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Objective: Living donor liver transplantation (LDLT) using small grafts, especially left lobe grafts (H1234-MHV) (LLG), continues to be a challenge due to small-for-size syndrome (SFSS). We herein demonstrate that with surgical modifications, outcomes with small grafts can be improved. Methods: Between 2012 and 2020, we performed 130 adult LDLT using 61 (47%) LLG (H1234-MHV) in a single Enterprise. The median graft-to-recipient weight ratio was 0.84%, with graft-to-recipient weight ratio <0.7% accounting for 22%. Splenectomy was performed in 72 (56%) patients for inflow modulation before (n=50) or after (n=22) graft reperfusion. In LLG-LDLT, venous outflow was achieved using all three recipient hepatic veins. In right lobe graft (H5678) (RLG)-LDLT, the augmented graft right hepatic vein was anastomosed to the recipient's cava with a large cavotomy. Outcome measures include SFSS, early allograft dysfunction (EAD), and survival. Results: Graft survival rates at 1, 3, and 5 years were 94%, 90%, and 83%, respectively, with no differences between LLG (H1234-MHV) and RLG (H5678). Splenectomy significantly reduced portal flow without increasing the complication rate. Despite the aggressive use of small grafts, SFSS and EAD developed in only 1 (0.8%) and 18 (13.8%) patients, respectively. Multivariable logistic regression revealed model for end-stage liver disease score and LLG (H1234-MHV) as independent risk factors for EAD and splenectomy as a protective factor (odds ratio: 0.09; P =0.03). For LLG (H1234-MHV)-LDLT, patients who underwent prereperfusion splenectomy tended to have better 1-year graft survival than those receiving postreperfusion splenectomy. Conclusions: LLG (H1234-MHV) are feasible in adult LDLT with excellent outcomes comparable to RLG (H5678). Venous outflow augmentation and splenectomy help lower the threshold of using small-for-size grafts without compromising graft survival. [ABSTRACT FROM AUTHOR]

Background and Objectives: There is a paucity of guidance on HIV pre-exposure prophylaxis (PrEP) implementation in an academic medical center. The objectives of this study were to describe interventions by a multidisciplinary PrEP task force at an academic medical center and compare metrics of PrEP implementation pre- and post-creation of this entity. Methods: The interventions of the task force are described within the rubric of the PrEP care continuum. Participants were adults prescribed PrEP for greater than or equal to 30 days at 9 clinical sites across a university health system. Metrics of PrEP implementation were compared over 12-month intervals before and after the creation of the task force. Results: An increased proportion of participants had HIV testing within 7 days of new PrEP prescriptions (92% vs 63%, P <.001) and were prescribed PrEP in increments of 90 days or shorter (74% vs 56%, P <.001) after the creation of the task force. There were higher rates of testing for bacterial sexually transmitted infections in men who had sex with men and transgender women in the post-intervention compared with pre-intervention period. Conclusions: A multidisciplinary team that focuses on optimizing PrEP delivery along each step of the care continuum may facilitate PrEP scale-up and best practices in an academic setting. [ABSTRACT FROM AUTHOR]

Keywords: chronic disease; diabetes; health status disparities; Indigenous peoples EN chronic disease diabetes health status disparities Indigenous peoples 153 155 3 07/15/22 20220719 NES 220719 I To heal a nation, we must first heal the individuals, the families and the communities. i - Art Solomon, Anishinaabe Elder, Songs for the People: Teachings on the Natural Way Indigenous peoples in Canada constitute 4.9% of the population, but they endure more chronic diseases. Chronic disease, diabetes, health status disparities, Indigenous peoples. [Extracted from the article]

SRs stimulate increased patient interaction, elicit higher levels of satisfaction, and improve performance on tasks in comparison with other remote patient-monitoring devices (eg, smart watches, digital blood pressure monitors, fitness trackers, medical alert systems, and continuous glucose monitors). Higher exercise and cardiac rehabilitation adherence were observed among patients enrolled in a SR intervention versus usual care, albeit with small sample sizes (Ns <28).[3] It is possible that SRs may mitigate the identified challenges of remote patient monitoring in cardiovascular care,[4] such as low patient engagement and patient-provider depersonalization, and may become a particularly efficacious virtual care tool. [Extracted from the article]

The coronavirus disease 2019 (COVID-19) pandemic has affected health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with preexisting cardiovascular disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of severe acute respiratory syndrome coronavirus 2 is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S-spike protein. The continued viral shedding in the asymptomatic and presymptomatic individuals enhances its community transmission. The virus uses the angiotensin converting enzyme 2 receptor for internalization, aided by transmembrane protease serine 2 protease. The tissue localization of the receptors correlates with COVID-19 presenting symptoms and organ dysfunction. Virus-induced angiotensin converting enzyme 2 downregulation may attenuate its function, diminish its anti-inflammatory role, and heighten angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyperstimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation and balanced immune response. Persistent immune activation in predisposed patients, such as elderly adults and those with cardiovascular risk, can lead to hemophagocytosis-like syndrome, with uncontrolled amplification of cytokine production, leading to multiorgan failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, in particular, in those showing continued rise, along with cytokines such as interleukin-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration, and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome, and thrombosis remain important. Specific evidence-based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history. [ABSTRACT FROM AUTHOR]

There have been major advances in our knowledge of the contribution of DNA sequence variations to cardiovascular disease and stroke. However, the inner workings of the body reflect the complex interplay of factors beyond the DNA sequence, including epigenetic modifications, RNA transcripts, proteins, and metabolites, which together can be considered the "expressed genome." The emergence of high-throughput technologies, including epigenomics, transcriptomics, proteomics, and metabolomics, is now making it possible to address the contributions of the expressed genome to cardiovascular disorders. This statement describes how the expressed genome can currently and, in the future, potentially be used to diagnose diseases and to predict who will develop diseases such as coronary artery disease, stroke, heart failure, and arrhythmias. [ABSTRACT FROM AUTHOR]

Background--There remains limited insight into the pathophysiology and therapeutic advances directed at improving prognosis for patients with heart failure with preserved ejection fraction (HFpEF). Recent studies have suggested a role for coronary microvascular dysfunction in HFpEF. Rb-82 cardiac positron emission tomography imaging is a noninvasive, quantitative approach to measuring myocardial flow reserve (MFR), a surrogate marker for coronary vascular health. The aim of this study was to determine whether abnormalities exist in MFR in patients with HFpEF without epicardial coronary artery disease. Methods and Results--A total of 376 patients with ejection fraction ≥50%, no known history of obstructive coronary artery disease, and a confirmed diagnosis of heart failure (n=78) were compared with patients with no evidence of heart failure (n=298), further stratified into those with (n=186) and without (n=112) hypertension. Global and regional left ventricular MFR was calculated as stress/rest myocardial blood flow using Rb-82 positron emission tomography. Patients with HFpEF were more likely to be older, female, and have comorbid hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, anemia, and renal dysfunction. HFpEF was associated with a significant reduction in global MFR (2.16±0.69 in HFpEF versus 2.54±0.80 in hypertensive controls; P<0.02 and 2.89±0.70 in normotensive controls; P<0.001). A diagnosis of HFpEF was associated with 2.62 times greater unadjusted odds of having low global MFR (defined as <2.0) and remained a significant predictor of reduced global MFR after adjusting for comorbidities. Conclusions--HFpEF, in the absence of known history for obstructive epicardial coronary artery disease, is associated with reduced MFR independent of other risk factors. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is associated with a high burden of morbidity and mortality. Hospital discharge is an opportunity for identification of modifiable prognostic factors in the transition to chronic HF.We examined the association of discharge heart rate with 30-day and 1-year mortality and hospitalization outcomes in a cohort of 9097 patients with HF discharged from hospital. Discharge heart rate was categorized into predefined groups: 40 to 60 (n=1333), 61 to 70 (n=2170), 71 to 80 (n=2631), 81 to 90 (n=1700), and >90 bpm (n=1263). There was a significant increase in all-cause 30-day mortality with adjusted odds ratios of 1.59 (95% confidence interval [CI], 1.18-2.14; P=0.003) for discharge heart rates 81 to 90 bpm and 1.56 (95% CI, 1.13-2.16; P=0.007) for heart rates >90 bpm when compared with the reference group (heart rates, 61-70 bpm). Cardiovascular death risk at 30 days was also higher with adjusted odds ratio 1.59 (discharge heart rates, 81-90 bpm; 95% CI, 1.09-2.33; P=0.017) and 1.65 (discharge heart rates, >90 bpm; 95% CI, 1.09-2.48; P=0.017). One-year all-cause mortality (adjusted odds ratio, 1.41; 95% CI, 1.16-1.72; P<0.001) and cardiovascular death (adjusted odds ratio, 1.47; 95% CI, 1.12-1.92; P=0.005) were higher with discharge heart rates >90 bpm when compared with the reference group (heart rates, 40-60 bpm). Readmissions for HF (adjusted hazard ratio, 1.26; 95% CI, 1.04-1.54; P=0.021) and cardiovascular disease (adjusted hazard ratio, 1.29; 95% CI, 1.08-1.54; P=0.004) within 30 days were also higher with discharge heart rates >90 bpm.Higher discharge heart rates were associated with greater risk of all-cause and cardiovascular mortality 1-year follow-up and an elevated risk of 30-day readmission for HF and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Pathological cardiac hypertrophy is a major risk factor for heart failure. In this study, we identified interferon regulatory factor 9 (IRF9), a member of the IRF family, as a previously unidentified negative regulator of cardiac hypertrophy. The level of IRF9 expression was remarkably elevated in the hearts from animals with aortic banding-induced cardiac hypertrophy. IRF9-deficient mice exhibited pronounced cardiac hypertrophy after pressure overload, as demonstrated by increased cardiomyocyte size, extensive fibrosis, reduced cardiac function, and enhanced expression of hypertrophy markers, whereas transgenic mice with cardiac-specific overexpression of murine IRF9 exhibited a significant reduction in the hypertrophic response. Mechanistically, IRF9 competes with p300 for binding to the transcription activation domain of myocardin, a coactivator of serum response factor (SRF). This interaction markedly suppresses the transcriptional activity of myocardin because IRF9 overexpression strongly inhibits the ability of myocardin to activate CArG box-dependent reporters. These results provide compelling evidence that IRF9 inhibits the development of cardiac hypertrophy by suppressing the transcriptional activity of myocardin in the heart. [ABSTRACT FROM AUTHOR]

The article presents a study which explained the effect of nocturnal hemodialysis on myocardial mechanics and cardiomyocyte gene expression. The researchers used 2-dimensional velocity vector imaging to asses myocardial mechanics in 48 patients with end-stage renal disease. They found that frequent hemodialysis has impact on improvement in myocardial mechanics and cardiac gene expression profile, which validates prognosis.

The article presents a study on the mechanisms of chronic iron overload that slows the heart rate. The study assesses the influence of iron on the function of sinoatrial node (SAN) of chronic iron overload (CIO) mouse model. Result shows the reduction on heart rate as well as the L-type calcium (Ca)2+current (ICa,L densities. Moreover, reduction on Cav1.3-mediated ICa,L; thus, lead to bradycardia, atrial fibrillation, and electrical conduction.

The development of cardiac hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response that may eventually lead to ventricular dilatation and heart failure. Cellular FLICE-inhibitory protein (cFLIP) is a homologue of caspase 8 without caspase activity that inhibits apoptosis initiated by death receptor signaling. Previous studies showed that cFLIP expression was markedly decreased in the ventricular myocardium of patients with end-stage heart failure. However, the critical role of cFLIP on cardiac remodeling remains unclear. To specifically determine the role of cFLIP in pathological cardiac remodeling, we used heterozygote cFLIP(+/-) mice and transgenic mice with cardiac-specific overexpression of the human cFLIP(L) gene. Our results demonstrated that the cFLIP(+/-) mice were susceptible to cardiac hypertrophy and fibrosis through inhibition of mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2 signaling, whereas the transgenic mice displayed the opposite phenotype in response to angiotensin II stimulation. These studies indicate that cFLIP protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure. [ABSTRACT FROM AUTHOR]

The article focuses on the development of pharmacological therapies for the treatment of acute heart failure syndromes (AHFS). It discusses various factors attributed to therapy failure including patient heterogeneity, lack of pathophysiological understanding and flaws in the designs of AHFS studies. It also mentions that Phase III studies on drug efficacy should consider all risk boundaries. Moreover, it notes that therapy standardization requires cooperation within the scientific community.

The article argues against the roadmap of long noncoding RNAs for cardiovascular development and disease.

An introduction is presented in which the editor discusses a study by Connors et al., which highlights the characterization of genetic mutations in the transthyretin protein (ATTRm) and wild-type transthyretin (ATTRwt) to heart failure.

The article discusses the study which examines the association of high blood pressure to the survival of stabilized patients with acute heart failure (HF) at hospital discharge in Ontario. It notes that the study evaluates the association of systolic high blood pressure and diastolic blood pressure long-term survival of the discharged patients with HF. It concludes that discharge blood pressure is associated with mortality of risk patients with HF.

The article presents a study which aims to identify the role of the monocarboxypeptidase Angiotensin-converting enzyme 2 (ACE2) in cardiac remodeling in response to myocardial infarction (MI). It establishes a link between ACE2 deficiency and the increased mortality, infarct expansion, adverse ventricular remodeling and greater post-MI systolic dysfunction in the heart. It also confirms the belief that ACE2 negatively regulates the renin-angiotensin system (RAS).

The article presents a study which determines the effect of gelsolin, a calcium-regulated actin severing and capping protein, to the cardiac muscles. The study reveals that gelsolin has the ability to regulate cardiac modeling after myocardial infarction by DNase I-Mediated Apoptosis. Moreover, it also identified that gelsolin inhibition has the possibility to form a novel target for heart failure therapy.

Day/night rhythms are recognized as important to normal cardiovascular physiology and timing of adverse cardiovascular events; however, their significance in disease has not been determined. We demonstrate that day/night rhythms play a critical role in compensatory remodeling of cardiovascular tissue, and disruption exacerbates disease pathophysiology. We use a murine model of pressure overload cardiac hypertrophy (transverse aortic constriction) in a rhythm-disruptive 20-hour versus 24-hour environment. Echocardiography reveals increased left ventricular end-systolic and -diastolic dimensions and reduced contractility in rhythm-disturbed transverse aortic constriction animals. Furthermore, cardiomyocytes and vascular smooth muscle cells exhibit reduced hypertrophy, despite increased pressure load. Microarray and real-time PCR demonstrate altered gene cycling in transverse aortic constriction myocardium and hypothalamic suprachiasmatic nucleus. With rhythm disturbance, there is a consequent altered cellular clock mechanism (per2 and bmal), whereas key genes in hypertrophic pathways (ANF, BNP, ACE, and collagen) are downregulated paradoxical to the increased pressure. Phenotypic rescue, including reversal/attenuation of abnormal pathology and genes, only occurs when the external rhythm is allowed to correspond with the animals' innate 24-hour internal rhythm. Our study establishes the importance of diurnal rhythm as a vital determinant in heart disease. Disrupted rhythms contribute to progression of organ dysfunction; restoration of normal diurnal schedules appears to be important for effective treatment of disease. [ABSTRACT FROM AUTHOR]

Background: Despite the potential usefulness of administrative databases for evaluating outcomes, coding of heart failure and associated comorbidities have not been definitively compared with clinical data.Objective: To compare the predictive value of heart failure diagnoses and secondary conditions identified in a large administrative database with chart-based records.Methods: The authors studied 1808 patient records sampled from 14 acute care hospitals and compared clinically recorded data with administrative records from the Canadian Institute for Health Information. The impact of comorbidity coding in the administrative data set according to the Charlson classification was examined in models of 30-day mortality.Results: The positive predictive value (PPV) of a primary diagnosis ICD-9 428 was 94.3% using the Framingham criteria and 88.6% using criteria previously validated with pulmonary capillary wedge pressure. There was reduced prevalence of secondary comorbid conditions in administrative data in comparison with clinical chart data. The specificities and PPV/negative predictive values of administratively identified index comorbidities were high. The sensitivities of index comorbidities were low, but were enhanced by examination of hospitalizations within 1 year prior to the index heart failure admission. Using information from prior hospitalizations modestly enhanced 30-day mortality model performance; however, the odds ratio point estimates of the index and enhanced administrative data sets were consistent with the clinical model.Conclusion: The ICD-9 428 primary diagnosis is highly predictive of heart failure using clinical criteria. Examination of hospitalization data up to 1 year prior to the index admission improves comorbidity detection and may provide enhancements to future studies of heart failure mortality. [ABSTRACT FROM AUTHOR]