ABSTRACT
Ramp studies are utilized for speed optimization of continuous flow left ventricular assist devices (CF-LVADs). We here report the utility of combined left and right heart catheterization during a ramp study to ensure a comprehensive understanding of the hemodynamic implications on both ventricles. Pressure-volume loop (PV loop) monitoring uncovered compromised systolic and mildly compromised right ventricular function with increasing LVAD speeds, despite improvement in left ventricular unloading. These findings informed patient management and highlight the potential utility of PV loop monitoring as an adjunct to left and right heart catheterization during ramp studies of next-generation LVADs.
Subject(s)
Heart Failure , Heart-Assist Devices , Humans , Ventricular Function, Right , Treatment Outcome , Hemodynamics , Cardiac Catheterization , Heart Failure/diagnosis , Heart Failure/therapy , Ventricular Function, LeftABSTRACT
Coenzyme A (CoA) is an essential cofactor required for over a hundred metabolic reactions in the human body. This cofactor is synthesized de novo in our cells from vitamin B5, also known as pantothenic acid, a water-soluble vitamin abundantly present in vegetables and animal-based foods. Neurodegenerative disorders, cancer, and infectious diseases have been linked to defects in de novo CoA biosynthesis or reduced levels of this coenzyme. There is now accumulating evidence that CoA limitation is a critical pathomechanism in cardiac dysfunction too. In the current review, we will summarize our current knowledge on CoA and heart failure, with emphasis on two primary cardiomyopathies, phosphopantothenoylcysteine synthetase and phosphopantothenoylcysteine decarboxylase deficiency disorders biochemically characterized by a decreased level of CoA in patients' samples. Hence, we will discuss the potential benefits of CoA restoration in these diseases and, more generally, in heart failure, by vitamin B5 and its derivatives pantethine and 4'-phosphopantetheine.
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BACKGROUND: Patients with diabetes (DM) and heart failure (HF) have worse outcomes than normoglycaemic HF patients. Cardiovascular magnetic resonance (CMR) can identify ischaemic heart disease (IHD) and quantify coronary microvascular dysfunction (CMD) using myocardial perfusion reserve (MPR). We aimed to quantify extent of silent IHD and CMD in patients with DM presenting with HF. METHODS: Prospectively recruited outpatients undergoing assessment into the aetiology of HF underwent inline quantitative perfusion CMR for calculation of stress and rest myocardial blood flow (MBF) and MPR. Exclusions included angina or history of IHD. Patients were followed up (median 3.0 years) for major adverse cardiovascular events (MACE). RESULTS: Final analysis included 343 patients (176 normoglycaemic, 84 with pre-diabetes and 83 with DM). Prevalence of silent IHD was highest in DM (31%), then pre-diabetes (20%) then normoglycaemia (17%). Stress MBF was lowest in DM (1.53±0.52), then pre-diabetes (1.59±0.54) then normoglycaemia (1.83±0.62). MPR was lowest in DM (2.37±0.85) then pre-diabetes (2.41±0.88) then normoglycaemia (2.61±0.90). During follow up 45 patients experienced at least one MACE. On univariate Cox regression analysis MPR and presence of silent IHD were both associated with MACE. However, after correction for HbA1c, age and left ventricular ejection fraction the associations were no longer significant. CONCLUSIONS: Patients with DM and HF had higher prevalence of silent IHD, more evidence of CMD and worse cardiovascular outcomes than their non-diabetic counterparts. These findings highlight the potential value of CMR for assessment of silent IHD and CMD in patients with DM presenting with HF.
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Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. The success of modRNA-based COVID-19 vaccines has demonstrated that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases, including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options, and MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and mitigates cardiac dysfunction. However, it remains unclear whether early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. We hypothesized that CCN5 would alleviate the adverse effects of myocardial infarction (MI) through its anti-fibrotic properties under stress conditions. To induce the rapid expression of CCN5, ModRNA-CCN5 was synthesized and administrated directly into the myocardium in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: (1) preventive intervention and (2) therapeutic intervention. Functional analyses, including echocardiography and magnetic resonance imaging (MRI), along with molecular assays, demonstrated that modRNA-mediated CCN5 gene transfer significantly attenuated cardiac fibrosis and improved cardiac function in both preventive and therapeutic models, without causing left ventricular rupture or any adverse cardiac remodeling. In conclusion, early intervention in CF by ModRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure.
Subject(s)
CCN Intercellular Signaling Proteins , Fibrosis , Genetic Therapy , Myocardial Infarction , RNA, Messenger , Animals , Humans , Male , Mice , CCN Intercellular Signaling Proteins/genetics , CCN Intercellular Signaling Proteins/metabolism , Disease Models, Animal , Gene Transfer Techniques , Genetic Therapy/methods , Mice, Inbred C57BL , Myocardial Infarction/therapy , Myocardial Infarction/genetics , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardium/metabolism , Myocardium/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Ventricular Remodeling/geneticsABSTRACT
Sleep-disordered breathing (SDB), including obstructive and central sleep apnea, significantly exacerbates heart failure (HF) through adverse cardiovascular mechanisms. This review aims to synthesize existing literature to clarify the relationship between SDB and HF, focusing on the pathophysiological mechanisms, diagnostic challenges, and the effectiveness of treatment modalities like continuous positive airway pressure (CPAP) and adaptive servo-ventilation ASV. We analyzed peer-reviewed articles from 2003 to 2024 sourced from PubMed, EMBASE, Scopus, and Web of Science databases. The prevalence of SDB in HF patients is high, often underdiagnosed, and underappreciated. Management strategies, including CPAP and ASV, have been shown to mitigate symptoms and improve cardiac function. However, despite the availability of effective treatments, significant challenges in screening and diagnosis persist, affecting patient management and outcomes. DB significantly impacts HF prognosis. Enhanced screening strategies and broader utilization of therapeutic interventions like CPAP and ASV are essential to improve the management and outcomes of HF patients with concomitant SDB. Future research should focus on refining diagnostic and treatment protocols to optimize care for HF patients with SDB.
Subject(s)
Continuous Positive Airway Pressure , Heart Failure , Sleep Apnea Syndromes , Humans , Heart Failure/therapy , Sleep Apnea Syndromes/therapy , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/diagnosis , PrognosisABSTRACT
BACKGROUND: A left ventricular assist device (LVAD) is a life-saving but intensive therapy for patients with end-stage heart failure. We evaluated the healthcare consumption in a cohort of LVAD patients in our centre over 6 years. METHODS: All patients with a primary LVAD implantation at the University Medical Centre Utrecht in Utrecht, the Netherlands from 2016 through 2021 were included in this analysis. Subsequent hospital stay, outpatient clinic visits, emergency department visits and readmissions were recorded. RESULTS: During the investigated period, 226 LVADs were implanted, ranging from 32 in 2016 to 45 in 2020. Most LVADs were implanted in patients aged 40-60 years, while they were supported by or sliding on inotropes (Interagency Registry for Mechanically Assisted Circulatory Support class 2 or 3). Around the time of LVAD implantation, the median total hospital stay was 41 days. As the size of the LVAD cohort increased over time, the total annual number of outpatient clinic visits also increased, from 124 in 2016 to 812 in 2021 (pâ¯= 0.003). The numbers of emergency department visits and readmissions significantly increased in the 6year period as well, with a total number of 553 emergency department visits and 614 readmissions. Over the years, the annual number of outpatient clinic visits decreased by 1 per patient-year follow-up, while the annual numbers of emergency department visits and readmissions per patient-year remained stable. CONCLUSION: The number of patients supported by an LVAD has grown steadily over the last years, requiring a more specialised healthcare in this particular population.
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RATIONALE & OBJECTIVE: Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF. PREDICTORS: Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters. OUTCOME: Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire [KCCQ] Overall Summary Score with a range of 0-100 where<75 reflects clinically significant symptoms). ANALYTICAL APPROACH: Latent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership. RESULTS: Five trajectories of KCCQ score were identified in the cohort of 3,044 adults, 45% of whom were female, and whose median age was 61 years. Group 1 (41.7%) had a stable high score (minimal symptoms, average score of 96); groups 2 (35.6%) and 3 (15.6%) had stable but lower scores (mild symptoms [average of 81] and clinically significant symptoms [average of 52], respectively). Group 4 (4.9%) had a substantial worsening in symptoms over time (mean 31-point decline), and group 5 (2.2%) had a substantial improvement (mean 33-point increase) in KCCQ score. A majority of group 1 was male, without diabetes or obesity, and this group had higher baseline kidney function. A majority of groups 2 and 3 had diabetes and obesity. A majority of group 4 was male and had substantial proteinuria. Group 5 had the highest proportion of baseline cardiovascular disease (CVD). LIMITATIONS: No validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption. CONCLUSIONS: Distinct HF-type symptom burden trajectories were identified in the setting of CKD, corresponding to different baseline characteristics. These results highlight the diversity of HF-type symptom experiences in individuals with CKD.
Subject(s)
Diabetes Mellitus , Heart Failure , Renal Insufficiency, Chronic , Vascular Diseases , Adult , Humans , Male , Female , Middle Aged , Prospective Studies , Cohort Studies , Quality of Life , Renal Insufficiency, Chronic/diagnosis , Heart Failure/diagnosis , Obesity , Glomerular Filtration RateABSTRACT
BACKGROUND: Diabetes increases the risk of heart failure (HF). 3-Hydroxyisobutyric acid (3-HIB) is a muscle-derived metabolite reflecting systemic insulin resistance. In this study, we investigated the prognostic impact of 3-HIB in patients with chronic HF.MethodsâandâResults: The KUNIUMI Registry chronic cohort is a community-based cohort study of chronic HF in Awaji Island, Japan. We analyzed the association between serum 3-HIB concentrations and adverse cardiovascular (CV) events in 784 patients from this cohort. Serum 3-HIB concentrations were significantly higher in patients with than without diabetes (P=0.0229) and were positively correlated with several metabolic parameters. According to Kaplan-Meier analysis, rates of CV death and HF hospitalization at 2 years were significantly higher among HF patients without diabetes in the high 3-HIB group (3-HIB concentrations above the median; i.e., >11.30 µmol/L) than in the low 3-HIB group (log-rank P=0.0151 and P=0.0344, respectively). Multivariable Cox proportional hazard models adjusted for established risk factors for HF revealed high 3-HIB as an independent predictor of CV death (hazard ratio [HR] 1.82; 95% confidence interval [CI] 1.16-2.85; P=0.009) and HF hospitalization (HR 1.72; 95% CI 1.17-2.53, P=0.006) in HF patients without diabetes, whereas no such trend was seen in subjects with diabetes. CONCLUSIONS: In a community cohort, circulating 3-HIB concentrations were associated with prognosis in chronic HF patients without diabetes.
Subject(s)
Diabetes Mellitus , Heart Failure , Humans , Cohort Studies , Prognosis , Heart Failure/etiology , Chronic Disease , Hospitalization , RegistriesABSTRACT
BACKGROUND: Heart failure (HF) continues to be the major cause of hospitalizations. Despite numerous significant therapeutic progress, the mortality rate of HF is still high. This longitudianl cohort study aimed to investigate the associations between hematologic inflammatory indices neutrophil percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and all-cause mortality in community-dwelling adults with HF. METHODS: Adults aged 20 and older with HF in the US National Health and Nutrition Examination Survey (NHANES) database 2005-2016 were included and were followed through the end of 2019. Univariate and multivariable Cox regression analyses were performed to determine the associations between the three biomarkers and all-cause mortality. The receiver operating characteristics (ROC) curve analysis was conducted to evaluate their predictive performance on mortality. RESULTS: A total of 1,207 subjects with HF were included, representing a population of 4,606,246 adults in the US. The median follow-up duration was 66.0 months. After adjustment, the highest quartile of NPAR (aHR = 1.81, 95%CI: 1.35, 2.43) and NLR (aHR = 1.59, 95%CI: 1.18, 2.15) were significantly associated with increased mortality risk compared to the lowest quartile during a median follow-up duration of 66.0 months. Elevated PLR was not associated with mortality risk. The area under the ROC curve (AUC) of NPAR, NLR, and PLR in predicting deaths were 0.61 (95%CI: 0.58, 0.65), 0.64 (95%CI: 0.6, 0.67), and 0.58 (95%CI:0.55, 0.61), respectively. CONCLUSIONS: In conclusion, elevated NPAR and NLR but not PLR are independently associated with increased all-cause mortality among community-dwelling individuals with HF. However, the predictive performance of NPAR and NLR alone on mortality was low.
Subject(s)
Heart Failure , Neutrophils , Adult , Humans , Nutrition Surveys , Cohort Studies , Independent Living , Prognosis , Platelet Count , Retrospective Studies , Lymphocytes , Blood Platelets , Heart Failure/diagnosis , Heart Failure/therapy , AlbuminsABSTRACT
Elevated circulating homocysteine (Hcy) is a well-known risk factor for cardiovascular diseases (CVDs), including coronary artery disease (CAD) and heart failure (HF). It remains unclear how Hcy and its derivatives relate to left ventricular (LV) diastolic function. The aim of the present study was to investigate the relationship between plasma Hcy-related metabolites and diastolic dysfunction (DD) in patients with heart disease (HD). A total of 62 HD patients with preserved LV ejection fraction (LVEF ≥ 50%) were enrolled. Plasma Hcy and its derivatives were measured by liquid chromatographyâmass spectrometry (LC-MS/MS). Spearman's correlation test and multiple linear regression models were used to analyze the associations between metabolite levels and LV diastolic function. The cystine/methionine (CySS/Met) ratio was positively correlated with LV diastolic function, which was defined from the ratio of mitral inflow E and mitral e' annular velocities (E/e') (Spearman's r = 0.43, p < 0.001). When the subjects were categorized into two groups by E/e', the high-E/e' group had a significantly higher CySS/Met ratio than the low-E/e' group (p = 0.002). Multiple linear regression models revealed that the CySS/Met ratio was independently associated with E/e' after adjustment for age, sex, body mass index (BMI), diabetes mellitus, hypertension, chronic kidney disease (CKD),ãhemoglobin, and lipid peroxide (LPO) {standardized ß (95% CI); 0.14 (0.04-0.23); p = 0.005}. Hcy, CySS, and Met did not show a significant association with E/e' in the same models. A high plasma CySS/Met ratio reflected DD in patients with HD.
Subject(s)
Cystine , Ventricular Dysfunction, Left , Humans , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/etiology , Methionine , Chromatography, Liquid , Tandem Mass Spectrometry , Ventricular Function, Left , Stroke Volume , DiastoleABSTRACT
OBJECTIVE: Prior studies have reported that heart failure typically affects elderly, multimorbid and socioeconomically deprived men. Women with heart failure are generally older, have a higher EF (ejection fraction) and have more heart failure-related symptoms than men. This study explored the disparities in the prevalence of heart failure between men and women in relation to age, multimorbidity level and socioeconomic status of the population in southern Sweden. DESIGN: A register-based, cross-sectional cohort study.Setting and subjects: The inhabitants from 20 years of age onwards (N = 981,383) living in southern Sweden in 2015.Main outcome measure: Prevalence and mean probability of having heart failure in both genders. CNI (Care Need Index) percentiles depend on the socioeconomic status of their listed primary healthcare centres. RESULTS: Men had a higher OR for HF - 1.70 (95% CI 1.65-1.75) - than women. The probability of men having heart failure increased significantly compared to women with advancing age and multimorbidity levels. At all CNI levels, the multimorbid patients had a higher prevalence of heart failure in men than in women. The disparity in the mean probability of heart failure between the most affluent and deprived CNI percentile was more apparent in women compared to men, especially from 80 years. CONCLUSIONS: The prevalence of heart failure differs significantly between the genders. Men had an increasing mean probability of heart failure with advancing age and multimorbidity level compared to women. Socioeconomic deprivation was more strongly associated with heart failure in women than in men. The probability of having heart failure differs between the genders in several aspects.Key PointsIndependently of socioeconomic status, men had a higher prevalence of heart failure than women among the multimorbid patients.The mean probability of men having heart failure increased significantly compared to women with advancing age and multimorbidity level.Socioeconomic status was more strongly associated with heart failure in women than in men.
Subject(s)
Heart Failure , Multimorbidity , Humans , Male , Female , Aged , Prevalence , Cross-Sectional Studies , Sweden/epidemiology , Social Class , Heart Failure/epidemiologyABSTRACT
Current drugs for treating heart failure (HF), for example, angiotensin II receptor blockers and ß-blockers, possess specific target molecules involved in the regulation of the cardiac circulatory system. However, most clinically approved drugs are effective in the treatment of HF with reduced ejection fraction (HFrEF). Novel drug classes, including angiotensin receptor blocker/neprilysin inhibitor (ARNI), sodium-glucose co-transporter-2 (SGLT2) inhibitor, hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, soluble guanylyl cyclase (sGC) stimulator/activator, and cardiac myosin activator, have recently been introduced for HF intervention based on their proposed novel mechanisms. SGLT2 inhibitors have been shown to be effective not only for HFrEF but also for HF with preserved ejection fraction (HFpEF). In the myocardium, excess cyclic adenosine monophosphate (cAMP) stimulation has detrimental effects on HFrEF, whereas cyclic guanosine monophosphate (cGMP) signaling inhibits cAMP-mediated responses. Thus, molecules participating in cGMP signaling are promising targets of novel drugs for HF. In this review, we summarize molecular pathways of cGMP signaling and clinical trials of emerging drug classes targeting cGMP signaling in the treatment of HF.
Subject(s)
Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Heart Failure/drug therapy , Stroke Volume , Heart , Myocardium , Angiotensin Receptor Antagonists , Calcium Channel Blockers , Cyclic AMP , Cyclic GMP , Vasodilator AgentsABSTRACT
Heart failure (HF) is one of the greatest problems in healthcare and it often coexists with declining renal function. The pathophysiology between the heart and the kidneys is bidirectional. Common mechanisms leading to the dysfunction of these organs result in a vicious cycle of cardiorenal deterioration. It is also associated with difficulties in the treatment of aggravating HF and chronic kidney disease (CKD) and, as a consequence, recurrent hospitalizations and death. As the worsening of renal function has an undeniably negative impact on the outcomes in patients with HF, searching for new treatment strategies and identification of biomarkers is necessary. This review is focused on the pathomechanisms in chronic kidney disease in patients with HF and therapeutic strategies for co-existing CKD and HF.
Subject(s)
Heart Failure , Renal Insufficiency, Chronic , Humans , Mineralocorticoid Receptor Antagonists/therapeutic use , Heart Failure/complications , Heart Failure/epidemiology , Heart Failure/therapy , Comorbidity , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/chemically induced , Angiotensin Receptor Antagonists/therapeutic use , Stroke Volume/physiologyABSTRACT
RATIONALE & OBJECTIVE: Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFRcys) and creatinine (eGFRcr) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Difference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr). OUTCOME: Incident HF hospitalization. ANALYTICAL APPROACH: Fine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFRdiff with incident HF. RESULTS: Of 4,512 participants, one-third had eGFRcys and eGFRcr values that differed by over 15 mL/min/1.73 m2. In multivariable-adjusted models, each 15 mL/min/1.73 m2 lower baseline eGFRdiff was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFRdiff less than -15 mL/min/1.73 m2 had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFRdiff ≥15 mL/min/1.73 m2 had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFRcys and eGFRcr. Participants with faster declines in eGFRcys relative to eGFRcr had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFRcys and eGFRcr declined in parallel. LIMITATIONS: Entry into the CRIC Study was determined by eGFRcr, which constrained the range of baseline eGFRcr-but not eGFRcys-values. CONCLUSIONS: Among persons with CKD who have large differences between eGFRcys and eGFRcr, risk for incident HF is more strongly associated with eGFRcys. Diverging slopes between eGFRcys and eGFRcr over time are also independently associated with risk of incident HF.
Subject(s)
Heart Failure , Renal Insufficiency, Chronic , Adult , Humans , Cystatin C , Creatinine , Prospective Studies , Individuality , Glomerular Filtration Rate , Renal Insufficiency, Chronic/epidemiology , Heart Failure/epidemiologyABSTRACT
RATIONALE & OBJECTIVE: In the general population, there is an association between higher levels of physical activity and lower risk for cardiovascular events and mortality, but this relationship has not been well evaluated in chronic kidney disease (CKD). We investigated the association between self-reported physical activity and outcomes in a CKD cohort. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,926 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Time-updated self-reported physical activity assessed by (1) quartile of moderate-to-vigorous physical activity (MVPA) and (2) meeting guideline-recommended level of physical activity (categorized as active, meeting guidelines; active, not meeting guidelines; or inactive). OUTCOME: Atherosclerotic events (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, and all-cause and cardiovascular death. ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: At baseline, compared with the lowest MVPA quartile, those in the highest quartile were more likely to be younger, male, not have prevalent cardiovascular disease, and have higher estimated glomerular filtration rate. Overall, 51% met the physical activity guidelines; of those who did not, 30% were inactive. During the median follow-up period of 13.4 years, there were 772 atherosclerotic events, 848 heart failure events, and 1,553 deaths, and 420 cardiovascular deaths. Compared with the participants in the lowest MVPA quartile, the highest quartile had a lower risk of atherosclerotic events (HR, 0.64 [95% CI, 0.51-0.79]), incident heart failure (HR, 0.71 [95% CI, 0.58-0.87]), and all-cause and cardiovascular death (HRs of 0.54 [95% CI, 0.46-0.63] and 0.47 [95% CI, 0.35-0.64], respectively). The findings were similar for analyses evaluating recommended level of physical activity. LIMITATIONS: Self-reported physical activity may result in some degree of misclassification. CONCLUSIONS: Higher self-reported physical activity was associated with lower risk of cardiovascular events and mortality in CKD patients, which may have important implications for clinical practice and the design of interventional studies. PLAIN-LANGUAGE SUMMARY: In this long-term study of 3,926 adults with chronic kidney disease, we found that individuals with higher levels of physical activity were less likely to experience an atherosclerotic event (for example, a heart attack, stroke, or peripheral arterial disease), new-onset heart failure, and death as compared with those with lower levels of physical activity. The findings were similar for the analyses evaluating adherence to guideline-recommended level of physical activity (that is, for more than 150 minutes per week), and they strengthen the evidence supporting the current guideline recommendations.
Subject(s)
Atherosclerosis , Cardiovascular Diseases , Heart Failure , Myocardial Infarction , Renal Insufficiency, Chronic , Stroke , Adult , Humans , Male , Prospective Studies , Self Report , Renal Insufficiency, Chronic/complications , Cohort Studies , Atherosclerosis/epidemiology , Atherosclerosis/etiology , Heart Failure/complications , Myocardial Infarction/complications , Exercise , Stroke/complications , Risk FactorsABSTRACT
The diagnosis and management of atherosclerotic renovascular disease (ARVD) is complex and controversial. Despite evidence from the ASTRAL (2009) and CORAL (2013) randomized controlled trials showing that percutaneous renal artery revascularization did not improve major outcomes compared with best medical therapy alone over 3-5 years, several areas of uncertainty remain. Medical therapy, including statin and antihypertensive medications, has evolved in recent years, and the use of renin-angiotensin-aldosterone system blockers is now considered the primary means to treat hypertension in the setting of ARVD. However, the criteria to identify kidneys with renal artery stenosis that have potentially salvageable function are evolving. There are also data suggesting that certain high-risk populations with specific clinical manifestations may benefit from revascularization. Here, we provide an overview of the epidemiology, diagnosis, and treatment of ARVD based on consensus recommendations from a panel of physician experts who attended the recent KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference on central and peripheral arterial diseases in chronic kidney disease. Most focus is provided for contentious issues, and we also outline aspects of investigation and management of ARVD that require further research.
Subject(s)
Atherosclerosis , Hypertension, Renovascular , Renal Artery Obstruction , Atherosclerosis/diagnosis , Atherosclerosis/epidemiology , Atherosclerosis/therapy , Humans , Hypertension, Renovascular/diagnosis , Hypertension, Renovascular/epidemiology , Hypertension, Renovascular/etiology , Kidney , Renal Artery , Renal Artery Obstruction/diagnosis , Renal Artery Obstruction/epidemiology , Renal Artery Obstruction/therapy , Renin-Angiotensin SystemABSTRACT
Volume overload, defined as excess total body sodium and water with expansion of extracellular fluid volume, characterizes common disorders such as congestive heart failure, end-stage liver disease, chronic kidney disease, and nephrotic syndrome. Diuretics are the cornerstone of therapy for volume overload and comprise several classes whose mechanisms of action, pharmacokinetics, indications, and adverse effects are essential principles of nephrology. Loop diuretics are typically the first-line treatment in the management of hypervolemia, with additional drug classes indicated in cases of diuretic resistance and electrolyte or acid-base disorders. Separately, clinical trials highlight improved outcomes in some states of volume overload, such as loop diuretics and sodium/glucose cotransporter 2 inhibitors in patients with congestive heart failure. Resistance to diuretics is a frequent, multifactorial clinical challenge that requires creative and physiology-based solutions. In this installment of AJKD's Core Curriculum in Nephrology, we discuss the pharmacology and therapeutic use of diuretics in states of volume overload and strategies to overcome diuretic resistance.
Subject(s)
Acid-Base Imbalance , Heart Failure , Water-Electrolyte Imbalance , Acid-Base Imbalance/chemically induced , Curriculum , Diuretics/pharmacology , Diuretics/therapeutic use , Heart Failure/drug therapy , Humans , Sodium , Sodium Potassium Chloride Symporter Inhibitors/pharmacology , Sodium Potassium Chloride Symporter Inhibitors/therapeutic use , Water-Electrolyte Imbalance/chemically inducedABSTRACT
RATIONALE & OBJECTIVE: The utility of conventional upper reference limits (URL) for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease. EXPOSURE: Estimated glomerular filtration rate (eGFR). OUTCOME: NT-proBNP and hsTnT at baseline. ANALYTICAL APPROACH: We described the proportion of participants above the conventional URL for NT-proBNP (125pg/mL) and hsTnT (14ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99th percentile, we modeled the association of eGFR with NT-proBNP and hsTnT. RESULTS: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above the conventional URL, respectively. In those with eGFR <30mL/min/1.73m2, 71% and 68% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, respectively. Among all CKD participants, the 99th percentile for NT-proBNP was 3,592 (95% CI, 2,470-4,849) pg/mL and for hsTnT it was 126 (95% CI, 100-144) ng/L. Each 15mL/min/1.73m2 decrement in eGFR was associated with a ~40% higher threshold for the 99th percentile of NT-proBNP (1.43 [95% CI, 1.21-1.69]) and hsTnT (1.45 [95% CI, 1.31-1.60]). LIMITATIONS: Study included ambulatory patients, and we could not test the accuracy of the URL of NT-proBNP and hsTnT in the acute care setting. CONCLUSIONS: In this ambulatory CKD population with no self-reported history of cardiovascular disease, a range of 40%-88% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, depending on eGFR strata. Developing eGFR-specific thresholds for these commonly used cardiac biomarkers in the setting of CKD may improve their utility for evaluation of suspected heart failure and myocardial infarction.
Subject(s)
Renal Insufficiency, Chronic , Troponin T , Biomarkers , Glomerular Filtration Rate , Humans , Natriuretic Peptide, Brain , Peptide Fragments , Renal Insufficiency, Chronic/epidemiologyABSTRACT
Methamphetamine (METH) abuse is a significant public health concern globally. Cardiac toxicity is one of the important characteristics of METH, in addition to its effects on the nervous system. However, to date, research on the cardiotoxic injury induced by METH consumption has been insufficient. To systematically analyze the potential molecular mechanism of cardiac toxicity in METH-associated heart failure (HF), a rat model was constructed with a dose of 10 mg/kg of METH consumption. Cardiac function was evaluated by echocardiography, and HE staining was used to clarify the myocardial histopathological changes. Integrated analyses, including mRNA, miRNA and lncRNA, was performed to analyze the RNA expression profile and the potential molecular mechanisms involved in METH-associated HF. The results showed that METH caused decreased myocardial contractility, with a decreased percent ejection fraction (%EF). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of the RNAs with expression changes revealed abnormal circadian rhythm regulation in the METH groups, with circadian rhythm-related genes and their downstream effectors expressed differentially, especially the aryl hydrocarbon receptor nuclear translocator-like (Arntl). Competing endogenous RNA (ceRNA) networks associated with circadian rhythm, including Arntl, was also observed. Therefore, this study revealed that long-term METH consumption was associated with the HF in a rat model by decreasing the %EF, and that the abnormal circadian rhythm could provide new directions for investigating the METH-associated HF, and that the differentially expressed genes in this model could provide candidate genes for the identification and assessment of cardiac toxicity in METH-associated HF, which is fundamental for further understanding of the disease.
Subject(s)
Chronobiology Disorders , Heart Failure , Methamphetamine , MicroRNAs , RNA, Long Noncoding , ARNTL Transcription Factors/genetics , Animals , Cardiotoxicity , Gene Regulatory Networks , Heart Failure/chemically induced , Heart Failure/genetics , Methamphetamine/toxicity , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Rats , TranscriptomeABSTRACT
PURPOSE OF REVIEW: In this review, we discuss the mechanisms of action of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and the purported protective effects for mitigating heart failure (HF)-related outcomes. RECENT FINDINGS: Major randomized clinical trials have demonstrated the cardiovascular safety and efficacy of SGLT-2i among patients without known HF and those with established HF with reduced ejection fraction or preserved ejection fraction (HFrEF and HFpEF respectively). Recent HF guidelines have incorporated SGLT-2i in HF treatment algorithms. SGLT-2i have emerged as a novel treatment for both prevention of HF and reduction of cardiovascular morbidity and mortality among patients with existing HFrEF or HFpEF.