Endothelial Dysfunction, Arterial Stiffness, and Heart Failure Marti, Catherine N., MD; Gheorghiade, Mihai, MD; Kalogeropoulos, Andreas P., MD, PhD ...
Journal of the American College of Cardiology,
10/2012, Letnik:
60, Številka:
16
Journal Article
Recenzirano
Odprti dostop
Outcomes for heart failure (HF) patients remain suboptimal. No known therapy improves mortality in acute HF and HF with preserved ejection fraction; the most recent HF trial results have been ...negative or neutral. Improvement in surrogate markers has not necessarily translated into better outcomes. To translate breakthroughs with potential therapies into clinical benefit, a better understanding of the pathophysiology establishing the foundation of benefit is necessary. Vascular function plays a central role in the development and progression of HF. Endothelial function and nitric oxide availability affect myocardial function, systemic and pulmonary hemodynamics, and coronary and renal circulation. Arterial stiffness modulates ventricular loading conditions and diastolic function, key components of HF with preserved ejection. Endothelial function and arterial stiffness may therefore serve as important physiological targets for new HF therapies and facilitate patient selection for improved application of existing agents.
Transthyretin amyloidosis (ATTR) is a rare, yet underdiagnosed disease characterized by progressive impairment of neurologic and cardiac function due to deposition of misfolded transthyretin. Despite ...great efforts, such as the introduction of orthotopic liver transplant, the devastating prognosis for both variant and wild‐type ATTR patients remained unchanged over the last decades, mainly due to a lack of specific therapies. Fortunately, recent years saw the introduction of promising targeted therapies, which aim to interfere with the deposition of misfolded transthyretin (TTR) at various stages of the cascade underlying ATTR progression. These include TTR tetramer stabilizers (tafamidis, diflunisal, epigallocatechin‐3‐gallate), TTR silencers (inotersen, patisiran) and fibril disruptors (monoclonal antibodies, doxycycline and tauroursodeoxycholic acid). In the context of this review we explain their mechanisms of action, analyse their efficacy on neurologic and cardiac function based on all clinical trials conducted to date and discuss their clinical applicability. Eventually suggestions for future clinical research into the field are provided.
Therapeutic Manipulation of Myocardial Metabolism Honka, Henri; Solis-Herrera, Carolina; Triplitt, Curtis ...
Journal of the American College of Cardiology,
04/2021, Letnik:
77, Številka:
16
Journal Article
Recenzirano
Odprti dostop
The mechanisms responsible for the positive and unexpected cardiovascular effects of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 ...diabetes remain to be defined. It is likely that some of the beneficial cardiac effects of these antidiabetic drugs are mediated, in part, by altered myocardial metabolism. Common cardiometabolic disorders, including the metabolic (insulin resistance) syndrome and type 2 diabetes, are associated with altered substrate utilization and energy transduction by the myocardium, predisposing to the development of heart disease. Thus, the failing heart is characterized by a substrate shift toward glycolysis and ketone oxidation in an attempt to meet the high energetic demand of the constantly contracting heart. This review examines the metabolic pathways and clinical implications of myocardial substrate utilization in the normal heart and in cardiometabolic disorders, and discusses mechanisms by which antidiabetic drugs and metabolic interventions improve cardiac function in the failing heart.
Display omitted
•Bioengineering of cardiac metabolism represents a novel strategy to improve cardiac function and slow the progression of myocardial disease.•Modification of myocardial metabolism by SGLT-2 inhibitors, GLP-1 RAs, and pioglitazone can reduce CV events in patients with type 2 diabetes.•The potential benefit of shifting fuel utilization pathways in patients with HF should be investigated in future trials.
Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction.
This ...study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).
Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization.
The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval CI: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group.
In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction EMPEROR-Reduced; NCT03057977)
Display omitted
Although patients with cardiovascular disease face excess risks of severe illness with coronavirus disease-2019 (COVID-19), there may be indirect consequences of the pandemic on this high-risk ...patient segment.
This study sought to examine longitudinal trends in hospitalizations for acute cardiovascular conditions across a tertiary care health system.
Acute cardiovascular hospitalizations were tracked between January 1, 2019, and March 31, 2020. Daily hospitalization rates were estimated using negative binomial models. Temporal trends in hospitalization rates were compared across the first 3 months of 2020, with the first 3 months of 2019 as a reference.
From January 1, 2019, to March 31, 2020, 6,083 patients experienced 7,187 hospitalizations for primary acute cardiovascular reasons. There were 43.4% (95% confidence interval CI: 27.4% to 56.0%) fewer estimated daily hospitalizations in March 2020 compared with March 2019 (p < 0.001). The daily rate of hospitalizations did not change throughout 2019 (–0.01% per day 95% CI: –0.04% to +0.02%; p = 0.50), January 2020 (–0.5% per day 95% CI: –1.6% to +0.5%; p = 0.31), or February 2020 (+0.7% per day 95% CI: –0.6% to +2.0%; p = 0.27). There was significant daily decline in hospitalizations in March 2020 (–5.9% per day 95% CI: –7.6% to –4.3%; p < 0.001). Length of stay was shorter (4.8 days 25th to 75th percentiles: 2.4 to 8.3 days vs. 6.0 days 25th to 75th percentiles: 3.1 to 9.6 days; p = 0.003) and in-hospital mortality was not significantly different (6.2% vs. 4.4%; p = 0.30) in March 2020 compared with March 2019.
During the first phase of the COVID-19 pandemic, there was a marked decline in acute cardiovascular hospitalizations, and patients who were admitted had shorter lengths of stay. These data substantiate concerns that acute care of cardiovascular conditions may be delayed, deferred, or abbreviated during the COVID-19 pandemic.
Display omitted
In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and ...corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre‐HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41–49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%.
Chronic heart failure (HF) is rare in the young and common in the elderly in the Western world. HF in the young is usually due to specific causes, predominantly or exclusively affecting the heart ...(adult congenital heart disease, different types of cardiomyopathies, myocarditis, or cardiotoxicity). In contrast, the mechanisms underlying HF development in the elderly have not been completely delineated. We propose that in most elderly patients, HF, regardless of the left ventricular ejection fraction (LVEF), is the consequence of the acceleration of cardiovascular aging by specific risk factors (usually hypertension, obesity, type 2 diabetes mellitus T2DM, coronary artery disease CAD, and valvular heart disease VHD), most affecting both the heart and the vasculature. These risk factors act individually or more commonly in groups, directly or indirectly (hypertension, obesity, and T2DM may lead to HF through an intervening myocardial infarction). The eventual HF phenotype and outcomes in the elderly are additionally dependent on the presence and/or development of comorbidities (atrial fibrillation, anemia, depression, kidney disease, pulmonary disease, sleep disordered breathing, other) and disease modifiers (race, sex, genes, other). The clinical implications of this paradigm are that aggressive treatment of hypertension, obesity, T2DM (preferably with metformin and sodium-glucose cotransporter-2 inhibitors), CAD, and VHD on top of measures that retard cardiovascular aging are the steadfast underpinning for HF prevention in the elderly, which represent the vast majority of HF patients.
PDF
