Sex Differences in Outcomes of Patients With Chronic Aortic Regurgitation: Closing the Mortality Gap

ObjectiveTo examine contemporary clinical differences between men and women with hemodynamically significant chronic aortic regurgitation (AR).Patients and MethodsWe retrospectively identified 1072 consecutive patients with moderate to severe or severe AR diagnosed between February 21, 2004, and April 29, 2019. Echocardiographic data, aortic valve surgical intervention (AVS), and all-cause death were analyzed.ResultsAt baseline, the 189 women in the study group were older than the 883 men (mean ± SD age, 64±18 years vs 58±17 years), had more advanced symptoms, and had larger left ventricular end-systolic dimension index (LVESDi) (all P<.001) despite similar AR severity. An LVESDi of greater than 20 mm/m² was noted in 60 of 92 asymptomatic women (65%) vs 225 of 559 asymptomatic men (40%) (P<.001). Median follow-up was 5.6 years (interquartile range, 2.5 to 10.0 years). Female sex was associated with less AVS (P=.009), and overall 10-year survival was better in men (76%±2%) than in women (64%±5%) (P=.004). However, 10-year post-AVS survival was similar between the sexes (P=.86), and women had better left ventricular reverse remodeling than men regarding end-diastolic dimension (P=.02). Multivariable independent predictors of death were age, advanced symptoms, LVESDi, ejection fraction, and AVS (all P≤.03) but not female sex. When compared with the age-matched US population, women exhibited a 1.3-fold increased relative risk of death (P=.0383) while men had similar survival (P=.11).ConclusionIn contemporary practice, women with AR continue to exhibit an overall survival penalty not related to female sex but to late referral markers, including more advanced symptoms, larger LVESDi, and less AVS. Nonetheless, women in our study exhibited outstanding post-AVS left ventricular remodeling and had good post-AVS survival, a step forward toward closing the sex-related mortality gap. The high percentage of LVESDi of 20 mm/m² or greater in asymptomatic women represents a window of opportunity for advanced-symptom prevention and timely AR surgical correction that may close the mortality gap.     

Sex Differences in Children and Young Adults With Bicuspid Aortic Valve Disease in First Two Decades of Life

ObjectiveTo elucidate sex differences in valve morphology, disease phenotype, progression, and outcomes among children and young adults with bicuspid aortic valve (BAV).Patients and MethodsThis is a retrospective cohort study examining all children and young adults (aged ≤22 years) with isolated BAV diagnosed, by excluding patients with concomitant congenital heart defects or genetic syndromes, from January 1, 1990, through December 1, 2016, at Mayo Clinic in Rochester, Minnesota.ResultsOf 1010 patients with BAV, 558 had isolated BAV. Distributions of morphology were right-left in 65.8% (n=367), right-noncoronary in 34% (n=190), and left-noncoronary cusp fusion in 0.2% (n=1) of patients; with no sex differences. Male to female ratio was 3:1. At the first echocardiographic evaluation in the study, there were no sex differences in terms of frequency of aortic valve stenosis or regurgitation. However, males had significantly higher grades of aortic valve regurgitation at 17 years of age onward (P<.0001). Males had significantly larger mid-ascending aorta (P=.01) and sinus of Valsalva dimensions (z score; P=.0001) as compared with females, with a novel finding of peak aortic dimensions around 8 years of age. Males also had more than 2-fold higher risk for sinus of Valsalva dilation (z score >2) as compared with females (odds ratio, 2.3; 95% CI, 1.2 to 4.2; P=.01). There were no significant sex differences in the primary cardiac outcomes of interventions on aortic valve and/or aorta, aortic dissection, or death.ConclusionIn children and young adults with BAV, males have a higher grade of aortic regurgitation in late adolescence, significantly larger aortic dimensions, different patterns of aortic growth, and more frequent sinus of Valsalva dilation as compared with females. Overall, the rate of primary cardiac events is lower in young patients, with no significant sex differences.     

A Contemporary Population-Based Profile of Infective Endocarditis Using the Expanded Rochester Epidemiology Project

ObjectiveTo develop a contemporary profile of infective endocarditis (IE) among a population in 6 counties of Olmsted, Dodge, Mower, Steele, Waseca, and Freeborn in southern Minnesota between 2014 and 2018.Patients and MethodsAll possible and definite cases of IE (≥18 years) among residents of 6 counties in southern Minnesota, including Olmsted County, diagnosed between January 1, 2014, and December 31, 2018, were included in this retrospective, population-based investigation, using the Expanded Rochester Epidemiology Project (E-REP).ResultsOverall, 137 patients with IE developed incident IE in the 6-county region, corresponding to an age- and sex-adjusted incidence rate of 11.9 per 100,000 person-years. Men had a significantly higher incidence of IE (17.9 vs 6.8 per 100,000 person-years), and rates increased exponentially with age in both sexes. The median age of incident cases was 68.2 years, and 67.9% were male patients. The percentage of patients with histories of injection-drug use was low, at 6.7%. Bicuspid aortic valve was the most common (9.6%) native valve predisposing condition. Staphylococcus aureus was identified as the predominant pathogen in the overall group (34.8%), with viridans-group streptococci accounting for only 19.3% cases. Central nervous system and musculoskeletal complications were common. The 30-day readmission rate was 27.9%, and the 6-month mortality rate was 31.8%.ConclusionTo our knowledge, this is the first time that the population-based E-REP has been used to determine an age- and sex-adjusted IE incidence. Older male patients predominated, and S aureus was the most common pathogen. Based on these findings, it is not surprising that IE complications were frequently seen.     

Prevalence and Natural History of Mitral Annulus Calcification and Related Valve Dysfunction

ObjectiveTo evaluate the prevalence and natural history of mitral annulus calcification (MAC) and associated mitral valve dysfunction (MVD) in patients undergoing clinically indicated echocardiography.MethodsA retrospective review was conducted of all adults who underwent echocardiography in 2015. Mitral valve dysfunction was defined as mitral regurgitation or mitral stenosis (MS) of moderate or greater severity. All-cause mortality during 3.0 (0.4 to 4.2) years of follow-up was compared between groups stratified according to the presence of MAC or MVD.ResultsOf 24,414 evaluated patients, 5502 (23%) had MAC. Patients with MAC were older (75±10 years vs 60±16 years; P<.001) and more frequently had MVD (MS: 6.6% vs 0.5% [P<.001]; mitral regurgitation without MS: 9.5% vs 6.1% [P<.001]). Associated with MS in patients with MAC were aortic valve dysfunction, female sex, chest irradiation, renal dysfunction, and coronary artery disease. Kaplan-Meier 1-year survival was 76% in MAC+/MVD+, 87% in MAC+/MVD?, 86% in MAC?/MVD+, and 92% in MAC?/MVD?. Adjusted for age, diabetes, renal dysfunction, cancer, chest irradiation, ejection fraction below 50%, aortic stenosis, tricuspid regurgitation, and pulmonary hypertension, MAC was associated with higher mortality during follow-up (adjusted hazard ratio, 1.40; 95% CI, 1.31 to 1.49; P<.001); MVD was associated with even higher mortality in patients with MAC (adjusted hazard ratio, 1.79; 95% CI, 1.58 to 2.01; P<.001). There was no significant interaction between MAC and MVD for mortality (P=.10).ConclusionIn a large cohort of adults undergoing echocardiography, the prevalence of MAC was 23%. Mitral valve dysfunction was more than twice as prevalent in patients with MAC. Adjusted mortality was increased in patients with MAC and worse with both MAC and MVD.     

A Population-Based Study of the Incidence and Natural History of Degenerative Thoracic Aortic Aneurysms

ObjectiveTo investigate the incidence and natural history of degenerative thoracic aortic aneurysms (TAAs) and compare results between ascending (aTAAs) and descending TAAs (dTAAs).Patients and MethodsThis population-based cohort study used the Rochester Epidemiology Project database from January 1, 1995, through December 31, 2015. Patients were classified as the aTAA or dTAA group.ResultsOf 238 Olmsted County residents studied, 131 (55.0%) were women; 154 (64.7%) were in the aTAA group, and 84 (35.3%) were in the dTAA group. Median age was 77.0 years (interquartile range, 69.1-83.8 years). The overall age- and sex-adjusted incidence rate was 13.8 per 100,000 person-years (95% CI, 12.1 to 15.6) and varied from 9.9 in 1995 to 1999 to 19.0 in 2005 to 2009. It was 9.0 (95% CI, 7.5 to 10.4) for the aTAA and 4.9 (95% CI, 3.8 to 5.9) for the dTAA group. Overall 5-year survival was 62.5%, lower than the expected survival of 73.7% for the US 2010 census population (P<.001). The 5-year survival was 42.9% for the aTAA and 73.4% for the dTAA group (P<.001). On multivariable analysis, advanced age and smoking status were associated with all-cause mortality. The 5-year estimate of freedom from an aortic-related event was 80.0%, lower for dTAAs (67.8%) than for aTAAs (85.2%; P<.001). Maximal aortic diameter and dTAAs were associated with aortic-related events.ConclusionThe incidence of TAAs was stable from 1995 to 2015 and mortality for those with TAAs remains higher than for the general population. Older age and smoking status were associated with overall mortality, whereas larger aneurysms and dTAAs were associated with aortic-related events.     

Age-Related 2-Year Mortality After Transcatheter Aortic Valve Replacement: the YOUNG TAVR Registry

ObjectiveTo comparatively assess the natural history of patients of different ages undergoing transcatheter aortic valve replacement (TAVR).Patients and MethodsFor this study, we used the YOUNG TAVR, an international, multicenter registry investigating mortality trends up to 2 years in patients with aortic valve stenosis treated by TAVR, classified according to 3 prespecified age groups: 75 years or younger (n=179), 76 to 86 years (n=602), and older than 86 years (n=221). A total of 1002 patients undergoing TAVR were included. Demographic, clinical, and outcome data in the youngest group were compared with those of patients 76 to 86 years and older than 86 years. Patients were followed up for up to 2 years.ResultsCompared with patients 75 years or younger (reference group), patients aged 76 to 86 years and older than 86 years had nonsignificantly different 30-day mortality (odds ratio, 0.76; 95% CI, 0.41-1.38; P=.37 and odds ratio, 1.27; 95% CI, 0.62-2.60; P=.51, respectively) and 1-year mortality (hazard ratio (HR), 0.72; 95% CI, 0.48-1.09; P=.12 and HR, 1.11; 95% CI, 0.88-1.40; P=.34, respectively). Mortality at 2 years was significantly lower among patients aged 76 to 86 years (HR, 0.62; 95% CI, 0.42-0.90; P=.01) but not among the older group (HR, 1.06; 95% CI, 0.68-1.67; P=.79). The Society of Thoracic Surgeons 30-day mortality score was lower in younger patients who, however, had a significantly higher prevalence of chronic obstructive pulmonary disease (P=.005 vs the intermediate group and P=.02 vs the older group) and bicuspid aortic valves (P=.02 vs both older groups), larger left ventricles, and lower ejection fractions.ConclusionIn the present registry, mortality at 2 years after TAVR among patients 75 years or younger was higher compared with that of patients aged 75 to 86 years and was not markedly different from that of patients older than 86 years. The findings are attributable at least in part to a greater burden of comorbidities in the younger age group that are not entirely captured by current risk assessment tools.     

Corynebacterium jeikeium-induced infective endocarditis and perivalvular abscess diagnosed by 16S ribosomal RNA sequence analysis: A case report

IntroductionCorynebacterium jeikeium normally presents on human skin, and it is often judged as contamination when it is cultured from blood. C. jeikeium can cause infective endocarditis, especially, that associated with cardiac surgery and prosthetic valvular endocarditis.Case reportA 66-year-old Japanese male patient was diagnosed with C. jeikeium-induced infective endocarditis (IE) and perivalvular abscess after a coronary artery bypass grafting and aortic valve replacement with bioprosthesis; pyogenic spondylodiscitis was also observed. Patch repair for aortic valve annulus and re-Bentall procedure with bioprosthesis was performed for IE and perivalvular abscess. The causative bacterium was confirmed as C. jeikeium on 16S ribosomal RNA sequencing of surgical sample and positive blood culture. The patient underwent six weeks of intravenous antibacterial treatment with vancomycin and an additional two weeks of oral treatment with linezolid, following which, his condition improved. Corynebacterium jeikeium can cause infective endocarditis and perivalvular abscess, which is a more severe condition than IE.Conclusion16S ribosomal RNA sequencing is useful in diagnosing bacterial species that can cause contamination, such as Corynebacterium spp.     

Pre-admission and In-Hospital Statin Use is Associated With Reduced Short-Term Mortality in Infective Endocarditis

ObjectiveTo investigate for potential protective effects of statin use among patients with infective endocarditis (IE) with consideration for underlying diseases and bacterial culture — variables which have prognostic implications and show considerable geographic variation yet are unappreciated in previous pharmacoepidemiological studies.Patients and MethodsPatients diagnosed with IE between January 1, 1996, and December 31, 2019, were identified. We estimated the effect on mortality of pre-admission statin use (≥90 cumulative days of use before index date) and in-hospital use (use beginning within 2 days of admission), compared with nonusers and discontinued users, respectively, through propensity score analytics.ResultsOf 6700 IE patients (mean age, 58.0 years; 63.3% male [n=4251]), 776 patients had pre-admission statin use, with 626 continuing statin use following admission (in-hospital users). Pre-admission statin users had a 31% lower risk of 1-year mortality (HR, 0.69; 95% CI, 0.58 to 0.82) compared with nonusers. In-hospital users had a 48% lower risk of 1-year mortality (HR, 0.52; 95% CI, 0.34 to 0.78) compared with discontinued users. Subgroup analyses showed significant protective effects of statin use for patients with varying causative agents, underlying diseases, and with or without prosthetic valves. Results were consistent across different statins, and were dose-dependent.ConclusionIn patients with IE, pre-admission and in-hospital use of statin, when compared with statin nonusers and discontinued users, respectively, were associated with a lower risk of 1-year mortality.     

Real-World Experience of Angiotensin Receptor–Neprilysin Inhibition in Reduced Ejection Fraction Heart Failure Patients With Advanced Kidney Disease

ObjectiveTo investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m²), which have been excluded from the landmark trials.Patients and MethodsThis study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m² were further analyzed (the Taiwan Society of Cardiology – Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints.ResultsAfter propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m²) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m² vs 21.4±17.5 mL/min per 1.73 m²; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users.ConclusionOur results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting.     

Robotic Mitral Valve Repair: Indication for Surgery Does Not Influence Early Outcomes

ObjectiveTo evaluate the outcomes of robotic mitral valve repair (MVr) by primary indication per American Heart Association guidelines for surgery: class I vs class IIa.Patients and MethodsFrom January 1, 2008, through September 30, 2016, 603 patients underwent robotic MVr for severe primary mitral regurgitation. Medical records of 576 consenting patients were retrospectively reviewed to determine the primary indication for surgery. Patients were stratified into class I or class IIa, and preoperative, intraoperative, and postoperative variables were compared.ResultsOf 516 patients, 428 (83%) had class I indication and 88 (17%) had class IIa indication for surgery. Preoperatively, no significant differences were observed between both cohorts. Importantly, a significantly higher number of patients with class I indication underwent MVr for bileaflet prolapse (172 of 428 [40%] vs 21 of 88 [25%]; P=.03). Early MVr outcomes indicated recurrent mitral regurgitation (moderate or greater) in only 12 of 576 (2%), and no significant differences were observed between classes (P=.23). Apart from parameters for ventricular size, all other intraoperative and postoperative variables were comparable between both cohorts.ConclusionComparable outcomes were indicated across all classes of indications for MVr surgery. These results continue to support the use of this surgical technique, even in less sick patients. Early referral along with more extensive robotic MVr experience will likely result in further improvements in long-term outcomes.     

Predicting 1-Year Mortality on Admission Using the Mayo Cardiac Intensive Care Unit Admission Risk Score

ObjectiveTo determine whether the Mayo Cardiac Intensive Care Unit (CICU) Admission Risk Score (M-CARS) accurately predicts 1-year mortality.MethodsWe retrospectively reviewed adult CICU patients admitted from January 1, 2007, through April 30, 2018, and calculated M-CARS using admission data. We examined the association between admission M-CARS, as continuous and categorical variables, and 1-year mortality.ResultsThis study included 12,428 unique patients with a mean age of 67.6±15.2 years (4686 [37.7%] female). A total of 2839 patients (22.8%) died within 1 year of admission, including 1149 (9.2%) hospital deaths and 1690 (15.0%) of the 11,279 hospital survivors. The 1-year survival decreased incrementally as a function of increasing M-CARS (P<.001), and all components of M-CARS were significant predictors of 1-year mortality (P<.001). The 1-year survival among hospital survivors decreased incrementally as a function of increasing M-CARS for scores below 3 (all P<.001); however, there was no further decrease in 1-year survival for hospital survivors with M-CARS of 3 or more (P=.99). The M-CARS components associated with 1-year mortality among hospital survivors included blood urea nitrogen, red blood cell distribution width, Braden skin score, and respiratory failure (all P<.001).ConclusionM-CARS predicted 1-year mortality among CICU admissions, with a plateau effect at high M-CARS of 3 or more for hospital survivors. Significant added predictors of 1-year mortality among hospital survivors included markers of frailty and chronic illness.     

Artificial Intelligence Application in Graves Disease: Atrial Fibrillation,Heart Failure and Menstrual Changes

ObjectiveTo study the utility of artificial intelligence (AI)–enabled electrocardiograms (ECGs) in patients with Graves disease (GD) in identifying patients at high risk of atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), and to study whether AI-ECG can reflect hormonal changes and the resulting menstrual changes in GD.Patients and MethodsPatients diagnosed with GD between January 1, 2009, and December 31, 2019, were included. We considered AF diagnosed at 30 days or fewer before or any time after GD and de novo HFrEF not explained by ischemia, valve disorder, or other cardiomyopathy at/after GD diagnosis. Electrocardiograms at/after index condition were excluded. A subset analysis included females younger than 45 years of age to study the association between ECG-derived female probability and menstrual changes (shorter, lighter, or newly irregular cycles).ResultsAmong 430 patients (mean age, 50±17 years; 337 (78.4%) female), independent risk factors for AF included ECG probability of AF (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.6 per 10%; P<.001), older age (HR, 1.05; 95% CI, 1.03 to 1.07 per year; P<.001), and overt hyperthyroidism (HR, 3.9; 95% CI, 1.2 to 12.7; P=.03). The C-statistic was 0.85 for the combined model. Among 495 patients (mean age, 52±17 years; 374 (75.6%) female), independent risk factors for HFrEF were ECG probability of low ejection fraction (HR, 1.4; 95% CI, 1.1 to 1.6 per 10%; P=.001) and presence of AF (HR, 8.3; 95% CI, 2.2 to 30.9; P=.002), and a C-statistic of 0.89 for the combined model. Lastly, of 72 females younger than 45 years, 30 had menstrual changes at time of GD and had a significantly lower AI ECG–derived female probability [median 77.3; (IQR 57.9 to 94.4)% vs. median 97.7 (IQR 92.4 to 99.5)%, P<.001].ConclusionAI-enabled ECG identifies patients at risk for GD-related AF and HFrEF and was associated with menstrual changes in women with GD.     

Outcomes and Echocardiographic Follow-up After Surgical Management of Tricuspid Regurgitation in Patients With Transvenous Right Ventricular Leads

ObjectiveTo evaluate outcomes of elective surgical management of tricuspid regurgitation (TR) in patients with transvenous right ventricular leads, and compare results between non–lead-induced and lead-induced TR patients.Patients and MethodsWe studied patients with right ventricular leads who underwent tricuspid valve surgery from January 1, 1993, through December 31, 2015, and categorized them as non–lead-induced and lead-induced TR. Propensity score (PS) for the tendency to have lead-induced TR was estimated from logistic regression and was used to adjust for group differences.ResultsFrom the initial cohort of 470 patients, 444 were included in PS-adjustment analyses (174 non–lead-induced TRs [123 repairs, 51 replacements], 270 lead-induced TRs [129 repairs, 141 replacements]). In PS-adjusted multivariable analysis, lead-induced TR was not associated with mortality (P=.73), but tricuspid valve replacement was (hazard ratio, 1.59; 95% CI, 1.13 to 2.25; P=.008). Five-year freedom from tricuspid valve re-intervention was 100% for non–lead-induced TR and 92.3% for lead-induced TR; rates adjusted for PS differed between groups (P=.005). There was significant improvement in TR postoperatively in each group (P<.001). In patients having tricuspid valve repair, TR grades tended to worsen over time, but the difference in trends was not significantly different between groups.ConclusionLead-induced TR did not affect long-term survival after elective tricuspid valve surgery. In patients with lead-induced TR, tricuspid valve re-intervention was more common. Improvement in TR was achieved in both groups after surgery; however, severity of TR tended to increase over follow-up after tricuspid valve repair.     

Population-Based Trends in Amputations and Revascularizations for Peripheral Artery Disease From 1990 to 2009

ObjectiveTo determine trends in amputations and revascularizations for peripheral artery disease (PAD) in a well-defined population.MethodsA population-based cohort study of Olmsted County, Minnesota, residents with PAD undergoing amputation or revascularization was conducted between January 1, 1990, and December 31, 2009. Population-level 5-year incidence trends for endovascular, open surgical, and hybrid revascularizations and major and minor amputations were determined. Limb-specific outcomes after revascularization, including major adverse limb events and amputation-free survival, were compared between initial surgical and endovascular or hybrid revascularization groups using Kaplan-Meier analysis.ResultsWe identified 773 residents who underwent 1906 limb-procedures, including 689 open revascularizations, 685 endovascular or hybrid revascularizations, and 220 major amputations. During the 20-year study period, the incidence of endovascular and hybrid revascularizations increased, whereas the incidence of open surgical revascularizations and major amputations decreased. Incidence of revascularizations for chronic limb-threatening ischemia (CLTI) did not change. Among residents with CLTI undergoing their first revascularization on a limb, endovascular revascularization was associated with more major adverse limb events and major amputations compared with surgical revascularization during the ensuing 15 years.ConclusionThe rising incidence of endovascular and hybrid revascularizations and the decreasing incidence of open surgical revascularizations for PAD were associated with a decreasing incidence of major amputations in this population between 1990 and 2009, despite a stable incidence of revascularizations for CLTI. With more major adverse limb events and major amputations after endovascular revascularization, these trends suggest that additional emphasis should be placed on improving limb salvage efforts beyond just mode of revascularization.     

Serum 25-Hydroxyvitamin D and Subsequent Cancer Incidence and Mortality: A Population-Based Retrospective Cohort Study

ObjectiveTo determine the relationship between 25-hydroxyvitamin D (25[OH]D) values and subsequent cancer incidence and mortality.Patients and MethodsWe identified all adult patients living in Olmsted County, Minnesota, between January 1, 2005, and December 31, 2011, who had at least 1 25(OH)D measurement and no prior diagnosis of cancer. Cancer outcomes were retrieved starting 30 days after 25(OH)D measurement and until patients’ final clinical visit as an Olmsted County resident; December 31, 2014; or death. Cox proportional hazards regression was used to analyze data.ResultsA total of 8700 individuals had a 25(OH)D measurement and no history of cancer, with a mean ± SD 25(OH)D value of 29.7±12.8 ng/mL (to convert to nmol/L, multiply by 2.496). The mean ± SD age was 51.5±16.4 years, and most were women (78.1%; n=6796) and White (85.7%; n=7460). A total of 761 individuals developed cancer (skin cancer, n=360; nonskin cancer, n=401) during a median follow-up of 4.6 (interquartile range, 3.4-6.1) years. Compared with participants with 25(OH)D values of 20 to 50 ng/mL (reference group), those with 25(OH)D values less than 12 ng/mL had a greater nonskin cancer incidence (hazard ratio [HR], 1.56; 95% CI, 1.03 to 2.36; P=.04) after adjustment. There was no association between 25(OH)D values and total cancer or skin cancer incidence. Compared with individuals from the reference group, 25(OH)D levels less than 12 ng/mL (HR, 2.35; 95% CI, 1.01 to 5.48; P=.047) and 12 to 19 ng/mL (HR, 2.10; 95% CI, 1.05 to 4.22; P=.04) were associated with increased cancer mortality.ConclusionLow 25(OH)D levels were associated with increased risk for incident nonskin cancer and cancer-related mortality.     

Survival in 222 Patients With Severe CSCI: An 8-Year Epidemiologic Survey in Western China

ObjectiveTo assess the survival and the predictors of mortality in patients with severe cervical spinal cord injuries (CSCI).DesignRetrospective study.ParticipantsFrom January 1, 2010, to May 31, 2018, patients who suffered from severe CSCIs in Western China were enrolled in this study (N=222).InterventionsNot applicable.Main Outcome MeasuresSurvival rates and mortality risk factors. Measures were calculated by the product-limit method (Kaplan-Meier) and the Cox model.ResultsThe overall 1-year, 3-year, 5-year, and 8-year postoperative mortalities were 24.4%, 30.6%, 33.3%, 36.2%, and 39.0%, respectively. Most deaths occurred within 36 months after the injury. According to the Cox proportional hazards model, the significant predictors of survival were as follows: (1) age; (2) neurologic level; (3) treatment options (surgical or conservative); (4) ventilator support (P<.05). The 8-year mortality for older patients (>50y) was 50.2%, which was significantly higher than that for younger patients (32.4%, <50y). The risk of death was 2.053 times higher in higher levels of injury (C1-C4) than in lower levels of injury (C5-C8) (P<.05). Compared with conservative treatment, patients who received surgical treatment (either anterior or posterior decompression) had a lower risk of death (P<.05). No significant difference was detected in the risk of death between early surgery (<3d) and mid-term surgery (3-7d) (P>.05). However, patients who received late-term surgery (>7d) had a higher mortality risk (P<.05). The overall 8-year mortality risk of patients who needed ventilator support was much higher than those who did not need ventilator support (P<.05).ConclusionsAge, neurologic level, ventilator dependence, treatment options, and timing to surgery were main risk factors for mortality in patients with severe CSCIs. Better understanding of the predictors for survival could possibly contribute to the improvement of survival rates.     

Adults With Tetralogy of Fallot: Early Postoperative Outcomes and Risk Factors for Complications

ObjectiveTo report the early postoperative outcomes in adults with tetralogy of Fallot (TOF) undergoing cardiac surgery and to identify patient factors associated with complications.Patients and MethodsWe performed a single-institution retrospective review of adults with TOF who underwent cardiac surgery from January 8, 2008, through June 21, 2018. Patients’ characteristics, preoperative imaging, surgical interventions, outcomes, and complications were analyzed.ResultsThere were 219 adults with TOF (mean age, 40 years; range, 18-83 years; 88 [40%] female) in the study. Surgical interventions included repair or replacement of the pulmonary valve (n=199 [91%]), tricuspid valve (n=70 [32%]), mitral valve (n=13 [5.9%]), and aortic valve (n=8 [3.7%]). Three patients (1.4%) underwent first-time TOF repair. The 30-day mortality rate was 1.4% (n=3). Early postoperative complications occurred in 66 (30%) and included arrhythmias requiring treatment, dialysis requirement, liver dysfunction, respiratory failure, infection, reoperation, cardiac arrest, mechanical circulatory support, and death. Multivariate analysis found older age at current surgery (odds ratio [OR], 1.04 per year; 95% CI, 1.01 to 1.06; P<.001), longer cardiopulmonary bypass time (OR, 1.01 per minute; 95% CI, 1.01 to 1.02; P<.001), right ventricular systolic dysfunction (OR, 1.31; 95%, CI 1.02 to 1.69; P=.03), diabetes mellitus (OR, 3.50; 95% CI, 1.20 to 10.2; P=.02), and history of initial palliative surgery (OR, 1.99; 95% CI, 1.01 to 3.91; P=.05) as independent predictors of complications.ConclusionSurgical interventions for adult patients with TOF can be performed with low early morbidity and mortality. Clinical characteristics and preoperative testing parameters can predict risk for complications in the postoperative period.     

Fitness and Mortality Among Persons 70 Years and Older Across the Spectrum of Cardiovascular Disease Risk Factor Burden: The FIT Project

ObjectiveTo determine whether fitness could improve mortality risk stratification among older adults compared with cardiovascular disease (CVD) risk factors.MethodsWe examined 6509 patients 70 years of age and older without CVD from the Henry Ford ExercIse Testing Project (FIT Project) cohort. Patients performed a physician-referred treadmill stress test between 1991 and 2009. Traditional categorical CVD risk factors (hypertension, hyperlipidemia, diabetes, and smoking) were summed from 0 to 3 or more. Fitness was grouped as low, moderate, and high (<6, 6 to 9.9, and ≥10 metabolic equivalents of task). All-cause mortality was ascertained through US Social Security Death Master files. We calculated age-adjusted mortality rates, multivariable adjusted Cox proportional hazards, and Kaplan-Meier survival models.ResultsPatients had a mean age of 75±4 years, and 3385 (52%) were women; during a mean follow-up of 9.4 years, there were 2526 deaths. A higher fitness level (P<.001), not lower CVD risk factor burden (P=.31), was associated with longer survival. The age-adjusted mortality rate per 1000 person-years was 56.7 for patients with low fitness and 0 risk factors compared with 24.9 for high fitness and 3 or more risk factors. Among patients with 3 or more risk factors, the adjusted mortality hazard was 0.68 (95% CI, 0.61 to 0.76) for moderate and 0.51 (95% CI, 0.44 to 0.60) for high fitness compared with the least fit.ConclusionAmong persons aged 70 years and older, there was no significant difference in survival of patients with 0 vs 3 or more risk factors, but a higher fitness level identified older persons with good long-term survival regardless of CVD risk factor burden.     

Prediction of Mortality in Coronary Artery Disease: Role of Machine Learning and Maximal Exercise Capacity

ObjectiveTo develop a prediction model for survival of patients with coronary artery disease (CAD) using health conditions beyond cardiovascular risk factors, including maximal exercise capacity, through the application of machine learning (ML) techniques.MethodsAnalysis of data from a retrospective cohort linking clinical, administrative, and vital status databases from 1995 to 2016 was performed. Inclusion criteria were age 18 years or older, diagnosis of CAD, referral to a cardiac rehabilitation program, and available baseline exercise test results. Primary outcome was death from any cause. Feature selection was performed using supervised and unsupervised ML techniques. The final prognostic model used the survival tree (ST) algorithm.ResultsFrom the cohort of 13,362 patients (60±11 years; 2400 [18%] women), 1577 died during a median follow-up of 8 years (interquartile range, 4 to 13 years), with an estimated survival of 67% up to 21 years. Feature selection revealed age and peak metabolic equivalents (METs) as the features with the greatest importance for mortality prediction. Using these 2 features, the ST generated a long-term prediction with a C-index of 0.729 by splitting patients in 8 clusters with different survival probabilities (P<.001). The ST root node was split by peak METs of 6.15 or less or more than 6.15, and each patient’s subgroup was further split by age or other peak METs cut points.ConclusionApplying ML techniques, age and maximal exercise capacity accurately predict mortality in patients with CAD and outperform variables commonly used for decision-making in clinical practice. A novel and simple prognostic model was established, and maximal exercise capacity was further suggested to be one of the most powerful predictors of mortality in CAD.     

Examination of the efficacy of olanexidine gluconate for surgical site infections in colorectal cancer elective surgery

IntroductionThe preoperative skin antiseptic, olanexidine gluconate (OLG), which has been available in Japan since 2015, is also known to be effective against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and Pseudomonas aeruginosa. This study attempted to clarify OLG efficacy against surgical site infections and antiseptic-related adverse events as compared to conventionally used povidone iodine (PVP–I).MethodsPropensity score matching was performed on 307 patients who underwent surgery for colorectal tumors at our hospital. All 116 cases (58 PVP-I cases, 58 OLG cases) who were diagnosed with colorectal cancer were included. We examined surgical site infection rate after disinfection using PVP-I and OLG, length of hospitalization stay (days) after surgery, adverse events associated with antiseptics, and additional medical costs associated with adverse events caused by antiseptics.ResultsThe surgical site infection rate was 8.6% in both the PVP-I and OLG groups, with no significant difference observed. The number of postoperative hospitalization days in the PVP-I group was 12.9 (±6.9) days and 16.4 (±14.6) days in the OLG group, which exhibited no significant difference (p = 0.10). Although no complications due to antiseptics were observed in the PVP-I group, skin-related side effects were observed in 8 patients (13.8%) in the OLG group. The median additional medical cost was 730 [120–1823] yen.ConclusionsOLG was as effective as the conventional PVP-I for surgical site infections during colorectal cancer elective surgery. However, significantly higher skin disorders occurred in OLG, thereby making it necessary to evaluate antiseptic use in conjunction with patient burden.