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: 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.

Purpose of review: In this review, we discuss the status of novel radiation shielding and other methods to reduce radiation exposure and its associated health risks within the CCL.

Recent findings: There are many devices on the market each with its unique advantages and inherent flaws. Several are available for widespread use with promising data, while others still in development. The field of percutaneous transcatheter interventions includes complex procedures often involving significant radiation exposure. Increased radiation exposes the proceduralist and CCL staff to potential harm from both direct effects of radiation but also from the ergonomic consequences of daily use of heavy personal protective equipment. Here we discuss several innovative efforts to reduce both radiation exposure and orthopedic injury within the CCL that are available, leading to a safer daily routine in a "lead [apron]-free" environment.

Purpose of review: Precision genetic medicine is evolving at a rapid pace and bears significant implications for clinical cardiology. Herein, we discuss the latest advancements and emerging strategies in gene therapy for cardiomyopathy and heart failure.

Recent findings: Elucidating the genetic architecture of heart failure has paved the way for precision therapies in cardiovascular medicine. Recent preclinical studies and early-phase clinical trials have demonstrated encouraging results that support the development of gene therapies for heart failure arising from a variety of etiologies. In addition to the discovery of new therapeutic targets, innovative delivery platforms are being leveraged to improve the safety and efficacy of cardiac gene therapies. Precision genetic therapy represents a potentially safe and effective approach for improving outcomes in patients with heart failure. It holds promise for radically transforming the treatment paradigm for heart failure by directly targeting the underlying etiology. As this new generation of cardiovascular medicines progress to the clinic, it is especially important to carefully evaluate the benefits and risks for patients.

Background: Obesity paradox in cardiovascular risk prediction has gained increasing attention in recent years. We aimed to investigate the impact of BMI on mortality following transcatheter aortic valve replacement (TAVR).

Methods: We performed a multi-center retrospective analysis of patients with severe aortic stenosis undergoing TAVR. Patients were categorized into: Underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30) and obese (BMI ≥ 30). Multivariate cox-proportional hazard model was used to compare all-cause mortality.

Results: Total of 6688 patients included (175 underweight, 2252 normal weight, 2368 overweight and 1893 with obesity). Mean age of patients was 81 ± 8 years with 55% males. Patients with obesity had higher prevalence of comorbidities but a lower overall STS score. Mortality at 30-days post-TAVR was lower in the obese population compared to underweight, normal weight, and overweight patients (1.6% vs. 6.9%, 3.6%, and 2.8%, respectively, p < 0.001). Similarly, 3-year mortality was lowest in patients with obesity (17.1% vs. 28.9%, 24.5% and 18.6%, respectively, p < 0.001). On multivariate analysis, long term all-cause mortality at 3-years remained significantly lower in patients with obesity compared to underweight (HR 1.74, 95% CI: 1.30-2.40, p < 0.001) and normal weight (HR: 1.41, 95% CI:1.21-1.63, p < 0.001) but not in overweight patients (HR: 1.10, 95% CI:0.94-1.28, p = 0.240).

Conclusion: In conclusion, patients with obesity have improved short and long term mortality following TAVR with an observed progressive increase in mortality with lower BMI ranges.

Purpose of review: In this article, we underscore the importance of identifying risk factors and monitoring pulmonary hypertension patients for signs of arrhythmias, as this proactive approach can reduce morbidity and mortality.

Recent findings: Atrial fibrillation is the most prevalent among cardiac arrhythmias and is associated with an increased risk of stroke, morbidity, and mortality. Smoking, obesity, hypertension, a sedentary lifestyle, and diabetes mellitus are some of the modifiable risk factors for atrial fibrillation. Recent studies show that the risk of atrial fibrillation is rising in patients with parenchymal and vascular lung disease. Stretching in the atria and pulmonary veins may lead to the onset of atrial fibrillation in cardiac conditions like hypertension, heart failure, and valvular disease. Atrial fibrillation in patients with pulmonary hypertension (PH) denotes a more advanced disease. Patients with PH are more susceptible to hemodynamic stress caused by tachycardia and an uncoordinated atrioventricular contraction. Therefore, atrial arrhythmias need to be treated because inadequate control of cardiac arrhythmias may result in poor clinical outcomes and lead to disease progression in PH patients. Aside from being a sign of severe disease, AF can also speed up and exacerbate the condition.

Purpose of review: This review provides an overview of the factor XI (FXI) inhibitor hypothesis for the development of novel anticoagulants which may be safer to those currently used in clinical practice and describes preliminary clinical data from phase 2 dose-ranging studies of patients with atrial fibrillation.

Recent findings: Recent data from phase 2 dose ranging studies demonstrate substantial reductions in bleeding with FXI pathway inhibition compared with currently approved anticoagulants. However, larger studies are necessary to demonstrate efficacy of FXI inhibition for stroke prevention in atrial fibrillation. FXI pathway inhibition holds great promise for revolutionizing the landscape of anticoagulation for atrial fibrillation, primarily by reducing bleeding risk; however, further data are necessary to demonstrate efficacy.