Hospital Volume Outcomes After Septal Myectomy

Research

Original Investigation Hospital Volume Outcomes After Septal Myectomy and Alcohol Septal Ablation for Treatment of Obstructive Hypertrophic Cardiomyopathy US Nationwide Inpatient Database, 2003-2011

Luke K. Kim, MD; Rajesh V. Swaminathan, MD; Patrick Looser, MD; Robert M. Minutello, MD; S. Chiu Wong, MD; Geoffrey Bergman, MD; Srihari S. Naidu, MD; Christopher L. F. Gade, MD; Konstantinos Charitakis, MD; Harsimran S. Singh, MD; Dmitriy N. Feldman, MD

Invited Commentary page 333 IMPORTANCE Previous data on septal myectomy (SM) and alcohol septal ablation (ASA) in and Editor's Note page 334 obstructive hypertrophic cardiomyopathy have been limited to small, nonrandomized, Supplemental content at single-center studies. Use of septal reduction therapy and the effect of institutional jamacardiology.com experience on procedural outcomes nationally are unknown.

OBJECTIVE To examine in-hospital outcomes after SM and ASA stratified by hospital volume within a large, national inpatient database.

DESIGN, SETTING, AND PARTICIPANTS This study analyzed all patients who were hospitalized for SM or ASA in a nationwide inpatient database from January 1, 2003, through December 31, 2011.

MAIN OUTCOMES AND MEASURES Rates of adverse in-hospital events (death, stroke, bleeding, acute renal failure, and need for permanent pacemaker) were examined. Multivariate logistic regression analysis was performed to compare overall outcomes after each procedure based on tertiles of hospital volume of SM and ASA.

RESULTS Of 71 888 761 discharge records reviewed, a total of 11 248 patients underwent septal reduction procedures, of whom 6386 (56.8%) underwent SM and 4862 (43.2%) underwent ASA. A total of 59.9% of institutions performed 10 SM procedures or fewer, whereas 66.9% of institutions performed 10 ASA procedures or fewer during the study period. Incidence of in-hospital death (15.6%, 9.6%, and 3.8%; P < .001), need for permanent pacemaker (10.0%, 13.8%, and 8.9%; P < .001), and bleeding complications (3.3%, 3.8%, and 1.7%; P < .001) after SM was lower in higher-volume centers when stratified by first, second, and third tertiles of hospital volume, respectively. Similarly, there was a lower incidence of death (2.3%, 0.8%, and 0.6%; P = .02) and acute renal failure (6.2%, 7.6%, and 2.4%; P < .001) after ASA in higher-volume centers. The lowest tertile of SM volume among hospitals was an independent predictor of in-hospital all-cause mortality (adjusted odds ratio, 3.11; 95% CI, 1.98-4.89) and bleeding (adjusted odds ratio, 3.77; 95% CI, 2.12-6.70), whereas being in the lowest tertile of ASA by volume was not independently associated with an Author Affiliations: Division of increased risk of adverse postprocedural events. Cardiology, Department of Medicine, Weill Cornell Medical College, New York Presbyterian Hospital, CONCLUSIONS AND RELEVANCE In US hospitals from 2003 through 2011, most centers that New York (Kim, Swaminathan, provide septal reduction therapy performed few SM and ASA procedures, which is below the Looser, Minutello, Wong, Bergman, threshold recommended by the 2011 American College of Cardiology Foundation/American Gade, Charitakis, Singh, Feldman); Division of Cardiology, Winthrop Heart Association Task Force Guideline for the Diagnosis and Treatment of Hypertrophic University Hospital, Mineola, Cardiomyopathy. Low SM volume was associated with worse outcomes, including higher New York (Naidu). mortality, longer length of stay, and higher costs. More efforts are needed to encourage Corresponding Author: Luke K. Kim, referral of patients to centers of excellence for septal reduction therapy. MD, Division of Cardiology, Department of Medicine, Weill Cornell Medical College, New York Presbyterian Hospital, 520 E 70th St, Starr Pavilion, 4th Floor, New York, JAMA Cardiol. 2016;1(3):324-332. doi:10.1001/jamacardio.2016.0252 NY 10021 ([email protected] Published online April 27, 2016. Corrected on January 4, 2017. .edu).

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ypertrophic cardiomyopathy (HCM) is one of the most commonly inherited cardiac conditions, affecting more Key Points than 700 000 people in the United States.1 Left ven- H Question How are septal myectomy and alcohol septal ablation tricular outflow tract (LVOT) obstruction in HCM is associated used in the United States, and what are the in-hospital outcomes with greater propensity to develop heart failure symptoms, ex- after these procedures by institutional procedural volume? ertional syncope, or sudden cardiac death.2 Surgical septal my- Findings In US hospitals from January 1, 2003, through December ectomy (SM), when performed in experienced centers, is con- 31, 2011, most centers that provide septal reduction therapy sidered to be the preferred strategy for relieving LVOT in patients performed few septal myectomy and alcohol septal ablation with HCM who are refractory to medical therapy and are good procedures annually, which is below the threshold recommended surgical candidates.3,4 Previous studies5,6 have revealed the ef- by the 2011 American College of Cardiology Foundation/American ficacy of SM in patients with severe LVOT obstruction and drug- Heart Association Task Force Guideline for the Diagnosis and refractory symptoms of heart failure, resulting in relief of heart Treatment of Hypertrophic Cardiomyopathy. Low septal myectomy volume was associated with worse in-hospital failure symptoms, improved quality of life, and possibly long- outcomes, including higher mortality. term survival. In experienced surgical centers, SM is associated with low periprocedural mortality of less than 1%; how- Meaning More efforts are needed to encourage referral of ever, such results are limited to few dedicated HCM centers with patients to high-volume centers of excellence for septal reduction therapy according to the guidelines. extensive SM experience.7,8 Alcohol septal ablation (ASA) is a minimally invasive alternative to surgery performed via a percutaneous catheter technique by using absolute alcohol to inpatient Sample (NIS) files from January 1, 2003, through De- duce a targeted septal myocardial infarction. Alcohol septal ab- cember 31, 2011.20 The NIS is a 20% stratified sample of all non- lation is performed in patients with certain anatomical criteria federal US hospitals and in 2011 contained deidentified and is favored in those with multiple comorbidities and in those information for 38 590 733 discharges from 1049 hospitals in at high risk for surgical intervention.9,10 Similar to SM, ASA is 46 states. Weill Cornell Medical College determined that in- associated with significant improvement in LVOT gradient, stitutional review board approval and informed consent were symptoms of heart failure, exercise capacity, and low peripro- not required for this study because this study uses a deiden- cedural morbidity and mortality.11,12 tified administrative database. Discharges are weighted based Multiple single- and multicenter studies11-15 from high- on the sampling scheme to permit inferences for a nationally volume centers have revealed the efficacy and safety of SM and representative population.20 Each record in the NIS includes ASA. The 2011 American College of Cardiology Foundation and all procedure and diagnosis International Classification of Dis- American Heart Association Task Force Guideline for the Di- eases (ICD) codes recorded for each patient’s hospital dis- agnosis and Treatment of Hypertrophic Cardiomyopathy rec- charge. From January 1, 2003, through December 31, 2011, hos- ommend that septal reduction therapy be performed only by pitalizations that led to SM and ASA were selected by searching experienced operators in dedicated HCM clinical programs.4 for the International Classification of Diseases, Ninth Revi- However, it is unknown whether patients are being referred sion, Clinical Modification (ICD-9-CM) procedure codes 37.33 to these centers of excellence for SM or ASA and whether pa- for SM and 37.34 for ASA in any of the 15 procedure fields in tients with higher surgical risk profiles are indeed being re- the database. Only adults with HCM were included by select- ferred preferentially to experienced centers for ASA as recom- ing for ICD-9 code 425.1 in the primary diagnosis. mended by the guidelines. In addition, higher-volume centers overall tend to have better surgical outcomes compared with Definition and End Points low-volume centers in a variety of cardiovascular proce- Patient-level and hospital-level variables were included as base- dures, such as coronary artery bypass surgery, carotid endar- line characteristics (eTable in the Supplement). Hospital- terectomy, heart transplantation, and acute aortic dissection level data elements were derived from the American Hospital repair.16-19 However, given the low prevalence of septal reduc- Association Annual Survey Database. The Agency for Health- tion procedures, data on the association between procedural care Research and Quality comorbidity measures based on the experience and outcomes after SM and ASA are limited. There- Elixhauser methods were used to identify comorbid fore, we sought to evaluate the trends, characteristics, and in- conditions.21 The outcome measures examined included in- hospital outcomes after SM and ASA and, importantly, to ex- hospital all-cause mortality, need for permanent pacemaker amine the association between institutional procedural volume (PPM), stroke, bleeding, and acute renal failure (ARF). Stroke and outcomes after each procedure in a large, comprehen- was identified using ICD-9 codes 997.02, 362.31, 368.12, 781.4, sive national database of hospital discharges from January 1, 433.11, 435, and 434. Major bleeding was identified by ICD-9 2003, through December 31, 2011. codes 430 to 432, 578.X, 719.1X, 423.0, 599.7, 626.2, 626.6, 626.8, 627.0, 627.1, 786.3, 784.7, and 459.0. Need for PPM was selected by ICD-9-CM procedure codes 37.80 to 83. Acute re- Methods nal failure was identified by ICD-9 code 584. Data Source and Study Population Statistical Analysis Data were obtained from Agency for Healthcare Research and For descriptive analyses, we compared baseline patient and Quality Healthcare Cost and Utilization Project Nationwide In- hospital characteristics of those undergoing SM and ASA.

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eling was performed to compare subgroups stratified accord- Figure 1. Number of Septal Myectomy and Alcohol Septal Ablation Procedures Performed Across Sites From January 1, 2003, ing to tertiles of hospital volume (with the third tertile as the Through December 31, 2011 reference), adjusting for all univariate predictors of outcomes (P < .10). Furthermore, we performed a sensitivity analysis by A Septal myectomy excluding any concomitant operations, such as aortic valve 160 surgery, mitral valve repair or replacement, or coronary artery bypass surgery, when performed together with SM and 140 then comparing subgroups stratified according to tertiles of 120 hospital SM volume using multivariable logistic regression 100 analysis. For all regression analyses, the Taylor linearization method with replacement design was used to compute vari- 80 ances. All statistical tests were 2-sided, and P < .05 was set a 60

No. of Hospitals No. priori to be statistically significant. All statistical analyses

40 were conducted using SAS statistical software, version 9.2 (SAS Institute Inc) and SPSS statistical software, version 20 20 a (SPSS, Inc). 0 10 20 30 40 50 60 70 80 90 100 No. of Procedures Results B Alcohol septal ablation

160 Study Population For each year from 2003 through 2011, the NIS data set in- 140 cluded discharges from all hospitals that performed SM and 120 ASA. Of 71 888 761 discharge records reviewed from 2003 through 2011, a total of 11 248 patients underwent septal re- 100 duction procedures, of whom 6386 (56.8%) underwent SM and 80 4862 (43.2%) underwent ASA. The annual rate of SM de-

60 creased by 24.5% from 2.00 procedures per million people per No. of Hospitals No. year in 2003 to 1.51 procedures per million adults per year in 40 2011. On the contrary, the annual rate of ASA increased by 20 56.2% from 1.60 procedures per million people per year in 2003 a 0 to 2.49 procedures per million adults per year in 2011. The 10 20 30 40 50 60 70 80 90 100 trends in overall rates of SM or ASA procedures during the study No. of Cases period, however, were not significant. The median numbers

a More than 100 cases. of cases for SM and ASA were 1.0 and 0.7 per year per institution, respectively. Figure 1 shows the frequency of SM and ASA procedures performed across institutions during the 9-year pe- Continuous variables are presented as medians; categorical riod. Four institutions performed 35.9% of all isolated SM op- variables are expressed as frequencies (percentages). To com- erations (1132 of 3157 cases), whereas 6 institutions per- pare baseline characteristics, Mann-Whitney and Wilcoxon formed 24.1% of all ASA procedures (1173 of 4862 cases). A total nonparametric tests or t tests were used for continuous vari- of 215 (59.9%) of 359 institutions performed 10 SM proce- ables, and Pearson χ2 tests were used for categorical vari- dures or fewer, 282 institutions (78.6%) performed 20 SM pro- ables. We calculated the procedure rates for SM and ASA as cedures or fewer, and 338 institutions (94.2%) performed 50 the weighted number of procedures divided by 20% of the SM procedures or fewer. Similarly, 164 (66.9%) of 245 institu- total number of US adults during the same periods. Estimates tions performed 10 ASA procedures or fewer, 195 institutions of the US adult population from January 1, 2003, through (79.6%) performed 20 ASA procedures or fewer, and 225 in- December 31, 2011, were obtained from the US Census stitutions (91.8%) performed 50 ASA procedures or fewer dur- Bureau.22 Trends in the annual rates of SM and ASA were ing the study period. assessed using time series modeling (autoregressive inte- Table 1 and Table 2 compare baseline characteristics grated moving average model). stratified by hospital volumes (in tertiles) for SM and ASA. Unadjusted rates of in-hospital outcomes were calculated Patients undergoing SM in highest-volume centers were more for subgroups within SM or ASA cohorts stratified according likely to be younger and undergo concomitant coronary to tertiles of hospital procedural volume. Hospital procedural artery bypass graft or valve operations. Highest-volume SM volume was used to divide institutions into tertiles based on centers (third tertile) were more likely to be larger and teach- the volume of SM and ASA performed from January 1, 2003, ing institutions. Length of stay in high-volume SM centers through December 31, 2011. The first tertile was defined as (median, 7.0 vs 8.0 days; P < .001) and cost of hospitalization centers with the lowest procedural volume. Within SM and were lower compared with lower-volume SM centers. ASA cohorts, weighted multivariate logistic regression mod- Patients having ASA performed in lowest- vs highest-volume

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Table 1. Baseline Patient and Hospital Characteristics for Patients Undergoing Septal Myectomy by Hospital Volume, 2003-2011a

Tertile First Second Third Characteristic (n = 120) (n = 120) (n = 119) P Value Age, mean (SD), y 59.9 (17.3) 59.6 (18.8) 55.7 (19.6) <.001 Female sex 375 (65.6) 672 (63.7) 2651 (55.7) <.001 White race 490 (85.7) 836 (79.2) 3921 (82.4) <.001 Hypertension 318 (55.6) 570 (54.0) 2579 (54.2) .80 Diabetes Uncomplicated 55 (9.6) 172 (16.3) 509 (10.7) <.001 Chronic complications 0 26 (2.5) 109 (2.3) .001 Anemia 66 (11.5) 173 (16.4) 647 (13.6) .01 Collagen vascular disease 5 (0.9) 26 (2.5) 67 (1.4) .01 Congestive heart failure 9 (1.6) 36 (3.4) 62 (1.3) <.001 Chronic pulmonary 138 (24.1) 233 (22.1) 923 (19.4) .009 disease Coagulopathy 121 (21.2) 205 (19.4) 795 (16.7) .007 Liver disease 10 (1.7) 11 (1.0) 57 (1.2) .47 Neurologic disorder 19 (3.3) 19 (1.8) 181 (3.8) .006 Obesity 38 (6.6) 166 (15.7) 638 (13.4) <.001 Peripheral vascular 34 (5.9) 66 (6.3) 219 (4.6) .04 disease Chronic renal failure 37 (6.5) 66 (6.3) 247 (5.2) .22 Concomitant CABG 178 (31.1) 262 (24.8) 857 (18.0) <.001 Valve surgery 289 (50.5) 611 (57.9) 2280 (47.9) <.001 Urban setting 526 (92.0) 1028 (97.4) 4745 (99.7) <.001 Payer Medicare 271 (47.3) 528 (50.0) 1918 (40.3) Medicaid 79 (13.8) 78 (7.4) 443 (9.3) <.001 Private 185 (32.3) 387 (36.7) 2218 (46.6) Uninsured 18 (3.1) 30 (2.8) 81 (1.7) Teaching hospital 283 (49.4) 610 (57.8) 4107 (86.3) <.001 Hospital bed size Small 38 (6.6) 81 (7.7) 286 (6.0) Medium 142 (24.8) 184 (17.4) 504 (10.6) <.001 Large 392 (68.5) 790 (4.9) 3969 (83.4) Hospital region Northeast 48 (8.4) 131 (12.4) 1009 (21.2) Midwest 177 (30.9) 250 (23.7) 1685 (35.4) <.001 South 225 (39.3) 420 (39.8) 1256 (26.4)

West 123 (21.5) 254 (24.1) 804 (16.9) Abbreviation: CABG, coronary artery Length of stay, mean (SD) 11.0 (9.8) [8.0] 11.4 (1.3) [8.0] 1.0 (8.9) [7.0] bypass graft. <.001 [median], d a Data are presented as number Cost, mean (SD) 147 666.6 (103 179.0) 162 203.0 (139 284.1) 146 777.6 (104 087.0) .002 (percentage) of patients unless [median], $ [113 551.8] [116 225.0] [104 087.0] otherwise indicated.

centers (first quartile vs third quartile) were older and more Outcomes Stratified by Hospital Volume likely to have anemia, diabetes mellitus, chronic pulmonary The unadjusted incidence of in-hospital death (15.6%, 9.6%, disease, congestive heart failure, chronic renal failure, and and 3.8%; P < .001), need for PPM (10.0%, 13.8%, and 8.9%; liver disease. Highest-volume centers were more likely to be a P < .001), and bleeding complications (3.3%, 3.8%, and 1.7%; teaching institution and a large hospital. Similarly to SM, P < .001) after SM was higher in lower-volume centers when undergoing ASA in highest-volume centers was associated stratified by first, second, and third tertiles of hospital vol- with shorter length of stay and lower cost of hospitalization. ume, respectively (Figure 2). Similarly, there was a higher in- Median length of hospitalization was significantly longer cidence of death (2.3%, 0.8%, and 0.6%; P = .02) and ARF (6.2%, with SM vs ASA (7.0 vs 3.0 days), with median hospital costs 7.6%, and 2.4%; P < .001) after ASA in lower-volume centers being 2.3 times greater for SM vs ASA. when stratified by first, second, and third tertiles of hospital

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Table 2. Baseline Patient and Hospital Characteristics for Patients Undergoing Alcohol Septal Ablation by Hospital Volume, 2003-2011a

Tertile First Second Third Characteristic (n = 83) (n = 83) (n = 82) P Value Age, mean (SD), y 62.4 (16.4) 59.4 (17.9) 59.2 (14.9) <.001 Female sex 221 (57.1) 293 (47.6) 2057 (53.1) .007 White race 303 (78.2) 456 (74.1) 3316 (85.6) <.001 Hypertension 205 (53.1) 271 (44.0) 2204 (56.9) <.001 Diabetes Uncomplicated 49 (12.6) 108 (17.5) 384 (9.9) <.001 Chronic complications 9 (2.3) 0 23 (0.6) <.001 Anemia 43 (11.0) 64 (10.4) 310 (8.0) .03 Collagen vascular disease 5 (1.3) 0 85 (2.2) .001 Congestive heart failure 18 (4.7) 15 (2.5) 15 (0.4) <.001 Chronic pulmonary disease 70 (18.0) 134 (21.8) 488 (12.6) <.001 Coagulopathy 27 (7.1) 17 (2.7) 101 (2.6) <.001 Liver disease 9 (2.3) 5 (0.8) 70 (1.8) .16 Neurologic disorder 24 (6.3) 26 (4.2) 74 (1.9) <.001 Obesity 38 (9.9) 47 (7.7) 434 (11.2) .04 Peripheral vascular disease 14 (3.7) 22 (3.5) 132 (3.4) .94 Chronic renal failure 38 (9.7) 46 (7.4) 159 (4.1) <.001 Urban setting 383 (99.0) 604 (98.2) 3785 (97.7) .24 Payer Medicare 182 (46.9) 269 (43.7) 1557 (40.2) Medicaid 38 (9.8) 57 (9.2) 225 (5.8) <.001 Private 139 (35.8) 253 (41.1) 1922 (49.6) Uninsured 9 (2.3) 5 (0.8) 77 (2.0) Teaching hospital 224 (57.9) 470 (76.4) 3587 (92.6) <.001 Hospital bed size Small 27 (7.0) 47 (7.6) 186 (4.8) Medium 110 (28.4) 80 (14.5) 325 (8.4) <.001 Large 250 (64.6) 479 (77.9) 3367 (86.9) Hospital region Northeast 42 (10.9) 149 (24.2) 806 (20.8) Midwest 68 (17.6) 203 (33.0) 713 (18.4) <.001 South 176 (45.5) 181 (29.4) 1402 (36.2) West 101 (26.1) 82 (13.3) 949 (24.5) Length of stay, mean (SD) 6.3 (7.5) [4.0] 6.0 (6.5) [4.0] 4.0 (4.8) [3.0] <.001 [median], d a Data are presented as number Cost, mean (SD) 84 040.9 (79 731.5) 77 435.6 (69 216.0) 62 340.2 (60 828.2) <.001 (percentage) of patients unless [median], $ [60 611.0] [53 342.0] [44 940.0] otherwise indicated.

volume, respectively (Figure 2). Being an SM center in the low- associated with increased odds of any in-hospital adverse events est-volume hospital tertile (first vs third tertile of volume) was after multivariable adjustment (Table 4). associated with significantly greater odds of all-cause mortality (adjusted odds ratio [OR], 3.11; 95% CI, 1.98-4.89; P < .001) and bleeding complications (adjusted OR, 3.77; 95% CI, 2.12- Discussion 6.70; P < .001) after adjustment with multivariate propensity score–adjusted logistic regression analysis (Table 3). A sensi- There are several important findings in this nationally repre- tivity analysis, excluding any concomitant operations sentative sample of US hospital discharge records examining performed together with SM, confirmed that SM centers in the outcomes after SM and ASA from January 1, 2003, through De- lowest-volume hospital tertile (first vs third tertile of volume) cember 31, 2011. First, most US institutions perform few SM were associated with significantly greater odds of all-cause mor- and ASA cases annually (defined as <10 per year). Second, un- tality (adjusted OR, 2.50; 95% CI, 1.69-3.69; P < .001) using mul- dergoing SM in centers that rarely perform septal reduction op- tivariable logistic regression analysis. However, lower ASA pro- erations was associated with worse postprocedural out- cedural volume (first vs third tertile of volume) was not comes compared with high-volume centers, with a 3-fold

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Figure 2. Adverse In-Hospital Event Rates After Septal Myectomy and Alcohol Septal Ablation by Tertiles of Hospital Volume

A Septal myectomy

18 Total P <.001 First 16 P <.001 Second 14 Third P =.12 12

6 P <.001 4 P =.23

Adverse In-Hospital Event Rates, % In-Hospital Event Adverse 2

0 Death PPM Stroke Bleeding ARF Total 5.2 9.8 1.8 2.2 9.7 First 15.6 10.0 2.4 3.3 8.6 Second 9.6 13.8 0.9 3.8 11.8 Third 3.8 8.9 1.9 1.7 9.4

B Alcohol septal ablation

16 P =.16

10 P <.001 8

4 P =.02 P =.80

Adverse In-Hospital Event Rates, % In-Hospital Event Adverse 2 P =.63

0 Death PPM Stroke Bleeding ARF Total 0.7 11.9 0.0 2.0 3.3 First 2.3 14.2 0.0 2.3 6.2 Second 0.8 12.4 0.0 1.6 7.6 Third 0.6 11.5 0.4 2.1 2.4 ARF indicates acute renal failure; PPM, permanent pacemaker.

higher mortality (in first- vs third-tertile institutions by vol- ited experience with this operation. However, when the first ume). On the other hand, undergoing ASA in lower-volume in- tertile of experience is excluded, mortality more closely mir- stitutions was not associated with worse outcomes after ASA rored that seen at major referral centers. A previous study24 compared with high-volume ASA centers. found an effect of an operator or institution learning curve, em- Our study is the first, to our knowledge, to report a na- phasizing the importance of surgical operator volume. Septal tionally representative experience with SM and ASA across a myectomy can be a technically demanding operation, with few representative spectrum of more than 1000 hospitals. Previ- centers currently having extensive surgical expertise in the pro- ous studies11-15 examining outcomes after these 2 procedures cedure. Most surgical centers perform 1 to 2 SM operations per were primarily retrospective from experienced single-center year as opposed to other commonly performed cardiac opera- institutions. In the early reports of SM, perioperative mortal- tions, such as coronary artery bypass and valve operations.25 ity was relatively high (≥5%), whereas more recent surgical re- Thus, previous reports4,26 of less than 1% postoperative mor- sults have markedly improved, with reported operative mortality after SM are likely seen in a relatively small number of tality at less than 1%.6,23 However, such improved outcomes high-volume HCM centers that perform SM in carefully se- may be limited to only a few high-volume centers. We found lected patients. Furthermore, this report suggests that small- significant variability in in-hospital mortality after SM when volume institutions are performing SM on older patients with hospital volume was taken into account (3.8% in the highest more comorbidities while using fewer concomitant valvular tertile vs 15.6% in the lowest volume tertile). Interestingly, our and coronary artery bypass graft operations. The American Col- findings indicate overall mortality after SM is much higher lege of Cardiology and American Heart Association guide- (5.2%) across US institutions, with most institutions having lim- lines suggest that operators and institutions should aim to

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Table 3. Unadjusted and Adjusted Association Between Hospital Volume and Outcomes After Septal Myectomy (With Third Tertile as the Reference)a

Outcome Unadjusted OR (95% CI) P Value Adjusted OR (95% CI)b P Value Death Abbreviations: ARF, acute renal failure; OR, odds ratio; First tertile 2.00 (1.47-2.73) <.001 3.11 (1.98-4.89) <.001 PPM, permanent pacemaker. Second tertile 2.32 (1.82-2.96) <.001 1.62 (1.13-2.32) .009 a P value for interaction <.001. Need for PPM b This model was adjusted for First tertile 1.02 (0.77-1.36) .88 0.70 (0.47-1.05) .09 statistically significant predictor variables that had significant Second tertile 1.62 (1.33-1.98) <.001 1.26 (0.98-1.61) .07 univariate association with Stroke outcomes from age, sex, race, First tertile 1.49 (0.85-2.60) .17 1.27 (0.55-2.93) .58 hospital bed size, hospital teaching status, hospital region, hospital Second tertile 0.42 (0.21-0.84) .01 0.56 (0.25-1.27) .17 volume status, region, payer status, Bleeding anemia, collagen vascular disease, First tertile 1.62 (0.99-2.65) .05 3.77 (2.12-6.70) <.001 congestive heart failure, chronic pulmonary disease, diabetes, Second tertile 2.09 (1.44-3.03) <.001 1.48 (0.88-2.49) .14 coagulopathy, hypertension, liver ARF disease, neurologic disorders, First tertile 0.87 (0.64-1.17) .35 0.65 (0.43-1.00) .05 obesity, peripheral vascular disorders, renal failure, and Second tertile 1.31 (1.07-1.62) .01 0.81 (1.48-2.53) .18 concomitant surgery.

Table 4. Unadjusted and Adjusted Association Between Hospital Volume and Outcomes After Alcohol Septal Abbreviations: ARF, acute renal Ablation (With Third Tertile as the Reference)a failure; OR, odds ratio; PPM, permanent pacemaker. Outcome Unadjusted OR (95% CI) P Value Adjusted OR (95% CI)b P Value a P value for interaction <.001. Death b This model was adjusted for First tertile 3.56 (1.70-7.47) .001 0.85 (0.20-3.62) .82 statistically significant predictor variables that had significant Second tertile 1.07 (0.43-2.66) .89 0.69 (0.11-4.21) .69 univariate association with Need for PPM outcomes from age, sex, race, First tertile 1.27 (0.94-1.71) .12 1.21 (0.82-1.79) .34 hospital bed size, hospital teaching status, hospital region, hospital Second tertile 1.06 (0.82-1.37) .65 0.56 (0.38-0.81) .002 volume status, region, payer status, Bleeding anemia, collagen vascular disease, First tertile 1.18 (0.60-2.34) .63 0.48 (0.12-1.83) .28 congestive heart failure, chronic pulmonary disease, diabetes, Second tertile 0.76 (0.36-1.47) .41 0.47 (0.18-1.21) .12 coagulopathy, hypertension, liver ARF disease, neurologic disorders, First tertile 2.02 (1.30-3.17) .002 0.81 (0.33-2.01) .66 obesity, peripheral vascular disorders, renal failure, and Second tertile 2.94 (2.07-4.17) <.001 1.73 (0.94-3.19) .08 concomitant surgery.

achieve mortality rates of less than 1% and major complica- creased need for PPM after ASA may be related to the evolu- tion rates of less than 3%.4 Although it is difficult to define mini- tion and refinements of the ASA technique, which were seen mum annual experience for the operators required to per- from 2000 through 2010. These refinements included use of form SM, current guidelines recommend (class I indication) that myocardial contrast echocardiography to target the septal per- only experienced operators with cumulative operator vol- forator, reduction in ethanol volume and rate of injection, and ume of at least 20 procedures should perform SM. However, more judicious ASA case selection. During the initial experi- our study reveals a potentially concerning practice pattern in ence with ASA, the rates of conduction abnormalities with ASA which approximately 80% of SMs were performed in hospi- were quite high, with approximately 20% to 25% of patients tals where the cumulative volume of SM was fewer than 20 requiring PPMs.13 The need for PPM after ASA in our study cases during the 9-year study period. This finding is particu- (11.9%) is similar to the rates of PPM implantation seen in more larly important given that SM procedures performed at low- contemporary reports (in the 8%-17% range).12,27,28 The rate volume centers were associated with in-hospital mortality that of PPM implantation after SM in our study (9.8%) is in line with far exceeds the recommended threshold. Therefore, given the the rates of 7.9% to 10% seen in previous studies29,30 and higher 3- to 10-fold higher mortality observed in the lowest-volume than the approximately 2% to 3% rates seen in early reports centers, referral to centers of excellence for SM would better of SM.31,32 Our study suggests that outcomes after ASA in this serve this challenging patient population. population are similar to those seen in the published litera- Our postprocedural outcomes after ASA, with a 0.7% mor- ture from experienced centers. In contrast to the observation tality rate, are similar to a previous report13 from the Mayo Clinic made in the SM cohort, after multivariate adjustment, there (1.4%) and the Multicenter North American Registry (<1%). Im- was no clear association between hospital volume of ASA and provements in overall outcomes (ie, mortality) and de- procedural outcomes, although there was a numerically higher

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rate of mortality in the lowest-tertile group. This finding could There are several limitations present in our study. First, this be a reflection of a significantly steeper learning curve asso- is a retrospective study based on an NIS sample, which ap- ciated with SM and the relative ease of adapting ASA by op- proximates the national distribution of key hospital character- erators with experience in catheter-based therapy. istics. Our estimates for SM and ASA were derived from a 20% Our study also suggests that the annual rate of ASA is in- sample. Individual hospitals may not have provided data for creasing while the annual rate of SM is slowly decreasing. Given the entire 2003-2011 duration, and it is possible that the over- the prevalent use of catheter-based coronary revasculariza- all volume of procedures was underrepresented or overrepre- tion in the United States, it is possible that more operators are sented by the sample. However, NIS has been used exten- performing ASA over time. The American College of Cardiol- sively to examine national health care trends, and its sampling ogy Foundation and American Heart Association 2011 Hyper- design has been validated in numerous publications.34,35 Sec- trophic Cardiomyopathy Guideline recommends that, in those ond, unmeasured confounders could not be accounted for, in- patients who are acceptable surgical candidates, SM should cluding preexisting conduction abnormalities, anatomical ab- generally be preferred (class IIa) over ASA (class IIb), whereas normalities, and current medications. The intent of this study in those patients who are not acceptable candidates for sur- was not to compare SM and ASA given the difficulty in adjust- gical intervention, ASA would be the favored treatment op- ing for confounders not captured in this administrative data- tion (class IIa).4 Further studies are necessary to determine base or for all factors that lead to referral bias for SM vs ASA. whether the guidelines are being applied in clinical practice Patients undergoing SM differ from patients undergoing ASA and that patients with HCM are properly delegated to appro- in type and severity of medical comorbidities and require- priate therapy. ment for concomitant surgical procedures. Therefore, our find- Our study examines a nationally representative sample of ing should not be used for comparison of procedural safety or outcomes of SM and ASA during a period of roughly 10 years efficacy between SM and ASA. Third, the NIS database pro- and the challenges we face in applying guidelines to clinical prac- vides only in-hospital outcomes. Therefore, our findings do not tice. Given higher procedural mortality seen in low-volume cen- address 30-day or long-term hemodynamic and clinical out- ters for SM and ASA, we need to increase the efforts of the car- comes or need for additional hospitalizations or procedures in diology community to refer patients to centers of excellence. the future. This limitation may be particularly important given Septal myectomy remains the criterion standard for treatment that ASA is associated with a potential risk of future ventricu- of refractory obstructive HCM. However, for geographic areas lar arrhythmias due to septal scar development.36 Fourth, our with limited access to surgical centers with expertise in SM, ASA study does not have data for patients with obstructive HCM who remains a viable option in anatomically and clinically appro- were not treated with an invasive strategy, potentially intro- priate patients. However, it is important to refer these patients ducing an additional selection bias. Finally, the NIS does not to centers of excellence in ASA as suggested by the guidelines. allow assessment of procedural success, including reduction This directive is especially important to acknowledge given the in LVOT gradient or improvement in heart failure symptoms. technical challenges associated with SM and the clear association of experience and outcomes after SM.27 In fact, ASA is in- creasingly used in many European centers because of several Conclusions factors, including physician and patient preference; minimally invasive; catheter-based nature of the procedure; local In the United States from 2003 through 2011, most institu- availability of experienced ASA operators; and lack of regional tions performed few SM and ASA cases annually, which are expertise in SM. Recent European Society of Cardiology guide- fewer than recommended by the guidelines. Importantly, low- lines support this practice, with SM and ASA receiving a class I volume centers were associated with worse in-hospital out- recommendation.33 Nevertheless, in experienced HCM cen- comes, including higher mortality, longer length of stay, and ters with a high volume of SM operations, SM as the primary higher hospital cost. More efforts by the cardiology commu- treatment option would seem appropriate given the long-term nity are needed to encourage referral of patients with HCM to data supporting favorable outcomes after SM.5,10 centers of excellence for septal reduction therapy.

ARTICLE INFORMATION Acquisition, analysis, or interpretation of data: Kim, Disclosure of Potential Conflicts of Interest. Dr Accepted for Publication: February 13, 2016. Looser, Minutello, Bergman, Naidu, Gade, Singh, Feldman reported receiving consulting/speaker’s Feldman. fees from Eli Lilly, Daiichi-Sankyo, Abbott Vascular, Correction: This article was corrected on October Drafting of the manuscript: Kim, Looser, Minutello, Pfizer, and Bristol-Myers Squibb. Dr Naidu reported 12, 2016, to fix a typographical error in the text and Feldman. receiving consulting fees from Abiomed, Abbott on January 4, 2017, for incorrect ICD-9 codes and Critical revision of the manuscript for important Vascular, Gilead, The Medicines Company, and percentages reported in tables. intellectual content: All authors. Maquet. No other disclosures were reported. Published Online: April 27, 2016. Statistical analysis: Kim, Minutello. Funding/Support: This work was supported by doi:10.1001/jamacardio.2016.0252. Obtained funding: Kim. grants from the Michael Wolk Heart Foundation and Author Contributions: Dr Kim had full access to all Administrative, technical, or material support: Kim, the New York Cardiac Center Inc (Dr Kim). Wong, Gade, Charitakis. the data in the study and takes responsibility for the Role of the Funder/Sponsor: The funding sources integrity of the data and the accuracy of the data Study supervision: Kim, Swaminathan, Naidu, Singh, Feldman. had no role in the design and conduct of the study; analysis. collection, management, analysis, and Study concept and design: Kim, Swaminathan, Conflict of Interest Disclosures: All authors have interpretation of the data; preparation, review, or Minutello, Wong, Naidu, Charitakis, Feldman. completed and submitted the ICMJE Form for approval of the manuscript; and the decision to submit the manuscript for publication.

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