A polyglutamine expansion disease protein sequesters PTIP to attenuate DNA repair and increase genomic instability.

Glutamine (Q) expansion diseases are a family of degenerative disorders caused by the lengthening of CAG triplet repeats present in the coding sequences of seemingly unrelated genes whose mutant proteins drive pathogenesis. Despite all the molecular evidence for the genetic basis of these diseases, how mutant poly-Q proteins promote cell death and drive pathogenesis remains controversial. In this report, we show a specific interaction between the mutant androgen receptor (AR), a protein associated with spinal and bulbar muscular atrophy (SBMA), and the nuclear protein PTIP (Pax Transactivation-domain Interacting Protein), a protein with an unusually long Q-rich domain that functions in DNA repair. Upon exposure to ionizing radiation, PTIP localizes to nuclear foci that are sites of DNA damage and repair. However, the expression of poly-Q AR sequesters PTIP away from radiation-induced nuclear foci. This results in sensitivity to DNA-damaging agents and chromosomal instabilities. In a mouse model of SBMA, evidence for DNA damage is detected in muscle cell nuclei and muscular atrophy is accelerated when one copy of the gene encoding PTIP is removed. These data provide a new paradigm for understanding the mechanisms of cellular degeneration observed in poly-Q expansion diseases.

Percutaneous Vacuum-Assisted Aspiration of Mobile Caseous Mitral Annulus Calcification.

A 68-year-old woman presented with an incidentally found intracardiac mass. Transesophageal echocardiography (TEE) showed a 26 × 8 mm mobile mass attached to a calcified posterolateral mitral annulus. The mass was removed with a commercially available percutaneous catheter system using cerebral embolic protection and TEE guidance. The pathologic examination showed caseous mitral annular calcification.

Safe Triage of STEMI Patients to General Telemetry Units After Successful Primary Percutaneous Coronary Intervention.

OBJECTIVE: To analyze outcomes of patients with ST-segment elevation myocardial infarction (STEMI) after successful primary percutaneous coronary intervention (PCI) triaged to the cardiac intensive care unit (CICU) vs a general telemetry unit by a Zwolle risk score-based algorithm. METHODS: We introduced a quality improvement protocol in 2014 encouraging admission of STEMI patients with Zwolle score of 3 or less to general telemetry units unless they were hemodynamically unstable. We subsequently conducted a retrospective single-center cohort study of consecutive STEMI patients who had undergone primary PCI from January 1, 2014, to December 31, 2018. Outcomes studied include immediate complications, need for urgent unplanned intervention, need for CICU care, length of hospitalization, and survival. RESULTS: We identified 547 patients, 406 with a Zwolle score of 3 or less. Of these, 192 (47.3%) were admitted to general telemetry and 214 (52.7%) to the CICU. Reasons for CICU admission included persistent chest pain, late presentation, and procedural complications. The average hospital length of stay was 2.1±1.4 days for non-CICU patients and 3.3±2.8 days for low-risk CICU patients (P<.001). Two patients initially admitted to general telemetry required transfer to the CICU. There were 26 patients who required unplanned cardiovascular intervention within 30 days, 5 from the general telemetry unit; 540 patients survived to discharge. One in-hospital death occurred among those initially triaged to the general telemetry unit, and this was due to a noncardiac cause. CONCLUSION: A Zwolle score-based algorithm can be used to safely triage post-PCI STEMI patients to a general telemetry unit.

Correlation of Intravascular Ultrasound and Instantaneous Wave-Free Ratio in Patients With Intermediate Left Main Coronary Artery Disease.

BACKGROUND: There is great degree of interobserver variability in the visual angiographic assessment of left main coronary disease (LMCD). Fractional flow reserve and intravascular ultrasound are often used in this setting. The use of instantaneous wave-free ratio (iFR) for evaluation of LMCD has not been well studied. The aim of this study is to evaluate the use of iFR in the assessment of angiographically intermediate LMCD. METHODS: This is an international multicenter retrospective observational study of patients who underwent both iFR and intravascular ultrasound evaluation for angiographically intermediate LMCD. An independent core laboratory performed blinded off-line analysis of all intravascular ultrasound data. A minimum lumen area of 6 mm2 was used as the cutoff for significant disease. RESULTS: One hundred twenty-five patients (mean age, 68.4±9.5 years, 84.8% male) were included in this analysis. Receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.77 (77% sensitivity, 66% specificity; P<0.0001). Among the 69 patients without ostial left anterior descending artery or left circumflex artery disease, receiver operating curve analysis showed that an iFR of ≤0.89 identified minimum lumen area <6 mm2 with an area under the curve of 0.84 (70% sensitivity, 84% specificity; P<0.0001). The correlation was not significantly different when the body surface area was considered. CONCLUSIONS: In this study, in patients with intermediate LMCD, iFR of ≤0.89 correlates with intravascular ultrasound minimum lumen area <6 mm2 regardless of body surface area. The current study supports the use of iFR for the evaluation of intermediate LMCD.

Preemptive Alcohol Septal Ablation to Prevent Left Ventricular Outflow Tract Obstruction after Transseptal Mitral Valve in Valve.

Acute obstruction of the neo-LVOT is a major and potentially fatal complication of transcatheter mitral valve implantation. Patients at high risk of this complication can be identified preoperatively with cardiac CT. We describe a case of a patient identified as high risk for developing neo-LVOT obstruction, who was preemptively treated with alcohol septal ablation prior to successful valve implantation.

Anatomic Considerations Relevant to Atrial and Ventricular Arrhythmias.

Knowledge of relevant cardiac anatomy is crucial in understanding the pathophysiology and treatment of arrhythmias, and helps avoid potential complications in mapping and ablation. This article explores the anatomy, relevant to electrophysiologists, relating to atrial flutter and atrial fibrillation, ventricular tachycardia relating to the outflow tracts as well as endocardial structure, and also epicardial considerations for mapping and ablation.

A Dangerous Dilemma: Thrombus in Transit During Pregnancy.

Pregnancy is associated with venous thromboembolism. Occasionally, thrombus can become entrapped across a patent foramen ovale, with risk of systemic embolism. This report presents a case of a pregnant woman who had thrombus in transit diagnosed by echocardiography, which was successfully removed by surgical thrombectomy. (Level of Difficulty: Intermediate.).

Fundamentals of Cardiac Mapping.

To characterize cardiac activity and arrhythmias, electrophysiologists can record the electrical activity of the heart in relation to its anatomy through a process called cardiac mapping (electroanatomic mapping, EAM). A solid understanding of the basic cardiac biopotentials, called electrograms, is imperative to construct and interpret the cardiac EAM correctly. There are several mapping approaches available to the electrophysiologist, each optimized for specific arrhythmia mechanisms. This article provides an overview of the fundamentals of EAM.

Stable Ischemic Heart Disease in Women.

PURPOSE OF THE REVIEW: Paradoxically, although women have a lower burden of coronary atherosclerosis, they experience more symptoms, more frequent hospitalizations, and a worse prognosis compared to men. This is in part due to biological variations in pathophysiology between the two sexes, and in part related to inadequate understanding of these differences, subconscious referral bias, and suboptimal application of existing women-specific guidelines. We sought to review the contemporary literature and provide an update on risk assessment, diagnosis, and management of IHD in women. RECENT FINDINGS: IHD in women is often secondary to diffuse non-obstructive atherosclerosis, coronary spasm, inflammation, and endothelial and microvascular dysfunction, and less commonly due to the male pattern of flow-limiting epicardial stenosis. Both IHD patterns likely represent sex-specific manifestations of the same disease process. Additionally, there is a differential expression of risk factors and symptoms between men and women. Application of male-pattern IHD risk factors and presentation to women contributes to under-recognition, under-testing, and under-treatment of IHD in women compared to men. Traditional diagnostic evaluation has focused on detection of epicardial disease, amenable to revascularization. Our improved understanding of sex-specific pathophysiology of IHD has enabled us to also develop tools for detection of microvascular disease. Advances in stress MRI, flow quantification on stress PET, and provocative invasive angiography have filled this void and offer important diagnostic and prognostic information. Despite our improved understanding of sex-specific differences in presentation, risk factors, pathophysiology, diagnostic testing, and management strategies of IHD, women with IHD continue to experience worse outcomes than men. This disparity underscores the need for improved research and understanding of biological sex differences, elimination of subconscious gender bias in referral patterns, and improved application of existing research into clinical practice.