Background: Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease ... more Background: Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease vs the general population, despite a lower prevalence of traditional risk factors, including hyperlipidemia. Mechanistic studies in patients with rheumatoid arthritis and psoriasis suggest that tofacitinib restores serum lipids to preinflammation levels by reversing inflammation-induced cholesterol metabolism changes. We reviewed data on lipid levels and cardiovascular events, alongside recommendations for managing lipid levels during tofacitinib treatment in patients with UC, based on up-to-date expert guidelines. Methods: Data were identified from a phase 3/open-label, long-term extension (OLE) tofacitinib UC clinical program (cutoff May 27, 2019). Literature was identified from PubMed (search terms "lipid," "cholesterol," "lipoprotein," "cardiovascular," "inflammation," "atherosclerosis," "tofacitinib," "rheumatoid arthritis," "psoriasis," "inflammatory bowel disease," "ulcerative colitis," "hyperlipidemia," and "guidelines") and author knowledge. Data were available from 4 phase 3 clinical trials of 1124 patients with moderately to severely active UC who received ≥1 dose of tofacitinib 5 or 10 mg twice daily in induction (two identical trials), maintenance, and OLE studies (treatment duration ≤6.8 years; 2576.4 patient-years of drug exposure).
Principal Guidance: COVID-19 is negatively influencing the mental health and healthy lifestyle ch... more Principal Guidance: COVID-19 is negatively influencing the mental health and healthy lifestyle choices of at least some patients with cardiovascular disease; both formal telehealth visits and emerging mobile health technologies may be considered to support healthy behavior during the pandemic
Principal Guidance: Home-based cardiac rehab has demonstrated comparable benefits to traditional ... more Principal Guidance: Home-based cardiac rehab has demonstrated comparable benefits to traditional hospital-based programs and may serve as a viable alternative during COVID-19; reimbursement, unfortunately, remains limited
OBJECTIVES To identify whether social vulnerability is associated with low cardiac rehabilitation... more OBJECTIVES To identify whether social vulnerability is associated with low cardiac rehabilitations (CR) use, a Class I recommendation by current treatment guidelines following acute myocardial infarction (AMI). METHODS We performed this cross-sectional study using the 2017 Behavioral Risk Factor Surveillance System (BRFSS) survey. The Centers for Disease Control and Prevention Social Vulnerability Index (CDC SVI) was calculated using 15 social risk factors from 4 main themes including socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. A higher SVI indicates higher social vulnerability. We used multivariable logistic regression models to evaluate the association of CR use with state-level SVI adjusted for demographic, behavioral, socioeconomic, and comorbidity variables. RESULTS A total 2093 participants with history of AMI were included. Out of total, 61.7% were older than 65 years, 42.5% female, 72.5% White, and 42.4% used CR. Participation in CR was lower among females (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.44-0.91), those without a primary care physician (OR, 0.45; 95% CI, 0.23-0.87), and higher with college degree education (OR, 1.95; 95% CI, 1.06-3.59). CR use decreased with increasing SVI tertiles (1st =61%, 2nd =52%, and 3rd =35%). Compared with those residing in states in the 1st tertile, CR use was lower in the 2nd (OR, 0.68; 95% CI, 0.47-0.98) and 3rd (OR, 0.33; 95% CI 0.23-0.48) SVI tertiles. CONCLUSION CR use following AMI is low and is associated with social vulnerability. Identifying social risk factors may help improve access to care among vulnerable populations.
Background: Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease ... more Background: Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease vs the general population, despite a lower prevalence of traditional risk factors, including hyperlipidemia. Mechanistic studies in patients with rheumatoid arthritis and psoriasis suggest that tofacitinib restores serum lipids to preinflammation levels by reversing inflammation-induced cholesterol metabolism changes. We reviewed data on lipid levels and cardiovascular events, alongside recommendations for managing lipid levels during tofacitinib treatment in patients with UC, based on up-to-date expert guidelines. Methods: Data were identified from a phase 3/open-label, long-term extension (OLE) tofacitinib UC clinical program (cutoff May 27, 2019). Literature was identified from PubMed (search terms "lipid," "cholesterol," "lipoprotein," "cardiovascular," "inflammation," "atherosclerosis," "tofacitinib," "rheumatoid arthritis," "psoriasis," "inflammatory bowel disease," "ulcerative colitis," "hyperlipidemia," and "guidelines") and author knowledge. Data were available from 4 phase 3 clinical trials of 1124 patients with moderately to severely active UC who received ≥1 dose of tofacitinib 5 or 10 mg twice daily in induction (two identical trials), maintenance, and OLE studies (treatment duration ≤6.8 years; 2576.4 patient-years of drug exposure).
American journal of preventive cardiology, Mar 1, 2021
ten important CVD risk factors towards the goal of preventing CVD events. [1] • Among factors tha... more ten important CVD risk factors towards the goal of preventing CVD events. [1] • Among factors that increase the risk of CVD include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood
Journal of the American College of Cardiology, 2022
not correlate particularly well with left ventricular ejection fraction (LVEF), nor with levels o... more not correlate particularly well with left ventricular ejection fraction (LVEF), nor with levels of cTn, natriuretic peptides, and C-reactive protein. Classic fi ndings on CMR include increased native T 1 ( fi brosis or in fl ammation) and T 2 (in fl ammation or edema) signals along with myocarditis and other forms of myocardial involvement, pericarditis, new or worsening myocardial ischemia due to obstructive coronary artery disease, microvascular dysfunction, nonischemic cardiomyopathy with involvement of the left and/or right ventricles, thromboembolism, cardiovascular sequelae of pulmonary disease (eg, pulmonary hypertension, right ventricular failure), and arrhythmia (eg, atrial fi brillation, premature ventricular contractions, nonsustained ventricular tachycardia). myocarditis with SARS-CoV-2 infection; 2) unknown rates of adverse outcomes with exercise resumption; and 3) reports of signi fi cant myocardial injury and poor outcomes among some hospitalized patients.
Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCV... more Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF)-along with their associated risk factors-have overlapping etiologies, and two or more of these conditions frequently occur in the same patient. Many recent cardiovascular outcome trials (CVOTs) have demonstrated the benefits of agents originally developed to control T2D, ASCVD, or CKD risk factors, and these agents have transcended their primary indications to confer benefits across a range of conditions. This evolution in CVOT evidence calls for practice recommendations that are not constrained by a single discipline to help clinicians manage patients with complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. The ultimate goal for these recommendations is to be comprehensive yet succinct and easy to follow by the nonexpert-whether a specialist or a primary care clinician. To meet this need, we formed a volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM Practice Recommendations, a multispecialty consensus on the comprehensive management of the patient with complicated metabolic disease. The task force recommendations are based on strong evidence and incorporate practical guidance that is clinically relevant and simple to implement, with the aim of improving outcomes in patients with DCRM. The recommendations are presented as 18 separate graphics covering lifestyle therapy, patient self-management education, technology for DCRM management, prediabetes, cognitive dysfunction, vaccinations, clinical tests, lipids, hypertension, anticoagulation and antiplatelet therapy, antihyperglycemic therapy, hypoglycemia, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), ASCVD, HF, CKD, and comorbid HF and CKD, as well as a graphical summary of medications used for DCRM.
tumor necrosis factor inhibitor failure (1.92; 1.15, 3.21; p<0.05) were herpes zoster risk factor... more tumor necrosis factor inhibitor failure (1.92; 1.15, 3.21; p<0.05) were herpes zoster risk factors. Although not significant in this model, Asian patients had a higher risk of herpes zoster (1.76; 0.97, 3.19; p=0.06). Conclusion: Most herpes zoster events were non-serious, cutaneous, limited to 1-2 dermatomes, and did not lead to discontinuation. Herpes zoster risk was dose dependent but did not increase with longer treatment duration. As reported in rheumatoid arthritis and the general population, elderly patients had increased risk of herpes zoster. Further research into herpes zoster risk mitigation is warranted for patients with UC receiving tofacitinib.
skin cancer was reported in: 2 (0.2%) Induction cohort patients, 3 Maintenance cohort patients (I... more skin cancer was reported in: 2 (0.2%) Induction cohort patients, 3 Maintenance cohort patients (IR 1.91; 95% CI 0.39, 5.59) (all 10 mg BID), and 11 Overall cohort patients (IR 0.67; 95% CI 0.33, 1.19). Non-melanoma skin cancer IRs in the Maintenance cohort for tofacitinib 5 mg BID (IR 0.00; 95% CI 0.00, 2.48) were not higher than placebo (IR 0.97; 95% CI 0.02, 5.40). Of the 11 Overall cohort patients with non-melanoma skin cancer, most (10/11) had been exposed to azathioprine or 6-mercaptopurine and most (10/11) failed treatment with tumor necrosis factor inhibitors. Conclusion: Malignancies occurred infrequently with tofacitinib treatment in the UC clinical program. The malignancies (nonmelanoma skin cancer, and excl. non-melanoma skin cancer) IRs were similar to those reported for tofacitinib in rheumatoid arthritis patients 3 and for UC patients treated with biologics. A dose-dependent increased risk of non-melanoma skin cancer could not be derived from the data.
Elevated low-density lipoprotein cholesterol (LDL-C) is a principally modifiable cause of atheros... more Elevated low-density lipoprotein cholesterol (LDL-C) is a principally modifiable cause of atherosclerotic cardiovascular disease; accordingly, recent European and US multisociety dyslipidaemia guidelines emphasise the importance of lowering LDL-C to reduce cardiovascular risk. This review provides perspectives on established and emerging agents that reduce LDL-C to help providers synthesize the abundance of new evidence related to prevention of cardiovascular disease. We provide hypothetical cases of patients with different cardiovascular risk factors and medical histories to illustrate application of current lipid-lowering guidelines in various clinical settings. As a core focus of preventive therapy, both European and US lipid management guidelines emphasise the importance of identifying patients at very high cardiovascular risk and treating to achieve LDL-C levels as low as possible, with European guidelines setting a goal of <1.4 mmol/L (<55 mg/dL) in patients with very high-risk cardiovascular disease. The proprotein convertase subtilisin/kexin type 9 inhibitors are now included in the guidelines and may fulfil an important unmet need for very high-risk patients who are not able to achieve LDL-C goals with conventional agents. The recently approved bempedoic acid and other promising agents under development will add to the armamentarium of lipid-lowering drugs available for clinicians to help patients meet their treatment goals.
Journal of Interventional Cardiac Electrophysiology, Aug 5, 2020
Purpose: Chronotropic incompetence (CI) in patients with heart failure is common and associated w... more Purpose: Chronotropic incompetence (CI) in patients with heart failure is common and associated with impaired exercise intolerance and adverse outcomes. This study sought to determine the effects of closed loop stimulation (CLS) rate-adaptive pacing on functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) and CI implanted with cardiac resynchronization therapy (CRT) devices. Methods: A randomized, blinded, cross-over designed trial enrolled patients with HFrEF and CI implanted with a Biotronik CRT-D to complete a quality of life questionnaire, 6-minute walk distance (6MWD), and cardiopulmonary exercise testing after two programmed periods: oneweek period of CLS and one-week period of standard accelerometer (DDDR). Results: Nine patients (6 males, mean age 71.4 years, 7 with New York Heart Association Class III, mean ejection fraction 398%) were enrolled. Quality of life trended higher in CLS as compared to DDDR (550.8123.9 vs 489.3164.9, p=0.06). There were no differences between CLS and DDDR in 6MWD (293.190.2 m vs 315.195.5 m, p=0.52), peak heart rate (HR) 110.714.7 bpm vs 109.7 bpm14.1, p=0.67), or peak VO2 (12.34.9 ml/kg/min vs 12.95.9, p=0.47). As tests were submaximal as indicated by low respiratory exchange ratios (0.980.11 vs 1.00.8, p=0.35), VE/VCO 2 slope also showed no difference between CLS and DDDR (35.85.6 vs 35.45.7, p=0.65). Five patients (56%) preferred CLS programming (p=1.0). 3 Conclusion: In patients with HFrEF and CI implanted with a CRT-D, peak HR, peak VO2 and 6MWD were equivalent, while there was a trend toward improved quality of life in CLS as compared to DDDR.
Acute myocardial infarction (MI) provokes a systemic inflammatory response that may contribute to... more Acute myocardial infarction (MI) provokes a systemic inflammatory response that may contribute to the development of left ventricular systolic dysfunction (LVSD) and heart failure (HF). Patients with post-infarct HF with concomitant LVSD have the most unfavourable long-term prognosis. Measurement of C-reactive protein (CRP) concentration reflecting an involvement of inflammatory pathways in post-infarct myocardial damage offers an attractive strategy to improve risk stratification and clinical decision-making for early management of high-risk patients. Despite growing evidence for the prognostic value of CRP both as a single factor and as a component of multi-marker approach in MI, CRP measurement is not yet incorporated into current guidelines. This may be due to conflicting results reported in existing studies related to various limitations in study designs, such as retrospective case control design, prior myocardial damage, CRP measurement with low-sensitivity assays, non-homogenous populations with acute coronary syndromes, different treatment strategies, small sample sizes, and the lack of left ventricular ejection fraction assessment and long-term clinical and echocardiographic monitoring. As a result, previous studies have not provided conclusive evidence of the prognostic value of CRP for post-infarct LVSD or HF. Future studies with an adequate design including upstream mediators of inflammation as inflammatory markers are needed to identify the best biomarker-based strategies for identifying high-risk patients. Further clinical trials involving anti-inflammatory therapies targeting different pathways of inflammatory activation in MI should test the inflammatory hypothesis of post-infarct LVSD and HF. Identifying high-risk patients with persistent post-infarct inflammatory response may allow incorporation of pathophysiological guidance for implementation of personalised treatment approaches.
Type 2 diabetes mellitus and congestive heart failure are highly prevalent diseases with signific... more Type 2 diabetes mellitus and congestive heart failure are highly prevalent diseases with significant morbidity and mortality. These 2 diseases often occur concurrently because of shared risk factors such as coronary artery disease, and also because type 2 diabetes mellitus has direct cardiotoxic effects. Type 2 diabetes mellitus likely has a causative role in the development and prognosis of patients with heart failure. Optimal prevention and treatment of type 2 diabetes mellitus and heart failure likely involves identifying and treating their shared pathophysiologic features. Novel drug therapies, such as sodium-glucose co-transporter 2 inhibitors, offer an exciting potential to better understand the relationship between type 2 diabetes mellitus and heart failure, and may prove to have beneficial effects on cardiovascular outcomes in patients affected by these diseases.
Background: Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease ... more Background: Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease vs the general population, despite a lower prevalence of traditional risk factors, including hyperlipidemia. Mechanistic studies in patients with rheumatoid arthritis and psoriasis suggest that tofacitinib restores serum lipids to preinflammation levels by reversing inflammation-induced cholesterol metabolism changes. We reviewed data on lipid levels and cardiovascular events, alongside recommendations for managing lipid levels during tofacitinib treatment in patients with UC, based on up-to-date expert guidelines. Methods: Data were identified from a phase 3/open-label, long-term extension (OLE) tofacitinib UC clinical program (cutoff May 27, 2019). Literature was identified from PubMed (search terms "lipid," "cholesterol," "lipoprotein," "cardiovascular," "inflammation," "atherosclerosis," "tofacitinib," "rheumatoid arthritis," "psoriasis," "inflammatory bowel disease," "ulcerative colitis," "hyperlipidemia," and "guidelines") and author knowledge. Data were available from 4 phase 3 clinical trials of 1124 patients with moderately to severely active UC who received ≥1 dose of tofacitinib 5 or 10 mg twice daily in induction (two identical trials), maintenance, and OLE studies (treatment duration ≤6.8 years; 2576.4 patient-years of drug exposure).
Principal Guidance: COVID-19 is negatively influencing the mental health and healthy lifestyle ch... more Principal Guidance: COVID-19 is negatively influencing the mental health and healthy lifestyle choices of at least some patients with cardiovascular disease; both formal telehealth visits and emerging mobile health technologies may be considered to support healthy behavior during the pandemic
Principal Guidance: Home-based cardiac rehab has demonstrated comparable benefits to traditional ... more Principal Guidance: Home-based cardiac rehab has demonstrated comparable benefits to traditional hospital-based programs and may serve as a viable alternative during COVID-19; reimbursement, unfortunately, remains limited
OBJECTIVES To identify whether social vulnerability is associated with low cardiac rehabilitation... more OBJECTIVES To identify whether social vulnerability is associated with low cardiac rehabilitations (CR) use, a Class I recommendation by current treatment guidelines following acute myocardial infarction (AMI). METHODS We performed this cross-sectional study using the 2017 Behavioral Risk Factor Surveillance System (BRFSS) survey. The Centers for Disease Control and Prevention Social Vulnerability Index (CDC SVI) was calculated using 15 social risk factors from 4 main themes including socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. A higher SVI indicates higher social vulnerability. We used multivariable logistic regression models to evaluate the association of CR use with state-level SVI adjusted for demographic, behavioral, socioeconomic, and comorbidity variables. RESULTS A total 2093 participants with history of AMI were included. Out of total, 61.7% were older than 65 years, 42.5% female, 72.5% White, and 42.4% used CR. Participation in CR was lower among females (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.44-0.91), those without a primary care physician (OR, 0.45; 95% CI, 0.23-0.87), and higher with college degree education (OR, 1.95; 95% CI, 1.06-3.59). CR use decreased with increasing SVI tertiles (1st =61%, 2nd =52%, and 3rd =35%). Compared with those residing in states in the 1st tertile, CR use was lower in the 2nd (OR, 0.68; 95% CI, 0.47-0.98) and 3rd (OR, 0.33; 95% CI 0.23-0.48) SVI tertiles. CONCLUSION CR use following AMI is low and is associated with social vulnerability. Identifying social risk factors may help improve access to care among vulnerable populations.
Background: Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease ... more Background: Patients with ulcerative colitis (UC) are at elevated risk of cardiovascular disease vs the general population, despite a lower prevalence of traditional risk factors, including hyperlipidemia. Mechanistic studies in patients with rheumatoid arthritis and psoriasis suggest that tofacitinib restores serum lipids to preinflammation levels by reversing inflammation-induced cholesterol metabolism changes. We reviewed data on lipid levels and cardiovascular events, alongside recommendations for managing lipid levels during tofacitinib treatment in patients with UC, based on up-to-date expert guidelines. Methods: Data were identified from a phase 3/open-label, long-term extension (OLE) tofacitinib UC clinical program (cutoff May 27, 2019). Literature was identified from PubMed (search terms "lipid," "cholesterol," "lipoprotein," "cardiovascular," "inflammation," "atherosclerosis," "tofacitinib," "rheumatoid arthritis," "psoriasis," "inflammatory bowel disease," "ulcerative colitis," "hyperlipidemia," and "guidelines") and author knowledge. Data were available from 4 phase 3 clinical trials of 1124 patients with moderately to severely active UC who received ≥1 dose of tofacitinib 5 or 10 mg twice daily in induction (two identical trials), maintenance, and OLE studies (treatment duration ≤6.8 years; 2576.4 patient-years of drug exposure).
American journal of preventive cardiology, Mar 1, 2021
ten important CVD risk factors towards the goal of preventing CVD events. [1] • Among factors tha... more ten important CVD risk factors towards the goal of preventing CVD events. [1] • Among factors that increase the risk of CVD include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood
Journal of the American College of Cardiology, 2022
not correlate particularly well with left ventricular ejection fraction (LVEF), nor with levels o... more not correlate particularly well with left ventricular ejection fraction (LVEF), nor with levels of cTn, natriuretic peptides, and C-reactive protein. Classic fi ndings on CMR include increased native T 1 ( fi brosis or in fl ammation) and T 2 (in fl ammation or edema) signals along with myocarditis and other forms of myocardial involvement, pericarditis, new or worsening myocardial ischemia due to obstructive coronary artery disease, microvascular dysfunction, nonischemic cardiomyopathy with involvement of the left and/or right ventricles, thromboembolism, cardiovascular sequelae of pulmonary disease (eg, pulmonary hypertension, right ventricular failure), and arrhythmia (eg, atrial fi brillation, premature ventricular contractions, nonsustained ventricular tachycardia). myocarditis with SARS-CoV-2 infection; 2) unknown rates of adverse outcomes with exercise resumption; and 3) reports of signi fi cant myocardial injury and poor outcomes among some hospitalized patients.
Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCV... more Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF)-along with their associated risk factors-have overlapping etiologies, and two or more of these conditions frequently occur in the same patient. Many recent cardiovascular outcome trials (CVOTs) have demonstrated the benefits of agents originally developed to control T2D, ASCVD, or CKD risk factors, and these agents have transcended their primary indications to confer benefits across a range of conditions. This evolution in CVOT evidence calls for practice recommendations that are not constrained by a single discipline to help clinicians manage patients with complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. The ultimate goal for these recommendations is to be comprehensive yet succinct and easy to follow by the nonexpert-whether a specialist or a primary care clinician. To meet this need, we formed a volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM Practice Recommendations, a multispecialty consensus on the comprehensive management of the patient with complicated metabolic disease. The task force recommendations are based on strong evidence and incorporate practical guidance that is clinically relevant and simple to implement, with the aim of improving outcomes in patients with DCRM. The recommendations are presented as 18 separate graphics covering lifestyle therapy, patient self-management education, technology for DCRM management, prediabetes, cognitive dysfunction, vaccinations, clinical tests, lipids, hypertension, anticoagulation and antiplatelet therapy, antihyperglycemic therapy, hypoglycemia, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), ASCVD, HF, CKD, and comorbid HF and CKD, as well as a graphical summary of medications used for DCRM.
tumor necrosis factor inhibitor failure (1.92; 1.15, 3.21; p<0.05) were herpes zoster risk factor... more tumor necrosis factor inhibitor failure (1.92; 1.15, 3.21; p<0.05) were herpes zoster risk factors. Although not significant in this model, Asian patients had a higher risk of herpes zoster (1.76; 0.97, 3.19; p=0.06). Conclusion: Most herpes zoster events were non-serious, cutaneous, limited to 1-2 dermatomes, and did not lead to discontinuation. Herpes zoster risk was dose dependent but did not increase with longer treatment duration. As reported in rheumatoid arthritis and the general population, elderly patients had increased risk of herpes zoster. Further research into herpes zoster risk mitigation is warranted for patients with UC receiving tofacitinib.
skin cancer was reported in: 2 (0.2%) Induction cohort patients, 3 Maintenance cohort patients (I... more skin cancer was reported in: 2 (0.2%) Induction cohort patients, 3 Maintenance cohort patients (IR 1.91; 95% CI 0.39, 5.59) (all 10 mg BID), and 11 Overall cohort patients (IR 0.67; 95% CI 0.33, 1.19). Non-melanoma skin cancer IRs in the Maintenance cohort for tofacitinib 5 mg BID (IR 0.00; 95% CI 0.00, 2.48) were not higher than placebo (IR 0.97; 95% CI 0.02, 5.40). Of the 11 Overall cohort patients with non-melanoma skin cancer, most (10/11) had been exposed to azathioprine or 6-mercaptopurine and most (10/11) failed treatment with tumor necrosis factor inhibitors. Conclusion: Malignancies occurred infrequently with tofacitinib treatment in the UC clinical program. The malignancies (nonmelanoma skin cancer, and excl. non-melanoma skin cancer) IRs were similar to those reported for tofacitinib in rheumatoid arthritis patients 3 and for UC patients treated with biologics. A dose-dependent increased risk of non-melanoma skin cancer could not be derived from the data.
Elevated low-density lipoprotein cholesterol (LDL-C) is a principally modifiable cause of atheros... more Elevated low-density lipoprotein cholesterol (LDL-C) is a principally modifiable cause of atherosclerotic cardiovascular disease; accordingly, recent European and US multisociety dyslipidaemia guidelines emphasise the importance of lowering LDL-C to reduce cardiovascular risk. This review provides perspectives on established and emerging agents that reduce LDL-C to help providers synthesize the abundance of new evidence related to prevention of cardiovascular disease. We provide hypothetical cases of patients with different cardiovascular risk factors and medical histories to illustrate application of current lipid-lowering guidelines in various clinical settings. As a core focus of preventive therapy, both European and US lipid management guidelines emphasise the importance of identifying patients at very high cardiovascular risk and treating to achieve LDL-C levels as low as possible, with European guidelines setting a goal of <1.4 mmol/L (<55 mg/dL) in patients with very high-risk cardiovascular disease. The proprotein convertase subtilisin/kexin type 9 inhibitors are now included in the guidelines and may fulfil an important unmet need for very high-risk patients who are not able to achieve LDL-C goals with conventional agents. The recently approved bempedoic acid and other promising agents under development will add to the armamentarium of lipid-lowering drugs available for clinicians to help patients meet their treatment goals.
Journal of Interventional Cardiac Electrophysiology, Aug 5, 2020
Purpose: Chronotropic incompetence (CI) in patients with heart failure is common and associated w... more Purpose: Chronotropic incompetence (CI) in patients with heart failure is common and associated with impaired exercise intolerance and adverse outcomes. This study sought to determine the effects of closed loop stimulation (CLS) rate-adaptive pacing on functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) and CI implanted with cardiac resynchronization therapy (CRT) devices. Methods: A randomized, blinded, cross-over designed trial enrolled patients with HFrEF and CI implanted with a Biotronik CRT-D to complete a quality of life questionnaire, 6-minute walk distance (6MWD), and cardiopulmonary exercise testing after two programmed periods: oneweek period of CLS and one-week period of standard accelerometer (DDDR). Results: Nine patients (6 males, mean age 71.4 years, 7 with New York Heart Association Class III, mean ejection fraction 398%) were enrolled. Quality of life trended higher in CLS as compared to DDDR (550.8123.9 vs 489.3164.9, p=0.06). There were no differences between CLS and DDDR in 6MWD (293.190.2 m vs 315.195.5 m, p=0.52), peak heart rate (HR) 110.714.7 bpm vs 109.7 bpm14.1, p=0.67), or peak VO2 (12.34.9 ml/kg/min vs 12.95.9, p=0.47). As tests were submaximal as indicated by low respiratory exchange ratios (0.980.11 vs 1.00.8, p=0.35), VE/VCO 2 slope also showed no difference between CLS and DDDR (35.85.6 vs 35.45.7, p=0.65). Five patients (56%) preferred CLS programming (p=1.0). 3 Conclusion: In patients with HFrEF and CI implanted with a CRT-D, peak HR, peak VO2 and 6MWD were equivalent, while there was a trend toward improved quality of life in CLS as compared to DDDR.
Acute myocardial infarction (MI) provokes a systemic inflammatory response that may contribute to... more Acute myocardial infarction (MI) provokes a systemic inflammatory response that may contribute to the development of left ventricular systolic dysfunction (LVSD) and heart failure (HF). Patients with post-infarct HF with concomitant LVSD have the most unfavourable long-term prognosis. Measurement of C-reactive protein (CRP) concentration reflecting an involvement of inflammatory pathways in post-infarct myocardial damage offers an attractive strategy to improve risk stratification and clinical decision-making for early management of high-risk patients. Despite growing evidence for the prognostic value of CRP both as a single factor and as a component of multi-marker approach in MI, CRP measurement is not yet incorporated into current guidelines. This may be due to conflicting results reported in existing studies related to various limitations in study designs, such as retrospective case control design, prior myocardial damage, CRP measurement with low-sensitivity assays, non-homogenous populations with acute coronary syndromes, different treatment strategies, small sample sizes, and the lack of left ventricular ejection fraction assessment and long-term clinical and echocardiographic monitoring. As a result, previous studies have not provided conclusive evidence of the prognostic value of CRP for post-infarct LVSD or HF. Future studies with an adequate design including upstream mediators of inflammation as inflammatory markers are needed to identify the best biomarker-based strategies for identifying high-risk patients. Further clinical trials involving anti-inflammatory therapies targeting different pathways of inflammatory activation in MI should test the inflammatory hypothesis of post-infarct LVSD and HF. Identifying high-risk patients with persistent post-infarct inflammatory response may allow incorporation of pathophysiological guidance for implementation of personalised treatment approaches.
Type 2 diabetes mellitus and congestive heart failure are highly prevalent diseases with signific... more Type 2 diabetes mellitus and congestive heart failure are highly prevalent diseases with significant morbidity and mortality. These 2 diseases often occur concurrently because of shared risk factors such as coronary artery disease, and also because type 2 diabetes mellitus has direct cardiotoxic effects. Type 2 diabetes mellitus likely has a causative role in the development and prognosis of patients with heart failure. Optimal prevention and treatment of type 2 diabetes mellitus and heart failure likely involves identifying and treating their shared pathophysiologic features. Novel drug therapies, such as sodium-glucose co-transporter 2 inhibitors, offer an exciting potential to better understand the relationship between type 2 diabetes mellitus and heart failure, and may prove to have beneficial effects on cardiovascular outcomes in patients affected by these diseases.
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