Coronary Microvascular Dysfunction: What Clinicians and Investigators Should Know.

PURPOSE OF REVIEW: Abnormal structure and function of the coronary microvasculature have been implicated in the pathophysiology of multiple cardiovascular disease processes. This article reviews recent research progress related to coronary microvascular dysfunction (CMD) and salient clinical takeaways. RECENT FINDINGS: CMD is prevalent in patients with signs and symptoms of ischemia and no obstructive epicardial coronary artery disease (INOCA), particularly in women. CMD is associated with adverse outcomes, including most frequently the development of heart failure with preserved ejection fraction. It is also associated with adverse outcomes in patient populations including hypertrophic cardiomyopathy, dilated cardiomyopathy, and acute coronary syndromes. In patients with INOCA, stratified medical therapy guided by invasive coronary function testing to define the subtype of CMD leads to improved symptoms. There are invasive and non-invasive methodologies to diagnose CMD that provide prognostic information and mechanistic information to direct treatment. Available treatments improve symptoms and myocardial blood flow; ongoing investigations aim to develop therapy to improve adverse outcomes related to CMD.

An abdominal skin lesion: to lump or split? a case presentation.

Syphilis has many atypical morphologies which can present a diagnostic challenge, especially in patients with HIV/AIDS who may have multiple concurrent conditions. We describe a 41-year-old man with recently diagnosed HIV who was admitted for acute right vision loss and a diffuse rash with involvement of the palms and soles. He received diagnoses of secondary syphilis and Kaposi sarcoma in the setting of AIDS. Examination revealed an unusual dark brown-to-purple umbilicated papule with a necrotic center on the abdomen, raising a diagnostic dilemma. Skin biopsy showed secondary syphilis, despite the concurrent diagnosis of Kaposi sarcoma. The patient was treated with antibiotic and antiretroviral therapy and symptoms resolved. This case aims to share the clinical reasoning behind diagnosing a patient with HIV/AIDS with multiple concurrent conditions and to raise awareness of the many atypical cutaneous manifestations of secondary syphilis.

Evaluation of Recurrent Takotsubo Syndrome.

Background: After an initial Takotsubo syndrome (TTS) event, there is growing recognition of adverse long-term outcomes, including recurrent TTS events. Recurrent events have been incompletely evaluated. Objectives: The objective of this study was to characterize recurrent TTS events and evaluate variables associated with recurrence. Methods: We studied 88 consecutive participants in the Cedars-Sinai Smidt Heart Institute Takotsubo Registry, an observational registry collecting retrospective and prospective data in TTS survivors. Detailed medical records are adjudicated. Standardized psychosocial questionnaires are administered remotely. Results: Of 88 participants with adjudicated TTS, 15 (17%) experienced at least 1 recurrent TTS event (median 3.30 years to first recurrent event, range 0.13-18.56 years). In 9 of these 15 participants, there were different patterns of wall motion abnormalities observed between events. The recurrence-free survival significantly differed based on the pattern of wall motion abnormalities at the index TTS event. Clinical, electrocardiographic, echocardiographic, and invasive data obtained at the index TTS event were similar between participants who went on to have at least 1 recurrent event and those who did not. Conclusions: Recurrent TTS episodes occurred in a significant proportion of cases, a median of 3.30 years after the index event. The recurrent episodes often had distinct triggers and different wall motion abnormalities compared to the index event. The wall motion pattern at the index event impacted the recurrence-free survival, though confirmatory studies are needed. TTS participants had a high rate of adverse psychosocial stress characteristics based on detailed questionnaires. (The Cedars-Sinai Smidt Heart Institute Takotsubo Registry & Proteomic Study; NCT03910569).

Predictors of All-Cause 30-Day Readmissions in Patients with Heart Failure at an Urban Safety Net Hospital: The Importance of Social Determinants of Health and Mental Health.

Introduction: Heart failure (HF) is a frequent cause of readmissions. Despite caring for underresourced patients and dependence on government funding, safety net hospitals frequently incur penalties for failing to meet pay-for-performance readmission metrics. Limited research exists on the causes of HF readmissions in safety net hospitals. Therefore, we sought to investigate predictors of 30-day all-cause readmission in HF patients in the safety net setting. Methods: We performed a retrospective chart review of patients admitted for HF from October 2018 to April 2019. We extracted data on demographics and medical comorbidities and performed patient-specific review of social determinants and mental health in 4 domains: race/ethnicity, housing status, substance use, and mental illness. Multivariable Poisson regression modeling was employed to evaluate associations with 30-day all-cause readmission. Results: The study population included 290 patients, among whom the mean age was 59 years and 71% (n = 207) were male; 42% (120) were Black/African American (AA), 22% (64) were Hispanic/Latino, and 96% (278) had public insurance; 28% (79) were not housed, 19% (56) had a diagnosis of mental illness, and active substance use was common. The 30-day readmission rate was 25.5% (n = 88). Factors that were associated with increased risk of readmission included self-identifying as Black/AA (relative risk 2.28, 95% confidence interval 1.00-5.20) or Hispanic/Latino (2.53, 1.07-6.00), experiencing homelessness (2.07, 1.21-3.56), living in a shelter (3.20, 1.27-8.02), or intravenous drug use (IVDU) (2.00, 1.08-3.70). Conclusion: Race/ethnicity, housing status, and substance use were associated with increased risk of 30-day all-cause readmission in HF patients in a safety net hospital. In contrast to prior studies, medical comorbidities were not associated with increased risk of readmission.

Effect of a Novel, Evidence-Based, Standardized Discharge Checklist on 30-Day All-Cause Readmissions in Patients Hospitalized for Heart Failure in an Urban Safety Net Hospital.

Safety net hospitals frequently incur financial penalties for high readmission rates. Heart failure (HF) is a common driver of readmissions, but effectively lowering readmission rates in patients with HF has proved challenging. There are few evidence-based interventions validated within safety net systems. Between October 2018 and April 2019, we implemented an evidence-based discharge checklist. We evaluated the hypothesis that it would reduce 30-day all-cause readmissions in patients admitted for HF at an urban safety net hospital. We retrospectively compared all-cause 30-day readmission rates between the cohort discharged using the checklist and historical controls. Demographics were similar between the intervention (n = 103) and control (n = 187) groups and reflected the diverse and vulnerable population cared for in the safety net. The mean age was 60 years, 71% were male, 42% were Black, 22% were Hispanic/Latinx, 28% were not housed, 35% used illicit stimulants, and 73% had a left ventricular ejection fraction ≤40%. Use of the checklist was associated with a 12.4% absolute reduction in the 30-day readmission rate (29.9% vs 17.5%, p = 0.02). The intervention group was more likely to be discharged on appropriate guideline-directed medical therapy for reduced systolic function, including ß blockers (93% vs 73%, p = 0.0004), angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (92% vs 66%, p <0.0001) and mineralocorticoid receptor antagonists (50% vs 27%, p = 0.0007). Multivariable analysis demonstrated that using the discharge checklist was associated with a lower risk of 30-day all-cause readmission (risk ratio 0.54, 0.33 to 0.90). Therefore, a low-cost, novel, evidence-based discharge checklist significantly reduced 30-day all-cause readmission rates in patients hospitalized for HF at a safety net hospital.

Sudden Cardiac Arrest Due to Ascending Aortic Thrombus Originating From Penetrating Aortic Ulcer.

Penetrating aortic ulcers typically occur in severely diseased vessels. We present the case of a 46-year-old woman, without extensive atherosclerosis, who had sudden cardiac arrest related to ischemia from a mobile intraluminal aortic thrombus adherent to a penetrating ulcer in the ascending aorta. (Level of Difficulty: Intermediate.).

Long-term outcomes of ablation for ventricular arrhythmias in mitral valve prolapse.

PURPOSE: Prior studies reporting efficacy of radiofrequency catheter ablation for complex ventricular ectopy in mitral valve prolapse (MVP) are limited by selective inclusion of bileaflet MVP, papillary muscle only ablation, or short-term follow-up. We sought to evaluate the long-term incidence of hemodynamically significant ventricular tachycardia (VT) or fibrillation (VF) in patients with MVP after initial ablation. METHODS: We studied consecutive patients with MVP undergoing ablation for complex ventricular ectopy between 2013 and 2017 at our institution. Of 580 patients with MVP, we included 15 (2.6%, 10 women; mean age 50 ± 14 years, 53% bileaflet) with complex ventricular ectopy treated with initial ablation. RESULTS: Over a median follow-up of 3406 (1875-6551) days or 9 years, 5 of 15 (33%) patients developed hemodynamically significant VT/VF after their initial ablation and underwent placement of an implantable cardioverter defibrillator (ICD). Three of 5 also underwent repeat ablations. Sustained VT was inducible prior to index ablation in all 5 who developed VT/VF, compared to none of the 10 patients who did not develop VT/VF after index ablation (p = 0.002). Complex ventricular ectopy at index ablation was multifocal in all 5 patients who underwent repeat intervention versus 4 of 10 patients (40%) who did not (p = 0.04). All 3 patients with subsequent VT/VF who underwent repeat ablation had a new clinically dominant focus of ventricular arrhythmia and 3 of the patients with ICD had appropriate VT/VF therapies. CONCLUSIONS: In the long term, a subset of MVP patients treated with ablation for ventricular arrhythmias, all with multifocal ectopy on initial EP study, develop hemodynamically significant VT/VF. Our findings suggest the progressive nature of ventricular arrhythmias in patients with MVP and multifocal ectopy.

Reopening of an obstructed third ventriculostomy: long-term success and factors affecting outcome in 215 infants.

OBJECT: The role of reopening an obstructed endoscopic third ventriculostomy (ETV) as treatment for ETV failure is not well defined. The authors studied 215 children with ETV closure who underwent successful repeat ETV to determine the indications, long-term success, and factors affecting outcome. METHODS: The authors retrospectively reviewed the CURE Children's Hospital of Uganda database from August 2001 through December 2012, identifying 215 children with failed ETV (with or without prior choroid plexus cauterization [CPC]) who underwent reopening of an obstructed ETV stoma. Treatment survival according to sex, age at first and second operation, time to failure of first operation, etiology of hydrocephalus, prior CPC, and mode of ETV obstruction (simple stoma closure, second membrane, or cisternal obstruction from arachnoid scarring) were assessed using the Kaplan-Meier survival method. Survival differences among groups were assessed using log-rank and Wilcoxon methods and a Cox proportional hazards model. RESULTS: There were 125 boys and 90 girls with mean and median ages of 229 and 92 days, respectively, at the initial ETV. Mean and median ages at repeat ETV were 347 and 180 days, respectively. Postinfectious hydrocephalus (PIH) was the etiology in 126 patients, and nonpostinfectious hydrocephalus (NPIH) in 89. Overall estimated 7-year success for repeat ETV was 51%. Sex (p = 0.46, log-rank test; p = 0.54, Wilcoxon test), age (< vs > 6 months) at initial or repeat ETV (p = 0.08 initial, p = 0.13 repeat; log-rank test), and type of ETV obstruction (p = 0.61, log-rank test) did not affect outcome for repeat ETV (p values ≥ 0.05, Cox regression). Those with a longer time to failure of initial ETV (> 6 months 91%, 3-6 months 60%, < 3 months 42%, p < 0.01; log-rank test), postinfectious etiology (PIH 58% vs NPIH 42%, p = 0.02; log-rank and Wilcoxon tests) and prior CPC (p = 0.03, log-rank and Wilcoxon tests) had significantly better outcome. CONCLUSIONS: Repeat ETV was successful in half of the patients overall, and was more successful in association with later failures, prior CPC, and PIH. Obstruction of the original ETV by secondary arachnoid scarring was not a negative prognostic factor, and should not discourage the surgeon from proceeding. Repeat ETV may be a more durable solution to failed ETV/CPC than shunt placement in this context, especially for failures at more than 3 months after the initial ETV. Some ETV closures may result from an inflammatory response that is less robust at the second operation.

Role of the CAI-1 fatty acid tail in the Vibrio cholerae quorum sensing response.

Quorum sensing is a mechanism of chemical communication among bacteria that enables collective behaviors. In V. cholerae, the etiological agent of the disease cholera, quorum sensing controls group behaviors including virulence factor production and biofilm formation. The major V. cholerae quorum-sensing system consists of the extracellular signal molecule called CAI-1 and its cognate membrane bound receptor called CqsS. Here, the ligand binding activity of CqsS is probed with structural analogues of the natural signal. Enabled by our discovery of a structurally simplified analogue of CAI-1, we prepared and analyzed a focused library. The molecules were designed to probe the effects of conformational and structural changes along the length of the fatty acid tail of CAI-1. Our results, combined with pharmacophore modeling, suggest a molecular basis for signal molecule recognition and receptor fidelity with respect to the fatty acid tail portion of CAI-1. These efforts provide novel probes to enhance discovery of antivirulence agents for the treatment of V. cholerae.

Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1α) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) is a principal regulator of mitochondrial biogenesis and oxidative metabolism. RESULTS: In this study, we examined whether PGC-1α plays a protective role in ALS by using a double transgenic mouse model where PGC-1α is over-expressed in an SOD1 transgenic mouse (TgSOD1-G93A/PGC-1α). Our results indicate that PGC-1α significantly improves motor function and survival of SOD1-G93A mice. The behavioral improvements were accompanied by reduced blood glucose level and by protection of motor neuron loss, restoration of mitochondrial electron transport chain activities and inhibition of stress signaling in the spinal cord. CONCLUSION: Our results demonstrate that PGC-1α plays a beneficial role in a mouse model of ALS, suggesting that PGC-1α may be a potential therapeutic target for ALS therapy.