David Scholl

Influence of pacing site characteristics on response to cardiac resynchronization therapy.

Background—Transmural scar occupying left ventricular (LV) pacing regions has been associated with reduced response to cardiac resynchronization therapy (CRT). However, spatial influences of lead tip delivery relative to scar at both pacing sites remain poorly explored. This study evaluated scar distribution relative to LV and right ventricular (RV) lead tip placement through coregistration of late gadolinium enhancement MRI and cardiac computed tomographic (CT) findings. Influences on CRT response were assessed by serial echocardiography. Methods and Results—Sixty patients receiving CRT underwent preimplant late gadolinium enhancement MRI, postimplant cardiac CT, and serial echocardiography. Blinded segmental evaluations of mechanical delay, percentage scar burden, and lead tip location were performed. Response to CRT was defined as a reduction in LV end-systolic volume ≥15% at 6 months. The mean age and LV ejection fraction were 64±9 years and 25±7%, respectively. Mean scar volume was higher among CRT nonresponders for both the LV (23±23% versus 8±14% [P=0.01]) and RV pacing regions (40±32% versus 24±30% [P=0.04]). Significant pacing region scar was identified in 13% of LV pacing regions and 37% of RV pacing regions. Absence of scar in both regions was associated with an 81% response rate compared with 55%, 25%, and 0%, respectively, when the RV, LV, or both pacing regions contained scar. LV pacing region dyssynchrony was not predictive of response. Conclusions—Myocardial scar occupying the LV pacing region is associated with nonresponse to CRT. Scar occupying the RV pacing region is encountered at higher frequency and seems to provide a more intermediate influence on CRT response.

Accuracy and reproducibility of semi-automated late gadolinium enhancement quantification techniques in patients with hypertrophic cardiomyopathy

BackgroundThe presence and extent of late gadolinium enhancement (LGE) has been associated with adverse events in patients with hypertrophic cardiomyopathy (HCM). Signal intensity (SI) threshold techniques are routinely employed for quantification; Full-Width at Half-Maximum (FWHM) techniques are suggested to provide greater reproducibility than Signal Threshold versus Reference Mean (STRM) techniques, however the accuracy of these approaches versus the manual assignment of optimal SI thresholds has not been studied. In this study, we compared all known semi-automated LGE quantification techniques for accuracy and reproducibility among patients with HCM.MethodsSeventy-six HCM patients (51 male, age 54 ±13 years) were studied. Total LGE volume was quantified using 7 semi-automated techniques and compared to expert manual adjustment of the SI threshold to achieve optimal segmentation. Techniques tested included STRM based thresholds of >2, 3, 4, 5 and 6 SD above mean SI of reference myocardium, the FWHM technique, and the Otsu-auto-threshold (OAT) technique. The SI threshold chosen by each technique was recorded for all slices. Bland-Altman analysis and intra-class correlation coefficients (ICC) were reported for each semi-automated technique versus expert, manually adjusted LGE segmentation. Intra- and inter-observer reproducibility assessments were also performed.ResultsFifty-two of 76 (68%) patients showed LGE on a total of 202 slices. For accuracy, the STRM >3SD technique showed the greatest agreement with manual segmentation (ICC =0.97, mean difference and 95% limits of agreement =1.6 ± 10.7 g) while STRM >6SD, >5SD, 4SD and FWHM techniques systematically underestimated total LGE volume. Slice based analysis of selected SI thresholds similarly showed the STRM >3SD threshold to most closely approximate manually adjusted SI thresholds (ICC =0.88). For reproducibility, the intra- and inter-observer reproducibility of the >3SD threshold demonstrated an acceptable mean difference and 95% limits of agreement of -0.5 ± 6.8 g and -0.9 ± 5.6 g, respectively.ConclusionsFWHM segmentation provides superior reproducibility, however systematically underestimates total LGE volume compared to manual segmentation in patients with HCM. The STRM >3SD technique provides the greatest accuracy while retaining acceptable reproducibility and may therefore be a preferred approach for LGE quantification in this population.

Stress Hypoperfusion and Tissue Injury in Hypertrophic Cardiomyopathy: Spatial Characterization Using High-Resolution 3-Tesla Magnetic Resonance Imaging

Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.Background— Ischemia and tissue injury are common in patients with hypertrophic cardiomyopathy. Cardiovascular magnetic resonance imaging offers combined evaluations of each phenomenon at sufficiently high resolution to examine transmural spatial distribution. In this prospective cohort study, we examine the spatial distribution of stress perfusion abnormalities and tissue injury in patients with hypertrophic cardiomyopathy. Methods and Results— One hundred consecutive patients with hypertrophic cardiomyopathy underwent cardiovascular magnetic resonance imaging. Cine, stress perfusion, late gadolinium enhancement, and T2-weighted imaging techniques were used. Each was spatially coregistered according to predefined segmental and subsegmental models and was blindly analyzed for abnormalities using validated techniques. Spatial associations among stress perfusion, late gadolinium enhancement, and T2 imaging were made at segmental and subsegmental levels. Of the 100 patients studied, the phenotype was septal in 86 and apical in 14. Late gadolinium enhancement imaging was abnormal in 79 patients (79%). Eighty-six patients met prespecified safety criteria to undergo stress perfusion, and ischemia was identified in 46 patients (57%). T2 imaging was available in 81 patients and was abnormal in 19 (29%). The dominant distribution of all 3 findings was to segment with hypertrophy. Subsegmental analysis revealed geographic dominance of ischemia within the subendocardial zones. However, this zone was most commonly spared from late gadolinium enhancement and T2 abnormalities, typically seen in midwall and subepicardial zones. Conclusions— Inducible hypoperfusion is a common finding in hypertrophic cardiomyopathy and is typically identified within segments exhibiting imaging markers of tissue injury. However, the respective transmural dominance of these phenomena seems distinct. Alternate factors contributing to a regional susceptibility to tissue injury are deserving of further study.

Model-Based Navigation of Left and Right Ventricular Leads to Optimal Targets for Cardiac Resynchronization Therapy A Single-Center Feasibility Study

Background—Left ventricular (LV) and right ventricular pacing site characteristics have been shown to influence response to cardiac resynchronization therapy (CRT). This study aimed to determine the clinical feasibility of image-guided lead delivery using a 3-dimensional navigational model displaying both LV and right ventricular (RV) pacing targets. Serial echocardiographic measures of clinical response and procedural metrics were evaluated. Methods and Results—Thirty-one consecutive patients underwent preimplant cardiac MRI with the generation of a 3-dimensional navigational model depicting optimal segmental targets for LV and RV leads. Lead delivery was guided by the model in matched views to intraprocedural fluoroscopy. Blinded assessment of final lead tip location was performed from postprocedural cardiac computed tomography. Clinical and LV remodeling response criteria were assessed at baseline, 3 months, and 6 months using a 6-minute hall walk, quality of life questionnaire, and echocardiography. Mean age and LV ejection fraction was 66±8 years and 26±8%, respectively. LV leads were successfully delivered to a target or adjacent segment in 30 of 31 patients (97%), 68% being nonposterolateral. RV leads were delivered to a target or adjacent segment in 30 of 31 patients (97%), 26% being nonapical. Twenty-three patients (74%) met standard criteria for response (LV end-systolic volume reduction ≥15%), 18 patients (58%) for super-response (LV end-systolic volume reduction ≥30%). LV ejection fraction improved at 6 months (31±8 versus 26±8%, P=0.04). Conclusions—This study demonstrates clinical feasibility of dual cardiac resynchronization therapy lead delivery to optimal targets using a 3-dimensional navigational model. High procedural success, acceptable procedural times, and a low rate of early procedural complications were observed. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01640769.

Validation of a novel modified wall motion score for estimation of left ventricular ejection fraction in ischemic and non-ischemic cardiomyopathy

BACKGROUND Visual determination of left ventricular ejection fraction (LVEF) by segmental scoring may be a practical alternative to volumetric analysis of cine magnetic resonance imaging (MRI). The accuracy and reproducibility of this approach for has not been described. The purpose of this study was to validate a novel segmental visual scoring method for LVEF estimation using cine MRI. METHODS 362 patients with known or suspected cardiomyopathy were studied. A modified wall motion score (mWMS) was used to blindly score the wall motion of all cardiac segments from cine MRI imaging. The same datasets were subjected to blinded volumetric analysis using endocardial contour tracing. The population was then separated into a model cohort (N=181) and validation cohort (N=181), with the former used to derive a regression equation of mWMS versus true volumetric LVEF. The validation cohort was then used to test the accuracy of this regression model to estimate the true LVEF from a visually determined mWMS. Reproducibility testing of mWMS scoring was performed upon a randomly selected sample of 20 cases. RESULTS The regression equation relating mWMS to true LVEF in the model cohort was: LVEF=54.23-0.5761×mWMS. In the validation cohort this equation produced a strong correlation between mWMS-derived LVEF and true volumetric LVEF (r=0.89). Bland and Altman analysis showed no systematic bias in the LVEF estimated using the mWMS (-0.3231%, 95% limits of agreement -12.22% to 11.58%). Inter-observer and intra-observer reproducibility was excellent (r=0.93 and 0.97, respectively). CONCLUSION The mWMS is a practical tool for reporting regional wall motion and provides reproducible estimates of LVEF from cine MRI.

Clinical feasibility of targeted cardiac resynchronization lead delivery using a 3D MRI cardiac model

Background Cardiac resynchronization therapy (CRT) aims to reduce dyssynchronous contraction through simultaneous pacing of the right ventricular (RV) septum and left ventricular (LV) lateral wall. Up to 40% of patients do not respond, largely attributed to lack of dysynchrony and/ or transmural scar at pacing sites. In this pilot study we tested the feasibility of guiding LV and RV leads to “optimal” segmental targets using a MRI-based 3D surface rendered cardiac model. Methods Ten consecutive patients planned for CRT were recruited. All patients underwent cardiac MRI inclusive of cine and delayed enhancement (DE) imaging using a 3T scanner. A blinded interpreter determined the time to maximal radial wall thickening (TmWT) and myocardial scar burden for each of 16 segments. All potential LV lead targets were ranked according to scar burden (lowest first) and then sub-ranked by TmWT (highest first). All potential RV lead targets were ranked according to scar burden (lowest first). These rankings were encoded onto a surface rendered cardiac model, displayed in standard fluoroscopic views (Figure 1A) and used to direct lead placement by fluoroscopy. A cardiac gated CT was then performed at a 1-month follow-up visit (Figure 1B) to assess procedural success for target achievement. Results

Abnormal Lymphatic Channels Detected by T2-Weighted MR Imaging as a Substrate for Ventricular Arrhythmia in HCM

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder associated with elevated risk of lethal ventricular arrhythmias. While the absence of myocardial fibrosis on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) appears to identify lower risk individuals, approximately two

Predictors of response to cardiac resynchronization therapy on pre-implantation cardiovascular magnetic resonance imaging

Background Cardiac resynchronization therapy (CRT) is an established treatment for severe heart failure. However, up to 40% of patients do not respond. While regional scar distribution has received focused attention, the predictive utility of global markers of remodeling and irreversible injury has not been well explored. Methods Sixty-eight patients receiving CRT underwent pre-implant cardiovascular MRI followed by serial echocardiography at 3 and 6 months. Blinded measurement of Left Ventricular (LV) and Right Ventricular (RV) chamber dimensions, volumes and mass were performed from short axis cine datasets. LV dysynchrony was measured by septal to lateral wall delay. Total LV scar burden was determined from Late Gadolinium Enhancement (LGE) images using manual contour tracing of endocardial and epicardial borders with application of a signal threshold ≥5SD above reference myocardium. Response to CRT was defined as a reduction in LV end-systolic volume (ESV) ≥15% at 6 months. Results The mean age was 66.3 ± 8.9 years with a mean LV Ejection fraction (EF) of 25.2 ± 7.2%. Overall, 47 patients (69%) responded. Among all baseline measures LVEDV (p=0.03), LVESV (p=0.045), RV EF (p=0.0349) and total scar burden (p=0.018) were the only significant predictors of CRT response. Multivariate analysis showed total scar burden to be the only independent predictor of CRT response (p=0.015). Conclusions Pre-implantation MRI offers markers for the prediction of response to CRT. Of these, total scar burden appears to be an independent predictor of response and may be of assistance in the selection of optimal candidates. Funding None

Paced segment characteristics predict clinical response to cardiac resynchronization therapy: results from the multimodality imaging assessment of pacing intervention in heart failure (MAPIT-HF) study

Cardiac Resynchronization Therapy (CRT) has been shown to improve quality of life and decrease mortality in heart failure patients. However, up to 40% of patients fail to respond to this therapy. Validation of a response prediction model that incorporates both myocardial scar and dyssynchrony of the paced myocardial segments would allow for a targeted approach to CRT lead delivery.

Model-Based Navigation of Left and Right Ventricular Leads to Optimal Targets for Cardiac Resynchronization TherapyCLINICAL PERSPECTIVE: A Single-Center Feasibility Study

Background—Left ventricular (LV) and right ventricular pacing site characteristics have been shown to influence response to cardiac resynchronization therapy (CRT). This study aimed to determine the clinical feasibility of image-guided lead delivery using a 3-dimensional navigational model displaying both LV and right ventricular (RV) pacing targets. Serial echocardiographic measures of clinical response and procedural metrics were evaluated. Methods and Results—Thirty-one consecutive patients underwent preimplant cardiac MRI with the generation of a 3-dimensional navigational model depicting optimal segmental targets for LV and RV leads. Lead delivery was guided by the model in matched views to intraprocedural fluoroscopy. Blinded assessment of final lead tip location was performed from postprocedural cardiac computed tomography. Clinical and LV remodeling response criteria were assessed at baseline, 3 months, and 6 months using a 6-minute hall walk, quality of life questionnaire, and echocardiography. Mean age and LV ejection fraction was 66±8 years and 26±8%, respectively. LV leads were successfully delivered to a target or adjacent segment in 30 of 31 patients (97%), 68% being nonposterolateral. RV leads were delivered to a target or adjacent segment in 30 of 31 patients (97%), 26% being nonapical. Twenty-three patients (74%) met standard criteria for response (LV end-systolic volume reduction ≥15%), 18 patients (58%) for super-response (LV end-systolic volume reduction ≥30%). LV ejection fraction improved at 6 months (31±8 versus 26±8%, P=0.04). Conclusions—This study demonstrates clinical feasibility of dual cardiac resynchronization therapy lead delivery to optimal targets using a 3-dimensional navigational model. High procedural success, acceptable procedural times, and a low rate of early procedural complications were observed. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01640769.