Genetic hypogonadal mouse model reveals niche-specific influence of reproductive axis and sex on intestinal microbial communities.

BACKGROUND: The gut microbiome has been linked to many diseases with sex bias including autoimmune, metabolic, neurological, and reproductive disorders. While numerous studies report sex differences in fecal microbial communities, the role of the reproductive axis in this differentiation is unclear and it is unknown how sex differentiation affects microbial diversity in specific regions of the small and large intestine. METHODS: We used a genetic hypogonadal mouse model that does not produce sex steroids or go through puberty to investigate how sex and the reproductive axis impact bacterial diversity within the intestine. Using 16S rRNA gene sequencing, we analyzed alpha and beta diversity and taxonomic composition of fecal and intestinal communities from the lumen and mucosa of the duodenum, ileum, and cecum from adult female (n = 20) and male (n = 20) wild-type mice and female (n = 17) and male (n = 20) hypogonadal mice. RESULTS: Both sex and reproductive axis inactivation altered bacterial composition in an intestinal section and niche-specific manner. Hypogonadism was significantly associated with bacteria from the Bacteroidaceae, Eggerthellaceae, Muribaculaceae, and Rikenellaceae families, which have genes for bile acid metabolism and mucin degradation. Microbial balances between males and females and between hypogonadal and wild-type mice were also intestinal section-specific. In addition, we identified 3 bacterial genera (Escherichia Shigella, Lachnoclostridium, and Eggerthellaceae genus) with higher abundance in wild-type female mice throughout the intestinal tract compared to both wild-type male and hypogonadal female mice, indicating that activation of the reproductive axis leads to female-specific differentiation of the gut microbiome. Our results also implicated factors independent of the reproductive axis (i.e., sex chromosomes) in shaping sex differences in intestinal communities. Additionally, our detailed profile of intestinal communities showed that fecal samples do not reflect bacterial diversity in the small intestine. CONCLUSIONS: Our results indicate that sex differences in the gut microbiome are intestinal niche-specific and that sampling feces or the large intestine may miss significant sex effects in the small intestine. These results strongly support the need to consider both sex and reproductive status when studying the gut microbiome and while developing microbial-based therapies.

Microbial communities in the intestinal tract, known as the gut microbiome, regulate many critical aspects of host physiology. Previous studies have shown that the diversity of the gut microbiome differs between the sexes. There are also many diseases with a sex bias linked to the gut microbiome, including autoimmune, metabolic, neurological, and reproductive disorders. The gut microbiome differentiates during puberty, but it is unknown if the reproductive axis, the system responsible for sexual maturation and production of gonadal sex hormones, is critical for this process. Furthermore, since most studies use feces to examine the gut microbiome, it is unknown how sex influences the microbial communities within different segments of the small and large intestine. To address this gap in knowledge, we used DNA-based molecular methods to compare the intestinal-specific microbiomes of a mouse model with a genetically inactivated reproductive axis to that of wild-type mice. We found that both sex and the reproductive axis impacted gut microbial diversity in an intestinal section-specific manner. We also detected significant differences in intestinal microbial diversity between male and female mutant mice, suggesting that sex chromosome factors also affect the gut microbiome. We also showed that fecal samples were dissimilar to small intestine microbial communities, indicating that studies only sampling feces likely miss sex differences specific to the small intestine. Our results strongly support the need to consider both sex and reproductive status when studying the gut microbiome and while developing microbial-based therapies.

Shaping Policy and Practice: Analyzing the Reach of Highly Cited and High Altmetrics Publications for Broader Impact on Physical Activity.

BACKGROUND: A significant gap remains between the availability of physical activity (PA) evidence-based interventions and their application in real-world settings in policy and practice areas. This study aims to describe highly cited and high altmetrics publications in PA research and explore their impact on PA policy and practice. METHODS: Mixed-methods sequential explanatory study including the identification and description of the top highly cited and high altmetrics PA publications from the last 10 years (including study design, population, type of PA study, number of citations, and altmetrics score), and interviews with key informants regarding research dissemination and implications on PA policy and practice. RESULTS: When considering publication type, the most frequent highly cited publications were health consequences (40%, altmetrics = 42%), measurement/trends (23%, altmetrics = 10%), and correlates/determinants (21%, altmetrics = 26%) studies. They were predominantly cross-sectional (50%, altmetrics = 28%), systematic reviews (38%, altmetrics = 18%), and longitudinal studies (8%, altmetrics = 37%). All authors who participated in the interviews agreed that the most important factors in disseminating findings and influencing PA policy and practice were the published peer-reviewed manuscript itself, the reputation of the journal, the communication strategy, and the use of online platforms. CONCLUSIONS: To have a real-world influence on PA policy and practice, it is not enough to publish the results in scientific journals and participate in media outreach. To successfully involve policymakers and communities in appropriating the evidence and evaluating the extent to which these findings affect policy and practice outcomes, it is critical to lead co-creation, co-dissemination, advocacy, and capacity building efforts.

Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.

BACKGROUND: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. METHODS: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. RESULTS: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). CONCLUSIONS: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.

Status and Trends of Physical Activity Surveillance, Policy, and Research in 164 Countries: Findings From the Global Observatory for Physical Activity-GoPA! 2015 and 2020 Surveys.

BACKGROUND: Physical activity (PA) surveillance, policy, and research efforts need to be periodically appraised to gain insight into national and global capacities for PA promotion. The aim of this paper was to assess the status and trends in PA surveillance, policy, and research in 164 countries. METHODS: We used data from the Global Observatory for Physical Activity (GoPA!) 2015 and 2020 surveys. Comprehensive searches were performed for each country to determine the level of development of their PA surveillance, policy, and research, and the findings were verified by the GoPA! Country Contacts. Trends were analyzed based on the data available for both survey years. RESULTS: The global 5-year progress in all 3 indicators was modest, with most countries either improving or staying at the same level. PA surveillance, policy, and research improved or remained at a high level in 48.1%, 40.6%, and 42.1% of the countries, respectively. PA surveillance, policy, and research scores decreased or remained at a low level in 8.3%, 15.8%, and 28.6% of the countries, respectively. The highest capacity for PA promotion was found in Europe, the lowest in Africa and low- and lower-middle-income countries. Although a large percentage of the world's population benefit from at least some PA policy, surveillance, and research efforts in their countries, 49.6 million people are without PA surveillance, 629.4 million people are without PA policy, and 108.7 million live in countries without any PA research output. A total of 6.3 billion people or 88.2% of the world's population live in countries where PA promotion capacity should be significantly improved. CONCLUSION: Despite PA is essential for health, there are large inequalities between countries and world regions in their capacity to promote PA. Coordinated efforts are needed to reduce the inequalities and improve the global capacity for PA promotion.

Endovascular Repair of a Traumatic Popliteal Artery Injury.

In patients who sustain a traumatic arterial injury to the lower extremities, timely intervention is key for limb salvage. Traditionally, patients with a popliteal injury have undergone an open surgical bypass but, in recent years, endovascular repair has become more frequent. We present the case of a 46-year-old male who sustained a right tibial/fibular fracture and an associated popliteal artery injury during a pedestrian versus car accident. At presentation, distal signals were not detectable on duplex ultrasonography, and computed tomography confirmed an occlusion of the P3 popliteal artery and proximal anterior tibial and tibioperoneal trunk, as well as a comminuted tibia and fibula fracture. He also had a subdural hematoma without midline shift. He was taken to the operating room emergently and, following external fixation of the tibial/fibular fracture, he underwent angiography of the right leg. There was no thrombus or extravasation but a static column of blood secondary to a flow-limiting intimal flap was present, and an endovascular repair of the popliteal artery with balloon angioplasty and Tack stents (Intact Vascular, Wayne, PA) was pursued. Heparin was not utilized due to the patient's intracranial hemorrhage. On hospital day four, he underwent internal fixation of the tibial/fibular fracture. The subarachnoid/subdural hematoma remained stable and a prophylactic dose of rivaroxaban and aspirin was started. The patient recovered well from these procedures and was discharged 16 days after the accident.

Longitudinal Cost of Septal Myectomy Versus Alcohol Septal Ablation for Hypertrophic Cardiomyopathy.

OBJECTIVE: To compare the postprocedural health care utilization and cost of septal myectomy (SM) and alcohol septal ablation (ASA). PATIENTS AND METHODS: Using the OptumLabs Data Warehouse, we analyzed de-identified claims data of adult patients undergoing SM and ASA for obstructive hypertrophic cardiomyopathy from January 1, 2006, through December 31, 2018. We used propensity score weighting to compare the 2-year incidence rates of emergency department visits and rehospitalizations after SM and ASA. RESULTS: We identified 953 patients in total: 660 underwent SM and 293 underwent ASA. There was no difference in the risk (odds ratio, 1.1; 95% CI, 0.6 to 1.8) or frequency (incidence rate ratio, 1.1; 95% CI, 0.8 to 1.5) of emergency department visits, but the annual risk of hospital readmission was 10.8% after SM and 25.9% after ASA during the second postoperative year (P=.004). In those who were ever readmitted, the average length of hospital stay within the first 2 years after ASA was 1.6 times as long as that after SM (incidence rate ratio, 1.6; 95% CI, 1.0 to 2.4). Overall, the 2-year cumulative postprocedural cost was significantly higher after ASA (P<.001). CONCLUSION: Compared with ASA, SM is associated with fewer hospital readmissions and lower 2-year postprocedural health care cost.

Isolated Gastritis Secondary to Immune Checkpoint Inhibitors Complicated by Superimposed Cytomegalovirus Infection.

Immune checkpoint inhibitors such as nivolumab increase the T-cell destruction of malignancies but can also trigger a broad variety of immune-related adverse events (irAEs). Colitis as an irAE is well-documented, but upper gastrointestinal tract involvement is primarily unrecognized. We present a patient who developed gastritis as an irAE after multiple cycles of nivolumab and initially responded well to steroid therapy but then developed superimposed cytomegalovirus infection. The similarity between both presentations highlights the importance of having a broad differential diagnosis in patients with gastrointestinal complaints treated with immune checkpoint inhibitors and the need for further studies to better characterize gastritis as an irAE.

Is there referral bias in outcomes of septal myectomy for hypertrophic cardiomyopathy?

PURPOSE: To determine the potential impact of referral bias on short- and long-term outcomes following septal myectomy for hypertrophic cardiomyopathy. METHODS: We reviewed 2303 adult patients who underwent transaortic septal myectomy for obstructive hypertrophic cardiomyopathy from January 1993 to April 2016. Patients were divided into 3 groups according to their permanent address: local (state) residents (n = 324), regional (surrounding 5 states) patients (n = 515), and national (outside 5 states) patients (n = 1464). RESULTS: Patient groups were similar for age, sex, preoperative New York Heart Association class, and left ventricular ejection fraction. Local patients had increased prevalence of diabetes mellitus (13%, 11%, 8%; P = .006), coronary artery disease (25%, 21%, 19%; P = .031), severe chronic lung disease (2.3%, 1.9%, 0.4%; P < .001), and atrial fibrillation (24%, 18%, 19%; P = .045) when compared with regional and national patients. Echocardiographic features did not differ between the 3 groups, including prevalence of moderate or greater mitral regurgitation (59%, 61%, 56%; P = .161). Local and regional patients were more likely to undergo concomitant procedures than national patients (P < .001). Mitral valve surgery was performed in 9.6% of the patients, more commonly in local and regional patients (12%, 12%, 8%; P = .018). There were 11 operative deaths (0.5%), and early mortality was similar among the groups. Geographic origin did not impact overall late survival. CONCLUSIONS: Compared with distant referrals, local patients who undergo septal myectomy at our institution have more comorbid conditions, and require more concomitant surgical procedures. Despite these differences, referral patterns did not impact early or late outcomes following transaortic septal myectomy.

Primary sclerosing cholangitis and pancreatic cancer: A retrospective cohort study of United States veterans.

Primary sclerosing cholangitis (PSC) is associated with hepatobiliary and colorectal cancers, but it remains uncertain if PSC increases the risk for pancreatic cancer. While some European studies have suggested an increased risk of pancreatic cancer in PSC patients, other studies have not. And these studies did not well account for presence or absence of concomitant inflammatory bowel disease (IBD). The purpose of this study is to investigate the prevalence of pancreatic cancer in United States veterans with PSC both with and without IBD. Methods: This retrospective study used International Classification of Diseases, Tenth Revision (ICD-10) codes to identify patients with PSC, IBD, and pancreatic cancer from the Veterans Affairs (VA) Corporate Data Warehouse. The prevalence of pancreatic cancer in patients with PSC only, IBD only, PSC with IBD, and neither PSC nor IBD were compared. Logistic regression was used to control for age, gender, chronic pancreatitis, diabetes mellitus, and tobacco and alcohol use. Results: A total of 946 patients with PSC were identified from a population of over 9 million veterans. 486 (51.4%) of these had concurrent IBD. Additionally 112,653 patients with IBD without PSC were identified. When adjusted for confounding factors, patients with PSC had a significantly higher prevalence of pancreatic cancer compared to the general population and those with IBD without PSC (2.4% vs. 0.2% and 0.5%, respectively). Conclusions: Veterans with PSC, particularly those without concomitant IBD, have a high prevalence of pancreatic cancer compared to the general veteran population. Our findings support the need for multicenter prospective studies investigating the benefits of screening for pancreatic cancer in patients with PSC.

Impact of Hematologic Malignancies on Outcome of Cardiac Surgery.

BACKGROUND: Previous studies suggest that patients with prior or current hematologic malignancy are at increased risk of intraoperative and postoperative complications when undergoing cardiac surgery. The aim of this review was to compare clinical outcomes of patients with a history of hematologic malignancy to those of similar patients with no known blood dyscrasia. METHODS: From January 1993 to June 2017, 37,839 patients underwent elective cardiac surgery at Mayo Clinic. We matched 612 patients (1.6%) with a history of hematologic malignancy to 612 controls, and compared operative details, early postoperative complications, and late survival. RESULTS: The median age of matched patients with hematologic malignancy was 71 years (interquartile range [IQR], 62 to 77) and 71 years (IQR, 62 to 77) for patients without cancer. Patients with prior diagnosis of malignancy had lower hemoglobin levels, 12.8 (IQR, 11.5 to 13.8) vs 13.5 (IQR, 12.2 to 14.6; P < .001), but similar platelet counts, 195 (IQR, 147 to 263) vs 203 (IQR, 170 to 245; P = .533). Patients with malignancy were at greater risk of receiving postoperative blood transfusions (47.4% vs 35.6%, P < .001). However, reoperations for postoperative bleeding (4.7% vs 3.3%, P = .253) and stroke (1.3% vs 1.3%, P > .999) were similar. Thirty-day mortality was 3.3% among patients with hematologic malignancy and 1.5% among matched controls (P = .061). Overall survival among patients with cancer was reduced (P < .0001). CONCLUSIONS: Although late survival is reduced in patients with hematologic malignancies, early outcomes are generally similar to those of matched controls. Therefore, surgery should not be withheld from patients with a diagnosis of hematologic malignancy who would benefit from cardiac procedures.

Late Health Status of Patients Undergoing Myectomy for Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Surgical myectomy eliminates symptoms in most patients with obstructive hypertrophic cardiomyopathy, but dyspnea and/or angina can recur in some. This study investigated clinical features associated with a lack of clinical improvement postoperatively. METHODS: Between March 2007 and December 2012, 963 patients underwent transaortic septal myectomy at our clinic. Six hundred one patients received standardized follow-up questionnaires, which were answered by 409 (68.1%). We compared clinical characteristics of patients with and without improvement and identified predictors of worsening health using a multivariable proportional odds ordinal logistic model. RESULTS: Of 409 patients, 329 (80.4%) indicated better health status at follow-up and 80 (19.6%) responded that their health had stayed the same or worsened. The median age of patients with perceived better health was 56.8 years (interquartile range, 47.4, 65.7) and those without improvement was 63.0 years (interquartile range, 50.0, 70.2). New York Heart Association class III/IV dyspnea was present in 90.3% of patients who reported improvement and in 79.7% who did not. In multivariable analysis the presence of coronary artery disease (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.17-6.50; P = .020), lower preoperative left ventricular ejection fraction (per interquartile range increase: OR, 0.76; 95% CI, 0.57-0.99; P = .047), and worse preoperative health status (eg, poor or fair: OR, 1.63; 95% CI, 1.05-2.54; P = 0.004) were associated with worse health status at follow-up. CONCLUSIONS: Septal myectomy leads to excellent symptomatic relief in most patients, and more than 80% report subjective improvement in health status. Important predictors of worsening health included coronary artery disease and poor preoperative health status.

Co-incidental C9orf72 expansion mutation-related frontotemporal lobar degeneration pathology and sporadic Creutzfeldt-Jakob disease.

BACKGROUND: The C9orf72 hexanucleotide expansion mutation is the most common cause of genetic frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and combined FTD-ALS. Its underlying neuropathology combines TDP-43 pathology and dipeptide repeat protein (DPR) deposits and may also associate with other neurodegeneration-associated protein aggregates. Herein we present a unique combination of C9orf72 mutation with sporadic Creutzfeldt-Jakob disease (CJD) in a 74-year-old patient with rapidly progressive dementia. METHODS: Detailed neuropathological examination including immunohistochemistry for several proteinopathies. Genetic analysis was conducted by repeat primed polymerase chain reaction (PCR). Furthermore, we analyzed additional C9orf72 mutation carriers for prion-protein (PrP) deposits in brain tissue and screened the cerebellar cortex of other CJD cases for p62/DPR neuronal inclusions to assess the frequency of combined pathologies. RESULTS: Postmortem brain examination of a patient with a rapidly progressive neurological deterioration of 8 months' duration confirmed the diagnosis of CJD. She harbored valine homozygosity at PRNP codon 129. In addition, a frontotemporal lobar degeneration (FTLD)-pattern with TDP-43 protein aggregates and p62+/C9RANT+ positive inclusions along with a high degree of Alzheimer-related pathology (A3B3C3) were identified. The suspected C9orf72 expansion mutation was confirmed by repeat-primed PCR. Screening of 13 C9orf72 cases showed no pathological PrP aggregates and screening of 100 CJD cases revealed no other C9orf72 expansion mutation carriers. CONCLUSION: A combination of a C9orf72 expansion mutation-related FTLD with sporadic CJD in the same patient is rare. While the rarity of both diseases makes this concurrence most likely to be coincidental, questions regarding a potential link between these two neurodegenerative pathologies deserve further studies.

Contemporary techniques for mitral valve repair-the Mayo Clinic experience.

Mitral valve repair for patients with degenerative or functional mitral valve regurgitation improves symptoms and prognosis, and several techniques have been described. Important principles in operation are simplicity, reproducibility, and durability of repair. At Mayo Clinic, we have operated on more than 6000 patients with degenerative mitral valve disease and valve prolapse, and this review details our approach to mitral valve repair, including robotic and minimally invasive techniques. Most patients with isolated leaflet prolapse can be managed with leaflet plication or triangular resection, and chordal replacement is reserved for repair of anterior leaflet prolapse. Posterior annuloplasty with a standard-sized flexible band is used to reduce annular circumference and improve leaflet coaptation. With these methods, early risk of mortality for mitral valve repair is low in the current era (< 1%), and rate of recurrent valve leakage is 1.5 per 100 patient-years during the first year post-repair and 0.9 per 100 patient-years thereafter. This paper also briefly summarizes important considerations for patients with mitral valve regurgitation and severe calcification, perforations due to endocarditis, and rheumatic heart disease.

Management of the mitral valve in patients with obstructive hypertrophic cardiomyopathy.

Septal myectomy is the gold standard treatment option for patients with obstructive hypertrophic cardiomyopathy whose symptoms do not respond to medical therapy. This operation reliably relieves left ventricular outflow tract gradients, systolic anterior motion of the mitral valve, and associated mitral valve regurgitation. However, there remains controversy regarding the necessity of mitral valve intervention at the time of septal myectomy. While some clinicians advocate for concomitant mitral valve procedures, others strongly believe that the mitral valve should only be operated on if there is intrinsic mitral valve disease. At Mayo Clinic, we have performed septal myectomy on more than 3000 patients with obstructive hypertrophic cardiomyopathy, and in our experience, mitral valve operation is rarely necessary for patients who do not have intrinsic mitral valve disease such as leaflet prolapse or severe calcific stenosis. In this paper, we review anatomical considerations, imaging, and surgical approaches in the management of the mitral valve in hypertrophic cardiomyopathy.

Septal Myectomy in patients with previous coronary revascularization - hypertrophic cardiomyopathy masquerading as ischemic heart disease.

BACKGROUND: Patients with obstructive hypertrophic cardiomyopathy (HCM) may have symptoms mimicking ischemic heart disease, including chest pain and shortness of breath. Some patients undergo coronary revascularization which may not lead to symptomatic improvement. This study assesses clinical presentations and outcomes of patients with previous coronary revascularization undergoing septal myectomy. METHOD: From 08/1996 to 07/2017, 166 adult patients with obstructive HCM underwent septal myectomy at our Clinic with a history of percutaneous coronary intervention (PCI, N = 153) or coronary artery bypass grafting (CABG, N = 13). We assessed their functional status before and after coronary intervention and outcomes following myectomy. RESULTS: The median (IQR) age was 65 (59-71) years, and 106 (64%) were male. Among 150 patients whose extent of disease was known, single vessel disease was identified in 109 (73%) who had PCI and 1 (9%) who had CABG. Following revascularization, many (59%) reported no improvement in shortness of breath from preoperative status. Myectomy was performed at a median of 3.2 (1.0-6.3) years following coronary revascularization, and 40 (25%) required myectomy within 1 year. Patients whose shortness of breath persisted after PCI/CABG (N = 90) underwent myectomy earlier than those whose symptoms initially improved (N = 63) after coronary revascularization (1.4 [0.6-4.0] years vs. 5.1 [2.8-9.5] years, p < .001). CONCLUSION: Almost 25% of patient's required septal myectomy within 1 year of coronary intervention for continued symptoms originally thought to be due to ischemic heart disease. These findings highlight the overlap of obstruction and ischemic symptoms and the importance of complete evaluation for dynamic obstruction in HCM.

Septal Myectomy and Concomitant Coronary Artery Bypass Grafting for Patients With Hypertrophic Cardiomyopathy and Coronary Artery Disease.

Severe coronary artery disease is associated with disproportionately increased risks of death in patients with hypertrophic cardiomyopathy. There is a paucity of data on the long-term effect of coronary revascularization at the time of myectomy. Between January 1, 1961, and October 31, 2017, 2913 adult patients underwent transaortic septal myectomy at Mayo Clinic. Concomitant coronary artery bypass grafting (CABG) was performed in 246 (8.4%). We compared baseline characteristics of patients who underwent septal myectomy with and without CABG and assessed the effect of surgical revascularization on the risk of all-cause mortality. Patients who underwent concomitant CABG were older (median [interquartile range], 66.3 [59.8-72.1] years vs 54.4 [43.5-64.8] years; P<.0001) and more likely to be male (63.0% vs 54.2%; P=.008) than those who did not undergo coronary revascularization at operation. There was no significant difference in preoperative left ventricular outflow tract gradients (55 [25-81] mm Hg vs 58 [25-88] mm Hg; P=.116). Overall operative mortality (≤30 days after surgery) was 1.0% and higher in patients who underwent concomitant CABG (2.2% vs 0.8%; P=.048). In multivariable analysis (n=2641), factors independently associated with mortality included concomitant CABG (hazard ratio [95% CI], 1.89 [1.39-2.58]; P<.0001), older age at operation (per interquartile range increase, 2.79 [1.95-3.98]; P<.0001), atrial fibrillation (1.46 [1.11-1.92]; P=.006), diabetes (1.45 [1.04-2.04]; P=.031), higher body mass index (change from 0.95 to 0.5 quantile, 1.95 [1.46-2.59]; P<.0001), and surgery performed earlier in the study period (2.02 [1.31-3.11]; P=.001). In conclusion, obstructive coronary artery disease severe enough to prompt concomitant CABG at the time of septal myectomy is an important risk factor for late mortality.