Abstract Heart failure is a systemic and multiorgan syndrome with metabolic failure as a fundamental mechanism. As a consequence of its impaired metabolism, other processes are activated in the ...failing heart, further exacerbating the progression of heart failure. Recent evidence suggests that modulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation represents a promising approach to the treatment of patients with heart failure. Clinical trials have demonstrated that the adjunct of trimetazidine to the conventional medical therapy improves symptoms, cardiac function and prognosis in patients with heart failure without exerting negative hemodynamic effects. This review focuses on the rationale and clinical benefits of trimetazidine by acting on cardiac metabolism in heart failure, and aims to draw attention to the readiness of this agent to be included in all the major guidelines dealing with heart failure.
Abstract Treatment of hypertensive patients with beta-blockers decreases central blood pressure (CBP) less than other antihypertensive drugs, which is believed to account for their lesser ...cardiovascular protection in this setting. Some authors have suggested that decreasing heart rate (HR) with beta-blockers would increase CBP. In contrast to beta-blockers, the anti-anginal agent ivabradine reduces HR without other hemodynamic effects, and represents an attractive tool for exploring the direct relationship between HR and CBP. Here, we review the available clinical data assessing the effect of selective HR reduction with ivabradine on CBP in patients with stable coronary artery disease (CAD). We collected data from five studies which report either increase, decrease, or neutral effects of ivabradine on CBP. Further studies are needed to clarify the exact role of ivabradine on CBP. However, as supported by its pharmacodynamic effect in patients with stable CAD, available evidence to date suggests that ivabradine does not negatively impact CBP when associated with beta-blocker. HR reduction with both beta-blockers and ivabradine remain well-established treatments for the symptomatic treatment of angina patients.
Background Although safety and tolerability of vericiguat were established in the VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial in patients ...with heart failure with reduced ejection fraction, some subgroups may be more susceptible to symptomatic hypotension, such as older patients, those with lower baseline systolic blood pressure (SBP), or those concurrently taking angiotensin receptor neprilysin inhibitors. We described the SBP trajectories over time and compared the occurrence of symptomatic hypotension or syncope by treatment arm in potentially vulnerable subgroups in VICTORIA. We also evaluated the relation between the efficacy of vericiguat and baseline SBP. Methods and Results Among patients receiving at least 1 dose of the study drug (n=5034), potentially vulnerable subgroups were those >75 years old (n=1395), those with baseline SBP 100-110 mm Hg (n=1344), and those taking angiotensin receptor neprilysin inhibitors (n=730). SBP trajectory was plotted as mean change from baseline over time. The treatment effect on time to symptomatic hypotension or syncope was evaluated overall and by subgroup, and the primary efficacy composite outcome (heart failure hospitalization or cardiovascular death) across baseline SBP was examined using Cox proportional hazards models. SBP trajectories showed a small initial decline in SBP with vericiguat in those >75 years old (versus younger patients), as well as those receiving angiotensin receptor neprilysin inhibitors (versus none), with SBP returning to baseline thereafter. Patients with SBP <110 mm Hg at baseline showed a trend to increasing SBP over time, which was similar in both treatment arms. Safety event rates were generally low and similar between treatment arms within each subgroup. In Cox proportional hazards analysis, there were similar numbers of safety events with vericiguat versus placebo (adjusted hazard ratio HR, 1.18; 95% CI, 0.99-1.39;
=0.059). No difference existed between treatment arms in landmark analysis beginning after the titration phase (ie, post 4 weeks) (adjusted HR, 1.14; 95% CI, 0.93-1.38;
=0.20). The benefit of vericiguat compared with placebo on the primary composite efficacy outcome was similar across the spectrum of baseline SBP (
for interaction=0.32). Conclusions These data demonstrate the safety of vericiguat in a broad population of patients with worsening heart failure with reduced ejection fraction, even among those predisposed to hypotension. Vericiguat's efficacy persisted regardless of baseline SBP. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02861534.
Abstract Hospitalization for heart failure (HF) places a major burden on healthcare services worldwide, and is a strong predictor of increased mortality especially in the first three months after ...discharge. Though undesirable, hospitalization is an opportunity to optimize HF therapy and advise clinicians and patients about the importance of continued adherence to HF medication and regular monitoring. The Optimize Heart Failure Care Program ( www.optimize-hf.com ), which has been implemented in 45 countries, is designed to improve outcomes following HF hospitalization through inexpensive initiatives to improve prescription of appropriate drug therapies, patient education and engagement, and post-discharge planning. It includes best practice clinical protocols for local adaptation, pre- and post-discharge checklists, and ‘My HF Passport’, a printed and smart phone application to improve patient understanding of HF and encourage involvement in care and treatment adherence. Early experience of the Program suggests that factors leading to successful implementation include support from HF specialists or ‘local leaders’, regular educational meetings for participating healthcare professionals, multidisciplinary collaboration, and full integration of pre- and post-hospital discharge checklists across care services. The Program is helping to raise awareness of HF and generate useful data on current practice. It is showing how good evidence-based care can be achieved through the use of simple clinician and patient-focused tools. Preliminary results suggest that optimization of HF pharmacological therapy is achievable through the Program, with little new investment. Further data collection will lead to a greater understanding of the impact of the Program on HF care and key indicators of success.
Hospitalization is an opportunity to optimize heart failure (HF) therapy. As optimal treatment for hospitalized HF patients in sinus rhythm with heart rate≥70bpm is unclear, we investigated the ...impact of combined beta-blocker (BB) and ivabradine versus BBs alone on short and longer term mortality and rehospitalization.
A retrospective analysis was performed on 370 hospitalized HF patients with heart rate≥70bpm (150 BB+ivabradine, 220 BB alone) in the Optimize Heart Failure Care Program in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Russia, Ukraine, and Uzbekistan, from October 2015 to April 2016.
At 1month, 3months, 6months and 12months, there were fewer deaths, HF hospitalizations and overall hospitalizations in patients on BB+ivabradine vs BBs alone. At 12months, all-cause mortality or HF hospitalization was significantly lower with BB+ivabradine than BBs (adjusted hazard ratio HR 0.45 (95% confidence interval CI 0.32–0.64, P<0.0001). Significantly greater improvement was seen in quality of life (QOL) from admission to 12months with BB+ivabradine vs BBs alone (P=0.0001). With BB+ivabradine, significantly more patients achieved ≥50% target doses of BBs at 12months than on admission (82.0% vs 66.6%, P=0.0001), but the effect was non-significant with BBs alone.
Heart rate lowering therapy with BB+ivabradine started in hospitalized HF patients (heart rate≥70bpm) is associated with reduced overall mortality and re-hospitalization over the subsequent 12months. A prospective randomized trial is needed to confirm the advantages of this strategy.
•Hospitalized heart failure patients with heart rate≥70 bpm have a higher mortality risk.•In those patients beta blockers (BB) + ivabradine reduced 12-month mortality/rehospitalization vs BB alone.•A large clinical trial is needed to confirm the advantages of this strategy
The coronavirus 2019 (COVID‐19) infection pandemic has affected the care of patients with heart failure (HF). Several consensus documents describe the appropriate diagnostic algorithm and treatment ...approach for patients with HF and associated COVID‐19 infection. However, few questions about the mechanisms by which COVID can exacerbate HF in patients with high‐risk (Stage B) or symptomatic HF (Stage C) remain unanswered. Therefore, the type of HF occurring during infection is poorly investigated. The diagnostic differentiation and management should be focused on the identification of the HF phenotype, underlying causes, and subsequent tailored therapy. In this framework, the relationship existing between COVID and onset of acute decompensated HF, isolated right HF, and cardiogenic shock is questioned, and the specific management is mainly based on local hospital organization rather than a standardized model. Similarly, some specific populations such as advanced HF, heart transplant, patients with left ventricular assist device (LVAD), or valve disease remain under investigated. In this systematic review, we examine recent advances regarding the relationships between HF and COVID‐19 pandemic with respect to epidemiology, pathogenetic mechanisms, and differential diagnosis. Also, according to the recent HF guidelines definition, we highlight different clinical profile identification, pointing out the main concerns in understudied HF populations.
Cardiogenic shock (CS) is a complex multifactorial clinical syndrome, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ ...failure and death. There is a large phenotypic variability in CS, as a result of the diverse aetiologies, pathogenetic mechanisms, haemodynamics, and stages of severity. Although early revascularization remains the most important intervention for CS in settings of acute myocardial infarction, the administration of timely and effective antithrombotic therapy is critical to improving outcomes in these patients. In addition, other clinical settings or non‐acute myocardial infarction aetiologies, associated with high thrombotic risk, may require specific regimens of short‐term or long‐term antithrombotic therapy. In CS, altered tissue perfusion, inflammation, and multi‐organ dysfunction induce unpredictable alterations to antithrombotic drugs' pharmacokinetics and pharmacodynamics. Other interventions used in the management of CS, such as mechanical circulatory support, renal replacement therapies, or targeted temperature management, influence both thrombotic and bleeding risks and may require specific antithrombotic strategies. In order to optimize safety and efficacy of these therapies in CS, antithrombotic management should be more adapted to CS clinical scenario or specific device, with individualized antithrombotic regimens in terms of type of treatment, dose, and duration. In addition, patients with CS require a close and appropriate monitoring of antithrombotic therapies to safely balance the increased risk of bleeding and thrombosis.
Introduction
Modus Vivendi was conducted in routine clinical practice to evaluate the effect of adding trimetazidine 80 mg once daily (TMZ 80 OD) to treat patients with persistent symptoms despite ...treatment with background antianginal therapies including maximally tolerated bisoprolol.
Methods
This multicenter, prospective, observational, open-label, uncontrolled study recruited adult outpatients with a confirmed diagnosis of stable angina to whom physicians had decided to prescribe TMZ 80 OD. All patients were symptomatic despite treatment, including maximally tolerated doses of bisoprolol. Data on number of angina attacks, use of short-acting nitrates, and quality of life (QoL) were collected at baseline (V1) and at 1-month (V2) and 3-month (V2) follow-up visits. Two sub-analyses assessed efficacy in patients who remained on a stable bisoprolol dose throughout the study, and in patients in whom background antianginal therapy was known.
Results
A total of 1939 patients were recruited (57.2% women). The mean age was 65.6 ± 8.8 years; 73.8% had class II and 26.2% class III angina. At V1, the mean number of angina attacks per week was 6.2 ± 6.5 despite antianginal therapy including maximally tolerated bisoprolol dosage. Following the addition of TMZ 80 OD, this decreased to 3.4 ± 4.2 attacks per week at V2, and 1.6 ± 2.6 at V3 (
P
< 0.05 at V2 and V3), with concomitant reductions in short-acting nitrate use (
P
< 0.05). Significant improvements in QoL were observed throughout the study. Subgroup analyses showed that the addition of TMZ 80 OD to guideline-recommended antianginal therapy was associated with significant reductions in the mean number of weekly angina attacks and consumption of short-acting nitrates and improvements in QoL whether patients were treated with maximally tolerated bisoprolol and TMZ 80 OD alone, or maximally tolerated bisoprolol and TMZ 80 OD on top of other antianginal therapies. Treatment was well tolerated.
Conclusion
The study findings support the addition of TMZ 80 OD to bisoprolol with or without other antianginal therapies for patients with persistent angina.
Trial Registration
This study was retrospectively registered under the number ISRCTN29992579.
The introduction of heart failure (HF) with mid-range ejection fraction (HFmrEF) as a distinct phenotype has achieved its aim of stimulating research into the underlying characteristics, ...pathophysiology and treatment of HF patients with left ventricular ejection fraction of 40-49 %. Comparison of clinical characteristics, comorbidities, outcomes and prognosis among patients with HF with preserved ejection fraction, HFmrEF and HF with reduced ejection fraction allowed consideration of HFmrEF as an intermediate phenotype, which often resembles HF with reduced ejection fraction more than HF with preserved ejection fraction. The latest findings suggest that patients with HFmrEF seem to benefit from therapies that have been shown to improve outcomes in HF with reduced ejection fraction.
The “Heart failure specialists of Tomorrow” (HoT) group gathers young researchers, physicians, basic scientists, nurses and many other professions under the auspices of the Heart Failure Association ...of the European Society of Cardiology. After its foundation in 2014, it has quickly grown to a large group of currently 925 members. Membership in this growing community offers many advantages during, before, and after the ‘Heart Failure and World Congress on Acute Heart Failure’. These include: eligibility to receive travel grants, participation in moderated poster sessions and young researcher and clinical case sessions, the HoT walk, the career café, access to the networking opportunities, and interaction with a large and cohesive international community that constantly seeks multinational collaborations.
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