Heart Failure In Adults Research Articles

Sacubitril/Valsartan for heart failure in adults with systemic right ventricle: A single center safety and efficacy experience

Heart failure in adult with congenital heart disease is an important cause of morbi-mortality. Sacubitril/Valsartan has been validated for the treatment of heart failure in adults with left ventricular dysfunction. The aim of this study was to assess safety and efficacy of Sacubitril/Valsartan in symptomatic adults with systemic right ventricle dysfunction. This is a retrospective and single center study (Quebec Heart and Lung Institute, Quebec City, Canada). Eight patients (mean age 41 ± 9.2 years, 5 males) with a significant systemic right ventricle dysfunction in New York functional class II–III despite optimal heart failure medication were included. Sacubitril/Valsartan was up titrated at the maximal dosage tolerated. The mean dosage reached was 85 ± 22 mg/90 ± 24 mg. During a median follow-up of 248 (213–430) days, systolic (121 ± 13 vs. 116 ± 13 mmHg, P = 0.238) and diastolic (76 ± 6 mmHg vs. 72 ± 5 mmHg, P = 0.105) blood pressure, potassium (4.1 ± 0.4 mmol/L vs. 3.9 ± 0.2 mmol/L, P = 0.111) and creatinine (71.7 ± 14.5 μmol/L vs. 68.9 ± 14.7 μmol/L, P = 0.516) levels remained stable. No discontinuation, reduction in dose or side effects were noted. A significant improvement in functional status was observed ( P = 0.03): 6 patients had a New York Heart Association class improvement and 2 remained in the same class ( Fig. 1 ). Maximal oxygen uptake, NTproBNP levels and echocardiographic data did not reach significant improvement. Sacubitril/Valsartan titration in a population of patients with congenital heart disease and significant right ventricle dysfunction was well tolerated and associated with significant improvement in functional status class. Whether Sacubitril/Valsartan improved right ventricle remodeling or decrease heart failure hospitalization or mortality in that population remained to determined.

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease.

Dapagliflozin (Farxiga) is now approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease with or without type 2 diabetes.

The VE/VCO2 slope: A useful tool to evaluate the physiological status of children with congenital heart disease

Cardio-pulmonary exercise test (CPET) is becoming a key examination to assess physical capacity and disease severity in paediatric cardiology. The VE/VCO2 slope has been increasingly used as a surrogate marker for morbidity and mortality in adult heart failure, pulmonary arterial hypertension and for adult patients with CHD. Nevertheless, the use of the VE/VCO2 slope in children remains limited in the absence of reference values and clearly identified clinical determinants. This study aimed to compare the VE/VCO2 slope in a paediatric cohort with CHD to that of age- and gender-adjusted healthy controls. We also intended to identify the clinical and CPET variables associated with VE/VCO2 slope in this population. This cross-sectional study was carried out between November 2010 and September 2015 in two tertiary care paediatric cardiology reference centres. A total of 700 children were enrolled (399 CHD and 301 healthy controls). The mean VE/VCO2 slope was significantly higher in CHD than in healthy subjects (31.6 ± 4.8 vs. 29.3 ± 4.8; P < 0.001). When considering CHD sub-groups, the VE/VCO2 slope was impaired in single ventricle, complex anomalies of ventriculo-arterial connections, anomalies of the atrioventricular junctions and valves. The VE/VCO2 slope according to the CHD physiological status was illustrated in the Fig. 1, it was higher in children with significant pulmonary regurgitation, tricuspid regurgitation, right ventricular hypertension and right ventricle outflow tract (RVOT) obstacle. In the CHD group, VE/VCO2 slope increase was associated with BMI, the presence of a RVOT obstacle, the number of cardiac catheter procedures, as well as low age, FVC, tidal volume, and PetCO2 (Fig. 1). Increased VE/VCO2 slope was predominantly in children with single ventricle and/or residual right heart abnormalities suggesting that maldistribution of pulmonary blood flow during exercise is an important CHD-unique determinant of VE/VCO2 slope.

Methamphetamine-Associated Heart Failure Hospitalizations Across the United States: Geographic and Social Disparities.

BackgroundAlthough methamphetamine abuse is associated with the development of heart failure (HF), nationwide data on methamphetamine‐associated HF (MethHF) hospitalizations are limited. This study evaluates nationwide HF hospitalizations associated with substance abuse to better understand MethHF prevalence trends and the clinical characteristics of those patients.Methods and ResultsThis cross‐sectional period‐prevalence study used hospital discharge data from the National Inpatient Sample to identify adult primary HF hospitalizations with a secondary diagnosis of abuse of methamphetamines, cocaine, or alcohol in the United States from 2002 to 2014. All 2014 MethHF admissions were separated by regional census division to evaluate geographical distribution. Demographics, payer information, and clinical characteristics of MethHF hospitalizations were compared with all other HF hospitalizations. Total nationwide MethHF hospitalizations increased from 547 in 2002 to 6625 in 2014 with a predominance on the West Coast. Methamphetamine abuse was slightly more common among primary HF hospitalizations compared with all‐cause hospitalizations (7.4 versus 6.4 per 1000; Cohen h=0.012; P<0.001). Among HF hospitalizations, patients with MethHF were younger (mean age, 48.9 versus 72.4 years; Cohen d=1.93; P<0.001), more likely to be on Medicaid (59.4% versus 8.8%; Cohen h=1.16; P<0.001) or uninsured (12.0% versus 2.6%; Cohen h=0.36; P<0.001), and more likely to present to urban hospitals (43.8% versus 28.3%; Cohen h=0.32; P<0.001) than patients with non‐methamphetamine associated HF. Patients with MethHF had higher rates of psychiatric comorbidities and were more likely to leave the hospital against medical advice.ConclusionsMethHF hospitalizations have significantly increased in the United States, particularly on the West Coast. Coordinated public health policies and systems of care are needed to address this rising epidemic.

HeartWare HVAD Market Withdrawal and Impact on the Pediatric Field.

HeartWare HVAD Market Withdrawal and Impact on the Pediatric Field.

At 180 days hidradenitis suppurativa readmission rate is comparable to heart failure: Analysis of the nationwide readmissions database

At 180 days hidradenitis suppurativa readmission rate is comparable to heart failure: Analysis of the nationwide readmissions database

The Role of Metabolism in Heart Failure and Regeneration.

Heart failure is the leading cause of death worldwide. The inability of the adult mammalian heart to regenerate following injury results in the development of systolic heart failure. Thus, identifying novel approaches toward regenerating the adult heart has enormous therapeutic potential for adult heart failure. Mitochondrial metabolism is an essential homeostatic process for maintaining growth and survival. The emerging role of mitochondrial metabolism in controlling cell fate and function is beginning to be appreciated. Recent evidence suggests that metabolism controls biological processes including cell proliferation and differentiation, which has profound implications during development and regeneration. The regenerative potential of the mammalian heart is lost by the first week of postnatal development when cardiomyocytes exit the cell cycle and become terminally differentiated. This inability to regenerate following injury is correlated with the metabolic shift from glycolysis to fatty acid oxidation that occurs during heart maturation in the postnatal heart. Thus, understanding the mechanisms that regulate cardiac metabolism is key to unlocking metabolic interventions during development, disease, and regeneration. In this review, we will focus on the emerging role of metabolism in cardiac development and regeneration and discuss the potential of targeting metabolism for treatment of heart failure.

Adult height and incidence of atrial fibrillation and heart failure in older men: The British Regional Heart Study.

AimsTaller stature has been associated with increased risk of atrial fibrillation (AF). AF and heart failure (HF) often co-occur but the association between height and risk of HF in older adults has not been well studied. We have examined the association between height and incident AF and incident HF in older adults.MethodsProspective study of 3346 men aged 60–79 years with no diagnosed HF, myocardial infarction or stroke at baseline (1998–2000) followed up for a mean period of 16 years, in whom there were 294 incident HF cases and 456 incident AF. Men were divided into 5 height groups: <168.2, 168.2–172.5, 172.6–176.9, 177.0–183.0 and >183.0 cms based on the 25th, 50th, 75th and 95th centiles distribution of height.ResultsCVD risk factors tended to decrease with increasing height but a positive association was seen between height and electrocardiographic QRS duration and incident AF. Both short stature (<168.2 cm) and tall stature (>183.0 cm) was associated with significantly increased risk of HF in age-adjusted analysis compared to those in the second height quartile [HR (95 %CI) = 1.62 (1.15, 2.26) and 2.04 (1.23, 3.39) respectively]. In short men the increased risk remained after adjustment for adverse CVD risk factors; in tall men the association was largely associated with AF and QRS duration.ConclusionTall stature is associated with significantly increased risk of AF leading to increased risk of HF. Short stature was associated with increased HF risk which was not explained by known adverse CVD risk factors.

Correlation between N-Terminal-Pro-Brain Natriuretic Peptide and Heart Failure in Children with Acyanotic Congenital Heart Disease Left-to-Right Shunt

Background: Heart failure is a significant problem causing morbidity and mortality in children with acyanotic CHD left-to-right shunt. Congenital heart disease is often associated with ventricular dysfunction, volume or pressure overload, resulting in a high risk of heart failure. N-Terminal-pro-Brain Natriuretic Peptide (NT- pro-BNP) is a biochemical marker in the left ventricle, which is used as a diagnostic marker for adult heart failure since it has depicted a significant correlation between heart failure and elevated levels of NT-pro-BNP. This study aimed to analyze the relationship between NT-pro-BNP levels and heart failure in children with acyanotic CHD left-to-right shunt. Methods: An observational analytic examination with a cross-sectional study design was conducted on children aged 1 month to 18 years with acyanotic CHD left-to-right shunt with suspected heart failure at the Pediatric Cardiology Outpatient Clinic, Emergency Department, and Pediatric Ward of Dr. Soetomo General Hospital Surabaya from September 2020 to March 2021. Statistical analysis was carried out using Mann-Whitney test and contingency correlation test of Chi-Square with a significance value of p < 0.05. Results: There were 43 subjects fulfilling the inclusion criteria in which 53.5% of them were female with a mean age of 48 months. Furthermore, the most common type of acyanotic CHD left-to-right shunt with heart failure was VSD, followed by ASD and PDA. There was a significant relationship between increasing NT-pro-BNP levels with heart failure with p < 0.001 based on chi-square test with moderate correlation strength (r = 0.57) based on the contingency correlation test. Conclusion: There is a significant positive correlation between NT-pro-BNP and heart failure in children with acyanotic CHD left-to-right shunt.

Amniotic fluid microRNA profiles in twin-twin transfusion syndrome with and without severe recipient cardiomyopathy

Twin-twin transfusion syndrome presents many challenges for clinicians, and the optimal means of identifying pregnancies that will benefit most from intervention is controversial. There is currently no clinically available biomarker to detect twin-twin transfusion syndrome or to stratify cases based on the risk factors. microRNAs are small RNAs that regulate gene expression and are biomarkers for various disease processes, including adult and pediatric heart failure. To date, no studies have investigated amniotic fluid microRNAs as biomarkers for disease severity, specifically for severe recipient cardiomyopathy in twin-twin transfusion syndrome cases. This study aimed to assess whether amniotic fluid microRNAs could be useful as biomarkers to identify pregnancies at greatest risk for severe recipient cardiomyopathy associated with twin-twin transfusion syndrome. Amniotic fluid was collected at the time of amnioreduction or selective fetoscopic laser photocoagulation from monochorionic diamniotic twin pregnancies with twin-twin transfusion syndrome at any stage. Fetal echocardiography was performed on all twins before the procedure, and severe cardiomyopathy was defined as a right ventricular myocardial performance index of the recipient fetus of >4 Z-scores. microRNA was extracted from the amniotic fluid samples and analyzed using an array panel assessing 379 microRNAs (TaqMan Open Array, ThermoFisher). Student t tests were performed to determine significant differences in microRNA expression between pregnancies with severe recipient cardiomyopathy and those with preserved cardiac function. A stringent q value of <.0025 was used to determine differential microRNA expression. Random forest plots identified the top 3 microRNAs that separated the 2 groups, and hierarchical cluster analysis was used to determine if these microRNAs properly segregated the samples according to their clinical groups. A total of 14 amniotic fluid samples from pregnancies with twin-twin transfusion syndrome with severe cardiomyopathy were compared with samples from 12 twin-twin transfusion syndrome control cases with preserved cardiac function. A total of 110 microRNAs were identified in the amniotic fluid samples. Twenty microRNAs were differentially expressed, and the top 3 differentiating microRNAs were hsa-miR-200c-3p, hsa-miR-17-5p, and hsa-miR-539-5p. Hierarchical cluster analysis based on these top 3 microRNAs showed a strong ability to differentiate severe cardiomyopathy cases from controls. The top 3 microRNAs were used to investigate the sensitivity and specificity of these microRNAs to differentiate between the 2 groups with a receiver operating characteristic curve demonstrating sensitivity and specificity of 80.8%. All 20 differentially expressed microRNAs were down-regulated in the group with severe cardiomyopathy. Amniotic fluid microRNAs demonstrated differential expression between twin-twin transfusion syndrome recipient fetuses with severe cardiomyopathy and those without and have the potential to be important biomarkers of disease severity in this population.

Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.

BackgroundVericiguat, a stimulator of soluble guanylate cyclase, has been developed as a first-in-class therapy for worsening chronic heart failure in adults with left ventricular ejection fraction < 45%.ObjectiveThe objective of this article was to characterize the pharmacokinetics and pharmacokinetic variability of vericiguat combined with guideline-directed medical therapy (standard of care), and identify exposure–response relationships for safety (hemodynamics) and pharmacodynamic markers of efficacy (N-terminal pro-B-type natriuretic peptide concentration [NT-proBNP]) in patients with heart failure and left ventricular ejection fraction < 45% in the SOCRATES-REDUCED study (NCT01951625).MethodsVericiguat and NT-proBNP plasma concentrations in 454 and 432 patients in SOCRATES-REDUCED, respectively, were analyzed using nonlinear mixed-effects modeling.ResultsVericiguat pharmacokinetics were well described by a one-compartment model with apparent clearance, apparent volume of distribution, and absorption rate constant. Age, bodyweight, plasma bilirubin, and creatinine clearance were identified as significant covariates on apparent clearance; sex and bodyweight on apparent volume of distribution; and bodyweight and plasma albumin level on absorption rate constant. Pharmacokinetic/pharmacodynamic analysis showed initial minor and transient effects of vericiguat on blood pressure with low clinical impact. There were no changes in heart rate following initial or repeated vericiguat administration. An exposure-dependent and time-dependent turnover pharmacokinetic/pharmacodynamic model for NT-proBNP described production and elimination rates and an demonstrated exposure-dependent reduction in [NT-proBNP] by vericiguat plus standard of care compared with placebo plus standard of care. This effect was dependent on baseline [NT-proBNP].ConclusionsVericiguat has predictable pharmacokinetics, with no long-term effects on blood pressure in patients with heart failure and left ventricular ejection fraction < 45%. A pharmacokinetic/pharmacodynamic model described a vericiguat exposure-dependent reduction of NT-proBNP.Clinical Trial IdentifierNCT01951625.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01024-y.

P006. Relationship of Heart Failure Patient Caregivers Mutuality and Preparedness to Caregiving Role Strain and Burden during COVID-19

<h3>Background</h3> The hospitalization rates among Heart Failure (HF) patients has increased from 23% in 2000 to 29% in 2010 necessitating the efforts to improve care and reduce cost (CDC, 2014). This is causing an increase burden on the health care system, families, and the society. At discharge, patients are educated on self-care, which is a non-pharmacological approach towards patients managing their own disease state. Self-care is a difficult concept for most Heart Failure patients to master because it requires adapting to new life-style changes. The caring burden increases as patient's advance in the disease state. HF patients rely on informal care givers who are family and friends (Hooker, Schmiege, Trivedi, Amoyal & Beleman, 2019). The sudden transition to the Heart failure patient's caregiver role can be a social, financial, emotional, and physical strain that effects effective role adaptation. It is important to consider mutuality and preparedness when preparing care givers to their new role. Caregiver mutuality and preparedness can have mediating effects on caregiver role strain and burden over time (Schumacher, Stewart, & Archbold, 2007). <h3>Methods</h3> The purpose of this cross-sectional correlational study was to investigate the relationship between Heart failure patient's caregiver mutuality and preparedness for caregiving to role strain and burden. Two hypotheses were tested in this study: 1) There will be a negative relationship between Heart failure patient's caregiver mutuality and preparedness to caregivers role strain and burden 2) There will be a negative relationship between mutuality and preparedness to caregivers role strain and burden. The Roy Adaptation Model guided this research. The sample consisted of 195 adult Heart failure patient caregivers who participated via Amazon Mechanical Turk (M Turk) a crowd sourcing marketplace for survey participation and data collection. Predictor measures included mutuality and preparedness. Mutuality was measured by the Mutuality Scale and preparedness was measured by the Preparedness for Caregiving Scale. The outcome measure, role strain, was measured by the caregiver's perception of financial, physical, and social strain, and burden was measured with the Zarit burden scale. <h3>Results</h3> This study demonstrated that there was a statistically significant negative relationship between caregiver mutuality and preparedness to role strain, r (195) =.058, <i>p</i> < .001 and a statistically significant negative relationship between caregiver mutuality and preparedness to burden, r(195) =.071, <i>p</i> < .001. These findings indicate that mutuality and preparedness are important predictors of caregiver role strain and burden. The Heart failure certified nurse is positioned to translate the evidence of caregiver role research to the assessment, planning, and evaluation of interventions that can assist the informal caregiver during the dynamic phases of caregiver role adaptation. <h3>Conclusion</h3> Assessing the caregiver's preparation for caregiving, in addition to caregiver mutuality, is an important step in individualizing interventions that will have a positive effect on the role transition to caregiver. Furthermore, individual interventions based on the demand of caregiving will assist in the preparation of the caregiver during the transition to the community setting. This output includes descriptive on the variables, custom tables that display the set of responses for each of your composite variables and a few regressions to explore your states hypotheses. •Regression (multivariate): Mutuality and Preparedness vs Strain ○ R2=.058 (low) and p=.001 (signif) ○ Coefficients: ▪ Mutuality: -.216 (p=.042) — a negative impact (decreases) on strain (not much, but significant) ▪ Preparedness: .435 (p=.000) – a positive impact (increases) on strain •Regression (bivariate): <b>Preparedness vs Strain</b> ○ R2=.042 (low) and p=.002 (signif) ○ Coefficient: .275 (p=.002) – a positive impact (increases) on strain •Regression (bivariate): <b>Mutuality vs Strain</b> ○ R2=-.004, p=.600 <b>NOTE:</b> Mutuality not statistically significant on its own. Interplay with Preparedness •Regression (bivariate): <b>Mutuality and Preparedness vs Burden</b> ○ R2=.071 (low), p=.001 (signif) ○ Coefficients: ▪ Mutuality: -.427 (p=.000) – negative impact (decreases) perceived Burden ▪ Preparedness: .475 (p=.000) – positive impact (increases) perceived Burden ○ Regression: Mutuality vs Burden – NOT SIGNIFICANT ○ Regression: Preparedness vs Burden –NOT SIGNIFICANT •Regression: <b>Burden vs Strain</b> ○ R2=.312 (stronger impact than those above), p=.000 (signif) ○ Coefficient for Burden = .515 (p=.000) (For each one point increase in the Burden score, there is a half point increase in the Strain score. Remember that these scores only range from 0 to 4, so this is a heavy hit

980-P: Existing Microvascular Complications and Risk of Subsequent Heart Failure (HF) in Type 1 Diabetes (T1D)

We aimed to quantify the association between existing microvascular diseases and risk of subsequent HF in adults with T1D. Participants from Pittsburgh Epidemiology of Diabetes Complication (EDC) Study without known baseline HF (n=655) were classified into 4 groups based on the number (n=0-3) of existing microvascular diseases, i.e., overt nephropathy, proliferative retinopathy, and confirmed distal symmetric polyneuropathy (CDSP). Overt nephropathy was defined as an AER &amp;gt;300mg/24h in ≥ 2 of three validated timed biennial urine collections. Proliferative retinopathy was based on stereoscopic fundus photographs or a history of receiving laser therapy for proliferative diabetes retinopathy. CDSP was identified by following the Michigan Neuropathy Screening Instrument and the Michigan Diabetes Neuropathy Score. HF was determined by hospitalization, cause-of-death records, clinic exams, and/or self-reports of physician diagnosis. We applied Cox PH models to quantify the association between the number of existing microvascular diseases and risk of subsequent HF over 25 years follow-up controlling for diabetes duration (or age), sex, HbA1c, and CAD comorbidity. Mean baseline age and T1D duration were 27 years and 19 years. The 25-year cumulative incidence of HF was 6.6% (43/655). Over half didn’t have any microvascular disease at baseline; 19.7%, 16.7% and 10.8% had 1, 2 and 3 microvascular diseases, respectively. In participants with 1, 2, and 3 microvascular diseases, the adjusted HR (95%CI) of any clinically defined HF was 3.1 (1.3, 7.6), 2.5 (0.9, 6.9), and 4.0 (1.3, 11.9), compared with those without any microvascular disease. The HR (95%CI) of hospitalization or death for HF was 2.0 (0.6, 7.3), 2.2 (0.6, 8.7), and 4.1 (1.0, 16.4). As microvascular disease burden increases so does the risk of HF, independently of diabetes duration, sex, HbA1c, and CAD among adults with long-duration childhood-onset T1D. Disclosure J. Guo: None. T. Costacou: None. R. G. Miller: None. T. J. Orchard: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK034818)

Copeptin as a predictive marker of incident heart failure.

AimsHeart failure (HF) is a common disease with increasing prevalence and poor prognosis. The vasopressin (VP) marker copeptin predicts development of diabetes mellitus, diabetic heart disease, coronary artery disease, and premature mortality. Copeptin is elevated in HF patients and predicts a worse outcome. This study aims to investigate whether copeptin can predict HF development.MethodsCopeptin was analysed in 5297 individuals (69.6% men) without prevalent HF from the Malmö Preventive Project, a population‐based prospective cohort. Cox proportional hazards models were used to analyse risk of incident HF by copeptin levels after adjusting for conventional cardiovascular risk factors.ResultsDuring a median follow‐up time of 11.1 years, 350 subjects (6.6%) were diagnosed with HF. Of these events, 99 were classified as myocardial infarction (MI) related HF and 251 as non‐MI‐related HF. Individuals in the top quartile of copeptin had, after multivariate adjustment for conventional risk factors (age, sex, systolic blood pressure, diabetes mellitus, body mass index, antihypertensive therapy, smoking, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol), a significantly increased risk of developing HF by 1.63 [confidence interval (CI) 1.20–2.21] for HF compared with the reference quartile 1. After adjustment for conventional risk factors, the hazard ratio (HR) per standard deviation increase of log‐transformed copeptin for any HF was 1.30 (95% CI 1.17–1.46), whereas it was 1.39 (CI 1.13–1.71) for MI‐related HF and 1.26 (CI 1.11–1.44) for non‐MI‐related HF. The associations remained after additional adjustment for estimated glomerular filtration rate [HR 1.24 (95% CI: 1.10–1.40)] and for pro atrial natriuretic peptide on top of conventional risk factors [HR 1.14 (95% CI: 1.02–1.28)].ConclusionsElevated copeptin predicts development of HF in older adults. Copeptin is a risk marker of VP‐driven HF susceptibility and a candidate to guide prevention efforts of HF targeting the VP system.

Abstract 016: Association Of Fat Mass, Lean Mass, And Waist Circumference With Risk Of Heart Failure Among Community Dwelling Adults

Introduction: Higher body mass index and obesity are associated with a higher risk of diabetes and heart failure (HF) development. However, the contribution of measures of body composition such as fat mass (FM), lean mass (LM), and central adiposity (waist circumference, WC) towards the risk of HF, and if these relationships are modified by diabetes status (DM) is unknown. Methods: Adults from visit 5 of the Atherosclerosis Risk in Communities Study without prevalent HF were included. FM and LM were measured using bioelectric impedance. Multivariable adjusted Cox proportional hazards models were created to evaluate the associations of FM, LM, and WC with the risk of HF after adjustment for potential confounders ( see Fig legend ). Multiplicative interaction testing and stratified analysis by DM status were performed using adjusted Cox models and restricted cubic splines to evaluate whether the association of body composition parameters and risk of HF were modified by DM status. Results: The present study included 5,555 participants (58.3% women, 79.3% white). Over a median follow-up of 4.6 years, there were 254 HF events (4.6%). In the overall cohort, higher LM was significantly associated with higher risk of HF (aHR [95% CI] per 1 SD higher LM: 1.34 [1.13-1.60]) with no interaction by DM status. However, the associations of FM and WC with risk of HF were modified by DM status (p-interaction: FM*diabetes = 0.03, WC*diabetes = 0.008). Higher FM and WC were each significantly associated with higher risk of HF in adults with DM (aHR [95% CI] per 1-SD higher FM: 1.23 [1.01-1.49], per 1SD higher WC: 1.57 [1.31 - 1.89]) but not among those without DM at baseline (aHR [95% CI] FM: 0.99 [0.80 - 1.23], WC: 1.06 [0.87 - 1.30]) ( Figure ). Conclusions: Higher LM was significantly associated with a higher risk of HF irrespective of diabetes status. In contrast, the association of FM and WC with the risk of HF was modified by the presence of DM such that higher FM and WC were associated with a higher risk of HF among adults with DM but not those without DM.

Loop Diuretics in Infants with Heart Failure.

Tremendous advances have been made in the last 5 decades in the surgical management of congenital heart disease (CHD). Most infants affected by clinically significant CHD are at risk for developing heart failure (HF). Adult HF management is mostly evidence-based and our knowledge in this field has expanded significantly in the past decade. However, data on management approaches for HF in infants are limited. The indications and implications for various medications and interventions in patients with HF secondary to CHD are an upcoming area of interest. It is critical that we expand our ability to prevent, detect, and manage HF in the pediatric population.

Myopathic Cardiac Genotypes Increase Risk for Myocarditis

Background: Acute myocarditis (AM) is an important cause of heart failure and cardiomyopathy in adults and children, but risk factors are poorly understood. Mutations in genes related to cardiomyopathies have been implicated in children, suggesting overlap with other genetic myocardial disorders. Objectives: This study aimed to assess the prevalence of mutations in cardiac genes, including those associated with cardiomyopathies and neuromuscular disorders, among predominantly adult patients with AM. Methods: Genomic DNAs were obtained or extracted from blood from AM subjects from three separate cohorts (N=117; AM1=26, AM2=72, AM3=19), and next generation sequencing performed. Sex- and ancestry-matched controls without AM or cardiac disease and with available exome sequencing data from the BioMe biobank were included (N=468). Rates of deleterious variants (DV) in 93 cardiac genes were compared for cases and controls. Associations between DV status and histologic, viral and clinical outcomes were analyzed as secondary endpoints. Results: Based on a pooled burden meta-analysis (random effects), cardiac DV were statistically enriched in cases (AM1 19.2%, AM2 11.1%, AM3 31.6%) vs. respectively matched controls (5.6%, 7.6%, 7.9%) (P=0.013). Thirteen genes were implicated; of these, three (DYSF, DSP and TTN) were the source of DV for > 1 AM subject. No statistical differences were found between DV+ vs. DV- subjects for histologic AM classification, viral status or clinical outcome. Conclusions: Putatively damaging variants in genes related to cardiomyocyte structural integrity, classically associated with cardiomyopathy or neuromuscular disorders affecting the heart, are associated with increased risk for AM. Understanding viral-host genetic interactions may improve mechanistic insights in AM and clinical genetic testing may identify at-risk individuals.

Current and Future Drug and Device Therapies for Pediatric Heart Failure Patients: Potential Lessons from Adult Trials.

This review discusses the potential drug and device therapies for pediatric heart failure (HF) due to reduced systolic function. It is important to realize that most drugs that are used in pediatric HF are extrapolated from adult cardiology practices or consensus guidelines based on expert opinion rather than on evidence from controlled clinical trials. It is difficult to conclude whether the drugs that are well established in adult HF trials are also beneficial for children because of tremendous heterogeneity in the mechanism of HF in children and variations in the pharmacokinetics and pharmacodynamics of drugs from birth to adolescence. The lessons learned from adult trials can guide pediatric cardiologists to design clinical trials of the newer drugs that are in the pipeline to study their efficacy and safety in children with HF. This paper’s focus is that the reader should specifically think through the pathophysiological mechanism of HF and the mode of action of drugs for the selection of appropriate pharmacotherapy. We review the drug and device trials in adults with HF to highlight the knowledge gap that exists in the pediatric HF population.

Development and evaluation of physiologically based pharmacokinetic drug-disease models for predicting captopril pharmacokinetics in chronic diseases

The advancement in the processing speeds of computing machines has facilitated the development of complex physiologically based pharmacokinetic (PBPK) models. These PBPK models can incorporate disease-specific data and could be used to predict pharmacokinetics (PK) of administered drugs in different chronic conditions. The present study aimed to develop and evaluate PBPK drug-disease models for captopril after incorporating relevant pathophysiological changes occurring in adult chronic kidney disease (CKD) and chronic heart failure (CHF) populations. The population-based PBPK simulator Simcyp was used as a modeling and simulation platform. The visual predictive checks and mean observed/predicted ratios (ratio(Obs/pred)) of the PK parameters were used for model evaluation. The developed disease models were successful in predicting captopril PK in all three stages of CKD (mild, moderate, and severe) and CHF, as the observed and predicted PK profiles and the ratio(obs/pred) for the PK parameters were in close agreement. The developed captopril PBPK models can assist in tailoring captopril dosages in patients with different disease severity (CKD and CHF).

Mackay Heart Failure Study: Examining the Root Causes, Compliance With Guideline-Based Therapy and Prognosis

Heart failure patients have poor outcomes comparable to some malignancies; however, the modern guideline directed medical therapy (GDMT) has improved its outcomes. The clinical characteristics and prescribers' compliance with GDMT for heart failure patients have not been studied in the Mackay region. A retrospective cohort study of 115 consecutive adult heart failure patients was conducted at our institution. The study cohort consisted of 80% (n=92) males. Ischaemia was the leading cause accounting for 54% (n=62) of the cohort, followed by idiopathic cardiomyopathy at 32% (n=37). Drug-induced and Takotsubo cardiomyopathies were responsible for 11% and 1% respectively. Two (2) patients (2%) had valvular heart disease. Hypertension was present in 57% while diabetes and atrial fibrillation were present in 32% and 43% of patients. Fifty-nine per cent (59%) had a smoking history. All, except four patients, had reduced left ventricular ejection fraction (LVEF <50%) at diagnosis. Among patients with coronary ischaemia, 37% and 31% were revascularised with percutaneous coronary interventions and bypass graft surgeries, respectively. Renin-angiotensin-aldosterone system inhibitors and beta blockers were prescribed in 94% and 95% of the patients, respectively. Mineralocorticoid inhibitors were used in 25% while ivabradine was given to 8% of patients. Nine per cent (9%) of patients received cardiac resynchronisation therapy. Most patients had improvement in functional class and LVEF during follow-up. There were very few mortalities at 3% (n=3) at the median follow-up of 403 (IQR 239-896) days. Our study has shed light on heart failure epidemiology in the Mackay region. We found excellent compliance with GDMT and good prognosis for most patients in terms of both symptom and survival.