SUPPLEMENTAL MATERIAL

Supplemental Methods

QRS complex processing

Custom software was used to annotate the beginning and end of the QRS complex of each

beat. Premature ventricular contractions and beats with excessive noise were excluded. The

median QRS complex from the annotated beats was obtained for each lead for each patient.

We first extracted the median QRS complex from each lead, and stretched it to a standard

length of 200 data points using linear interpolation. The stretched QRS complexes from each of

the 12 leads were concatenated into a single vector of 2400 data points. QRSd was then added

to the end of the vector. Therefore, each patient’s QRS complex information was represented by

a feature vector with 2401 elements. The feature vector was standardized by subtracting each

element’s mean and dividing by its standard deviation in the dataset. QRS complex processing

was performed with custom software in MATLAB.

Dimensionality reduction

Dimensionality reduction consists of techniques that distill the amount of information

represented by a large number of variables (“dimensions”) into fewer dimensions. PCA is a well-

established linear dimensionality reduction approach that transforms a set of variables into new

variables, termed “principal components,” that are linearly uncorrelated1. The first component

accounts for the largest amount of variance within the data, while subsequent components

account for sequentially less variance within the data. Performing PCA on high-dimensional

data and retaining only the first few principal components allows a large amount of data

variance to be represented by relatively few dimensions. In this study, we performed PCA on

our dataset of 2401 dimensions. To determine the number of components to retain, we plotted

the percent variance explained by each principal component, and retained the number of
components prior to the greatest drop-off in explained variance (Supplemental Figure 1). We

call the standardized feature vector for the nth patient xn. The nth patient’s score for dimension

one, sn,1, was obtained by mapping xn with a same-dimensional vector of coefficients w1, such

that

sn,1 = xn●w1 (Equation 1).

Similarly, the score for dimension i was obtained as sn,i = xn●wi, where wi is the mapping

vector for dimension i. Dimensionality reduction analyses were performed in MATLAB.

K-means clustering

Once we embedded the QRS complex information into a two-dimensional space using PCA, we

used k-means clustering to aggregate patients into groups based on their QRS PCA

representation. K-means clustering is a popular clustering algorithm that partitions data points

into k number of clusters such that each data point is a member of the cluster with the closest

mean value2. Because a binary cutoff is typically identified for ECG metrics to stratify risk, we

used k=2 to identify two groups. K=3 and k=4 were also assessed to determine if any additional

patterns emerged. We used 1000 replicates to obtain consistent clusters, and we used

Euclidean distance to compute the clusters. Clustering was performed in MATLAB.

QRS PCA stability

Stability of the mapping vectors wi was assessed by repeating PCA on subsets of the data

generated by randomly sampling 10%, 20%, 30%, …, 90% of the available observations and

plotting wi.

QRS lead subset analysis

To evaluate the impact of coordinated analysis of all 12 leads, we repeated the PCA and

unsupervised clustering process using subsets of the ECG leads and examined the primary
outcomes between the unsupervised clustering groups. We assessed the following lead

subsets: each of the individual leads, the set of precordial leads (V1-V6), the set of lateral leads

(I, aVL, V5, V6), and the linearly independent leads (I, II, V1-V6).

Validation analysis

In the validation analysis, the objective was to directly apply the QRS PCA transformation that

was derived on the Primary Cohort to new data. The same mathematical operations that were

used to obtain the QRS PCA representation from the 12-lead QRS patterns from patients in the

Primary Cohort were used to generate QRS PCA representations from 12-lead QRS patterns of

patients in the validation cohorts. Patients in the validation cohorts were assigned to one of two

groups. Group were assigned based on which of the two cluster centroids defined by k-means

clustering on the Primary Cohort had the shortest distance to the two-dimensional QRS PCA

representation of patients in the validation cohorts.

Cluster stability

To assess cluster stability, the PCA and clustering process was independently repeated in the

validation cohorts. The patient characteristics and clinical outcomes of the groups identified by

repeating the clustering process in the validation cohorts were compared to those identified in

the Primary Cohort. In addition, the overlap of the groups identified by repeating the PCA and

clustering process in the validation cohorts with the groups identified by applying the PCA

mapping vector and clusters derived from the Primary Cohort was quantified.

Alternative forms of dimensionality reduction

PCA is a linear method of dimensionality reduction, and thus may not capture nonlinear

relationships when distilling information from a high-dimensional space. The dimensionality

reduction process was also attempted with non-linear methods followed by k-means clustering.
Primary outcomes were compared between the identified groups. The following non-linear

methods were assessed: t-distributed stochastic network embedding (t-SNE), isomap, locally

linear embedding (LLE), and multidimensional scaling (MDS). This sub-analysis was conducted

across the entire study population.

Alternative ECG inputs to clustering

The primary analysis used PCA on feature vectors of 12-lead QRS waveforms and QRSd.

Alternative feature vectors were also assessed, including (1) 12-lead QRS waveforms without

QRSd, (2) 12-lead waveforms and QRS area, and (3) 12-lead waveforms and both QRSd and

QRS area. Additionally, the effect of reducing 12-lead QRS waveforms to 2 dimensions, then (4)

adding QRSd as a third dimension, (5) adding QRS area as a third dimension, or (6) adding

QRSd as a third dimension and QRS area as a fourth dimension, prior to k-means clustering

was assessed. The primary outcomes of the two groups identified after k-means clustering with

the 6 aforementioned ECG inputs were assessed. The percent overlap in cluster assignment

compared to the primary PCA and clustering method was also computed. This sub-analysis was

conducted across the entire study population.

Supervised machine learning approach

To assess the impact of using a supervised learning approach, machine learning classifiers

were trained to predict CRT response using ECG variables. CRT response was defined by

absolute LVEF improvement greater than 10%.

First, we assessed the impact of adding QRS area and QRS PCA representation to an

ECG-only model. The baseline classifier was a logistic regression of QRSd and presence of

LBBB. The classifier was also compared to a QRS area alone, QRS PCA dimensions alone,

and logistic regression and random forest using input of QRSd, presence of LBBB, QRS area,

and QRS PCA dimensions.

 Second, we assessed the impact of adding QRS area and QRS PCA representation to a

baseline classifier model using 9 common clinical variables3 (QRSd, QRS morphology, gender,

ischemic etiology of cardiomyopathy, NYHA status, LVEF, LVEDD, history of atrial fibrillation,

and epicardial LV lead). This baseline classifier was compared to a random forest model with

the same variables, and both a logistic regression a

The mean area under curve (AUC) of classifiers were evaluated through 100 iterations

of 5-fold cross-validation on the Primary Cohort. Statistical significance to the baseline classifier

during cross-validation was evaluated using a modified t-test for repeated iterations of cross-

validation.

After cross-validation, the best-performing classifier was trained on the entirety of the

Primary Cohort, and tested on the validation cohorts. The AUC of predictions on the Echo

Validation Cohort was computed. Models incorporating clinical variables were unable to be

assessed on the Echo Validation Cohort due to unavailable necessary clinical data. In the

Survival Validation Cohort, the c-index of the classifier output was computed. C-indexes for

discriminating long-term survival were computed and compared with the nonparametric method

by Kang et al4.

Left ventricular lead location analysis

LV lead location was determined radiographically using lateral and posteroanterior chest x-ray

after CRT implant. LV lead location was categorized along the longitudinal axis (basal,

midventricle, or apical) as well as the short axis (posterior, lateral, or anterior). First, primary

outcomes were compared between locations on the long axis as well as between locations on

the short axis. Next, primary outcomes ( (1) survival free from death, LVAD, or heart transplant

and (2) degree of LVEF change) were compared between lead locations within QRS PCA

groups to assess for any significant interactions between QRS PCA groups and lead location.
Supplemental References

1. Jolliffe IT, Cadima J. Principal component analysis: a review and recent developments.

Philos Trans A Math Phys Eng Sci. 2016; 374.

2. Berkhin P. Grouping Multidimensional Data: Recent Advances in Clustering (Springer Berlin

Heidelberg, 2006). (eds. Kogan, J., Nicholas, C. & Teboulle, M.) 25–71 doi:10.1007/3-540-

28349-8_2.

3. Feeny AK, Rickard J, Patel D, Toro S, Trulock KM, Park CJ, LaBarbera MA, Varma N,

Niebauer MJ, Sinha S, et al. Machine Learning Prediction of Response to Cardiac

Resynchronization Therapy. Circ Arrhythm Electrophysiol. 2019; 12, e007316.

4. Kang L, Chen W, Petrick NA, Gallas BD. Comparing two correlated C indices with right-

censored survival outcome: a one-shot nonparametric approach. Stat Med. 2015; 34, 685–

703.
Supplemental Table 1. Baseline characteristics in the Primary Cohort

QRS PCA QRS PCA

Entire cohort
Group 1 Group 2 p
(n=539)
(n=305) (n=234)

Demographics and medical history

Age (years) 66.5±11.9 65.8±12.2 67.4±11.5 0.12

Male sex 345 (64.2%) 166 (54.6%) 179 (76.8%) <0.001

Body mass index (kg/m2) 28.9 ± 6.1 28.8 ± 6.0 29.0 ± 6.3 0.62

Ischemic cardiomyopathy 273 (50.6%) 120 (39.3%) 153 (65.4%) <0.001

NYHA functional class 0.27

I 6 ( 1.1%) 3 ( 1.0%) 3 ( 1.3%)

II 64 (11.9%) 38 (12.5%) 26 (11.1%)

III 445 (82.6%) 255 (83.6%) 190 (81.2%)

IV 24 ( 4.5%) 9 ( 3.0%) 15 ( 6.4%)

History of atrial fibrillation 271 (50.3%) 132 (43.3%) 139 (59.4%) <0.001

Hypertension 345 (64.0%) 201 (65.9%) 144 (61.5%) 0.34

Tobacco use 325 (60.7%) 181 (59.9%) 144 (61.8%) 0.73

Hyperlipidemia 330 (61.2%) 180 (59.0%) 150 (64.1%) 0.27

Chronic obstructive
82 (15.2%) 47 (15.4%) 35 (15.0%) 0.98
pulmonary disease

Cerebrovascular accident or
61 (11.3%) 34 (11.1%) 27 (11.5%) 0.99
transient ischemic attack

History of malignancy 77 (14.3%) 43 (14.1%) 34 (14.5%) 0.99

End-stage renal disease on

17 ( 3.2%) 5 ( 1.6%) 12 ( 5.1%) 0.041
hemodialysis

Diabetes mellitus 212 (39.3%) 123 (40.3%) 89 (38.0%) 0.65

Echocardiography

LVEF (%) 23.2 ± 8.4 23.0 ± 8.4 23.3 ± 8.5 0.70

LVEDD (cm) 6.1 ± 1.0 6.0 ± 1.1 6.1 ± 1.0 0.75

LVESD (cm) 5.1 ± 1.2 5.1 ± 1.2 5.1 ± 1.1 0.81

MR grade (1-9) 3 [1.0-5.0] 3.0 [1.0-5.0] 3.5 [2.0-5.0] 0.24

Electrocardiography

QRS area (μVs) 111.5 ± 47.2 138.9 ± 41.3 75.8 ± 25.8 <0.001

QRSd (ms) 155.9 ± 20.6 160.5 ± 20.1 149.9 ± 19.7 <0.001

LBBB 352 (65.3%) 274 (89.8%) 78 (33.3%) <0.001

RBBB 57 (10.9%) 0 ( 0.0%) 57 (25.2%) <0.001

IVCD 130 (24.1%) 31 (10.2%) 99 (42.3%) <0.001

Laboratory

Serum creatinine (mg/dL) 1.1 [0.9-1.4] 1.0 [0.8-1.3] 1.2 [0.9-1.6] <0.001

White blood cell count (109

7.5 ± 2.5 7.5 ± 2.4 7.6 ± 2.6 0.71
cells/L)

Hemoglobin (g/dL) 12.7 ± 1.9 12.8 ± 1.8 12.5 ± 2.0 0.16

Pharmacotherapy

Beta-blocker 462 (88.0%) 263 (89.2%) 199 (86.5%) 0.43

Angiotensin converting

enzyme inhibitor or 432 (82.3%) 247 (83.7%) 185 (80.4%) 0.39

angiotensin-receptor blocker

Diuretic 402 (76.6%) 225 (76.3%) 177 (77.0%) 0.94

Nitrate 129 (24.6%) 58 (19.7%) 71 (30.9%) 0.004

Hydralazine 59 (11.2%) 32 (10.8%) 27 (11.7%) 0.86

Aldosterone antagonist 173 (33.0%) 96 (32.5%) 77 (33.5%) 0.89

Statin 305 (58.1%) 159 (53.9%) 146 (63.5%) 0.034

 Warfarin 143 (27.2%) 63 (21.4%) 80 (34.8%) 0.001

Clopidogrel 77 (14.7%) 43 (14.6%) 34 (14.8%) 0.99

Digoxin 168 (32.0%) 87 (29.5%) 81 (35.2%) 0.19

Antiarrhythmic 79 (15.0%) 32 (10.8%) 47 (20.4%) 0.003

Aspirin 343 (65.3%) 199 (67.2 %) 144 (62.6%) 0.29

Outcomes

Median follow-up time

7.2 [3.9-9.8]
(years)

Composite endpoint 306 (57%)

Deaths 277 (51%)

LVAD placement 9 (0.2%)

Heart transplant 129 (24.6%)

Echocardiogram follow-up
9.1 [5.7-16.1]
(months)

Echocardiogram follow-up
22 (4%)
less than 60 days

LVEF change 8.5% ± 11.7%.

Normally distributed variables are reported as mean ± standard deviation. Non-normally

distributed variables are reported as median [25th-75th percentile]. Categorical variables are

reported as n (%). PCA = principal components analysis. NYHA = New York Heart Association.

LVEF = left ventricular ejection fraction. LVEDD = left ventricular end-diastolic diameter. LVESD

= left ventricular end-systolic diameter. MR = mitral regurgitation. LBBB = left bundle branch

block. RBBB = right bundle branch block. IVCD = intraventricular conduction delay.
Supplemental Table 2. Primary outcomes in subgroups of the Primary Cohort: (1) Cox

proportional hazards model for death, heart transplantation, or LVAD, and (2) LVEF

change

Composite
LVEF %
endpoint
p change p
hazard ratio
(mean ± SD)
[95% CI]

Entire cohort (n = 539)

QRS PCA Group 2 (n = 234) vs. 4.6 ± 10.0 vs.

0.44 [0.35-0.55] <0.001 <0.001
QRS PCA Group 1 (n = 305) 11.4 ± 12.1

Non-LBBB (n = 187) vs. 3.7 ± 10.1 vs.

0.50 [0.40-0.63] <0.001 <0.001
LBBB (n = 352) 11.0 ± 11.8

QRS area ≤95 (n = 227) vs. 4.6 ± 10.1 vs.

0.50 [0.40-0.63] <0.001 <0.001
QRS area >95 (n = 315) 11.3 ± 12.1

LBBB (n = 352)

QRS PCA Group 2 (n = 78) vs. 6.1 ± 9.2 vs.

0.42 [0.30-0.58] <0.001 <0.001
QRS PCA Group 1 (n = 274) 12.4 ± 12.0

QRSd <150 (n = 95) vs. 9.3 ± 11.6 vs.

0.86 [0.62-1.20] 0.38 0.091
QRSd ≥150 (n = 257) 11.7 ± 11.8

QRS area ≤95 (n = 77) vs. 6.4 ± 9.5 vs.

0.47 [0.34-0.65] <0.001 <0.001
QRS area >95 (n = 275) 12.3 ± 12.0

LBBB and QRSd ≥150 (n = 257)

QRS PCA Group 2 (n = 49) vs. 6.9 ± 8.4 vs.

0.36 [0.24-0.54] <0.001 0.003
QRS PCA Group 1 (n = 208) 12.8 ± 12.2

QRS area ≤95 (n = 34) vs. 7.9 ± 8.8 vs.

0.39 [0.25-0.60] <0.001 0.054
QRS area >95 (n = 223) 12.2 ± 12.1
Non-LBBB (n = 187)

QRS PCA Group 2 (n = 156) vs. 3.9 ± 10.4 vs.

0.78 [0.48-1.27] 0.31 0.47
QRS PCA Group 1 (n = 31) 2.4 ± 8.8

QRSd <150 (n = 115) vs. 2.7 ± 9.9 vs.

0.78 [0.55-1.12] 0.18 0.11
QRSd ≥150 (n = 72) 5.2 ± 10.4

QRS area ≤95 (n = 147) vs. 3.7 ± 10.3 vs.

0.98 [0.65-1.48] 0.93 0.98
QRS area >95 (n = 40) 3.7 ± 9.7

QRSd <150 (n = 210)

QRS PCA Group 2 (n = 119) vs. 3.4 ± 10.2 vs.

0.48 [0.34-0.70] <0.001 <0.001
QRS PCA Group 1 (n = 91) 8.9 ± 11.6

Non-LBBB (n = 115) vs. 2.7 ± 9.9 vs.

0.51 [0.36-0.73] <0.001 <0.001
LBBB (n = 95) 9.3 ± 11.6

QRS area ≤95 (n = 140) vs. 3.9 ± 10.0 vs.

0.61 [0.42-0.90] 0.012 <0.001
QRS area >95 (n = 70) 9.6 ± 12.4

QRS PCA Group 1 (n = 305)

Non-LBBB (n = 31) vs. 2.4 ± 8.8 vs.

0.48 [0.30-0.79] 0.004 <0.001
LBBB (n = 274) 12.4 ± 12.0

QRS area ≤95 (n = 43) vs. 8.2 ± 9.7 vs.

0.73 [0.46-1.16] 0.18 0.061
QRS area >95 (n = 262) 11.9 ± 12.4

QRS PCA Group 2 (n = 234)

Non-LBBB (n = 156) vs. 3.9 ± 10.4 vs.

0.91 [0.66-1.26] 0.58 0.14
LBBB (n = 78) 6.1 ± 9.2

QRS area ≤95 (n = 181) vs. 3.8 ± 10.0 vs.

0.77 [0.53-1.11] 0.16 0.017
QRS area >95 (n = 53) 7.6 ± 9.7

QRS area >95 (n = 315)

Non-LBBB (n = 40) vs. 0.41 [0.27-0.62] <0.001 3.7 ± 9.7 vs. <0.001
 LBBB (n = 275) 12.3 ± 12.0

QRS PCA Group 2 (n = 53) vs. 7.6 ± 9.7 vs.

0.50 [0.35-0.73] <0.001 0.019
QRS PCA Group 1 (n = 262) 12.0 ± 12.4

QRS area ≤95 (n = 224)

Non-LBBB (n = 147) vs. 3.7 ± 10.3 vs.

0.87 [0.63-1.22] 0.43 0.061
LBBB (n = 77) 6.4 ± 9.5

QRS PCA Group 2 (n = 181) vs. 3.8 ± 10.0 vs.

0.54 [0.34-0.85] 0.008 0.010
QRS PCA Group 1 (n = 43) 8.2 ± 9.7

QRSd units in ms. QRS area units in μVs. LVAD = left ventricular assist device. LVEF = left

ventricular ejection fraction. CI = confidence interval. SD = standard deviation. LBBB = left

bundle branch block. PCA = principal components analysis.

Supplemental Table 3. Baseline characteristics in the Survival Validation Cohort
QRS PCA QRS PCA
Entire cohort
Group 1 Group 2 p
(n=301)
(n =149) (n=152)

Demographics and medical history

Age (years) 66.7±10.9 66.1±10.6 67.4±11.2 0.31

Male sex 217 (72.6%) 95 (64.6%) 122 (80.3%) 0.004

Body mass index (kg/m2) 28.37±6.22 28.9±6.4 27.8±6.0 0.14

Ischemic cardiomyopathy 197 (65.4%) 82 (55.0%) 115 (75.7%) <0.001

NYHA functional class 0.019

I 5 ( 1.6%) 5 ( 3.4%) 0 ( 0.0%)

II 23 ( 7.6%) 16 (10.7%) 7 ( 4.6%)

III 256 (85.0%) 123 (82.6%) 133 (87.5%)

IV 17 ( 5.6%) 5 ( 3.4%) 12 ( 7.9%)

History of atrial fibrillation 130 (43.2%) 60 (40.3%) 70 (46.1%) 0.37

Hypertension 187 (62.1%) 97 (65.1%) 90 (59.2%) 0.35

Tobacco use 169 (57.7%) 82 (56.2%) 87 (59.2%) 0.69

Hyperlipidemia 172 (57.1%) 79 (53.0%) 93 (61.2%) 0.19

Chronic obstructive

pulmonary disease 34 (11.3%) 17 (11.4%) 17 (11.2%) 0.99

Cerebrovascular accident or

transient ischemic attack 30 (10.0%) 10 ( 6.7%) 20 (13.2%) 0.094

History of malignancy 23 ( 7.6%) 11 ( 7.4%) 12 ( 7.9%) 0.99

End-stage renal disease on

hemodialysis 6 ( 2.0%) 2 ( 1.3%) 4 ( 2.6%) 0.70

Diabetes mellitus 110 (36.5%) 52 (34.9%) 58 (38.2%) 0.64

Echocardiography

LVEF (%) 22.3±8.9 22.2±8.6 22.5±9.2 0.83

LVEDD (cm) 6.2±1.0 6.1±1.2 6.2±0.9 0.83

LVESD (cm) 5.3±1.7 5.4±2.2 5.2±1.0 0.41

MR grade (1-9) 4.0 [2.0-5.0] 4.0 [2.0-5.0] 4.0 [1.8-5.0] 0.68

Electrocardiography

QRS area (μVs) 104.1±47.9 133.8±47.0 75.0±25.9 <0.001

QRSd (ms) 156.2±21.2 159.20±22.5 153.2±19.4 0.013

LBBB 164 (54.5%) 120 (80.5%) 44 (28.9%) <0.001

RBBB 52 (17.3%) 1 ( 0.7%) 51 (33.6%) <0.001

IVCD 79 (26.2%) 23 (15.4%) 56 (36.8%) <0.001

Laboratory

Serum creatinine (mg/dL) 1.2 [0.9-1.6] 1.1 [0.9-1.4] 1.3 [1.0, 1.8] 0.001

White blood cell count (109

cells/L) 7.7±2.5 7.6±2.4 7.7±2.6 0.73

Hemoglobin (g/dL) 12.2±2.1 12.4±2.0 11.9±2.2 0.032

Pharmacotherapy

Beta-blocker 246 (84.2%) 134 (91.8%) 112 (76.7%) 0.001

Angiotensin converting

enzyme inhibitor or

angiotensin-receptor blocker 212 (72.6%) 114 (78.1%) 98 (67.1%) 0.049

Diuretic 223 (76.4%) 109 (74.7%) 114 (78.1%) 0.58

Nitrate 72 (24.7%) 32 (21.9%) 40 (27.6%) 0.33

Hydralazine 35 (12.0%) 13 ( 8.9%) 22 (15.2%) 0.14

Aldosterone antagonist 109 (37.5%) 55 (37.7%) 54 (37.2%) 0.99

Statin 165 (56.7%) 76 (52.1%) 89 (61.4%) 0.14

 Warfarin 93 (32.0%) 41 (28.1%) 52 (35.9%) 0.20

Clopidogrel 39 (13.4%) 16 (11.0%) 23 (15.9%) 0.29

Digoxin 98 (33.7%) 50 (34.2%) 48 (33.1%) 0.93

Antiarrhythmic 51 (17.5%) 19 (13.0%) 32 (22.1%) 0.060

Aspirin 193 (66.1%) 88 (60.3%) 105 (71.9%) 0.048

Outcomes

Median follow-up time

5.4 [1.2-8.9]
(years)

Composite endpoint 207 (69%)

Deaths 198 (66%)

LVAD placement 4 (1.3%)

Heart transplant 5 (1.7%)

Normally distributed variables are reported as mean ± standard deviation. Non-normally

distributed variables are reported as median [25th-75th percentile]. Categorical variables are

reported as n (%). PCA = principal components analysis. NYHA = New York Heart Association.

LVEF = left ventricular ejection fraction. LVEDD = left ventricular end-diastolic diameter. LVESD

= left ventricular end-systolic diameter. MR = mitral regurgitation. LBBB = left bundle branch

block. RBBB = right bundle branch block. IVCD = intraventricular conduction delay.
Supplemental Table 4. Event-free survival in the Survival Validation Cohort: Cox

proportional hazards model for death, heart transplantation, or left ventricular assist

device

Composite endpoint
p
hazard ratio [95% CI]
Entire cohort (n = 301)
QRS PCA Group 2 (n = 152) vs.
QRS PCA Group 1 (n = 149) 0.49 [0.37-0.65] <0.001
Non-LBBB (n = 137) vs.
LBBB (n = 164) 0.58 [0.44-0.77] <0.001
QRS area ≤95 (n = 143) vs.
QRS area >95 (n = 158) 0.43 [0.32-0.56] <0.001
LBBB (n = 164)
QRS PCA Group 2 (n = 44) vs.
QRS PCA Group 1 (n = 120) 0.43 [0.29-0.65] <0.001
QRSd <150 (n = 63) vs.
QRSd ≥150 (n = 101) 0.67 [0.44-1.01] 0.058
QRS area ≤95 (n = 39) vs.
QRS area >95 (n = 125) 0.35 [0.23-0.53] <0.001
LBBB and QRSd ≥150 (n = 101)
QRS PCA Group 2 (n = 35) vs.
QRS PCA Group 1 (n = 66) 0.54 [0.31-0.94] 0.029
QRS area ≤95 (n = 29) vs.
QRS area >95 (n = 72) 0.41 [0.21-0.80] 0.009
Non-LBBB (n = 137)
QRS PCA Group 2 (n = 108) vs.
QRS PCA Group 1 (n = 29) 0.77 [0.47-1.23] 0.27
QRSd <150 (n = 53) vs.
QRSd ≥150 (n = 84) 0.88 [0.60-1.28] 0.51
QRS area ≤95 (n = 104) vs.
QRS area >95 (n = 33) 0.63 [0.40-1.00] 0.048
QRSd <150 (n = 116)
QRS PCA Group 2 (n = 67) vs. 0.46 [0.29-0.72] <0.001
 QRS PCA Group 1 (n = 49)
Non-LBBB (n = 53) vs.
LBBB (n = 63) 0.71 [0.46-1.09] 0.12
QRS area ≤95 (n = 86) vs.
QRS area >95 (n = 30) 0.36 [0.21-0.62] <0.001
QRS PCA Group 1 (n = 149)
Non-LBBB (n = 29) vs.
LBBB (n = 120) 0.56 [0.34-0.92] 0.022
QRS area ≤95 (n = 25) vs.
QRS area >95 (n = 124) 0.53 [0.31-0.90] 0.020
QRS PCA Group 2 (n = 152)
Non-LBBB (n = 108) vs.
LBBB (n = 44) 0.99 [0.68-1.46] 0.98
QRS area ≤95 (n = 118) vs.
QRS area >95 (n = 34) 0.51 [0.32-0.81] 0.004
QRS area >95 (n = 158)
Non-LBBB (n = 33) vs.
LBBB (n = 125) 0.64 [0.39-1.03] 0.065
QRS PCA Group 2 (n = 34) vs.
QRS PCA Group 1 (n = 124) 0.75 [0.46-1.23] 0.26
QRS area ≤95 (n = 143)
Non-LBBB (n = 104) vs.
LBBB (n = 39) 1.09 [0.73-1.62] 0.68
QRS PCA Group 2 (n = 118) vs.
QRS PCA Group 1 (n = 25) 0.70 [0.42-1.18] 0.18

QRSd units in ms. QRS area units in μVs. LVAD = left ventricular assist device. CI = confidence

interval. PCA = principal components analysis. LBBB = left bundle branch block.
Supplemental Table 5. Baseline characteristics in the Echo Validation Cohort
QRS PCA QRS PCA
Entire cohort
Group 1 Group 2 p
(n=106)
(n =67) (n=39)

Demographics and medical history

Age (years) 66.3±13.6 65.4±13.3 68.0±14.2 0.35

Male sex 66 (62.3%) 40 (59.7%) 26 (66.7%) 0.61

Body mass index (kg/m2) 29.8±8.0 29.7±8.3 30.1±7.7 0.81

Echocardiography

LVEF (%) 28.5±8.9 27.9±7.9 29.6±10.4 0.33

LVEDD (cm) 5.9±0.9 5.8±0.9 6.0±0.9 0.42

LVESD (cm) 5.0±0.9 5.0±0.8 5.1±1.0 0.63

Electrocardiography

QRS area (μVs) 111.1±41.6 128.1±38.8 82.0±28.2 <0.001

QRSd (ms) 156.3±17.0 157.7±16.7 153.9±17.5 0.26

LBBB 82 (77.4%) 62 (92.5%) 20 (51.3%) <0.001

RBBB 10 ( 9.4%) 0 ( 0.0%) 10 (25.6%) <0.001

IVCD 14 (13.2%) 5 ( 7.5%) 9 (23.1%) 0.046

Outcomes

Echocardiogram follow-up

time (months) 6.6 ± 1.7

Echocardiogram follow-up

less than 60 days 0 (0%)

LVEF change (%) 8.2 ± 9.4

Normally distributed variables are reported as mean ± standard deviation. Non-normally

distributed variables are reported as median [25th-75th percentile]. Categorical variables are

reported as n (%). PCA = principal components analysis. LVEF = left ventricular ejection

fraction. LVEDD = left ventricular end-diastolic diameter. LVESD = left ventricular end-systolic

diameter. LBBB = left bundle branch block. RBBB = right bundle branch block. IVCD =

intraventricular conduction delay.

Supplemental Table 6. Left ventricular ejection fraction (LVEF) change in the Echo

Validation Cohort

LVEF % change
p
(mean ± SD)
Entire cohort (n = 106)
QRS PCA Group 2 (n = 39) vs.
QRS PCA Group 1 (n = 67) 5.5 ± 7.9 vs. 9.8 ± 10.0 0.025
Non-LBBB (n = 24) vs.
LBBB (n = 82) 2.3 ± 7.3 vs. 10.0 ± 9.3 <0.001
QRS area ≤95 (n = 37) vs.
QRS area >95 (n = 69) 5.0 ± 9.4 vs. 10.0 ± 9.0 0.009
LBBB (n = 82)
QRS PCA Group 2 (n = 20) vs.
QRS PCA Group 1 (n = 62) 7.9 ± 7.5 vs. 10.6 ± 9.8 0.26
QRSd <150 (n = 22) vs.
QRSd ≥150 (n = 60) 7.9 ± 8.0 vs. 10.7 ± 9.7 0.20
QRS area ≤95 (n = 17) vs.
QRS area >95 (n = 65) 7.5 ± 10.9 vs. 10.6 ± 8.9 0.22
LBBB and QRSd ≥150 (n = 60)
QRS PCA Group 2 (n = 15) vs.
QRS PCA Group 1 (n = 45) 8.3 ± 7.3 vs. 11.5 ± 10.3 0.27
QRS area ≤95 (n = 9) vs.
QRS area >95 (n = 51) 8.6 ± 12.5 vs. 11.1 ± 9.2 0.47
Non-LBBB (n = 24)
QRS PCA Group 2 (n = 19) vs.
QRS PCA Group 1 (n = 5) 3.1 ± 7.6 vs. -0.6 ± 5.7 0.33
QRSd <150 (n = 14) vs.
QRSd ≥150 (n = 10) 1.2 ± 6.2 vs. 3.8 ± 8.7 0.41
QRS area ≤95 (n = 20) vs.
QRS area >95 (n = 4) 2.9 ± 7.7 vs. -0.8 ± 4.9 0.37
QRSd <150 (n = 36)
QRS PCA Group 2 (n = 15) vs.
QRS PCA Group 1 (n = 21) 3.4 ± 7.3 vs. 6.6 ± 8.3 0.24
 Non-LBBB (n = 14) vs.
LBBB (n = 22) 1.2 ± 6.2 vs. 7.9 ± 8.0 0.012
QRS area ≤95 (n = 20) vs.
QRS area >95 (n = 16) 3.6 ± 7.8 vs. 7.4 ± 7.9 0.16
QRS PCA Group 1 (n = 67)
Non-LBBB (n = 5) vs.
LBBB (n = 62) -0.6 ± 5.7 vs. 10.6 ± 9.8 0.014
QRS area ≤95 (n = 11) vs.
QRS area >95 (n = 56) 7.7 ± 13.4 vs. 10.2 ± 9.3 0.46
QRS PCA Group 2 (n = 39)
Non-LBBB (n = 19) vs.
LBBB (n = 20) 3.1 ± 7.6 vs. 7.9 ± 7.5 0.053
QRS area ≤95 (n = 26) vs.
QRS area >95 (n = 13) 3.8 ± 7.2 vs. 8.9 ± 8.3 0.056
QRS area >95 (n = 69)
Non-LBBB (n = 4) vs.
LBBB (n = 65) -0.8 ± 4.9 vs. 10.6 ± 8.8 0.014
QRS PCA Group 2 (n = 13) vs.
QRS PCA Group 1 (n = 56) 8.9 ± 8.3 vs. 10.2 ± 9.3 0.65
QRS area ≤95 (n = 37)
Non-LBBB (n = 20) vs.
LBBB (n = 17) 2.9 ± 7.7 vs. 7.5 ± 10.9 0.14
QRS PCA Group 2 (n = 26) vs.
QRS PCA Group 1 (n = 11) 3.8 ± 7.2 vs. 7.7 ± 13.4 0.26

QRSd units in ms. QRS area units in μVs. LVEF = left ventricular ejection fraction. SD =

standard deviation. PCA = principal components analysis. LBBB = left bundle branch block.
Supplemental Table 7: Primary outcomes between unsupervised clustering groups

derived from PCA using lead subsets

Lead subset Composite p LVEF % change p

endpoint (mean ± SD)

hazard ratio

[95% CI]

I 0.60 [0.47-0.75] <0.001 6.3 ± 11.1 vs. 11.2 ± 12.0 <0.001

II 0.83 [0.66-1.04] 0.11 8.2 ± 11.6 vs. 8.8 ± 11.9 0.54

III 0.87 [0.69-1.09] 0.22 7.3 ± 11.6 vs. 9.7 ± 11.8 0.021

aVR 0.50 [0.40-0.64] <0.001 6.4 ± 11.4 vs. 10.9 ± 11.7 <0.001

aVL 0.71 [0.57-0.89] 0.003 6.9 ± 11.5 vs. 10.1 ± 11.8 0.002

aVF 1.00 [0.80-1.25] 0.99 8.2 ± 11.9 vs. 8.9 ± 11.5 0.51

V1 0.66 [0.50-0.87] 0.003 3.9 ± 8.9 vs. 9.4 ± 12.0 <0.001

V2 0.51 [0.40-0.64] <0.001 3.2 ± 8.1 vs. 10.6 ± 12.3 <0.001

V3 0.64 [0.51-0.80] <0.001 5.6 ± 10.6 vs. 11.3 ± 12.1 <0.001

V4 0.79 [0.63-1.00] 0.049 7.1 ± 11.3 vs. 10.5 ± 12.2 0.001

V5 0.75 [0.6-0.94] 0.014 7.6 ± 11.6 vs. 9.4 ± 11.9 0.085

V6 0.56 [0.44-0.71] <0.001 5.9 ± 10.9 vs. 11.5 ± 12.0 <0.001

Precordial (V1-V6) 0.49 [0.39-0.61] <0.001 3.4 ± 9.2 vs. 11.3 ± 12.0 <0.001

Lateral (I, aVL, V5, V6) 0.6 [0.47-0.76] <0.001 6.5 ± 11.1 vs. 11.6 ± 12.0 <0.001

Independent (I, II, V1-V6) 0.44 [0.35-0.55] <0.001 4.1 ± 9.6 vs. 11.3 ± 12.1 <0.001

12 leads 0.44 [0.35-0.55] <0.001 4.6 ± 10.0 vs. 11.4 ± 12.1 <0.001
Hazard ratios and LVEF change comparisons were made with Group 2 vs Group 1. PCA =

principal components analysis. CI = confidence interval. LVEF = left ventricular ejection fraction.

SD = standard deviation.
Supplemental Table 8: Primary outcomes in groups identified by independently repeating

PCA and k-means clustering in validation cohorts

Percent Composite
LVEF %
overlap in endpoint
Validation method p change p
cluster hazard ratio
(mean ± SD)
assignment [95% CI]

Applying PCA mapping

vector and nearest cluster

5.5 ± 7.9 vs.
from the Primary Cohort n/a 0.49 [0.37-0.65] <0.001 0.025
9.8 ± 10.0
to each patient in the

validation cohort

Independently repeating

the PCA and clustering 5.7 ± 8.6 vs.

92% 0.53 [0.41-0.70] <0.001 0.079
process on the validation 9.2 ± 9.6

cohorts
Supplemental Table 9: LVEF Responder Rates
Responder Super-responder

(LVEF increase p (LVEF increase p

of at least 5%) of at least 20%)

Entire cohort (n = 946)

QRS PCA Group 2 (n = 425) vs.

50% vs. 69% <0.001 9% vs. 26% <0.001
QRS PCA Group 1 (n = 521)

Non-LBBB (n = 348) vs.

44% vs. 70% <0.001 7% vs. 24% <0.001
LBBB (n = 598)

QRS area ≤95 (n = 404) vs.

49% vs. 69% <0.001 9% vs. 25% <0.001
QRS area >95 (n = 542)

LBBB (n = 598)

QRS PCA Group 2 (n = 142) vs.

60% vs. 73% 0.020 9% vs. 28% <0.001
QRS PCA Group 1 (n = 456)

QRSd <150 (n = 165) vs.

64% vs. 72% 0.086 20% vs. 25% 0.24
QRSd ≥150 (n = 433)

QRS area ≤95 (n = 133) vs.

57% vs. 74% 0.002 12% vs. 27% 0.003
QRS area >95 (n = 465)

LBBB and QRSd ≥150 (n = 433)

QRS PCA Group 2 (n = 87) vs.

66% vs. 74% 0.23 8% vs. 29% <0.001
QRS PCA Group 1 (n = 346)

QRS area ≤95 (n = 56) vs.

65% vs. 73% 0.26 13% vs. 27% 0.045
QRS area >95 (n = 377)

Non-LBBB (n = 348)

QRS PCA Group 2 (n = 283) vs.

45% vs. 36% 0.38 9% vs. 0% 0.076
QRS PCA Group 1 (n = 65)
 QRSd <150 (n = 197) vs.
43% vs. 43% 0.97 5% vs. 11% 0.099
QRSd ≥150 (n = 151)

QRS area ≤95 (n = 271) vs.

45% vs. 37% 0.33 7% vs. 7% 0.98
QRS area >95 (n = 77)

QRSd <150 (n = 362)

QRS PCA Group 2 (n = 201) vs.

46% vs. 62% 0.014 7% vs. 19% 0.006
QRS PCA Group 1 (n = 161)

Non-LBBB (n = 197) vs.

43% vs. 64% 0.002 5% vs. 20% <0.001
LBBB (n = 165)

QRS area ≤95 (n = 246) vs.

47% vs. 65% 0.008 8% vs. 20% 0.0042
QRS area >95 (n = 116)

QRS PCA Group 1 (n = 521)

Non-LBBB (n = 65) vs.

36% vs. 73% <0.001 0% vs. 28% <0.001
LBBB (n = 456)

QRS area ≤95 (n = 79) vs.

58% vs. 71% 0.061 19% vs. 27% 0.23
QRS area >95 (n = 442)

QRS PCA Group 2 (n = 425)

Non-LBBB (n = 283) vs.

45% vs. 60% 0.016 9% vs. 9% 0.95
LBBB (n = 142)

QRS area ≤95 (n = 325) vs.

47% vs. 60% 0.065 7% vs. 16% 0.022
QRS area >95 (n = 100)

QRS area >95 (n = 542)

Non-LBBB (n = 77) vs.

37% vs. 74% <0.001 073% vs. 27% 0.006
LBBB (n = 465)

QRS PCA Group 2 (n = 53) vs.

60% vs. 71% 0.084 16% vs. 27% 0.070
QRS PCA Group 1 (n = 262)
QRS area ≤95 (n = 404)

Non-LBBB (n = 271) vs.

45% vs. 57% 0.065 7% vs. 12% 0.21
LBBB (n = 133)

QRS PCA Group 2 (n = 325) vs.

47% vs. 58% 0.14 7% vs. 19% 0.005
QRS PCA Group 1 (n = 79)
Supplemental Table 10: Secondary outcomes in QRS PCA groups

Primary QRS PCA QRS PCA

p
Cohort Group 1 Group 2

LVEF post-implant (%) 31.7 ± 12.9 34.5 ± 13.1 28.1 ± 11.7 <0.001

LVEDD post-implant (cm) 5.8 ± 1.1 5.5 ± 1.1 6.1 ± 1.0 <0.001

LVESD post-implant (cm) 4.6 ± 1.2 4.3 ± 1.3 5.0 ± 1.1 <0.001

NYHA post-implant 2.1 ± 0.7 2.0 ± 0.7 2.2 ± 0.7 0.001

MR grade post-implant (1-9) 3.0 ± 2.2 2.7 ± 2.2 3.4 ± 2.2 0.001

Change in LVEF (absolute %) 8.5 ± 11.7 11.4 ± 12.1 4.6 ± 10.0 <0.001

Change in LVEDD (cm) -0.3 ± 0.9 -0.6 ± 0.9 0.0 ± 0.8 <0.001

Change in LVESD (cm) -0.5 ± 1.1 -0.8 ± 1.2 -0.1 ± 1.0 <0.001

Change in NYHA class -0.8 ± 0.8 -0.9 ± 0.8 -0.7 ± 0.8 0.003

Change in MR grade -0.5 ± 2.2 -0.7 ± 2.2 -0.2 ± 2.1 0.011

PCA = principal components analysis. LVEF = left ventricular ejection fraction. LVEDD = left

ventricular end-diastolic diameter. LVESD: left ventricular end-systolic diameter. NYHA = New

York Heart Association. MR = mitral regurgitation.

Supplemental Table 11: Primary outcomes in groups identified by nonlinear

dimensionality reduction methods followed by k-means clustering

Dimensionality reduction Composite endpoint p LVEF % change p

method hazard ratio (mean ± SD)

[95% CI] Group 2 vs. Group 1

Group 2 vs. Group 1

t-SNE 4.9 ± 9.9 vs.

0.44 [0.37-0.53] <0.001 11.5 ± 11.7 <0.001

Isomap 4.0 ± 9.2 vs.

0.43 [0.36-0.52] <0.001 10.9 ± 11.7 <0.001

Locally linear embedding 2.9 ± 8.5 vs.

0.60 [0.48-0.76] <0.001 9.3 ± 11.5 <0.001

Multidimensional scaling 4.3 ± 9.4 vs.

0.45 [0.38-0.54] <0.001 10.8 ± 11.7 <0.001

Supplemental Table 12. Primary outcomes of groups identified using different ECG

clustering input

Composite
Overlap in LVEF %
endpoint
Clustering input cluster p change p
hazard ratio
assignment (mean ± SD)
[95% CI]

QRS waveforms, QRSd 4.3 ± 9.4 vs.

n/a 0.45 [0.38-0.54] <0.001 <0.001
reduced to 2 dimensions 10.8 ± 11.7

QRS waveforms reduced to 4.3 ± 9.4 vs.

99.9% 0.45 [0.38-0.54] <0.001 <0.001
2 dimensions 10.8 ± 11.7

QRS waveforms, QRS area 4.3 ± 9.4 vs.

100% 0.45 [0.38-0.54] <0.001 <0.001
reduced to 2 dimensions 10.8 ± 11.7

QRS waveforms, QRSd,

4.3 ± 9.4 vs.
QRS area reduced to 2 100% 0.45 [0.38-0.54] <0.001 <0.001
10.8 ± 11.7
dimensions

QRS waveforms reduced to

4.5 ± 9.6 vs.
2 dimensions, QRSd added 82.9% 0.48 [0.40-0.57] <0.001 <0.001
11.6 ± 11.7
as a 3rd dimension

QRS waveforms reduced to 6.1 ± 10.6

2 dimensions, QRS area 73.5% 0.49 [0.41-0.60] <0.001 vs. <0.001

added as a 3rd dimension 12.1 ± 11.6

QRS waveforms reduced to

6.1 ± 10.6
2 dimensions, QRSd added
73.5% 0.48 [0.40-0.59] <0.001 vs. <0.001
as 3rd dimension, QRS area
12.1 ± 11.5
added as a 4th dimension
Supplemental Table 13. Multivariable models for primary outcomes

LVEF %
Hazard coefficient
change
for death, heart
p regression p
transplant, or
coefficient ±
LVAD [95% CI]
standard error

Age 1.02 [1.01-1.03] <0.001 0.01 ± 0.04 0.86

Male sex 1.40 [1.13-1.75] 0.003 -2.5 ± 1.1 0.024

Ischemic cardiomyopathy 1.45 [1.18-1.79] <0.001 -3.7 ± 1.1 <0.001

QRS duration <150 ms 1.28 [1.06-1.54] 0.010 -2.7 ± 1.1 0.011

Non-LBBB 1.14 [0.91-1.43] 0.27 -3.0 ± 1.4 0.026

History of atrial fibrillation 1.29 [1.08-1.56] 0.005 -1.2 ± 1.0 0.22

Creatinine >1.2 mg/dL 1.62 [1.34-1.95] <0.001 -1.0 ± 1.1 0.34

End-stage renal disease

1.66 [1.01-2.70] 0.044 -4.1 ± 2.9 0.15
hemodialysis

QRS PCA Group 2 (low

1.50 [1.20-1.88] <0.001 -2.3 ± 1.3 0.07
QRS PCA score)

LVAD = left ventricular assist device. CI = confidence interval. LVEF = left ventricular ejection

fraction. LBBB = left bundle branch block. PCA = principal components analysis.
Supplemental Table 14. Results of supervised machine learning classification

Cross-validation results: Effect of adding QRS area, QRS PCA to QRSd and LBBB

P
P
Model Mean area under curve (versus QRS
(versus LR 1)
PCA score)

LR 1: Logistic regression

using QRSd and presence 0.61 ± 0.04 n/a <0.001

of LBBB

QRS area 0.66 ± 0.05 0.010 0.13

QRS PCA score 0.67 ± 0.05 <0.001 n/a

Logistic regression: QRSd,

LBBB, QRS area, QRS PCA 0.68 ± 0.05 <0.001 0.57

representation

Random forest: QRSd,

LBBB, QRS area, QRS PCA 0.66 ± 0.05 0.016 0.11

representation

Cross-validation results: Effect of adding QRS area, QRS PCA to clinical variables

P
Model Mean area under curve
(versus LR 2)

LR 2: Logistic regression
0.72 ± 0.05 n/a
with 9 clinical variables

Random forest: 9 clinical

0.70 ± 0.05 0.35
variables
Logistic regression: 9 clinical

variables, QRS area, QRS 0.72 ± 0.05 0.86

PCA representation

Random forest: 9 clinical

variables, QRS area, QRS 0.70 ± 0.05 0.41

PCA representation

Testing results: echo validation (n = 106)

P
Area under curve
Model P (versus LR 1) (versus QRS
[95% CI]
PCA Score)

LR 1: Logistic regression
0.69 [0.59 – 0.79] n/a 0.65
(QRSd, LBBB)

QRS PCA Score 0.66 [0.55 – 0.76] 0.65 n/a

QRS area 0.69 [0.59 – 0.80] 0.89 0.38

Logistic regression (QRSd,

0.70 [0.60 – 0.80] 0.80 0.09
LBBB, QRS PCA, QRS area)

Testing results: survival validation (n = 301)

Effect of adding QRS area, QRS PCA to QRSd and LBBB

Model C-index P (versus LR 1)

LR1 (QRSd, LBBB) 0.583 n/a

Logistic regression (QRSd, LBBB,

QRS PCA, QRS area) 0.625 <0.001

Testing results: survival validation (n = 301)

 Effect of adding QRS area, QRS PCA to 9 clinical variables

Model C-index P (versus LR 2)

LR 2 (9 common clinical variables) 0.598 n/a

Logistic regression: 9 clinical

variables, QRS area, QRS PCA

representation 0.610 0.009

Supplemental Table 15. Primary outcomes of reclassified patients by using QRS area and

QRS PCA groups to stratify QRS morphology instead of QRS duration: (1) Cox

proportional hazards model for death, heart transplantation, or LVAD, and (2) LVEF

change

Composite

endpoint LVEF % change

p p
hazard ratio (mean ± SD)

[95% CI]

LBBB and QRSd ≥150

 n = 433
 n = 373 with survival
 n = 304 with echo
QRS area >95 or QRS PCA Group 1
 n = 397
11.8% ± 11.5%
 n = 343 with survival
 n = 282 with echo 0.29
<0.001 0.041
QRS area ≤95 and QRS PCA Group 2 [0.19 – 0.44]
 n = 36
6.7% ± 7.9%
 n = 30 with survival
 n = 22 with echo
LBBB and QRSd <150
 n = 165
 n = 143 with survival
 n = 116 with echo
QRS area >95 or QRS PCA Group 1
 n = 116
11.3% ± 11.1%
 n = 98 with survival
 n = 86 with echo 0.40
<0.001 <0.001
QRS area ≤95 and QRS PCA Group 2 [0.26 – 0.62]
 n = 49
2.6% ± 7.5%
 n = 45 with survival
 n = 30 with echo
Non-LBBB and QRSd ≥150
 n = 151
 n = 141 with survival
 n = 81 with echo
QRS area >95 or QRS PCA Group 1
 n = 51
5.6% ± 9.2%
 n = 49 with survival
0.86
 n = 24 with echo 0.47 0.73
[0.57 – 1.30]
QRS area ≤95 and QRS PCA Group 2
 n = 100 4.8% ± 10.6%
 n = 92 with survival
  n = 57 with echo
Non-LBBB and QRSd <150
 n = 197
 n = 183 with survival
 n = 122 with echo
QRS area >95 or QRS PCA Group 1
 n = 57
1.7% ± 8.0%
 n = 51 with survival
 n = 31 with echo 0.68
0.052 0.56
QRS area ≤95 and QRS PCA Group 2 [0.46 – 1.00]
 n = 140
2.8% ± 10.0%
 n = 132 with survival
 n = 91 with echo

QRSd units in ms. QRS area units in μVs. PCA = principal components analysis. LVAD = left

ventricular assist device. LVEF = left ventricular ejection fraction. CI = confidence interval. SD =

standard deviation. LBBB = left bundle branch block. PCA = principal components analysis.
Supplemental Figure 1: Percent variance explained by principal components

The percentage of variance explained by each of the first ten principal components. The “elbow”

of the plot occurs at principal component 3, where the largest drop in explained variance

occurred from principal component two to three (15% to 8%). Subsequently, only the first two

principal components were retained.

Supplemental Figure 2: QRS PCA mapping vector stability

In our stability analysis, the mapping vector w1 was obtained by repeating our methods using

only 10%, 20%, 30%, …, 90% of the available patients. w1 showed a robust pattern across

leads, especially as the percentage of included data approached 100%.

Supplemental Figure 3: Clusters and primary outcomes when using k = 3 and k = 4

during k-means clustering.

Clustering using 3 and 4 groups affirmed that survival and reverse remodeling outcomes

improved with greater QRS PCA scores (dimension 1).

Supplemental Figure 4: Interactions between QRS PCA groups and LV lead locations
Supplemental Figure 5: Mapping vectors for QRS PCA and Kors transformation

The mapping vector w1 used to obtain the QRS PCA score is interestingly similar to the Kors

transformation vector* used to reconstruct the Z-axis in vectorcardiography, especially among

the precordial leads. Lead II was the only lead with discrepant coefficients. This suggests that

the QRS area on the VCG Z-axis is a good representation of the dominant component of

variance in patients with conduction delay. Note: the Kors transformation vector does not use

lead III or the augmented limb leads. The Kors transformation coefficients were uniformly

rescaled to match the magnitude of w1 for visualization purposes.