BACKGROUND: Exercise training is a well-established intervention for patients with heart failure with reduced and preserved ejection fraction. Still, the evidence of its effects on mortality, hospitalization, and quality of life needs to be more conclusive. We aim to evaluate exercise training clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).
METHODS: We searched five databases and three clinical trial registries for RCTs that compared exercise training plus usual care versus usual care alone in congestive heart failure (CHF) patients. We extracted data on all-cause mortality, hospital admission, heart failure hospitalization, and health-related quality of life measured by the Minnesota Living with HF questionnaire (MLHFW) and other scales. We pooled the data using random-effects or fixed-effects models, depending on the heterogeneity of the outcomes. We performed subgroup analyses for patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).
RESULTS: We included 61 RCTs with 9062 participants. There was no mortality benefit, but exercise training improved health-related quality of life, reduced hospital admission at 12 months and longer follow-up, and reduced heart failure hospitalization. We observed substantial enhancement in health-related quality of life and a greater decrease in hospital admissions in the HFpEF group compared to the HFrEF group.
CONCLUSIONS: Despite the lack of mortality benefit, exercise training is a beneficial intervention for CHF patients, improving health-related quality of life and reducing hospitalization.

The growing research regarding the implementation of angiotensin-converting enzyme-2 inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in the treatment of COVID-19 in patients with pre-existing cardiac comorbidities has become a large topic of discussion since the onset of the pandemic. Previous research primarily associates positive outcomes to the use of these drug classes due to their mechanism of action, which involves the downregulation of angiotensin I-converting enzyme 2 (ACE2) in the renin-angiotensin-aldosterone-system (RAAS) pathway, inflammatory mediators, and cytokines. Thus, these medications can convey preventative and protective effects in patients suffering from a SARS-CoV-2 infection. While we explored the studies that supported the positive outcomes of the use of these drugs in the first half of this review, we also expanded on the limitations of these studies in the latter portion. We also further explored the contradictory studies that indicated that using these antihypertensives can paradoxically increase the severity of COVID-19 infection as well. The studies in support of the use of these medications should consider epigenetic variations, ACE2 variants and acknowledge inherent genetic variations in certain ethnic groups as some have a predisposition for a severe COVID-19 infection. Additionally, mortality rates need to be taken into consideration in these studies as they naturally differ throughout the trajectory of the COVID-19 pandemic. While some studies are in support of the use of these antihypertensives despite other studies suggesting otherwise, further research is needed to explore the long-term effects of these antihypertensives and observe whether they are truly beneficial or not in reducing the severity of COVID-19 infections.

UNASSIGNED: In patients with type 2 diabetes (T2D) and a history of heart failure (HF), sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiovascular (CV) benefits. However, the comparative efficacy of individual SGLT2is remains uncertain. This network meta-analysis (NMA) compared the efficacy and safety of five SGLT2is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin) on CV outcomes in these patients.
UNASSIGNED: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to September 23, 2022, to identify all randomized controlled trials (RCTs) comparing SGLT2is to placebo in T2D patients with HF. The main outcomes included composite CV death/heart failure hospitalization (HFH), HFH, CV death, all-cause mortality, and adverse events. Pairwise and NMA approaches were applied.
UNASSIGNED: Our analysis included 11 RCTs with a total of 20,438 patients with T2D and HF. All SGLT2is significantly reduced HFH compared to standard of care (SoC) alone. \"Add-on\" SGLT2is, except ertugliflozin, significantly reduced composite CV death/HFH relative to SoC alone. Moreover, canagliflozin had lower composite CV death/HFH compared to dapagliflozin. Based on the surface under the cumulative ranking curve (SUCRA), the top-ranked SGLT2is for reducing HFH were canagliflozin (95.5%), sotagliflozin (66.0%), and empagliflozin (57.2%). Head-to-head comparisons found no significant differences between individual SGLT2is in reducing CV death. \"Add-on\" SGLT2is reduced all-cause mortality compared with SoC alone, although only dapagliflozin was statistically significant. No SGLT2is were significantly associated with serious adverse events. A sensitivity analysis focusing on HF-specific trials found that dapagliflozin, empagliflozin, and sotagliflozin significantly reduced composite CV death/HFH, consistent with the main analysis. However, no significant differences were identified from their head-to-head comparisons in the NMA. The SUCRA indicated that sotagliflozin had the highest probability of reducing composite CV death/HFH (97.6%), followed by empagliflozin (58.4%) and dapagliflozin (44.0%).
UNASSIGNED: SGLT2is significantly reduce the composite CV death/HFH outcome. Among them, canagliflozin may be considered the preferred treatment for patients with diabetes and a history of heart failure, but it may also be associated with an increased risk of any adverse events compared to other SGLT2is. However, a sensitivity analysis focusing on HF-specific trials identified sotagliflozin as the most likely agent to reduce CV death/HFH, followed by empagliflozin and dapagliflozin.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42022353754.

Romosozumab is a humanized monoclonal antibody that targets the sclerostin protein, which regulates bone formation and resorption. It is a novel therapy in the treatment of post-menopausal women with osteoporosis. The evidence regarding romosozumab\'s cardiovascular safety is conflicting. We report the first post-marketing case demonstrating cardiac events (i.e., atrial fibrillation and congestive heart failure) in a female patient with osteoporosis likely triggered by romosozumab. A literature review on romosozumab and cardiovascular disease is discussed extensively. For osteoporotic patients with cardiovascular risk factors (e.g., hypertension, coronary artery disease, and stroke), the benefits of fracture prevention should be weighed against potential cardiovascular risks before prescribing romosozumab. Real-world data on post-marketing surveillance will shed light on the potential safety signals of romosozumab.

UNASSIGNED: Intravenous nitrates are a primary therapy for hypertensive congestive heart failure (CHF) with acute pulmonary edema (APE) in the hospital setting. Historically, sublingual nitrates are the mainstay of emergency medical services (EMS) pharmacologic therapy for these patients. We aimed to evaluate the safety of prehospital bolus dose intravenous nitroglycerin in patients with APE.
UNASSIGNED: This is a retrospective evaluation of EMS data between March 15, 2018, and March 15, 2022, where CHF with APE was suspected and bolus-dose intravenous nitroglycerin was administered. Protocol inclusion criteria were hypertension (systolic blood pressure [SBP] >160 mmHg) and acute respiratory distress, with a presumption of decompensated CHF with APE. These patients received 1 mg intravenous nitroglycerin, with the option to repeat once for ongoing distress if the SBP remained >160 mmHg. The primary outcomes were adverse events, defined as hypotension (SBP <90 mmHg), syncope, vomiting, or dysrhythmia.
UNASSIGNED: The final analysis included 235 patients. In patients receiving intravenous bolus nitroglycerin, the median (interquartile range [IQR]) initial and final EMS SBP values decreased from 198 mmHg (180-218) to 168 (148-187), respectively. The median (IQR) pulse decreased from 108 (92-125) to 103 (86-119), and the median oxygen saturation increased from 89% (82-95) to 98% (96-99). Three episodes (1.3%) of asymptomatic hypotension occurred, and none required intervention.
UNASSIGNED: This study supports a favorable safety profile for prehospital bolus-dose intravenous nitroglycerin for decompensated CHF with APE. Blood pressure, heart rate, and oxygen saturation improvements are also demonstrated. Further, prospective studies are needed to confirm these findings.

Mycoplasma pneumoniae is well known to cause pulmonary infection. However, it often has extrapulmonary manifestations as well. We diagnosed and treated a 41-year-old female who presented with symptoms of pneumonia along with multisystem involvement, including rash, acute hepatitis, and new onset heart failure that improved with steroids and doxycycline. Subsequent guideline-directed medical therapy for non-ischemic cardiomyopathy (NICM) coincided with the complete recovery of the left ventricular function in three months. We also did a brief literature review with similar prior reported cases.

Cardiovascular disorders (CVDs) represent a global challenge and are regarded as one of the leading causes of mortality. The role of inflammation as a risk factor in these disorders has been studied, with the accelerated atherosclerotic process being a crucial factor in the pathogenesis. Several inflammatory biomarkers such as C-reactive protein (CRP), Interleukins (ILs), Tumor Necrosis Factor-alpha (TNF-α), and others have been identified that play a role in the atherosclerotic process, thus linking systemic inflammatory conditions with CVDs, including acute myocardial infarction (AMI), chronic heart failure (CHF), venous thromboembolism (VTE) and others. These markers could be used to predict the risk of CVDs. Understanding the precise mechanisms can lead to therapeutic strategies targeted at pro-inflammatory processes. We aim to provide an overview of the existing literature on the role of inflammation in various cardiovascular disorders and identify different inflammatory biomarkers and therapeutic targets in this comprehensive literature review. We reviewed 190 references published between 2013 and August 3, 2023, in well-reputed journals and analyzed eight selected papers in-depth. We describe the pathophysiologic pathways that lead to atherosclerosis and other cardiovascular pathologies. Several inflammatory cytokines encompassing various groups were identified to be causing endothelial dysfunction, leading to an increased risk for CVDs. Polymorphisms in the genes for different cytokines also led to different levels of susceptibility to CVDs. Nevertheless, future research detailing the inflammatory pathways and their link with CVDs would lead to better outcomes for patients with preexisting and new onset of CVDs as well as chronic inflammatory disorders.

Several studies have shown that an association exists between hyperuricemia and heart failure. Despite several innovative management strategies, heart failure is a significant cause of mortality worldwide. Hyperuricemia in heart failure patients leads to poorer outcomes. Additionally, hyperuricemia can be a strong surrogate marker for increased oxidative stress in heart failure patients. This oxidative stress leads to vascular endothelial damage and is linked to worsening heart failure and subsequent mortality. Hence, the measurement of serum uric acid levels in these patients can predict the present and future risk of complications of heart failure. Despite this knowledge, serum uric acid levels are not usually followed up in heart failure patients. This systematic review aims to give additional clarity to this association. We used research from the last twenty years (2002 to 2022) obtained from databases such as PubMed, PubMed Central (PMC), Google Scholar, and Science Direct. We used the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 guidelines. We removed duplicates, screened articles on the basis of title and abstract, applied eligibility criteria, and performed quality appraisal. Eventually, 15 articles were selected for review. There were 12 observational studies, two randomized controlled trials, and one meta-analysis. Our review showed that serum uric acid elevation is associated with the severity and complications of congestive heart failure. Serum uric acid can serve as a useful surrogate marker of oxidative stress in congestive heart failure (CHF) patients. The role of xanthine oxidase inhibitors needs to be evaluated further in CHF patients.

Mechanical circulatory support has been an indispensable treatment for severe heart failure. While the development of a total artificial heart has failed, left ventricular assist devices (LVAD) have evolved from extracorporeal to implantable types. The first generation implantable LVAD (pulsatile device) was used as a bridge to transplantation, and demonstrated improvement in survival rate and activity of daily living. The evolution from the first-generation (pulsatile device) to the second-generation (continuous flow device: axial flow pump and centrifugal pump) has resulted in many clinical benefits by reducing mechanical failures and minimizing device size. Furthermore, third-generation devices, which use a moving impeller suspended by magnetic and/or hydrodynamic forces, have improved overall device reliability and durability. Unfortunately, there are still many device-related complications, and further device development and improvement of patient management methods are required. However, we expect to see further development of implantable VADs, including for destination therapy, in future.

BACKGROUND: Heart and kidney dysfunction frequently coexist in patients with acute heart failure due to the overlap between these two organ systems. Cardiorenal syndrome (CRS) results from pathology occurring in the heart and kidneys along with the consequences of dysfunction in one organ contributing to dysfunction in the other and vice versa.
OBJECTIVE: To evaluate the use of erythropoietin (EPO) in patients with CRS and its effects on hemoglobin (Hb), major cardiovascular (CV) events, and hospitalization rates.
METHODS: On February 24, 2022, searches were conducted using PubMed, MEDLINE, and EMBASE, and 148 articles were identified. A total of nine studies were considered in this systematic review. We assessed the included articles based on the National Heart, Lung, and Blood Institute quality assessment tools for controlled intervention and observational cohort or cross-sectional studies. An assessment of bias risk was conducted on the chosen studies, and data relevant to our review was extracted.
RESULTS: The systematic review of these studies concluded that most existing literature indicates that EPO improves baseline Hb levels and decreases myocardial remodeling and left ventricular dysfunction without reducing CV mortality. In addition, the effect of EPO on the hospitalization rate of patients with CRS needs to be further studied since this relationship is unknown. Future studies, such as randomized controlled clinical trials and prospective cohort studies, should be conducted to enhance the literature on the potential of EPO therapy in patients with CRS.
CONCLUSIONS: Our systematic review suggests that EPO therapy may have a significant role in managing CRS. The review highlights the potential benefits of EPO in improving baseline Hb levels, reducing the risk of major CV events, improving cardiac remodeling, myocardial function, New York Heart Association class, and B-type natriuretic peptide levels. However, the effect of EPO treatment on hospitalization remains unclear and needs further exploration.