Mechanical or biological prosthesis for aortic valve replacement in patients aged 45 to 74 years.

OBJECTIVE: The selection of valve prostheses for patients undergoing surgical aortic valve replacement remains controversial. In this study, we compared the long-term outcomes of patients undergoing aortic valve replacement with biological or mechanical aortic valve prostheses. METHODS: We evaluated late results among 5762 patients aged 45 to 74 years who underwent biological or mechanical aortic valve replacement with or without concomitant coronary artery bypass from 1989 to 2019 at 4 medical centers. The Cox proportional hazards model was used to compare late survival; the age-dependent effect of prosthesis type on long-term survival was evaluated by an interaction term between age and prosthesis type. Incidences of stroke, major bleeding, and reoperation on the aortic valve after the index procedure were compared between prosthesis groups. RESULTS: Overall, 61% (n = 3508) of patients received a bioprosthesis. The 30-day mortality rate was 1.7% (n = 58) in the bioprosthesis group and 1.5% (n = 34) in the mechanical group (P = .75). During a mean follow-up of 9.0 years, the adjusted risk of mortality was higher in the bioprosthesis group (hazard ratio, 1.30, P < .001). The long-term survival benefit associated with mechanical prosthesis persisted until 70 years of age. Bioprosthesis (vs mechanical prosthesis) was associated with a similar risk of stroke (P = .20), lower risk of major bleeding (P < .001), and higher risk of reoperation (P < .001). CONCLUSIONS: Compared with bioprostheses, mechanical aortic valves are associated with a lower adjusted risk of long-term mortality in patients aged 70 years or less. Patients aged less than 70 years undergoing surgical aortic valve replacement should be informed of the potential survival benefit of mechanical valve substitutes.

Improvement in gastrointestinal bleeding after septal myectomy for hypertrophic cardiomyopathy.

OBJECTIVE: Patients with obstructive hypertrophic cardiomyopathy may have occult gastrointestinal bleeding. In this study, we analyzed outcomes of septal myectomy in patients who had a history of gastrointestinal bleeding preoperatively to understand patient characteristics and impact of septal reduction on recurrent gastrointestinal bleeding. METHODS: We analyzed 73 adult patients who had a history of gastrointestinal bleeding before transaortic septal myectomy for obstructive hypertrophic cardiomyopathy and compared outcomes to 219 patients without gastrointestinal bleeding preoperatively. RESULTS: Patients with preoperative history of gastrointestinal bleeding were older (median (IQR) age, 65 (59-69) years, P < .001) and were more likely to have systemic hypertension (70% vs 53%, P = .020) and coronary artery disease (25% vs 13%, P = .026). Preoperatively, patients with gastrointestinal bleeding had a larger left atrial volume index (median, 53 mL/m2; interquartile range, 42-67; P = .006) and greater right ventricular systolic pressure (median, 36 mm Hg; interquartile range, 32-49; mm Hg, P = .005) but no significant difference in severity of outflow tract obstruction (P = .368). There were no perioperative deaths. The estimated 5- and 10-year survivals were 96.6% and 81.8%, respectively. At a median of 3.4 (interquartile range, 1.9-9.1) years after septal myectomy, 11 patients (15%) had recurrence of gastrointestinal bleeding, which was attributed to angiodysplasia or unknown causes in 6 patients (8%). CONCLUSIONS: Patients with a preoperative history of gastrointestinal bleeding have favorable short- and long-term outcomes after septal myectomy for obstructive hypertrophic cardiomyopathy. Remission of gastrointestinal bleeding was observed in 85% of patients postprocedure, and only 8% of the patients had recurrent gastrointestinal bleeding due to angiodysplasia or unknown causes.

Outcomes of concomitant myectomy and left ventricular apical aneurysm repair in patients with hypertrophic cardiomyopathy.

OBJECTIVES: Hypertrophic cardiomyopathy with left ventricular apical aneurysm is a phenotype associated with a 4-fold increase in the risk for sudden cardiac death. In this study, we describe the surgical outcome of concomitant apical aneurysm repair in patients undergoing transapical myectomy for hypertrophic cardiomyopathy. METHODS: We identified 67 patients with left ventricular apical aneurysms who underwent transapical myectomy and apical aneurysm repair between July 2000 and August 2020. Long-term survival was compared with that of 2746 consecutive patients undergoing transaortic septal myectomy for obstructive hypertrophic cardiomyopathy with subaortic obstruction. RESULTS: Transapical myectomy was indicated for midventricular obstruction (n = 44) or left ventricular remodeling for diastolic heart failure (n = 29). Preoperatively, 74.6% (n = 50) of patients were in New York Heart Association class III/IV heart failure, and 34.3% (n = 23) of patients had experienced syncope or presyncope. Atrial fibrillation was documented in 22 patients (32.8%), and episodes of ventricular arrhythmias were recorded in 30 patients (44.8%). Thrombus was present in the apical aneurysm in 6 patients. During a median (interquartile range) follow-up of 4.9 (1.8-7.6) years, the estimated 1- and 5-year survivals were 98.5% and 94.5%, respectively, which were not significantly different from that of patients undergoing transaortic septal myectomy for obstructive hypertrophic cardiomyopathy (P = .52) or an age- and sex-matched US general population (P = .40). CONCLUSIONS: Apical aneurysm repair in conjunction with septal myectomy is a safe procedure, and the good long-term survival of patients suggests that the procedure may reduce cardiac-related death in this high-risk hypertrophic cardiomyopathy population.

Genomic landscape of 891 RET fusions detected across diverse solid tumor types.

In this study, we report the clinicopathologic and genomic profiles of 891 patients with RET fusion driven advanced solid tumors. All patient samples were tested using a tissue-based DNA hybrid capture next generation sequencing (NGS) assay and a subset of the samples were liquid biopsies tested using a liquid-based hybrid capture NGS assay. RET fusions were found in 523 patients with NSCLC and in 368 patients with other solid tumors. The two tumor types with the highest number of RET fusion were lung adenocarcinoma and thyroid papillary carcinoma, and they had a prevalence rate 1.14% (455/39,922) and 9.09% (109/1199), respectively. A total of 61 novel fusions were discovered in this pan-tumor cohort. The concordance of RET fusion detection across tumor types among tissue and liquid-based NGS was 100% (8/8) in patients with greater than 1% composite tumor fraction (cTF). Herein, we present the clinicopathologic and genomic landscape of a large cohort of RET fusion positive tumors and we observed that liquid biopsy-based NGS is highly sensitive for RET fusions at cTF ≥1%.

Cardiopulmonary exercise test in patients with obstructive hypertrophic cardiomyopathy.

OBJECTIVE: The study objective was to analyze performance on cardiopulmonary exercise testing and its prognostic value in patients with obstructive hypertrophic cardiomyopathy undergoing septal myectomy. METHODS: We reviewed patients with obstructive hypertrophic cardiomyopathy who had cardiopulmonary exercise testing before septal myectomy from 2005 to 2016. Causes of functional impairment and their impact on survival were analyzed. RESULTS: A total of 752 patients had cardiopulmonary exercise testing at a median of 16 days (interquartile range, 2-56) before myectomy. The median exercise time was 6.6 (5.3-8.0) minutes. Functional aerobic capacity was 64% (53%-75%) of predicted, and metabolic equivalent of task was 5.2 (4.1-6.4). The peak oxygen consumption was 18.0 (14.2-21.9) mL/kg/min, which was 60% (49%-72%) of the predicted value. The primary causes for low peak oxygen consumption were impaired cardiac output (73.7%), limited heart rate reserve (52.0%), and obesity (48.2%). Resting outflow tract gradient correlated poorly to peak oxygen consumption, but the use of beta-blockers was associated with reduced peak oxygen consumption. During a median (interquartile range) of 9.0 (6.8-11.7) years of follow-up, the estimated 5- and 10-year survivals were 97% and 91%, respectively. Greater adjusted peak oxygen consumption (hazard ratio, 0.98; P = .011) and abnormal pulse oxygen increase (hazard ratio, 0.44; P = .003) were independently associated with better long-term survival after myectomy. CONCLUSIONS: Among patients with hypertrophic cardiomyopathy undergoing septal myectomy, functional capacity is severely impaired despite receiving optimal medical treatment. We identified risk factors of reduced long-term survival from preoperative cardiopulmonary exercise testing that may aid risk stratification in patients undergoing septal myectomy.

Transapical Ventricular Remodeling for Hypertrophic Cardiomyopathy With Systolic Cavity Obliteration.

BACKGROUND: Some patients with hypertrophic cardiomyopathy (HCM) present with reduced left ventricular (LV) stroke volume and elongated systolic cavity obliteration due to symmetric LV hypertrophy. In this report, we detail our experience with transapical septal myectomy to enlarge the LV volume and to relieve cavity obliteration in this unique subgroup of patients with HCM. METHODS: We analyzed 38 patients with HCM who had extended symmetric LV hypertrophy and underwent transapical septal myectomy to enlarge the LV cavity from February 2001 to May 2021. RESULTS: At the time of evaluation for operation, 84.2% (n = 32) of the patients were in New York Heart Association class III/IV. The peak oxygen consumption was 51.5% (44.0%-58.0%) of the normal predicted values on the preoperative exercise stress test (n = 16). Preoperative left atrial sizes in this cohort were enlarged (left atrial volume index, 39.0 [33.5-51.5] mL/m2), despite only 4 patients with moderate or greater mitral valve regurgitation. All patients underwent transapical septal myectomy to enlarge the LV cavity size. There was no postoperative (within 30 days) death. During a median (interquartile range) follow-up of 3.4 (0.7-6.9) years, the estimated survival rates were 100%, 92%, and 87% at 1, 3, and 5 years, respectively. Follow-up surveys suggested that 16 of the 17 contacted patients experienced improvement in their heart function after the procedure. CONCLUSIONS: Transapical myectomy to enlarge LV cavity volume can be performed safely with good early survival and functional results. This procedure is an important alternative to cardiac transplantation for HCM patients with systolic cavity obliteration and progressive heart failure.

Surgical management of diastolic heart failure after septal myectomy for obstructive hypertrophic cardiomyopathy.

OBJECTIVE: Some patients with obstructive hypertrophic cardiomyopathy may remain limited after surgical relief of the subaortic obstruction. In this report, we describe experience in surgical management of patients with advanced diastolic heart failure symptoms after adequate transaortic septal myectomy for obstructive hypertrophic cardiomyopathy. METHODS: We identified adult patients who presented with heart failure symptoms after previous transaortic septal myectomy for obstructive hypertrophic cardiomyopathy and underwent repeat sternotomy for transapical myectomy to enlarge a small left ventricular cavity. Functional recovery after hospital dismissal was assessed through a questionnaire-based survey. RESULTS: Six patients with previous septal myectomy presented with New York Heart Association functional class III symptoms. Preoperative transthoracic Doppler echocardiography confirmed adequate relief of subaortic outflow tract obstruction with only trivial or mild mitral valve regurgitation; left atrial volume index was increased at 46 mL/m2 (range, 44-47 mL/m2). Following transapical myectomy, the left ventricular diameter was enlarged from 23 mm (range, 21-27 mm) to 29 mm (range, 27-31 mm) at end-systole and from 40 mm (range, 38-42 mm) to 43 mm (range, 42-50 mm) at end-diastole. All the patients were alive after a median follow-up of 0.6 years (range, 0.4-3.5 years), and 5 patients responded to a postoperative survey and indicated improvement in their heart condition compared with functional status before the repeat myectomy. CONCLUSIONS: Patients with diastolic heart failure after septal myectomy for obstructive hypertrophic cardiomyopathy may present with systolic cavity obliteration due to excessive myocardial hypertrophy. Repeat transapical myectomy can enlarge the left ventricular chamber and augment the diastolic volume, which results in improved physical capacity and patient-perceived functional status.

Safety of Bariatric Surgery in Obese Patients With Hypertrophic Cardiomyopathy.

Obesity is an independent risk factor for heart failure in patients with hypertrophic cardiomyopathy (HC). In this study, we examined national trends and early outcomes of bariatric surgery for obesity in patients with HC. Using the weighted discharge data from the National Inpatient Sample, we identified adult patients with HC who underwent elective bariatric surgery for obesity between 2011 and 2017. A total of 443 obese patients with HC were identified, and 42% (n = 185) had obstructive HC. The annual number of patients increased from 18 in 2011 to 130 in 2017. Overall, the median (interquartile range) age was 50 (43 to 57) years, and 85 patients (19%) were 60 years or older. Approximately 20% (n = 90) of the patients had heart failure at the time of operation. Atrial fibrillation was present in 83 patients (19%), and 22% (n = 95) of the cohort had a pacemaker or automatic cardiac defibrillator implanted before the operation. Laparoscopic sleeve gastrectomy (72%, n = 318) and laparoscopic Roux-en-Y gastric bypass (25%, n = 110) were the most commonly performed bariatric procedures. Overall, patients stayed in the hospital for a median (interquartile range) of 2 (1 to 2) days. During the hospital stay, there were no deaths, myocardial infarctions, or documented episodes of thromboembolism. In conclusion, bariatric surgery in patients with HC is performed more frequently in recent years and is safe and associated with few perioperative complications. Because of the impact of obesity on long-term survival, clinicians should strongly consider bariatric surgery for obese HC patients who do not respond to conservative weight loss measures.

Patient-Reported Atrial Fibrillation After Septal Myectomy for Hypertrophic Cardiomyopathy.

BACKGROUND: Patient-reported outcomes are important metrics of medical and surgical care. In this study, we investigated the prevalence and risk factors of patient-reported postdischarge atrial fibrillation (AF) after septal myectomy for obstructive hypertrophic cardiomyopathy. METHODS: Patients undergoing transaortic septal myectomy from August 2001 to January 2017 were contacted regarding postdischarge AF through questionnaire-based surveys sent at 3, 5, and 10 years post procedure. For each patient, the most recent survey response was analyzed. RESULTS: Among 949 patients, 248 (26.1%) last responded at 3 years post procedure, 353 (37.2%) at 5 years, and 348 (36.7%) at 10 years. The overall incidence of patient-reported postdischarge AF was 34.4% (n = 326), and at 3, 5, and 10 years, the incidences were 22.2%, 34.8%, and 42.5% (P < .001). After multivariable adjustment, history of preoperative AF (odds ratio [OR] 5.566, P < .001), early postoperative AF within the first 30 days (OR 2.211, P < .001), preoperative left atrial volume index (OR 1.014, P = .005), postoperative right ventricular systolic pressure (OR 1.021, P = .013), postoperative moderate or greater mitral valve regurgitation (OR 1.893, P = .022), and preoperative septal thickness (OR 1.043, P = .036) were independently associated with patient-reported postdischarge AF. CONCLUSIONS: The incidence of patient-reported postdischarge AF increases with increasing length of follow-up after septal myectomy. We identified several risk factors for late postdischarge AF that were associated with chronicity of left ventricular outflow tract obstruction, and earlier intervention may mitigate late atrial arrhythmias.

Impact of Body Mass Index on Outcome of Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Obesity is highly prevalent in patients with obstructive hypertrophic cardiomyopathy (HCM). In this study, we investigated the impact of body mass index (BMI) in patients undergoing septal myectomy (SM) for obstructive HCM. METHODS: We reviewed 2746 patients who underwent transaortic SM for obstructive HCM from February 1993 through September 2018. Patients were stratified into 3 groups based on BMI (normal weight, <25 kg/m2; overweight, 25 to <30 kg/m2; and obese, ≥30 kg/m2). RESULTS: Preoperatively, the median left ventricular outflow tract gradient was 58 mm Hg, and there was no difference in gradients across BMI strata (P = .35). The percentage of obese patients with moderate or greater mitral valve regurgitation was lower (45.8%) compared with normal weight (52.9%) and overweight (55.4%) patients (P < .001). However, patients with a higher BMI were more likely to have New York Heart Association Functional Classification III/IV limitation at presentation (P < .001). After myectomy, anteroseptal thickness (P = .115) and left ventricular outflow tract gradient (P = .210) did not differ between groups. There were 14 (0.5%) deaths within 30 days postoperatively, and the risk was similar across BMI strata (P = .448). Model-estimated changes in average BMI at 10 years postprocedure showed stratum-specific increases ranging from 0.60 to 1.56 kg/m2. During a median follow-up of 7.2 years (interquartile range, 3.2-13.3 years), a higher BMI was associated with reduced survival after adjusting for baseline covariates (P = .001). CONCLUSIONS: SM is safe and effective in HCM patients with obesity, but the risk of late death increased with increasing BMI. Attention to risk factor management through weight loss may improve late results after SM.

Transapical Septal Myectomy for Hypertrophic Cardiomyopathy With Midventricular Obstruction.

BACKGROUND: Midventricular obstruction (MVO) is an uncommon variant of hypertrophic cardiomyopathy (HCM). In patients receiving septal myectomy for HCM, failure to recognize the concurrent MVO in the context of basal septum thickening can lead to inadequate excision and residual gradient. In this report, we detail the operative outcomes of MVO with and without coexistent basal septal hypertrophy. METHODS: From February 1997 through September 2018, 196 patients underwent midventricular myectomy. Medical records and follow-up databases were reviewed to obtain patient characteristics and perioperative features. RESULTS: At baseline, 156 patients (80%) were in New York Heart Association Functional Classification III/IV. Obstruction was isolated to the midventricle in 80 patients, and 63 (79%) were treated by isolated transapical myectomy. The remaining 116 patients had intraventricular obstruction at both subaortic and midcavity levels; in 108 (93%), a combined transaortic and transapical approach was adopted to achieve complete relief of the obstruction. After septal myectomy, the resting peak instantaneous gradient decreased from a median 48 mm Hg (interquartile range [IQR], 23-77 mm Hg) preoperatively to 8 mm Hg (IQR, 0-19 mm Hg) before hospital dismissal. Median follow-up was 2.9 years (IQR, 0.7-5.0 years), and the estimated 1-, 5-, and 10-year survivals were 99%, 98%, and 90%, respectively. There were no late complications attributable to the transapical incision. CONCLUSIONS: Transapical exposure is a safe and effective approach for relief of midventricular obstruction, and hemodynamic results are similar to those achieved by standard myectomy for subaortic obstruction. The technique can be combined with transaortic myectomy for patients with left ventricular outflow obstruction at both levels.

Nonobstructive Hypertrophic Cardiomyopathy in a Patient With Mitral Prosthesis.

Transapical septal myectomy can be performed for patients with nonobstructive hypertrophic cardiomyopathy and diastolic dysfunction to enlarge the LV cavity. The procedure may also include limited shaving of severely hypertrophied papillary muscles. This report illustrates the usefulness of papillary muscle resection to enlarge the left ventricle in a patient with nonobstructive hypertrophic cardiomyopathy and preexisting mitral valve prosthesis.

Phylogenetic analysis of two single-copy nuclear genes revealed origin of tetraploid barley Hordeum marinum.

Sea barley Hordeum marinum is an important germplasm resource. However, the origin of this tetraploid H. marinum subsp. gussoneanum is still unclear, which has caused great perplexity to the exploration and utilization of germplasm resources. We used two single-copy nuclear genes, thioredoxin-like gene (TRX) and waxy1 gene encoding granule-bound starch synthase (WAXY1) to analyze 41 accessions of Hordeum marinum. The phylogenies of different genes told different story of evolution of tetraploids of H. marinum subsp. gussoneanum. The phylogenetic trees showed that two distinct copies of sequences from both genes were detected for some accessions of the tetraploids of H. marinum subsp. gussoneanum, and diploid marinum might also contribute to the origin and evolution of the tetraploid gussoneanum. Our findings suggested that tetraploid more likely originated from the diploids of H. marinum subsp. gussoneanum and another ancestor that might be an extinct unknown diploid species. Homogenization of gene in tetraploids also occurred after polyploidization as both TRX and WAXY1 sequences in some accessions of tetraploid H. marinum subsp. gussoneanum cannot be distinguished, indicating the complicated evolution of this tetraploid.

A prospective study of serum metabolites and risk of ischemic stroke.

OBJECTIVE: To identify promising blood-based biomarkers and novel etiologic pathways of disease risk, we applied an untargeted serum metabolomics profiling in a community-based prospective study of ischemic stroke (IS). METHODS: In 3,904 men and women from the Atherosclerosis Risk In Communities study, Cox proportional hazard models were used to estimate the association of incident IS with the standardized level of 245 fasting serum metabolites individually, adjusting for age, sex, race, field center, batch, diabetes, hypertension, current smoking status, body mass index, and estimated glomerular filtration rate. Validation of results was carried out in an independent sample of 114 IS cases and 112 healthy controls. RESULTS: Serum levels of 2 long-chain dicarboxylic acids, tetradecanedioate and hexadecanedioate, were strongly correlated (r = 0.88) and were associated with incident IS after adjusting for covariates (hazard ratio [95% confidence interval (CI)] 1.11 [1.06-1.16] and 1.12 [1.07-1.17], respectively; p < 0.0001). Analyses by IS subtypes suggested that these associations were specific to cardioembolic stroke (CES). Associations of tetradecanedioate and hexadecanedioate with IS were independently confirmed (odds ratio [95% CI] 1.76 [1.21; 2.56] and 1.60 [1.11; 2.32], respectively). CONCLUSION: Two serum long-chain dicarboxylic acids, metabolic products of ω-oxidation of fatty acids, were associated with IS and CES independently of known risk factors. Pathways related to intracellular hexadecanedioate synthesis or those involved in its clearance from the circulation may mediate IS risk. These results highlight the potential of metabolomics to discover novel circulating biomarkers for stroke and to unravel novel pathways for IS and its subtypes.

E2f8 mediates tumor suppression in postnatal liver development.

E2F-mediated transcriptional repression of cell cycle-dependent gene expression is critical for the control of cellular proliferation, survival, and development. E2F signaling also interacts with transcriptional programs that are downstream of genetic predictors for cancer development, including hepatocellular carcinoma (HCC). Here, we evaluated the function of the atypical repressor genes E2f7 and E2f8 in adult liver physiology. Using several loss-of-function alleles in mice, we determined that combined deletion of E2f7 and E2f8 in hepatocytes leads to HCC. Temporal-specific ablation strategies revealed that E2f8's tumor suppressor role is critical during the first 2 weeks of life, which correspond to a highly proliferative stage of postnatal liver development. Disruption of E2F8's DNA binding activity phenocopied the effects of an E2f8 null allele and led to HCC. Finally, a profile of chromatin occupancy and gene expression in young and tumor-bearing mice identified a set of shared targets for E2F7 and E2F8 whose increased expression during early postnatal liver development is associated with HCC progression in mice. Increased expression of E2F8-specific target genes was also observed in human liver biopsies from HCC patients compared to healthy patients. In summary, these studies suggest that E2F8-mediated transcriptional repression is a critical tumor suppressor mechanism during postnatal liver development.