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Inotropes are pharmacological agents that are indicated for the treatment of patients presenting with acute heart failure (AHF) with concomitant hypoperfusion due to decreased cardiac output. They are usually administered for a short period during the initial management of AHF until haemodynamic stabilisation and restoration of peripheral perfusion occur. They can be used for longer periods to support patients as a bridge to a more definite treatment, such as transplant of left ventricular assist devices, or as part of a palliative care regimen. The currently available inotropic agents in clinical practice fall into three main categories: beta-agonists, phosphodiesterase III inhibitors and calcium sensitisers. However, due to the well-documented potential for adverse events and their association with increased long-term mortality, physicians should be aware of the indications and dosing strategies suitable for different types of patients. Novel inotropes that use alternative intracellular pathways are under investigation, in an effort to minimise the drawbacks that conventional inotropes exhibit.

Cognitive impairment (CI) represents a common but often veiled comorbidity in patients with acute heart failure (AHF) that deserves more clinical attention. In the AHF setting, it manifests as varying degrees of deficits in one or more cognitive domains across a wide spectrum ranging from mild CI to severe global neurocognitive disorder. On the basis of the significant negative implications of CI on quality of life and its overwhelming association with poor outcomes, there is a compelling need for establishment of detailed consensus guidelines on cognitive screening methods to be systematically implemented in the population of patients with heart failure (HF). Since limited attention has been drawn exclusively on the field of CI in AHF thus far, the present narrative review aims to shed further light on the topic. The underlying pathophysiological mechanisms of CI in AHF remain poorly understood and seem to be multifactorial. Different pathophysiological pathways may come into play, depending on the clinical phenotype of AHF. There is some evidence that cognitive decline closely follows the perturbations incurred across the long-term disease trajectory of HF, both along the time course of stable chronic HF as well as during episodes of HF exacerbation. CI in AHF remains a rather under recognized scientific field that poses many challenges, since there are still many unresolved issues regarding cognitive changes in patients hospitalized with AHF that need to be thoroughly addressed.

Aims: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. Methods and Results: We retrospectively studied all adult patients with COVID-19 admitted to our institution from March 1st to 2nd May 2020. Patients were grouped based on the presence or absence of HF. We used competing events survival models to examine the association between HF and death, need for intubation, or need for dialysis during hospitalization. Of 4043 patients admitted with COVID-19, 335 patients (8.3%) had a prior diagnosis of HF. Patients with HF were older, had lower body mass index, and a significantly higher burden of co-morbidities compared to patients without HF, yet the two groups presented to the hospital with similar clinical severity and similar markers of systemic inflammation. Patients with HF had a higher cumulative in-hospital mortality compared to patients without HF (49.0% vs. 27.2%, p < 0.001) that remained statistically significant (HR = 1.383, p = 0.001) after adjustment for age, body mass index, and comorbidities, as well as after propensity score matching (HR = 1.528, p = 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. Conclusions: The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19.

Background: Hydroxychloroquine or chloroquine with or without the concomitant use of azithromycin have been widely used to treat patients with SARS-CoV-2 infection, based on early in vitro studies, despite their potential to prolong the QTc interval of patients. Objective: This is a systematic review and metanalysis designed to assess the effect of hydroxychloroquine with or without the addition of azithromycin on the QTc of hospitalized patients with COVID-19. Materials and methods: PubMed, Scopus, Cochrane and MedRxiv databases were reviewed. A random effect model meta-analysis was used, and I-square was used to assess the heterogeneity. The prespecified endpoints were ΔQTc, QTc prolongation > 500 ms and ΔQTc > 60 ms. Results: A total of 18 studies and 7179 patients met the inclusion criteria and were included in this systematic review and meta-analysis. The use of hydroxychloroquine with or without the addition of azithromycin was associated with increased QTc when used as part of the management of patients with SARS-CoV-2 infection. The combination therapy with hydroxychloroquine plus azithromycin was also associated with statistically significant increases in QTc. Moreover, the use of hydroxychloroquine alone, azithromycin alone, or the combination of the two was associated with increased numbers of patients that developed QTc prolongation > 500 ms. Conclusion: This systematic review and metanalysis revealed that the use of hydroxychloroquine alone or in conjunction with azithromycin was linked to an increase in the QTc interval of hospitalized patients with SARS-CoV-2 infection that received these agents.

Heart failure (HF) is a complex syndrome with a wide range of presentations and acuity, ranging from outpatient care to inpatient management due to acute decompensated HF, cardiogenic shock or advanced HF. Frequently, the etiology of a patient's decompensation is diminished cardiac output and peripheral hypoperfusion. Consequently, there is a need for use of inotropes, agents that increase cardiac contractility, optimize hemodynamics and ensure adequate perfusion. Inotropes are divided into 3 major classes: beta agonists, phosphodiesterase III inhibitors and calcium sensitizers. Additionally, as data from prospective studies accumulates, novel agents are emerging, including omecamtiv mecarbil and istaroxime. The aim of this review is to summarize current data on the optimal use of inotropes and to provide an expert opinion regarding their current and future use in the management of HF. The use of inotropes has long been linked to worsening mortality, tachyarrhythmias, increased myocardial oxygen consumption and ischemia. Therefore, individualized and evidence-based treatment plans for patients who require inotropic support are necessary. Also, better quality data on the use of existing inotropes is imperative, while the development of newer and safer agents will lead to more effective management of patients with HF in the future. [ABSTRACT FROM AUTHOR]

Cognitive impairment (CI) is an important comorbidity in patients with heart failure (HF). Its prevalence parallels the severity of heart failure, while it is an independent prognostic marker of adverse events. Various factors contribute to cognitive decline in HF, influencing self-care. There are no standardized screening methods for the diagnosis and management of these patients. The aim of the present manuscript is to provide an overview of the impact of cognitive impairment in HF, describe the utility of assessment tools and imaging methods for the evaluation of CI, and propose a comprehensive diagnostic and management approach. [ABSTRACT FROM AUTHOR]

Aim: The role of coronary computed tomography angiography (CCTA) in evaluating the etiology of heart failure with reduced ejection fraction (HFrEF) is unclear. This is a meta-analysis assessing the pooled diagnostic accuracy of CCTA in diagnosing significant coronary artery disease in HFrEF. Materials & methods: Electronic databases were searched for studies comparing CCTA with invasive coronary angiography in HFrEF. A random-effects model meta-analysis was conducted. Results: Five studies comprising 269 patients were included. On patient-based analysis, pooled sensitivity and specificity of CCTA were 0.99 (95% CI: 0.94-1.00) and 0.94 (95% CI: 0.90-0.97), respectively. On segment-based analysis, pooled sensitivity and specificity were 0.74 (95% CI: 0.67-0.80) and 0.99 (95% CI: 0.98-0.99), respectively. Conclusion: CCTA has excellent diagnostic accuracy in diagnosing significant coronary artery disease in newly diagnosed HFrEF. [ABSTRACT FROM AUTHOR]

High-intensity statins are recommended for patients with peripheral artery disease (PAD). Critical limb ischemia (CLI) is the most advanced presentation of PAD. The benefit of statins in the CLI population is unclear based on the existent studies. Our objective was to perform a systematic review and meta-analysis regarding the efficacy of statin therapy in patients with CLI. PRISMA guidelines were followed. PubMed, EMBASE, and Cochrane CENTRAL databases were reviewed up to April 30, 2019. The primary outcomes included amputation rates and all-cause mortality. Secondary outcomes included primary patency rates, amputation-free survival and major adverse cardiac or cerebrovascular events (MACCE). Risk of bias was assessed with the Robins-I tool for observational studies. A random-effects model meta-analysis was performed. Heterogeneity was assessed with I2. Funnel plots and Egger's test were used to assess publication bias. Nineteen studies including 26,985 patients with CLI were included in this systematic review. Among patients with known data on statin status, 12,292 (49.6%) were on statins versus 12,513 (50.4%) not on statins. Patients treated with statins were 25% less likely to undergo amputation (HR 0.75; 95% CI: 0.59–0.95; I2 = 79%) and 38% less likely to have a fatal event (HR 0.62; 95% CI: 0.52–0.75; I2 = 41.2%). Statin therapy was also associated with increased overall patency rates and lower incidence of MACCE. There was substantial heterogeneity in the analysis for amputation and amputation-free survival (I2 > 70%). In conclusion, statins are associated with decreased risk for amputation, mortality, and MACCE, as well as increased overall patency rates among patients with CLI. Future studies should assess whether other lipid-lowering medications in addition to high-intensity statins can further improve outcomes among patients with CLI. (PROSPERO registration number: CRD42019134160) [ABSTRACT FROM AUTHOR]

Acute heart failure (AHF) is a common clinical challenge that a wide spectrum of physicians encounters in every practice. In many cases, AHF is due to decompensation of chronic heart failure. This decompensation may be triggered by various reasons, with sepsis being a notable one. Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection and is associated with a very high mortality, which may reach 25%. Alarmingly, the increase in the mortality rate of patients with combined cardiac dysfunction and sepsis is extremely high (may reach 90%). Thus, these patients need urgent intervention. Management of patients with AHF and sepsis is challenging since cornerstone interventions for AHF may be contraindicated in sepsis and vice versa (e.g., diuretic treatment). Unfortunately, no relevant guidelines are yet available, and treatment remains empirical. This review attempts to shed light on the intricacies of the available interventions and suggests routes of action based on the existing bibliography. [ABSTRACT FROM AUTHOR]

Introduction: Nebulized antibiotics use has become common practice in the therapeutics of pneumonia in cystic fibrosis patients. There is an increasing interest in their use for respiratory infections in mechanically ventilated (MV) patients in order to a) overcome pharmacokinetic issues in the lung compartment with traditional systemic antibiotic use and b) prevent the emergence of multi-drug-resistant (MDR) pathogens. Areas covered: The beneficial effects of antibiotic nebulization in MV patients e.g. increasing efficacy, reduced toxicity and prevention of resistance are described. Physicochemical parameters of optimal lung deposition, characteristics of currently available nebulizers, practical aspects of the procedure, including drug preparation and adjustments of ventilator and circuit parameter are presented. Antibiotics used in nebulized route, along with efficacy in various clinical indications and safety issues are reviewed. Expert commentary: The safety of nebulization of antibiotics has been proven in numerous studies; efficacy as adjunctive treatment to intravenous regimens or as monotherapy has been demonstrated in ventilator-associated pneumonia or ventilator-associated tracheobronchitis due to MDR or susceptible pathogens. However, due to the heterogeneity of studies, multiple meta-analyses fail to demonstrate a clear effect. Clarification of indications, standardization of technique and implementation of clinical practice guidelines, based on new large-scale trials will lead to the optimal use of nebulized antibiotics. [ABSTRACT FROM AUTHOR]

Routine endomyocardial biopsies (rEMB) are performed for early detection of allograft rejection, from 1 week to one year after heart transplantation (HT). The optimal frequency of rEMB is unclear in the current era of immunosuppressive agents. Our aim was to investigate the yield of the first rEMB performed a week post HT. A single center retrospective analysis on consecutive adult patients undergoing HT between 01/2014 to 09/2021 all had rEMB performed one week after HT. rEMB with International Society for Heart and Lung Transplantation (ISHLT) grade 1R/1B or more was considered as acute cellular rejection (ACR). A total of 260 patients were included, in 37 (14%) rEMB performed at a median of 7 days [IQR 2] after HT showed ACR. Of these patients, mean age was 51±17, 25 (74%) were males, 14 (38%) had an ISHLT grade 1R/1B rejection, 13 (35%) 1R/2, 9 (24%) 2R/3A and 1 (3%) 3R/4. Only 3 of these 37 patients had none of the following high risk clinical factors: Pre HT panel reactive antibodies class I/II > 20% (n = 12), echocardiogram at EMB day showing left ventricular ejection fraction < 40% (n = 2), continuous sub-therapeutic tacrolimus levels (n = 19), need for mechanical circulatory support during the first week after HT or for vasopressors support until the day of rEMB (n = 6). Two of these 3 patients had 1R/1b rejection with normal echocardiograms at the day of EMB and no change in their immunosuppression was made, while a third patient with 2R/3A ACR, had moderate-severe right ventricular dysfunction on echocardiogram and 6/7 days of sub-therapeutic tacrolimus levels. The great majority of patients with ACR diagnosed on first week rEMB had at least one high-risk clinical feature suggesting the need for EMB. No patients without any clinical risk factor had 2R rejection or worse. Routine surveillance EMB one week after HT should not be performed absent clinical signs or risk factors for rejection. [ABSTRACT FROM AUTHOR]

In this review, we briefly outline our current knowledge on the epidemiology, outcomes, and pathophysiology of heart failure (HF) with mid-range ejection fraction (HFmrEF), and discuss in more depth the evidence on current treatment options for this group of patients. In most studies, the clinical background of patients with HFmrEF is intermediate between that of patients with HF and reduced ejection fraction (HFrEF) and patients with HF and preserved ejection fraction (HFpEF) in terms of demographics and comorbid conditions. However, the current evidence, stemming from observational studies and post hoc analyses of randomized controlled trials, suggests that patients with HFmrEF benefit from medications that target the neurohormonal axes, a pathophysiological behavior that resembles that of HFrEF. Use of β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and sacubitril/valsartan is reasonable in patients with HFmrEF, whereas evidence is currently scarce for other therapies. In clinical practice, patients with HFmrEF are treated more like HFrEF patients, potentially because of history of systolic dysfunction that has partially recovered. Assessment of left ventricular systolic function with contemporary noninvasive modalities, e.g., echocardiographic strain imaging, is promising for the selection of patients with HFmrEF who will benefit from neurohormonal antagonists and other HFrEF-targeted therapies. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common atrial arrhythmia following coronary artery bypass graft (CABG). Its prevalence is 15-45% and is associated with poor long-term prognosis. Risk factors can be patient-related, intraoperative, and/or postoperative. Therapeutic and preventive strategies have been developed to curtail AF burden. Cardioversion is recommended for unstable or symptomatic patients and rate control if asymptomatic. Anticoagulation is challenging with risk of thromboembolism and bleeding. However, patients should be anticoagulated after cardioversion or if AF persists >48 h and risk factors of stroke exist. A minimum of 4 weeks is recommended but longer duration should be considered in patients at high risk of stroke irrespective of recurrence of AF. [ABSTRACT FROM AUTHOR]