Carpal Tunnel Syndrome and Transthyretin Amyloidosis in the All of Us Research Program.

OBJECTIVE: To evaluate the association of carpal tunnel syndrome (CTS) with incident heart failure and incident amyloidosis and to assess the risk of CTS in pathogenic TTR genetic variant carriers. METHODS: This prospective cohort study included multiethnic US adults 18 years of age and older without prevalent heart failure and amyloidosis with available genotypic data from the All of Us Research Program. The primary outcomes were incident heart failure and incident amyloidosis. The association of incident heart failure and incident amyloidosis with CTS was assessed using multivariable adjusted Cox models accounting for age, sex, race and ethnicity, obesity, hypertension, diabetes, statin use, and smoking status. RESULTS: Of the 166,987 individuals included, the median age was 54 (38 to 66) years; 105,279 (63.0%) were female, and 92,780 (55.6%) were non-Hispanic White individuals; CTS was identified in 12,407 (7.4%) individuals. Compared with individuals without CTS, the adjusted hazard ratio for incident heart failure was 1.13 (95% CI, 1.02 to 1.26) in individuals with CTS. The risk of amyloidosis was ∼3-fold higher (adjusted hazard ratio, 2.86; 95% CI, 1.71 to 4.77) in individuals with CTS compared with those without CTS. Individuals carrying a pathogenic TTR variant had an approximately 40% higher risk (adjusted hazard ratio, 1.38; 95% CI, 1.16 to 1.65) for development of CTS compared with noncarriers. CONCLUSION: Cardiac amyloidosis screening programs may use CTS as a sentinel event and use genetic testing to identify individuals at a higher risk of TTR amyloidosis.

Incident Heart Failure Risk Reclassification With Race-Independent Estimated Glomerular Filtration Rate: A National Heart, Lung, and Blood Institute Pooled Cohorts Analysis.

BACKGROUND: This study compared the predictive value of the race-independent creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) and the race-dependent creatinine-based eGFR (eGFRcr) for incident heart failure (HF). METHODS: This study combined the participant-level data from ARIC (Atherosclerosis Risk in Communities) (visit 4) and MESA (Multi-Ethnic Study of Atherosclerosis) (visit 1) to calculate eGFRcr-cys and eGFRcr. The primary outcome of the study was adjudicated incident HF over a follow-up period of 10 years. Multivariable Cox models were used to assess the risk of incident HF with the quartiles of eGFRcr-cys and eGFRcr. RESULTS: Among 15,615 individuals (median age: 62 [57-68] years; 55.0% females; 23.9% Black), the median eGFRcr-cys and eGFRcr were 91.4 (79.4, 102.0) mL/min/1.73m2 and 84.7 (72.0, 94.7) mL/min/1.73m2, respectively. Compared with the fourth quartile of eGFRcr-cys, the hazard ratio for incident HF was 1.02 (95% CI:0.80-1.30) in the third quartile, 1.02 (95% CI:0.80-1.30) in the second quartile, and 1.47 (95% CI:1.16-1.86) in the first quartile. Compared with the 4th quartile of the eGFRcr, the risk of incident HF was similar in the 3rd (HRadj:0.90 [95% CI:0.73-1.12]), 2nd (HRadj: 0.96 [95% CI:0.77-1.20]), and 1st (HRadj:1.15 [95% CI:0.93-1.44]) quartiles. C-statistics were similar for the multivariable-adjusted Cox models for incident HF using eGFRcr (0.80 [0.79-0.81]) and eGFRcr-cys (0.80 [0.79-0.82]). CONCLUSION: The eGFRcr and eGFRcr-cys had comparable predictive values for incident HF.

Update on Immunotherapy Cardiotoxicity: Checkpoint Inhibitors, CAR T, and Beyond.

OPINION STATEMENT: Immunotherapy is an innovative approach to cancer treatment that involves using the body's immune system to fight cancer. The landscape of immunotherapy is constantly evolving, as new therapies are developed and refined. Some of the most promising approaches in immunotherapy include immune checkpoint inhibitors (ICIs): these drugs target proteins on the surface of T-cells that inhibit their ability to attack cancer cells. By blocking these proteins, checkpoint inhibitors allow T-cells to recognize and destroy cancer cells more effectively. CAR T-cell therapy: this therapy involves genetically modifying a patient's own T-cells to recognize and attack cancer cells. CAR T-cell therapy exhibits favorable response in many patients with refractory hematological cancers with growing clinical trials in solid tumors. Immune system modulators: these drugs enhance the immune system's ability to fight cancer by stimulating the production of immune cells or inhibiting the activity of immune-suppressing cells. While immunotherapy has shown great promise in the treatment of cancer, it can also pose significant cardiac side effects. Some immunotherapy drugs like ICIs can cause myocarditis, which can lead to chest pain, shortness of breath, and heart failure. Other cardiac side effects of ICIs include arrhythmias, pericarditis, vasculitis, and accelerated atherosclerosis. It is important for patients receiving immunotherapy to be monitored closely for these side effects, as prompt treatment can help prevent serious complications. Patients should also report any symptoms to their healthcare providers right away, so that appropriate action can be taken. CAR T-cell therapy can also illicit an exaggerated immune response creating cytokine release syndrome (CRS) that may precipitate cardiovascular events: arrhythmias, myocardial infarction, and heart failure. Overall, while immune modulating therapy is a promising and expanding approach to cancer treatment, it is important to weigh the potential benefits against the risks and side effects, especially in patients with high risk for cardiovascular complications.

Trends of cardiovascular health in Asian American individuals: A national health and nutrition examination survey study.

Objective: Oversampling of Asian American individuals in the National Health and Nutrition Examination Survey (NHANES) provides a unique opportunity to assess the population-level cardiovascular health (CVH) in the fastest-growing racial group in the US. Methods: The Life's Essential 8 (LE8) score and its components were calculated in self-reported Asian American individuals ≥20 years of age and free of cardiovascular disease in the NHANES cycles from 2011-March 2020. Multivariable adjusted linear and logistic regression models were used for analysis. Results: Among 2,059 Asian American individuals, the weighted mean LE8 score was 69.1 (0.4) with US-born [69.0 (0.8)] and foreign-born individuals [69.1 (0.4)] having similar CVH. From 2011 to March 2020, CVH in the overall population [69.7 (0.8) to 68.1 (0.8); Ptrend: 0.009] and foreign-born individuals [69.7 (0.8) to 67.7 (0.8); Ptrend: 0.005] declined. Decreasing trends were noted in the body mass index score irrespective of stratification and in the blood pressure scores in the overall population and foreign-born Asian American individuals. Compared with US-born individuals, the odds of ideal levels of smoking [ORadj:<5 years: 2.23 (95%CI: 1.45-3.44); 5-15 years: 1.97 (95%CI: 1.27-3.05); 15-30 years: 1.61 (95%CI: 1.11-2.34); ≥30 years: 1.69(95%CI:1.20-2.36)] and diet [ORadj: <5 years: 1.87 (95%CI: 1.26-2.79); 5-15 years: 2.00 (95%CI: 1.38-2.89); 15-30 years: 1.74 (95%CI: 1.14-2.68)] were higher in foreign-born individuals. Foreign-born individuals had lower odds of ideal physical activity levels [ORadj: 5-15 years: 0.55 (95%CI: 0.39-0.79); 15-30 years: 0.68 (95%CI: 0.49-0.95)] and ideal cholesterol levels [ORadj: 5-15 years: 0.59 (95%CI: 0.42-0.82); 15-30 years: 0.54 (95%CI :0.38-0.76); ≥30 years: 0.52 (95%CI: 0.38-0.76)]. Conclusion: The CVH in Asian American individuals declined from 2011 to March 2020. The odds of ideal CVH decreased with increasing duration of stay in the US, with foreign-born individuals residing in the US for ≥30 years having ∼28% lower odds of ideal CVH compared with US-born individuals.

Complications Associated With Transesophageal Echocardiography in Transcatheter Structural Cardiac Interventions.

BACKGROUND: Transesophageal echocardiograms (TEEs) performed during transcatheter structural cardiac interventions may result in greater complications than those performed in the nonoperative setting or even those performed during cardiac surgery. However, there are limited data on complications associated with TEE during these procedures. We evaluated the prevalence of major complications among these patients in the United States. METHODS: A retrospective cohort study was conducted using an electronic health record database (TriNetX Research Network) from large academic medical centers across the United States for patients undergoing TEE during transcatheter structural interventions from January 2012 to January 2022. Using the American Society of Echocardiography-endorsed International Statistical Classification of Diseases and Related Health Problems Clinical Modifications (10th edition) codes, patients undergoing TEE during a transcatheter structural cardiac intervention, including transaortic, mitral or tricuspid valve repair, left atrial appendage occlusion, atrial septal defect closure, patent foramen ovale closure, and paravalvular leak repair, were identified. The primary outcome was major complications within 72 hours of the procedure (composite of bleeding and esophageal and upper respiratory tract injury). The secondary aim was the frequency of major complications, death, or cardiac arrest within 72 hours in patients who completed intraoperative TEE during surgical valve replacement. RESULTS: Among 12,043 adult patients (mean age, 74 years old; 42% female) undergoing TEE for transcatheter structural cardiac interventions, 429 (3.6%) patients had a major complication. Complication frequency was higher in patients on anticoagulation or antiplatelet therapy compared with those not on therapy (3.9% vs 0.5%; risk ratio [RR] = 8.09, P < .001). Compared with those patients <65 years of age, patients ≥65 years of age had a higher frequency of major complications (3.9% vs 2.2%; RR = 1.75, P < .001). Complication frequency was similar among male and female patients (3.5% vs 3.7%; RR = 0.96, P = .67). Among 28,848 patients who completed surgical valve replacement with TEE guidance, 728 (2.5%) experienced a major complication. CONCLUSIONS: This study found that more than 3% of patients undergoing TEE during transcatheter structural cardiac interventions have a major complication, which is more common among those on anticoagulant or antiplatelet therapy or who are elderly. With a shift of poor surgical candidates to less invasive percutaneous procedures, the future of TEE-guided procedures relies on comprehensive risk discussion and updating practices beyond conventional methods to minimize risk for TEE-related complications.

Inhibition of indoleamine dioxygenase leads to better control of tuberculosis adjunctive to chemotherapy.

The expression of indoleamine 2,3-dioxygenase (IDO), a robust immunosuppressant, is significantly induced in macaque tuberculosis (TB) granulomas, where it is expressed on IFN-responsive macrophages and myeloid-derived suppressor cells. IDO expression is also highly induced in human TB granulomas, and products of its activity are detected in patients with TB. In vivo blockade of IDO activity resulted in the reorganization of the granuloma with substantially greater T cells being recruited to the core of the lesions. This correlated with better immune control of TB and reduced lung M. tuberculosis burdens. To study if the IDO blockade strategy can be translated to a bona fide host-directed therapy in the clinical setting of TB, we studied the effect of IDO inhibitor 1-methyl-d-tryptophan adjunctive to suboptimal anti-TB chemotherapy. While two-thirds of controls and one-third of chemotherapy-treated animals progressed to active TB, inhibition of IDO adjunctive to the same therapy protected macaques from TB, as measured by clinical, radiological, and microbiological attributes. Although chemotherapy improved proliferative T cell responses, adjunctive inhibition of IDO further enhanced the recruitment of effector T cells to the lung. These results strongly suggest the possibility that IDO inhibition can be attempted adjunctive to anti-TB chemotherapy in clinical trials.

Exopolyphosphatases PPX1 and PPX2 from Mycobacterium tuberculosis regulate dormancy response and pathogenesis.

Stress adaptation and virulence of various bacterial pathogens require stringent response pathways involving guanosine pentaphosphate and inorganic polyphosphate (PolyP). In M. tuberculosis, intracellular PolyP levels are maintained by the activities of polyphosphate kinase (PPK-1, PPK-2) and exopolyphosphatases (PPX-1, PPX-2). We demonstrate that these exopolyphosphatases cumulatively contribute to biofilm formation and survival of M. tuberculosis in nutrient limiting, low oxygen growth conditions and in macrophages. Characterization of single (Δppx2) and double knock out strain (dkppx) of M. tuberculosis demonstrated that these exopolyphosphatases are essential for establishing infection in guinea pigs and mice. Transcriptional profiling revealed that relative to the parental strain the expression of genes belonging to DosR regulon were significantly reduced in mid-log phase cultures of dkppx strain. We also show that PolyP inhibited the autophosphorylation activities associated with DosT and DosS sensor kinases. Host RNA-seq analysis revealed that transcripts involved in various antimicrobial pathways such as apoptosis, autophagy, macrophage activation, calcium signalling, innate and T-cell response were differentially expressed in lung tissues of dkppx strain infected mice. Taken together, we demonstrate that enzymes involved in PolyP homeostasis play a critical role in physiology and virulence of M. tuberculosis. These enzymes are attractive targets for developing novel interventions that might be active against drug-sensitive and drug-resistant M. tuberculosis.

Innovations in Cardio-oncology Resulting from the COVID-19 Pandemic.

OPINION STATEMENT: The COVID pandemic has transformed our approach to patient care, research, and training in cardio-oncology. While the early phases of the COVID pandemic were exceptionally frightening, we now can reflect on the innovative changes that brought more effective and patient-centered care to our doorsteps: expansion of telemedicine, integration of digital health, wider adoption of cardiac biomarkers, consolidation, and coordination of cardio-oncology testing. Normally, it takes years for health care systems to adopt new technology or modify patient care pathways; however, COVID pushed healthcare providers and the health systems to change at warp speed. All of these innovations have improved our efficacy and provided a more "patient-centered" approach for our cardio-oncology patients. The changes we have made in cardio-oncology will likely remain well beyond the pandemic and continue to grow improving the cardiovascular care of oncology patients.

Association of Transthyretin Val122Ile Variant With Incident Heart Failure Among Black Individuals.

Importance: A genetic variant in the TTR gene (rs76992529; Val122Ile), present more commonly in individuals with African ancestry (population frequency: 3%-4%), causes misfolding of the tetrameric transthyretin protein complex that accumulates as extracellular amyloid fibrils and results in hereditary transthyretin amyloidosis. Objective: To estimate the association of the amyloidogenic Val122Ile TTR variant with the risk of heart failure and mortality in a large, geographically diverse cohort of Black individuals. Design, Setting, and Participants: Retrospective population-based cohort study of 7514 self-identified Black individuals living in the US participating in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study with genetic data available and without heart failure at baseline. The participants were enrolled at the baseline visit (2003-2007). The end of follow-up for the majority of outcomes was on December 31, 2018. All-cause mortality data were available through December 31, 2020. Exposures: TTR Val122Ile (rs76992529) genotype. Main Outcome and Measures: The primary outcome was incident heart failure (first hospitalization for heart failure or death due to heart failure). The secondary outcomes were heart failure mortality, cardiovascular mortality, and all-cause mortality. The multivariable Cox proportional hazards regression analyses were adjusted for genetic ancestry and demographic, clinical, and social factors. Results: Among 7514 Black participants (median age, 64 years [IQR, 57-70 years]; 61% women), the population frequency of the TTR Val122Ile variant was 3.1% (232 variant carriers and 7282 noncarriers). During a median follow-up of 11.1 years (IQR, 5.9-13.5 years), incident heart failure occurred in 535 individuals (34 variant carriers and 501 noncarriers) and the incidence of heart failure was 15.64 per 1000 person-years among variant carriers vs 7.16 per 1000 person-years among noncarriers (adjusted hazard ratio [HR], 2.43 [95% CI, 1.71-3.46]; P < .001). Deaths due to heart failure occurred in 141 individuals (13 variant carriers and 128 noncarriers) and the incidence of heart failure mortality was 6.11 per 1000 person-years among variant carriers vs 1.85 per 1000 person-years among noncarriers (adjusted HR, 4.19 [95% CI, 2.33-7.54]; P < .001). Deaths due to cardiovascular causes occurred in 793 individuals (34 variant carriers and 759 noncarriers) and the incidence of cardiovascular death was 15.18 per 1000 person-years among variant carriers vs 10.61 per 1000 person-years among noncarriers (adjusted HR, 1.69 [95% CI, 1.19-2.39]; P = .003). Deaths due to any cause occurred in 2715 individuals (100 variant carriers and 2615 noncarriers) and the incidence of all-cause mortality was 41.46 per 1000 person-years among variant carriers vs 33.94 per 1000 person-years among noncarriers (adjusted HR, 1.46 [95% CI, 1.19-1.78]; P < .001). There was no significant interaction between TTR variant carrier status and sex on incident heart failure and the secondary outcomes. Conclusions and Relevance: Among a cohort of Black individuals living in the US, being a carrier of the TTR Val122Ile variant was significantly associated with an increased risk of heart failure.

Coronary artery bypass graft surgery outcomes in the United States: Impact of the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: There has been a substantial decline in patients presenting for emergent and routine cardiovascular care in the United States after the onset of the coronavirus disease 2019 (COVID-19) pandemic. We sought to assess the risk of adverse clinical outcomes among patients undergoing coronary artery bypass graft (CABG) surgery during the 2020 COVID-19 pandemic period and compare the risks with those undergoing CABG before the pandemic in the year 2019. METHODS: A retrospective cross-sectional analysis of the TriNetX Research Network database was performed. Patients undergoing CABG between January 20, 2019, and September 15, 2019, contributed to the 2019 cohort, and those undergoing CABG between January 20, 2020, and September 15, 2020, contributed to the 2020 cohort. Propensity-score matching was performed, and the odds of mortality, acute kidney injury, stroke, acute respiratory distress syndrome, and mechanical ventilation occurring by 30 days were evaluated. RESULTS: The number of patients undergoing CABG in 2020 declined by 35.5% from 5534 patients in 2019 to 3569 patients in 2020. After propensity-score matching, 3569 patient pairs were identified in the 2019 and the 2020 cohorts. Compared with those undergoing CABG in 2019, the odds of mortality by 30 days were 0.96 (95% confidence interval [CI], 0.69-1.33; P = .80) in those undergoing CABG in 2020. The odds for stroke (odds ratio [OR], 1.201; 95% CI, 0.96-1.39), acute kidney injury (OR, 0.76; 95% CI, 0.59-1.08), acute respiratory distress syndrome (OR, 1.01; 95% CI, 0.60-2.42), and mechanical ventilation (OR, 1.11; 95% CI, 0.94-1.30) were similar between the 2 cohorts. CONCLUSIONS: The number of patients undergoing CABG in 2020 has substantially declined compared with 2019. Similar odds of adverse clinical outcomes were seen among patients undergoing CABG in the setting of COVID-19 compared with those in 2019.

Increased awareness, inadequate treatment, and poor control of cardiovascular risk factors in American young adults: 2005-2016.

INTRODUCTION: There are little contemporary data about cardiovascular risk factors among young adults. We defined trends in diabetes mellitus (DM), hypertension, and hypercholesterolemia in American adults aged 18-44 years. METHODS: The National Health and Nutrition Examination Study serial cross-sectional surveys were used to define three time periods: 2005-2008, 2009-2012, and 2013-2016. Age-adjusted weighted trends of prevalence, awareness, treatment, and control of DM, hypertension, and hypercholesterolemia were calculated by linear regression modelling in the overall sample, males, and females. Trends were calculated after adjustment for age, race, body mass index, smoking status, education attainment, income, insurance status, and number of healthcare visits. RESULTS: From 2005-2008 to 2013-2016, 15,171 participants were identified. DM prevalence was stable ∼3%, hypertension prevalence was stable ∼11.0%, and hypercholesterolemia prevalence declined from 11.5% to 9.0% (ptrend = 0.02). DM awareness stayed stable between 61.1 and 74.1%, hypertension awareness increased from 68.7 to 77.7% (ptrend = 0.05), and hypercholesterolemia awareness was stable between 46.8 and 54.1%. DM and hypertension treatment improved markedly (ptrend < 0.001 and 0.05, respectively) but the hypercholesterolemia treatment was stable ∼30%. DM control improved across survey periods (7.7-17.4%, ptrend = 0.04) but hypertension control (∼50%) and hypercholesterolemia control (∼13%) remained stable. Prevalence, awareness, treatment, and control trends also differed between males and females. CONCLUSIONS: There is a stable prevalence of DM, high and stable prevalence of hypertension, and declining prevalence of hypercholesterolemia among young Americans. Despite stable or increasing awareness of diabetes and hypertension, there are inadequate treatment and control trends for DM, hypertension, and hypercholesterolemia.

Geographic Variation in Cardiovascular Health Among American Adults.

OBJECTIVE: To evaluate the contemporary geographic trends in cardiovascular health in the United States and its relationship with geographic distribution of cardiovascular mortality. METHODS: By use of a retrospective cross-sectional design, the 2011-2017 Behavioral Risk Factor Surveillance System (BRFSS) was queried to determine the age-adjusted prevalence of cardiovascular health index (CVHI) metrics (sum of ideal blood pressure, blood glucose concentration, lipid levels, body mass index, smoking, physical activity, and diet). Cardiovascular health was estimated as both continuous (0 to 7 points) and categorical (ideal, intermediate, poor) variables from the BRFSS. Age-adjusted cardiovascular mortality for 2017 was obtained from the Centers for Disease Control and Prevention WONDER database. RESULTS: Among 1,362,529 American adult participants of the BRFSS 2011-2017 and all American residents in 2017, the CVHI score increased from 3.89±0.004 in 2011 to 3.96±0.005 in 2017 (Ptrend<.001) nationally, with modest improvement across all regions (Ptrend<.05 for all). Ideal cardiovascular health prevalence improved in the northeastern (Ptrend=.03) and southern regions (Ptrend=.002). In 2017, the prevalence of coronary heart disease (6.8%; 95% CI, 6.5% to 7.1%) and stroke (3.7%; 95% CI, 3.4% to 3.9%) was highest in the southern region. The CVHI score (3.81±0.01) and the prevalence of ideal cardiovascular health (12.2%; 95% CI, 11.7% to 12.7%) were lowest in the southern United States. This corresponded to the higher cardiovascular mortality in the southern region (233.0 [95% CI, 232.2- to 33.8] per 100,000 persons). CONCLUSION: Despite a modest improvement in CVHI, only 1 in 6 Americans has ideal cardiovascular health with significant geographic differences. These differences correlate with the geographic distribution of cardiovascular mortality. An urgent unmet need exists to mitigate the geographic disparities in cardiovascular morbidity and mortality.

Geographic Variation in Racial Disparities in Health and Coronavirus Disease-2019 (COVID-19) Mortality.

OBJECTIVE: To evaluate the race-stratified state-level prevalence of health determinants and the racial disparities in coronavirus disease 2019 (COVID-19) cumulative incidence and mortality in the United States. PATIENTS AND METHODS: The age-adjusted race-stratified prevalence of comorbidities (hypertension, diabetes, dyslipidemia, and obesity), preexisting medical conditions (pulmonary disease, heart disease, stroke, kidney disease, and malignant neoplasm), poor health behaviors (smoking, alcohol abuse, and physical inactivity), and adverse socioeconomic factors (education, household income, and health insurance) was computed in 435,139 American adult participants from the 2017 Behavioral Risk Factor Surveillance System survey. Correlation was assessed between health determinants and the race-stratified COVID-19 crude mortality rate and infection-fatality ratio computed from respective state public health departments in 47 states. RESULTS: Blacks had a higher prevalence of comorbidities (63.3%; 95% CI, 62.4% to 64.2% vs 55.1%; 95% CI, 54.7% to 55.5%) and adverse socioeconomic factors (47.0%; 95% CI, 46.0% to 47.9% vs 30.9%; 95% CI, 30.6% to 31.3%) than did whites. The prevalence of preexisting medical conditions was similar in blacks (30.4%; 95% CI, 28.8% to 32.1%) and whites (30.8%; 95% CI, 30.2% to 31.4%). The prevalence of poor health behaviors was higher in whites (57.2%; 95% CI, 56.3% to 58.0%) than in blacks (50.2%; 95% CI,46.2% to 54.2%). Comorbidities and adverse socioeconomic factors were highest in the southern region, and poor health behaviors were highest in the western region. The cumulative incidence rate (per 100,000 persons) was 3-fold higher in blacks (1546.4) than in whites (540.4). The crude mortality rate (per 100,000 persons) was 2-fold higher in blacks (83.2) than in whites (33.2). However, the infection-fatality ratio (per 100 cases) was similar in whites (6.2) and blacks (5.4). Within racial groups, the geographic distribution of health determinants did not correlate with the state-level COVID-19 mortality and infection-fatality ratio (P>.05 for all). CONCLUSION: Racial disparities in COVID-19 are largely driven by the higher cumulative incidence of infection in blacks. There is a discordance between the geographic dispersion of COVID-19 mortality and the regional distribution of health determinants.

Author Correction: Establishing Virulence Associated Polyphosphate Kinase 2 as a drug target for Mycobacterium tuberculosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Implications of Atrial Fibrillation Among Patients With Atherosclerotic Cardiovascular Disease Undergoing Noncardiac Surgery.

Atrial fibrillation (AF) is a common perioperative arrhythmia. However, its occurrence and implications remain poorly defined in the setting of noncardiac procedures. We sought to define the incidence, prevalence, and prognostic implications of AF among patients with atherosclerotic cardiovascular disease (ASCVD) undergoing noncardiac surgery. Using a previously validated approach that employed unique patient-linked variables in the New York State Inpatient Database from January 1, 2012, to December 31, 2014, the frequency of new-onset and pre-existing AF was determined in adults with ASCVD aged ≥18 years undergoing noncardiac surgery. The secondary outcomes were stroke within 1 month and all-cause mortality. Using multivariable logistic regression models, the factors and outcomes associated with new-onset AF after noncardiac surgery were assessed. Nine surgical subgroups of major noncardiac surgery served as exposure. A total of 184,775 patients were identified during the study period. Age ≥65, anemia, history of heart failure, valvular heart disease, and thoracic surgery were predictors of new-onset AF after noncardiac surgery. Among 3,806 patients (2.5%) developed new-onset AF and 31,603 (17.5%) patient had pre-existing AF. After multivariable-adjusted modeling, new-onset AF was associated with increased odds of stroke within 1 month (odds ratio: 1.31, 95% confidence interval: 1.12 to 1.53; p < 0.001)], mortality (odds ratio: 3.74; 95% confidence interval: 3.30 to 4.24; p < 0.001) and longer length of stay in the hospital (10 days; interquartile range: 6 to 16 days; p < 0.001). New-onset AF portends a poor prognosis in patients with ASCVD undergoing noncardiac surgeries. The risk profile of patients that develop new-onset AF differs across patient phenotypes and by surgical procedure.

Clinical, Demographic, and Imaging Correlates of Anemia in Heart Failure With Preserved Ejection Fraction (from the RELAX Trial).

Anemia is a commonly occurring comorbidity among patients of heart failure with preserved ejection fraction (HFpEF) but limited data exists on the cardiovascular phenotype of anemia in HFpEF. We sought to characterize the clinical features, exercise capacity, and outcomes in patients with HFpEF to elucidate the phenotype and pathophysiology of anemia in HFpEF. Post hoc analyses of participants enrolled in the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial was performed. Anemia was defined as hemoglobin <13 g/dL in men and <12 g/dL in women. Multivariate adjusted regression modeling was done to assess for differences in peak oxygen uptake. Adjusted hazard ratios were generated to assess difference in hospitalization events using a Cox proportional hazards model. Anemic HFpEF patients were more likely to be older, male, and have worse renal function (p <0.05 for all). N-terminal pro-B-type natriuretic peptide, troponin I, pro-collagen III N-terminal peptide, C-telopeptide for type I collagen, uric acid, cystatin-c, and galectin-3 (p <0.05 for all) levels were higher in anemic HFpEF patients. In adjusted models, anemic HFpEF patients had worse exercise capacity (peak oxygen uptake: 11.3 vs 12.1 mL/kg/min; p = 0.004). The hazard for cardiac or renal cause of hospitalization in those with anemia was 2.0 (95% confidence interval: 0.9 to 4.3). Anemic HFpEF patients have worse exercise capacity and are more likely to be hospitalized. A better understanding of the physiologic phenotypes of HFpEF patients may allow for greater personalization of treatment and prognostication in HFpEF patients.

Strategies to Prevent Cardiotoxicity.

OPINION STATEMENT: Cardiovascular disease is a leading cause of death among cancer survivors. While the field of cardiology as a whole is driven by evidence generated through robust clinical trials, data in cardio-oncology is limited to a relatively small number of prospective clinical trials with heterogeneous groups of cancer patients. In addition, many pharmaceutical trials in oncology are flawed from a cardiovascular perspective because they exclude patients with significant cardiovascular (CV) history and have wide variation in the definitions of CV events and cardiotoxicity. Ultimately, oncology trials often underrepresent the possibility of cardiovascular events in a "real world" population. Thus, the signal for CV toxicity from a cancer treatment is often not manifested until phase IV studies; where we are often caught trying to mitigate the CV effects rather than preventing them. Most of the data about cardiotoxicity from cancer therapy and cardioprotective strategies has been developed from our experience in using anthracyclines for over 50 years with dramatic improvement in cancer survivorship. However, as we are in an era where cancer drug discovery is moving at lightning pace with increasing survival rates, it is imperative to move beyond anthracyclines and commit to research on the cardiovascular side effects of all aspects of cancer therapy with a focus on prevention. We emphasize the role of pre-cancer treatment CV assessment to anticipate cardiac issues and ultimately optimizing CV risk prior to cancer therapy as an opportunity to mitigate cardiovascular risk from cancer therapy.