The Use of CRISPR-Cas9 Genetic Technology in Cardiovascular Disease: A Comprehensive Review of Current Progress and Future Prospective.

Over the last century, there have been major landmark developments in the field of medicine, enabling us to control and cure various diseases on a larger scale. A few of these include the discovery of antibiotics, the development of vaccines, and the origin of organ and tissue transplants. The continued quest for innovation in microbiology and medicine has helped humankind save millions of lives and decrease morbidity at the global level. Genetic medicine has grown significantly in the last two decades and appears to be the next frontier of curative therapies for chronic diseases. One important landmark in genetic medicine is the development of CRISPR (clustered, regularly interspaced short palindromic repeats) technology. In this article, we describe the basic structure and function of the CRISPR-Cas9 system, which, simply put, consists of an RNA part and a protein. It works as a molecular scissor that can perform targeted cuts followed by repairs in and around the genes of interest to attain favorable translational outcomes. We focused on summarizing recent studies using CRISPR-Cas9 technology in diagnosing and treating cardiovascular disease. These studies are primarily experimental and limited to animal models. However, their results are promising enough to anticipate that this technology will undoubtedly be available in clinical medicine in the coming years. CRISPR-Cas9-mediated gene editing has been used to study and potentially treat congenital heart disease, hyperlipidemias, arrhythmogenic cardiomyopathies, and the prevention of ischemia-reperfusion injury. Despite the current progress, we recognize the several challenges this technology faces, including funding for research, improving precision and reproducible results for human subjects, and establishing protocols for ethical compliance so that it is acceptable to the scientific community and the general public.

Arrhythmogenic Left Ventricular Cardiomyopathy Associated With a Phospholamban Gene Mutation in a Young Female: A Case Report and Literature Review.

Arrhythmogenic cardiomyopathy (ACM) is a myocardium disease characterized by phenotypic features of myocardial scarring due to fibrofatty myocardial replacement often associated with global or regional ventricular dysfunction. For years after arrhythmogenic right ventricular cardiomyopathy (ARVC) was first described, the left ventricle (LV) was generally considered normal or minimally involved. In recent years, however, LV involvement has been recognized. It usually presents with early-on arrhythmias more than heart failure symptoms compared to dilated cardiomyopathy. It can be right ventricular, biventricular, or left ventricular. The underlying pathophysiology involves either desmosomal or non-desmosomal mutations. Phospholamban (PLN) mutation is one of those and is associated with more severe arrhythmias and SCD. Primary prevention with ICD implantation should be considered in these patients, even the ones with an ejection fraction greater than 35%. In addition, if such patients progress to Stage D heart failure, they need to be evaluated for advanced heart failure therapies.

Diagnostic and Therapeutic Challenges Associated With Left Ventricular Tumors.

Cardiac tumors are uncommon. Sometimes it is challenging to differentiate non-invasively between different kinds of cardiac tumors and thrombi, which is critical to dictate the subsequent treatment. In addition, not all high-risk cardiac tumors are amenable to surgical resection posing a therapeutic challenge. We report a case of cardiac papillary fibroelastoma in the left ventricular cavity with a 10-year follow-up, with no embolic complications.

Stem cell therapy for heart failure in the clinics: new perspectives in the era of precision medicine and artificial intelligence.

Stem/progenitor cells have been widely evaluated as a promising therapeutic option for heart failure (HF). Numerous clinical trials with stem/progenitor cell-based therapy (SCT) for HF have demonstrated encouraging results, but not without limitations or discrepancies. Recent technological advancements in multiomics, bioinformatics, precision medicine, artificial intelligence (AI), and machine learning (ML) provide new approaches and insights for stem cell research and therapeutic development. Integration of these new technologies into stem/progenitor cell therapy for HF may help address: 1) the technical challenges to obtain reliable and high-quality therapeutic precursor cells, 2) the discrepancies between preclinical and clinical studies, and 3) the personalized selection of optimal therapeutic cell types/populations for individual patients in the context of precision medicine. This review summarizes the current status of SCT for HF in clinics and provides new perspectives on the development of computation-aided SCT in the era of precision medicine and AI/ML.

Right Ventricular Dysfunction and Short-Term Outcomes Following Left-Sided Valvular Surgery: An Echocardiographic Study.

Background The prognostic value of echocardiographic evaluation of right ventricular (RV) function in patients undergoing left-sided valvular surgery has not been well described. The objective of this study is to determine the role of broad echocardiographic assessment of RV function in predicting short-term outcomes after valvular surgery. Methods and Results Preoperative echocardiographic data, perioperative adverse outcomes, and 30-day mortality were analyzed in patients who underwent left-sided valvular surgery from 2006 to 2014. Echocardiographic parameters used to evaluate RV function include RV fractional area change, tricuspid annular plane systolic excursion, systolic movement of the RV lateral wall using tissue Doppler imaging (S'), RV myocardial performance index, and RV dP/dt. Subjects with at least 3 abnormal parameters out of the 5 aforementioned indices were defined as having significant RV dysfunction. The study included 269 patients with valvular surgery (average age: 67±15, 60.6% male, 148 aortic, and 121 mitral). RV dysfunction was found in 53 (19.7%) patients; 30-day mortality occurred in 20 patients (7.5%). Compared with normal RV function, patients with RV dysfunction had higher 30-day mortality (22.6% versus 3.8%; P=0.01) and were at risk for developing multisystem failure/shock (13.2% versus 3.2%; P=0.01). Multivariate analyses showed that preexisting RV dysfunction was the strongest predictor of increased 30-day mortality (odds ratio: 3.5; 95% CI, 1.1-11.1; P<0.05). Conclusions Preoperative RV dysfunction identified by comprehensive echocardiographic assessment is a strong predictor of adverse outcomes following left-sided valvular surgery.

Safety and Clinical Outcomes of Endovascular Treatment of Adult-Onset Pulmonary Artery Stenosis.

BACKGROUND: Pulmonary artery stenosis (PAS) in adults is a rare condition. The role of endovascular stent implantation as a therapeutic option has not been clearly defined. METHODS AND RESULTS: We performed a retrospective review of all cases of adult-onset PAS published in Pubmed/Medline from 1990 to 2013. A total of 126 cases of adult-onset PAS were identified, out of which 46 cases (37%) were treated with an endovascular intervention. Symptomatic improvement was reported in 98% of cases. Average translesional gradient at baseline was 47 ± 20 mm Hg, which reduced to 8 ± 11 mm Hg after stenting (P<.001). Mean preprocedural pulmonary systolic artery pressures were 79 ± 26 mm Hg, which reduced post procedure to 50 ± 20 mm Hg (P=.02). There were no immediate adverse events reported related to procedure. In-stent restenosis was reported in 7 cases on follow-up. CONCLUSION: Endovascular treatment appears safe and effective for symptom relief in adult-onset PAS and should be considered as an alternative treatment option in patients with prohibitive surgical risk.

Hypertriglyceridemia-Induced Pancreatitis in Psychiatric Patients: A Case Report and Review of Literature.

Hypertriglyceridemia is a known cause of 2%-7% of cases of acute pancreatitis. Although there are numerous potential causes, the use of atypical antipsychotics has been linked to elevated triglycerides and pancreatitis. Here, we present the case of a 42-year-old male patient with a diagnosis of schizoaffective disorder who presented to our hospital with acute pancreatitis due to hypertriglyceridemia, which was exacerbated after he was started on quetiapine.