Is hyperkalaemia in heart failure a risk factor or a risk marker? Implications for renin–angiotensin–aldosterone system inhibitor use

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143644/1/ejhf1175.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143644/2/ejhf1175_am.pd

Canine Cyclin T1 Rescues Equine Infectious Anemia Virus Tat Trans-Activation in Human Cells

AbstractHuman immunodeficiency virus-1 Tat protein and human Cyclin T1 mediate transcriptional activation by enhancing the elongation efficiency of RNA polymerase II. Activation of transcription of the related equine infectious anemia virus (EIAV) requires a similar protein known as eTat, which does not function in human cells. Expression of equine Cyclin T1 in human cells rescues eTat function, suggesting a general mechanism of transcription activation among lentiviruses. Here we present the cloning of Cyclin T1 from canine D17 osteosarcoma cells, which support EIAV transactivation, and show that canine Cyclin T1 confers eTat transactivation to human cells. A two-amino-acid change, from 79–proline–glycine–80 to 79–histidine–arginine–80, confers on the human Cyclin T1 the ability to cooperate with eTat in transcriptional activation. These findings suggested that the regions of Cyclin T1 that interact with lentiviral Tat proteins and TAR RNA elements form an extended domain, which very likely has a conserved fold

Focusing on Referral Rather than Selection for Advanced Heart Failure Therapies

Despite advances in heart failure treatment, advanced heart failure affects 5–10% of people with the condition and is associated with poor prognosis. Selection for heart transplantation and left ventricular assist device implantation is a rigorous and validated process performed by specialised heart failure teams. This entails comprehensive assessment of complex diagnostic tests and risk scores, and selecting patients with the optimal benefit-risk profile. In contrast, referral for advanced heart failure evaluation is an arbitrary and poorly studied process, performed by generalists, and patients are often referred too late or not at all. The study elaborates on the differences between selection and referral and proposes some simple strategies for optimising timely referral for advanced heart failure evaluation

Congestion and Diuretic Resistance in Acute or Worsening Heart Failure

Hospitalisation for acute heart failure (AHF) is associated with high mortality and high rehospitalisation rates. In the absence of evidence-based therapy, treatment is aimed at stabilisation and symptom relief. The majority of AHF patients have signs and symptoms of fluid overload, and, therefore, decongestion is the number one treatment goal. Diuretics are the cornerstone of therapy in AHF, but the treatment effect is challenged by diuretic resistance and poor diuretic response throughout the spectrum of chronic to worsening to acute to post-worsening HF. Adequate dosing and monitoring and evaluation of diuretic effect are important for treatment success. Residual congestion at discharge is a strong predictor of worse outcomes. Therefore, achieving euvolaemia is crucial despite transient worsening renal function

Persistent High Burden of Heart Failure Across the Ejection Fraction Spectrum in a Nationwide Setting

Background Heart failure (HF) has a dramatic impact on worldwide health care systems that is determined by the growing prevalence of and the high exposure to cardiovascular and noncardiovascular events. Prognosis remains poor. We sought to compare a large population with HF across the ejection fraction (EF) spectrum with a population without HF for patient characteristics, and HF, cardiovascular, and noncardiovascular outcomes. Methods and Results Patients with HF registered in the Swedish HF registry in 2005 to 2018 were compared 1:3 with a sex-, age-, and county-matched population without HF. Outcomes were cardiovascular and noncardiovascular mortality and hospitalizations. Of 76 453 patients with HF, 53% had reduced EF, 23% mildly reduced EF, and 24% preserved EF. Compared with those without HF, patients with HF had more cardiovascular and noncardiovascular comorbidities and worse socioeconomic status. Incidence of cardiovascular and noncardiovascular events was higher in people with HF versus non-HF, with increased risk of all-cause (hazard ratio [HR], 2.53 [95% CI, 2.50-2.56]), cardiovascular (HR, 4.67 [95% CI, 4.59-4.76]), and noncardiovascular (HR, 1.49 [95% CI, 1.46-1.52]) mortality, 2- to 5-fold higher risk of first/repeated cardiovascular and noncardiovascular hospitalizations, and ~4 times longer in-hospital length of stay for any cause. Patients with HF with reduced EF had higher risk of HF hospitalizations, whereas those with HF with preserved EF had higher risk of all-cause and noncardiovascular hospitalization and mortality. Conclusions Patients with HF exert a high health care burden, with a much higher risk of cardiovascular, all-cause, and noncardiovascular events, and nearly 4 times as many days spent in hospital compared with those without HF. These epidemiological data may enable strategies for optimal resource allocation and HF trial design