useful for predicting which patients are likely to remodel in response to CRT both for dilated cardiomyopathy and ischemic cardiomyopathy. Using AHR has the potential to guide LV lead positioning and improve response rates.

Biophysical Modeling to Simulate the Response to Multisite Left Ventricular Stimulation Using a Quadripolar Pacing Lead

Background:  Response to cardiac resynchronization therapy (CRT) is reduced in patients with posterolateral scar. Multipolar pacing leads offer the ability to select desirable pacing sites and/or stimulate from multiple pacing sites concurrently using a single lead position. Despite this potential, the clinical evaluation and identification of metrics for optimization of multisite CRT (MCRT) has not been performed.

The estimation of patient-specific cardiac diastolic functions from clinical measurements

An unresolved issue in patients with diastolic dysfunction is that the estimation of myocardial stiffness cannot be decoupled from diastolic residual active tension (AT) because of the impaired ventricular relaxation during diastole. To address this problem, this paper presents a method for estimating diastolic mechanical parameters of the left ventricle (LV) from cine and tagged MRI measurements and LV cavity pressure recordings, separating the passive myocardial constitutive properties and diastolic residual AT. Dynamic C1-continuous meshes are automatically built from the anatomy and deformation captured from dynamic MRI sequences. Diastolic deformation is simulated using a mechanical model that combines passive and active material properties. The problem of non-uniqueness of constitutive parameter estimation using the well known Guccione law is characterized by reformulation of this law. Using this reformulated form, and by constraining the constitutive parameters to be constant across time points during diastole, we separate the effects of passive constitutive properties and the residual AT during diastolic relaxation. Finally, the method is applied to two clinical cases and one control, demonstrating that increased residual AT during diastole provides a potential novel index for delineating healthy and pathological cases.

A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study

AIMS Alternative forms of cardiac resynchronization therapy (CRT), including biventricular endocardial (BV-Endo) and multisite epicardial pacing (MSP), have been developed to improve response. It is unclear which form of stimulation is optimal. We aimed to compare the acute haemodynamic response (AHR) and electrophysiological effects of BV-Endo with MSP via two separate coronary sinus (CS) leads or a single-quadripolar CS lead. METHODS AND RESULTS Fifteen patients with a previously implanted CRT system received a second temporary CS lead and left ventricular (LV) endocardial catheter. A pressure wire and non-contact mapping array were placed into the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. Conventional CRT, BV-Endo, and MSP were then performed (MSP-1 via two epicardial leads and MSP-2 via a single-quadripolar lead). The best overall AHR was found using BV-Endo pacing with a 19.6 ± 13.6% increase in AHR at the optimal endocardial site over baseline (P < 0.001). There was an increase in LVdP/dtmax with MSP-1 and MSP-2 compared with conventional CRT, but this was not statistically significant. Biventricular endocardial pacing from the optimal site was significantly superior to conventional CRT (P = 0.039). The AHR achieved when BV-Endo pacing was highly site specific. Within individuals, the best pacing modality varied and was affected by the underlying substrate. Left ventricular activation times did not predict the optimal haemodynamic configuration. CONCLUSION Biventricular endocardial pacing and not MSP was superior to conventional CRT, but was highly site specific. Within individuals, however, different methods of stimulation are optimal and may need to be tailored to the underlying substrate.

Benefits of endocardial and multisite pacing are dependent on the type of left ventricular electric activation pattern and presence of ischemic heart disease: insights from electroanatomic mapping.

Background—There is considerable heterogeneity in the myocardial substrate of patients undergoing cardiac resynchronization therapy (CRT), in particular in the etiology of heart failure and in the location of conduction block within the heart. This may account for variability in response to CRT. New approaches, including endocardial and multisite left ventricular (LV) stimulation, may improve CRT response. We sought to evaluate these approaches using noncontact mapping to understand the underlying mechanisms. Methods and Results—Ten patients (8 men and 2 women; mean [SD] age 63 [12] years; LV ejection fraction 246%; QRS duration 161 [24] ms) fulfilling conventional CRT criteria underwent an electrophysiological study, with assessment of acute hemodynamic response to conventional CRT as well as LV endocardial and multisite pacing. LV activation pattern was assessed using noncontact mapping. LV endocardial pacing gave a superior acute hemodynamic response compared with conventional CRT (26% versus 37% increase in LV dP/dtmax, respectively; P<0.0005). There was a trend toward further incremental benefit from multisite LV stimulation, although this did not reach statistical significance (P=0.08). The majority (71%) of patients with nonischemic heart failure etiology or functional block responded to conventional CRT, whereas those with myocardial scar or absence of functional block often required endocardial or multisite pacing to achieve CRT response. Conclusions—Endocardial or multisite pacing may be required in certain subsets of patients undergoing CRT. Patients with ischemic cardiomyopathy and those with narrower QRS, in particular, may stand to benefit.

Multi-site left ventricular pacing as a potential treatment for patients with postero-lateral scar: insights from cardiac magnetic resonance imaging and invasive haemodynamic assessment.

AIMS Multi-site left ventricular (LV) pacing may be superior to single-site stimulation in correcting dyssynchrony and avoiding areas of myocardial scar. We sought to characterize myocardial scar using cardiac magnetic resonance imaging (CMR). We aimed to quantify the acute haemodynamic response to single-site and multi-site LV stimulation and to relate this to the position of the LV leads in relation to myocardial scar. METHODS Twenty patients undergoing cardiac resynchronization therapy had implantation of two LV leads. One lead (LV1) was positioned in a postero-lateral vein, the second (LV2) in a separate coronary vein. LV dP/dtmax was recorded using a pressure wire during stimulation at LV1, LV2, and both sites simultaneously (LV1 + 2). Patients were deemed acute responders if ΔLV dP/dtmax was ≥ 10%. Cardiac magnetic resonance imaging was performed to assess dyssynchrony as well as location and burden of scar. Scar anatomy was registered with fluoroscopy to assess LV lead position in relation to scar. RESULTS LV dP/dtmax increased from 726 ± 161 mmHg/s in intrinsic rhythm to 912 ± 234 mmHg/s with LV1, 837 ± 188 mmHg/s with LV2, and 932 ± 201 mmHg/s with LV1 and LV2. Nine of 19 (47%) were acute responders with LV1 vs. 6/19 (32%) with LV2. Twelve of 19 (63%) were acute responders with simultaneous LV1 + 2. Two of three patients benefitting with multi-site pacing had the LV1 lead positioned in postero-lateral scar. CONCLUSION Multi-site LV pacing increased acute response by 16% vs. single-site pacing. This was particularly beneficial in patients with postero-lateral scar identified on CMR.

Cardiac magnetic resonance-derived anatomy, scar, and dyssynchrony fused with fluoroscopy to guide LV lead placement in cardiac resynchronization therapy: a comparison with acute haemodynamic measures and echocardiographic reverse remodelling

AIMS Left ventricular (LV) lead positioning for cardiac resynchronization therapy (CRT) is largely empirical and operator-dependent. Our aim was to determine whether cardiac magnetic resonance (CMR)-guided CRT may improve the acute and the chronic response. METHODS AND RESULTS CMR-derived anatomical models and dyssynchrony maps were created for 20 patients. The CMR targets (three latest activated segments with <50% scar) were overlaid on to live fluoroscopy. Acute haemodynamic response (AHR) to LV pacing was assessed using an intra-ventricular pressure wire. Chronic CRT response (end-systolic volume reduction ≥15%) was assessed 6 months post-implantation. All patients underwent successful CMR-guided LV lead placement. A CMR target segment was paced in 75% of patients. The mean change in LVdP/dtmax for the CMR target was +14.2 ± 12.5 vs. +18.7 ± 11.9% for the best AHR in any segment and +12.0 ± 13.8% for the segment based on coronary sinus (CS) venography. Using CMR guidance, the acute responder rate was 60 vs. 50% on the basis of venography. At 6 months 60% of patients were echocardiographic responders. Of the echocardiographic responders, 92% were successfully paced in a CMR target segment compared with only 50% of non-responders (P = 0.04). CONCLUSION CMR guidance compared well when validated against the AHR. Lead placement was possible in the CMR target region in most patients with an AHR comparable with the best achieved in any CS branch. The chronic response was significantly better in patients paced in a CMR target segment. These results suggest that CMR guidance may represent a clinically useful tool for CRT.

Myocardial tissue characterization by cardiac magnetic resonance imaging using T1 mapping predicts ventricular arrhythmia in ischemic and non-ischemic cardiomyopathy patients with implantable cardioverter-defibrillators

BACKGROUND Diffuse myocardial fibrosis may provide a substrate for the initiation and maintenance of ventricular arrhythmia. T1 mapping overcomes the limitations of the conventional delayed contrast-enhanced cardiac magnetic resonance (CE-CMR) imaging technique by allowing quantification of diffuse fibrosis. OBJECTIVE The purpose of this study was to assess whether myocardial tissue characterization using T1 mapping would predict ventricular arrhythmia in ischemic and non-ischemic cardiomyopathies. METHODS This was a prospective longitudinal study of consecutive patients receiving implantable cardioverter-defibrillators in a tertiary cardiac center. Participants underwent CMR myocardial tissue characterization using T1 mapping and conventional CE-CMR scar assessment before device implantation. The primary end point was an appropriate implantable cardioverter-defibrillator therapy or documented sustained ventricular arrhythmia. RESULTS One hundred thirty patients (71 ischemic and 59 non-ischemic) were included with a mean follow-up period of 430 ± 185 days (median 425 days; interquartile range 293 days). At follow-up, 23 patients (18%) experienced the primary end point. In multivariable-adjusted analyses, the following factors showed a significant association with the primary end point: secondary prevention (hazard ratio [HR] 1.70; 95% confidence interval [95% CI] 1.01-1.91), noncontrast T1(_native) for every 10-ms increment in value (HR 1.10; CI 1.04-1.16; 90-ms difference between the end point-positive and end point-negative groups), and Grayzone(_2sd-3sd) for every 1% left ventricular increment in value (HR 1.36; CI 1.15-1.61; 4% difference between the end point-positive and end point-negative groups). Other CE-CMR indices including Scar(_2sd), Scar(_FWHM), and Grayzone(_2sd-FWHM) were also significantly, even though less strongly, associated with the primary end point as compared with Grayzone(_2sd-3sd). CONCLUSION Quantitative myocardial tissue assessment using T1 mapping is an independent predictor of ventricular arrhythmia in both ischemic and non-ischemic cardiomyopathies.

Advanced image fusion to overlay coronary sinus anatomy with real-time fluoroscopy to facilitate left ventricular lead implantation in CRT.

Background: Failure rate for left ventricular (LV) lead implantation in cardiac resynchronization therapy (CRT) is up to 12%. The use of segmentation tools, advanced image registration software, and high‐fidelity images from computerized tomography (CT) and cardiac magnetic resonance (CMR) of the coronary sinus (CS) can guide LV lead implantation. We evaluated the feasibility of advanced image registration onto live fluoroscopic images to allow successful LV lead placement.

Acute effects of multisite left ventricular pacing on mechanical dyssynchrony in patients receiving cardiac resynchronization therapy.

BACKGROUND A novel quadripolar left ventricular (LV) pacing lead has the ability to deliver multisite LV pacing (MSLV). We set out to characterize the safety and changes in acute mechanical dyssynchrony with MSLV in cardiac resynchronization therapy (CRT) patients. METHODS AND RESULTS Prospective multicenter study in 52 patients receiving CRT. An acute pacing protocol comprising 8 MSLV configurations covering a range of delays was compared with conventional CRT (baseline). Transthoracic tissue Doppler imaging (TDI) was used to measure the standard deviation of time to peak contraction of 12 LV segments (Ts-SD) and delayed longitudinal contraction. No ventricular arrhythmia occurred in any of the 52 patients. Complete TDI datasets were collected in 41 patients. Compared with baseline: 1) The mean Ts-SD was significantly lower for the optimal MSLV configuration (35.3 ± 36.4 vs 50.2 ± 29.1 ms; P < .001); 2) at least 1 MSLV configuration exhibited a significant dyssynchrony improvement in 63% of patients; and 3) the mean number of LV segments with delayed longitudinal contractions was significantly reduced with the optimal MSLV configuration (0.37 ± 7.99 vs 2.20 ± 0.19; P < .001). CONCLUSIONS Acute MSLV was acutely safe, and a proportion of MSLV vectors resulted in a significant reduction in echocardiographic dyssynchrony compared with conventional CRT.