Arrhythmias in Female Patients: Incidence, Presentation and Management.

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.

Nucleolar PARP-1 Expression Is Decreased in Alzheimer's Disease: Consequences for Epigenetic Regulation of rDNA and Cognition.

Synaptic dysfunction is thought to play a major role in memory impairment in Alzheimer's disease (AD). PARP-1 has been identified as an epigenetic regulator of plasticity and memory. Thus, we hypothesize that PARP-1 may be altered in postmortem hippocampus of individuals with AD compared to age-matched controls without neurologic disease. We found a reduced level of PARP-1 nucleolar immunohistochemical staining in hippocampal pyramidal cells in AD. Nucleolar PARP-1 staining ranged from dispersed and less intense to entirely absent in AD compared to the distinct nucleolar localization in hippocampal pyramidal neurons in controls. In cases of AD, the percentage of hippocampal pyramidal cells with nucleoli that were positive for both PARP-1 and the nucleolar marker fibrillarin was significantly lower than in controls. PARP-1 nucleolar expression emerges as a sensitive marker of functional changes in AD and suggests a novel role for PARP-1 dysregulation in AD pathology.

Modulatory profiling identifies mechanisms of small molecule-induced cell death.

Cell death is a complex process that plays a vital role in development, homeostasis, and disease. Our understanding of and ability to control cell death is impeded by an incomplete characterization of the full range of cell death processes that occur in mammalian systems, especially in response to exogenous perturbations. We present here a general approach to address this problem, which we call modulatory profiling. Modulatory profiles are composed of the changes in potency and efficacy of lethal compounds produced by a second cell death-modulating agent in human cell lines. We show that compounds with the same characterized mechanism of action have similar modulatory profiles. Furthermore, clustering of modulatory profiles revealed relationships not evident when clustering lethal compounds based on gene expression profiles alone. Finally, modulatory profiling of compounds correctly predicted three previously uncharacterized compounds to be microtubule-destabilizing agents, classified numerous compounds that act nonspecifically, and identified compounds that cause cell death through a mechanism that is morphologically and biochemically distinct from previously established ones.

Intra-procedural arrhythmia during cardiac catheterization: A systematic review of literature.

BACKGROUND: Cardiac catheterization is among the most performed medical procedures in the modern era. There were sporadic reports indicating that cardiac arrhythmias are common during cardiac catheterization, and there are risks of developing serious and potentially life-threatening arrhythmias, such as sustained ventricular tachycardia (VT), ventricular fibrillation (VF) and high-grade conduction disturbances such as complete heart block (CHB), requiring immediate interventions. However, there is lack of systematic overview of these conditions. AIM: To systematically review existing literature and gain better understanding of the incidence of cardiac arrhythmias during cardiac catheterization, and their impact on outcomes, as well as potential approaches to minimize this risk. METHODS: We applied a combination of terms potentially used in reports describing various cardiac arrhythmias during common cardiac catheterization procedures to systematically search PubMed, EMBASE and Cochrane databases, as well as references of full-length articles. RESULTS: During right heart catheterization (RHC), the incidence of atrial arrhythmias (premature atrial complexes, atrial fibrillation and flutter) was low (< 1%); these arrhythmias were usually transient and self-limited. RHC associated with the development of a new RBBB at a rate of 0.1%-0.3% in individuals with normal conduction system but up to 6.3% in individuals with pre-existing left bundle branch block. These patients may require temporary pacing due to transient CHB. Isolated premature ventricular complexes or non-sustained VT are common during RHC (up to 20% of cases). Sustained ventricular arrhythmias (VT and/or VF) requiring either withdrawal of catheter or cardioversion occurred infrequently (1%-1.3%). During left heart catheterizations (LHC), the incidence of ventricular arrhythmias has declined significantly over the last few decades, from 1.1% historically to 0.1% currently. The overall reported rate of VT/VF in diagnostic LHC and coronary angiography is 0.8%. The risk of VT/VF was higher during percutaneous coronary interventions for stable coronary artery disease (1.1%) and even higher for patients with acute myocardial infarctions (4.1%-4.3%). Intravenous adenosine and papaverine bolus for fractional flow reserve measurement, as well as intracoronary imaging using optical coherence tomography have been reported to induce VF. Although uncommon, LHC and coronary angiography were also reported to induce conduction disturbances including CHB. CONCLUSION: Cardiac arrhythmias are common and potentially serious complications of cardiac catheterization procedures, and it demands constant vigilance and readiness to intervene during procedures.

Biventricular Thrombi in a Patient With Heart Failure With Severely Reduced Ejection Fraction and Heterozygous Prothrombin 20210G/A and Homozygous Methylenetetrahydrofolate Reductase 677C/T Mutations.

Thrombus in the heart is known to be one of the many sequelae of anterior wall myocardial infarction, atrial fibrillation and coagulation disorders. However, biventricular thrombi are relatively rarely found, even in conditions with a high possibility of thrombus formation. We report the case of a 75-year-old-woman with newly diagnosed systolic heart failure secondary to a nonischemic cardiomyopathy, who was found to have large biventricular thrombi. Further coagulopathy work-up revealed that she was heterozygous for the prothrombin 20210G/A and homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C/T mutations. We, herein, review and discuss previous case reports and published literature regarding ventricular thrombosis and its treatment. To the best of our knowledge, this is the first case of biventricular thrombosis with prothrombin 20210G/A and MTHFR 677C/T mutations.

A Mild Version of Danon Disease Caused by a Newly Recognized Mutation in the Lysosome-associated Membrane Protein-2 Gene.

We present the case of a patient with dilated cardiomyopathy caused by a novel mutation in the lysosome-associated membrane protein-2 (LAMP-2) gene. Patients with pathogenic mutations of this gene typically suffer from Danon disease - a condition that leads to cognitive decline, severe skeletal myopathy, and severe hypertrophic cardiomyopathy. Our patient's presentation and clinical course, however, is different and much less severe than other patients with this disease. He did not suffer from neurologic and musculoskeletal complications. He is also possibly the longest-known survivor of this disease without a heart transplant. This disease is unfamiliar to many physicians, and our case highlights the importance of an awareness of this disorder, particularly because of its implications for both the patient and his family.