Current Cardiology Reports最新文献

Purpose of Review

Outline the growing suite of novel genome editing tools powered by CRISPR-Cas9 technology that are rapidly advancing towards the clinic for the treatment of cardiovascular disorders.

Recent Findings

A diversity of new genome editors and modulators are being developed for therapies across myriad human diseases. Recent breakthroughs have improved the efficacy, safety, specificity, and delivery of CRISPR-mediated therapies that could impact heart disease in the next decade, though several challenges remain.

Summary

Many iterations of the original CRISPR system have been developed seeking to leverage its vast therapeutic potential. As examples, nuclease-free editing, precision single-nucleotide editing, gene expression regulation, and epigenomic modifications are now feasible with the current CRISPR-mediated suite of enzymes. These emerging tools will be indispensable for the development of novel cardiovascular therapeutics as demonstrated by recent successes in both basic research laboratories and pre-clinical models. Here, we provide an overview of current and emerging CRISPR-mediated technologies as they pertain to the cardiovascular system, highlighting successful implementations and future challenges.

Purpose of Review

To discuss the evolution in the approach to pericardial effusions and drainage from a historical perspective, the present state, and pathways for future innovative therapies.

Recent Findings

Incorporation of advanced imaging tools has dramatically improved the safety profile of pericardial interventions. Outcome data allow for refined approaches to management of pericardial disease in special populations, such as pulmonary arterial hypertension. Consideration of intrapericardial interventions and pharmacotherapy represent novel and promising approaches to management of pericardial effusions moving forward.

Summary

Although the impact of excess or rapidly accumulating pericardial fluid on hemodynamics has been recognized for centuries, the therapeutic approaches have only recently become more refined with the routine incorporation of such tools as echocardiography and fluoroscopy. The most utilized approaches for pericardiocentesis include the apical, subxiphoid, and parasternal, and the most favorable approach is that in which the pericardial fluid is closest to the body surface, where intervening vital structures are least likely to be damaged. With the notable exception of patients with pre-existing pulmonary hypertension, complete decompression of pericardial fluid with careful drain management reduces likelihood of pericardial effusion recurrence. In addition, percutaneous balloon pericardiotomies have been demonstrated to reduce recurrence in nonmalignant effusions.

Purpose of review

This review aims to evaluate the potential of CRISPR-based gene editing tools, particularly prime editors (PE), in treating genetic cardiac diseases. It seeks to answer how these tools can overcome current therapeutic limitations and explore the synergy between PE and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for personalized medicine.

Recent findings

Recent advancements in CRISPR technology, including CRISPR-Cas9, base editors, and PE, have demonstrated precise genome correction capabilities. Notably, PE has shown exceptional precision in correcting genetic mutations. Combining PE with iPSC-CMs has emerged as a robust platform for disease modeling and developing innovative treatments for genetic cardiac diseases.

Summary

The review finds that PE, when combined with iPSC-CMs, holds significant promise for treating genetic cardiac diseases by addressing their root causes. This approach could revolutionize personalized medicine, offering more effective and precise treatments. Future research should focus on refining these technologies and their clinical applications.

Purpose of review: Cardiovascular disease (CVD) is the leading cause of death globally and is closely associated with obesity and type 2 diabetes mellitus (T2DM). This review examines the interplay between obesity, T2DM, and CVD, highlighting the increasing prevalence and economic burden of these conditions.

Recent findings: Pharmacologic therapies, particularly glucagon-like peptide-1 receptor agonists, show promise in substantial weight loss and subsequent reduction of adverse cardiovascular events in obese individuals with and without diabetes. Obesity significantly contributes to the development of insulin resistance and T2DM, further escalating CVD risk. The common co-occurrence of these three conditions may involve several other pathophysiological mechanisms, such as chronic inflammation, increased visceral adiposity, and endothelial dysfunction. Until recently, lifestyle modifications and bariatric surgery had been the primary methods for weight loss and mitigating obesity-associated cardiovascular risk. Newer pharmacological options have led to a paradigm shift in our approach to obesity management as they provide substantial benefits in weight loss, glycemic control, and cardiovascular risk reduction.

Purpose of review: Elevated blood pressure is the leading modifiable risk factor for cardiovascular morbidity and mortality in the US. Older individuals, Black adults, and those with comorbidities such as chronic kidney disease, have higher levels of uncontrolled and resistant hypertension. This review focuses on resistant hypertension, specifically in the US Black population, including potential benefits and limitations of current and investigational agents to address the disparate toll.

Recent findings: There is a necessity to implement public health measures, including early screening, detection, and evidence-based hypertension treatment with lifestyle, approved and investigational agents. The evidence highlights the importance of implementing feasible and cost-effective public health measures to advocate for early screening, detection, and appropriate treatment of hypertension. A team-based approach involving physicians, advanced practice nurses, physician assistants, pharmacists, social workers, and clinic staff to implement proven approaches and the delivery of care within trusted community settings may mitigate existing disparities.

Purpose of review: Body fat distribution plays a significant role in the cardiometabolic consequences of obesity. We review the impact of visceral and hepatic fat and highlight important interventions.

Recent findings: Several epidemiologic studies have established a clear association between visceral fat and cardiovascular disease. The association between hepatic fat and cardiovascular disease is less clear with discordant results. Novel evidence demonstrates sodium glucose co-transporter-2 (SGLT2) inhibitors facilitate modest weight loss and reductions in ectopic fat depots in patient with type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with decreased visceral/hepatic fat and reductions in MACE in populations with type 2 diabetes and with overweight/obesity. Clear associations between visceral fat and cardiometabolic outcomes have been established, whereas the impact of hepatic fat remains less clear. Lifestyle modification and pharmacologic interventions remain the initial therapies, while surgical intervention is associated with improved long-term outcomes. Emerging therapies have demonstrated a profound impact on body fat distribution and cardiometabolic risk.

Introduction: Heart failure (HF) is a significant worldwide concern due to its substantial impact on mortality rates and recurrent hospitalizations. The relationship between recurrent hospitalizations and mortality in individuals diagnosed with heart failure has been the subject of conflicting findings in previous studies. A meta-analysis was conducted to investigate the association between recurrent heart failure hospitalizations (HFHs) and mortality.

Methods: We conducted a systematic search across various online databases, such as PubMed, Embase, Web of Science, ProQuest, Scopus, Science Direct, and Google Scholar, to locate studies that examined the connection between recurrent HFHs and cardiovascular (CV) mortality as well as all-cause mortality until January 2023. To evaluate the heterogeneity among the studies, we employed I2 and Cochran's Q test.

Results: In total, 143,867 participants from seven studies were included in the analysis. Recurrent HFHs were found to be strongly associated with elevated risks of both cardiovascular (CV) mortality and all-cause mortality. The pooled hazard ratios (HRs) indicated a non-significant association for CV mortality (HR = 4.28, 95% CI: 0.86-7.71) but a significant association for all-cause mortality (HR = 2.76, 95% CI: 2.05-3.48). Subgroup analyses revealed a reduction in heterogeneity when stratified by factors such as quality score, sample size, hypertension comorbidity, number of recurrent HFHs, and follow-up time. A clear correlation was observed between the frequency of HFH and the mortality risk. Various subgroups, including those with diabetes, atrial fibrillation, and chronic kidney disease, showed significant associations between recurrent HFHs and all-cause mortality. Additionally, recurrent HFHs were significantly associated with CV mortality in subgroups such as heart failure with reduced ejection fraction (HFrEF), atrial fibrillation, and diabetes.

Conclusion: This meta-analysis provides evidence of an association between recurrent HFH and elevated risk of both CV mortality and all-cause mortality. The findings consistently indicate that a higher frequency of HFH is strongly associated with an increased likelihood of mortality.

Purpose of review: Considerable current interest is directed at pharmacological agents for producing significant weight loss. However, healthy lifestyle choices can also lead to clinically meaningful weight loss and improvements in cardiovascular disease (CVD) risk factors.

Recent findings: In this review, we summarize the recent research from our PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) randomized controlled trial and review previous data on the potential benefits of cardiac rehabilitation and exercise training (CRET) programs to produce weight loss and improvements in CVD risk factors. Although obesity medications are becoming extremely attractive for secondary and even primary CVD prevention, high-intensity non-pharmacological therapies with healthy lifestyle choices reviewed herein can also lead to substantial health improvements in patients with obesity, including improvements in body weight and other body composition parameters as well as overall CVD risk.

Purpose of review: Cardiac sarcoidosis (CS) refers to cardiac involvement in sarcoidosis and is usually associated with worse outcomes. This comprehensive review aims to elucidate the electrocardiographic (ECG) signs and features associated with CS, as well as examine modern techniques and their importance in CS evaluation.

Recent findings: The exact pathogenesis of CS is still unclear, but it stems from an abnormal immunological response triggered by environmental factors in individuals with genetic predisposition. CS presents with non-cardiac symptoms; however, conduction system abnormalities are common in patients with CS. The most common electrocardiographic (ECG) signs include atrioventricular blocks and ventricular tachyarrhythmia. Distinct patterns, such as fragmented QRS complexes, T-wave alternans, and bundle branch blocks, are critical indicators of myocardial involvement. The application of advanced ECG techniques such as signal-averaged ECG, Holter monitoring, wavelet-transformed ECG, microvolt T-wave alternans, and artificial intelligence-supported analysis holds promising outcomes for opportune detection and monitoring of CS. Timely utilisation of inexpensive and readily available ECG possesses the potential to allow early detection and intervention for CS. The integration of artificial intelligence models into ECG analysis is a promising approach for improving the ECG diagnostic accuracy and further risk stratification of patients with CS.

Purposeof review: Cardiac sarcoidosis is an inflammatory condition that has been associated with deleterious cardiac manifestations. The diagnosis of cardiac sarcoidosis is challenging and can be guided by advanced cardiac imaging.

Recent findings: Endomyocardial biopsy lacks sensitivity in confirming a diagnosis of cardiac sarcoidosis. Studies have shown that the use of cardiac magnetic resonance imaging (MRI) and cardiac Positron Emission Testing (PET) are associated with increased sensitivity and specificity in the diagnosis of cardiac sarcoidosis. Cardiac MRI and cardiac PET CT, although distinct entities, are complimentary in the diagnosis, prognostication of major cardiac events, and aid in the treatment algorithm in patients with cardiac sarcoidosis.