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A Review of Cardiovascular Outcomes Trials of Glucose-Lowering Therapies and Their Effects on Heart Failure Outcomes.
Nassif, ME, Kosiborod, M
The American journal of cardiology. 2019;:S12-S19
Abstract
Type 2 diabetes mellitus has long been recognized as a major risk factor for adverse atherosclerotic cardiovascular disease events; however, recent data indicate that heart failure is now emerging as the most common and morbid cardiovascular complication of type 2 diabetes mellitus. When heart failure develops in patients with type 2 diabetes, prognosis is ominous, highlighting the need for glucose-lowering therapies that can prevent heart failure, improve outcomes, or both. Prior to 2008, there was a paucity of randomized controlled trials evaluating long-term cardiovascular outcomes with glucose-lowering therapies. This changed after guidance on the assessment of novel glucose-lowering agents was issued by both the US Food and Drug Administration and the European Medicines Agency. Since then, significant progress has been made as a result of large cardiovascular outcomes trials. Though randomized controlled trials on insulin, sulfonylureas, and metformin are still limited, cardiovascular outcomes trials on newer glucose-lowering agents have included hundreds of thousands of patients with multiple years of follow-up. The increased risk of thiazolidinediones on heart failure had been well theorized and is now established; however, the increase in heart failure hospitalization with certain dipeptidyl peptidase-4 inhibitors was unexpected. The reasons for discrepancies with regard to heart failure risk with different dipeptidyl peptidase-4 inhibitors remain unclear, and further mechanistic studies are ongoing. The role of glucagon-like peptide-1 receptor agonists among patients with heart failure also remains unclear, and their effects may differ in patients with and without established heart failure, particularly those with decompensated heart failure with reduced ejection fraction.
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Primary Prevention of Heart Failure in Women.
Daubert, MA, Douglas, PS
JACC. Heart failure. 2019;(3):181-191
Abstract
The incidence of heart failure (HF) is increasing, particularly among women, and constitutes a rapidly growing public health problem. The primary prevention of HF in women should involve targeted, sex-specific strategies to increase awareness, promote a heart healthy lifestyle, and improve treatments that optimally control the risk factors for HF with reduced ejection fraction and HF with preserved ejection fraction. Epidemiological and pathophysiological differences in both HF subtypes strongly suggest that sex-specific preventive strategies and risk factor reduction may be particularly beneficial. However, significant gaps in sex-specific knowledge exist and are impeding preventive efforts. To overcome these limitations, women need to be adequately represented in HF research, sex differences must be prospectively investigated, and effective sex-specific interventions should be incorporated into clinical practice guidelines. This review summarizes the existing evidence that supports the primary prevention of HF in women and identifies potential strategies that are most likely to be effective in reducing the burden of HF among women.
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Intelligent Imaging: Radiomics and Artificial Neural Networks in Heart Failure.
Currie, G, Iqbal, B, Kiat, H
Journal of medical imaging and radiation sciences. 2019;(4):571-574
Abstract
BACKGROUND Our previous work with 123iodine meta-iodobenzylguanidine (123I-mIBG) radionuclide imaging among patients with cardiomyopathy reported limitations associated with the prognostic power of global parameters derived from planar imaging [1]. Employing multivariate analysis, we further showed the regional washout associated with territories adjacent to infarcted myocardium obtained from single-photon emission computed tomography imaging (SPECT) yielded superior prognostic power over the other planar and SPECT indices in predicting future cardiac events [1]. The aim of this study was to apply an artificial neural network (Neural Analyser version 2.9.5) to the original data from the same patient cohort to evaluate the most potent prognostic index for future cardiac events among patient with cardiomyopathy. METHODS The original data were reevaluated using an artificial neural network (Neural Analyser version 2.9.5). There were 84 input variables in the original 22 patients from clinical data, electrocardiogram (rest, stress, and continuous ambulatory electrocardiogram recording), transthoracic echocardiography, coronary angiogram, sestamibi myocardial perfusion SPECT, planar and SPECT 123I-mIBG, and genetic and biomarkers, detailed in the previous work. A single binary output was a cardiac event or no cardiac event in the follow-up period. RESULTS Following training and validation phases, the optimal number of inputs was determined to be two with a training loss of 0.025 and selection loss <0.001. The final architecture had inputs of a change in left ventricular ejection fraction (Δ > -10%) and 123I-mIBG planar global washout (>30%), two hidden layers of 6 and 1 node, respectively, and a binary output. Using receiver operator characteristics analysis demonstrated an area under the curve of 0.75 correlating to a sensitivity of 100% and specificity of 50%. CONCLUSION The premise that regional washout of 123I-mIBG SPECT from noninfarcted tissue is the best predictor of cardiac events was built on has a sound and logical foundation. By artificial neural network analysis; however, 123I-mIBG planar global washout of >30% was shown to be the best indicator for risk of cardiac event when accompanied by a decline in left ventricular ejection fraction of >10%. Further investigation should be undertaken assessing assimilation into big data and the potential for automated feature extraction from raw image datasets with convolutional neural networks.
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Mechanism by which dipeptidyl peptidase-4 inhibitors increase the risk of heart failure and possible differences in heart failure risk.
Sano, M
Journal of cardiology. 2019;(1):28-32
Abstract
Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral antidiabetic drugs that safely reduce the blood glucose level over the long term. In Japan, DPP-4 inhibitors have become the oral antidiabetic drugs most frequently prescribed for patients with type 2 diabetes. However, the results of several cardiovascular outcomes studies have suggested that some DPP-4 inhibitors may increase the risk of hospitalization for heart failure. In patients with diabetes, heart failure is the most frequent cardiovascular condition, and it has a negative impact on the quality of life as well as being a potentially fatal complication. Therefore, it is important to determine whether an increased risk of heart failure is associated with certain DPP-4 inhibitors or is a class effect of these drugs. This review explores the mechanism by which DPP-4 inhibitors may increase the risk of heart failure and possible differences among these drugs. The available research suggests that DPP-4 inhibitors cause sympathetic activation as a class effect and this may increase the risk of heart failure. Unlike other DPP-4 inhibitors, sitagliptin and alogliptin are mainly excreted in the urine and suppress renal sodium-hydrogen exchanger 3 activity. These two drugs did not increase the risk of hospitalization for heart failure in large-scale cardiovascular outcomes studies.
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Recent advances in the treatment of chronic heart failure.
Buckley, LF, Shah, AM
F1000Research. 2019
Abstract
After more than a decade of relatively modest advancements, heart failure therapeutic development has accelerated, with the PARADIGM-HF trial and the SHIFT trial demonstrated significant reductions in cardiovascular death and heart failure hospitalization for sacubitril-valsartan and in heart failure hospitalization alone for ivabradine. Several heart failure therapies have since received or stand on the verge of market approval and promise substantive advances in the treatment of chronic heart failure. Some of these improve clinical outcomes, whereas others improve functional or patient-reported outcomes. In light of these rapid advances in the care of adults living with chronic heart failure, in this review we seek to update the general practitioner on novel heart failure therapies. Specifically, we will review recent data on the implementation of sacubitril-valsartan, treatment of functional mitral regurgitation, sodium-glucose co-transporter-2 (SGLT-2) inhibitor therapy, agents for transthyretin amyloid cardiomyopathy, treatment of iron deficiency in heart failure, and the use of biomarkers or remote hemodynamic monitoring to guide heart failure therapy.
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Clinical applications of machine learning in cardiovascular disease and its relevance to cardiac imaging.
Al'Aref, SJ, Anchouche, K, Singh, G, Slomka, PJ, Kolli, KK, Kumar, A, Pandey, M, Maliakal, G, van Rosendael, AR, Beecy, AN, et al
European heart journal. 2019;(24):1975-1986
Abstract
Artificial intelligence (AI) has transformed key aspects of human life. Machine learning (ML), which is a subset of AI wherein machines autonomously acquire information by extracting patterns from large databases, has been increasingly used within the medical community, and specifically within the domain of cardiovascular diseases. In this review, we present a brief overview of ML methodologies that are used for the construction of inferential and predictive data-driven models. We highlight several domains of ML application such as echocardiography, electrocardiography, and recently developed non-invasive imaging modalities such as coronary artery calcium scoring and coronary computed tomography angiography. We conclude by reviewing the limitations associated with contemporary application of ML algorithms within the cardiovascular disease field.
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Updates in the management of heart failure for the chronic kidney disease patient.
Hsu, S, Bansal, N
Current opinion in nephrology and hypertension. 2019;(3):262-266
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Abstract
PURPOSE OF REVIEW Heart failure is highly prevalent in patients with chronic kidney disease (CKD) and a leading cause of morbidity and mortality in this population. Heart failure therapies proven to benefit the general population may have different risk-benefit profiles in patients with concurrent CKD, plausibly because of the unique pathophysiology of heart failure in this population. The present review highlights recent advances in heart failure treatment as they apply to patients with CKD. RECENT FINDINGS Several recent publications have shown possible benefits of established heart failure therapies to improve clinical outcomes in patients with CKD; while others conclude neutral or even harmful effects of heart failure therapies in CKD patients. Novel heart failure therapies show promise to improve outcomes in the general population and should be evaluated in future studies to further elucidate the efficacy and safety of these novel therapies specifically in patients with CKD. SUMMARY Knowledge of heart failure treatment to improve clinical outcomes in the CKD population remains limited. Future studies should focus on patients with CKD to evaluate the generalizability of heart failure therapies to this patient population.
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8.
[Hyperkalemia in heart failure: new solutions for an old problem].
Romani, S, Porcari, A, Fabris, E, Sinagra, G
Giornale italiano di cardiologia (2006). 2019;(10):543-551
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Abstract
Potassium is the main intracellular ion and its homeostasis is finely regulated by the renal and gastrointestinal tract. Renal failure and hyperkalemia are conditions commonly found in patients with heart failure, the result of a complex interaction between heart and kidney (e.g. cardio-renal syndrome) and the side effects of drugs commonly used for treating heart disease (e.g. renin-angiotensin-aldosterone system inhibitors). Although hyperkalemia increases the risk of heart conduction disorders and life-threatening arrhythmias, its prognostic significance in heart failure is uncertain. Hyperkalemia and progression of renal damage are the main limitations to the introduction and titration of heart failure therapies. New drugs for the prevention and chronic treatment of hyperkalemia allow the introduction and modulation of anti-neurohormonal therapies in patients with heart failure otherwise excluded from these treatments due to excessively high serum potassium levels.This review illustrates the pathophysiological, epidemiological and prognostic aspects of hyperkalemia and analyses the possible treatments for this condition in heart failure patients.
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Chronic heart failure: advances in pharmacological treatment and future perspectives.
Kuster, GM, Pfister, O
Swiss medical weekly. 2019;:w20036
Abstract
Besides noticeable progress in device therapy during the past decade, more recent advances in the management of chronic heart failure have led to exciting new pharmacological options. Among these, the combined angiotensin II receptor/neprilysin inhibitor (ARNI) valsartan/sacubitril has already proven highly effective in heart failure with reduced ejection fraction (HFrEF), and convincing data are available regarding the cardioprotective effects of sodium-glucose-co-transporter 2 (SGLT2) inhibitors. These two treatments have earned a class I and a class II recommendation, respectively, in the European Society of Cardiology guidelines for the diagnosis and treatment of heart failure. Whereas progress with respect to heart failure with preserved ejection fraction (HFpEF) is still slow, both ARNIs and SGLT2 inhibitors hold great promise for this condition as well, and large clinical trials are currently ongoing. In addition, new diagnostic algorithms have recently been developed to improve the diagnostic accuracy for HFpEF, which will ultimately aid the search for effective therapies in future clinical trials. In this review article, these most recent advances in the diagnosis and pharmacological management of HFrEF and HFpEF are highlighted, and set-backs as well as opportunities for future developments (e.g., tafamidis for the treatment of transthyretin amyloid cardiomyopathy) are discussed.
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Predisposing factors to heart failure in diabetic nephropathy: a look at the sympathetic nervous system hyperactivity.
Komici, K, Femminella, GD, de Lucia, C, Cannavo, A, Bencivenga, L, Corbi, G, Leosco, D, Ferrara, N, Rengo, G
Aging clinical and experimental research. 2019;(3):321-330
Abstract
Diabetes mellitus (DM) and heart failure (HF) are frequent comorbidities among elderly patients. HF, a leading cause of mortality and morbidity worldwide, is characterized by sympathetic nervous system hyperactivity. The prevalence of diabetes mellitus (DM) is rapidly growing and the risk of developing HF is higher among DM patients. DM is responsible for several macro- and micro-angiopathies that contribute to the development of coronary artery disease (CAD), peripheral artery disease, retinopathy, neuropathy and diabetic nephropathy (DN) as well. Independently of CAD, chronic kidney disease (CKD) and DM increase the risk of HF. Individuals with diabetic nephropathy are likely to present a distinct pathological condition, defined as diabetic cardiomyopathy, even in the absence of hypertension or CAD, whose pathogenesis is only partially known. However, several hypotheses have been proposed to explain the mechanism of diabetic cardiomyopathy: increased oxidative stress, altered substrate metabolism, mitochondrial dysfunction, activation of renin-angiotensin-aldosterone system (RAAS), insulin resistance, and autonomic dysfunction. In this review, we will focus on the involvement of sympathetic system hyperactivity in the diabetic nephropathy.