Hepatitis C Virus Reinfection Among Men Who Have Sex With Men With HIV in New York City.

BACKGROUND: Hepatitis C virus (HCV) reinfection rates are substantially higher than primary infection rates among men who have sex with men (MSM) with human immunodeficiency virus (HIV) in European cohorts. The behaviors mediating this high rate of transmission among MSM are poorly characterized. METHODS: We performed a prospective cohort study in New York City (NYC) of MSM with HIV who cleared HCV to determine the incidence of and risk factors for HCV reinfection. We assessed the risk behaviors for primary HCV in NYC: receipt of semen in the rectum, and sexualized methamphetamine use, along with route of use. Multivariable analysis was performed with Andersen-Gill extension of the Cox proportional hazards model. RESULTS: From 2000 through 2018, among 304 MSM with HIV who cleared HCV, 42 reinfections occurred over 898 person-years, for an incidence rate of 4.7 per 100 person-years. Assessing 1245 postclearance visits, only receipt of semen into the rectum was associated with reinfection (hazard ratio, 9.7 [95% confidence interval: 3.3-28.3], P < .001); methamphetamine use was not. CONCLUSIONS: The high HCV reinfection rate over almost 2 decades demonstrates that sexual transmission of HCV is not inefficient or unusual and that direct-acting antiviral treatment is not sufficient for HCV elimination among MSM in NYC. The contrasts between both the rates of and risk factors for primary and HCV reinfection suggest that HCV prevalence is highly heterogenous among sexual networks and that sexualized methamphetamine use, rather than mediating transmission, is instead a surrogate marker for the highest HCV prevalence networks. As neither condoms nor treatment have been successful strategies for HCV prevention in NYC, novel interventions are needed to stem this sexually transmitted HCV epidemic.

Sexually Acquired Hepatitis C Infection in HIV-Uninfected Men Who Have Sex With Men Using Preexposure Prophylaxis Against HIV.

Sexually acquired hepatitis C virus (HCV) infections among human immunodeficiency virus (HIV)-uninfected men who have sex with men (MSM) have been rare. With the introduction of preexposure prophylaxis (PrEP) against HIV, we hypothesized that these infections would increase. Between 2013 and 2018, we diagnosed 15 likely sexually acquired HCV infections among 14 MSM using PrEP. Most (87%) were asymptomatic, detected by routine alanine transaminase (ALT) or HCV monitoring. Half reported increasing sex partners and drug use after starting PrEP; 5 reported injection of methamphetamine. Interventions are needed to prevent sexually acquired HCV infections by MSM using PrEP. Centers for Disease Control and Prevention guidelines for monitoring during PrEP should include regular ALT and HCV testing.

Effects of pinacidil on electrophysiological properties of epicardial border zone of healing canine infarcts: possible effects of K(ATP) channel activation.

BACKGROUND: K(ATP) channels, activated by ischemia, participate in the arrhythmogenic response to acute coronary occlusion. The function of these channels in border zones of healing infarcts, where arrhythmias also arise, has not been investigated. Do these channels remain maximally activated during infarct healing, or do they downregulate after a period of time? Both might preclude further activation. METHODS AND RESULTS: Myocardial infarction was produced in dogs by ligation of the left anterior descending coronary artery. Impulse propagation in the epicardial border zone (EBZ) of 4-day-old healing infarcts was mapped during administration of pinacidil, a K(ATP) channel activator, directly into the EBZ coronary blood supply. Pinacidil restored conduction and excitability when the EBZ was initially inexcitable and had large regions of block (6 of 8 experiments). This allowed reentrant circuits to form in the EBZ, causing tachycardia (4 of 8 experiments). In hearts with an initially excitable EBZ, pinacidil shortened the effective refractory period and abolished conduction block at short cycle lengths (7 experiments). This effect prevented initiation of reentry (1 of 2 experiments). CONCLUSIONS: The response to pinacidil indicates that K(ATP) channels in the EBZ remain functional and can be activated to influence electrophysiological properties and arrhythmogenesis.

Left ventricular catheter ablation using direct, intramural ethanol injection in swine.

INTRODUCTION: Limitations in lesion volume and particularly lesion depth may negatively effect the efficacy of catheter ablation procedures using radiofrequency energy. This study evaluated the safety and efficacy of myocardial ablation using direct intramural injection of ethanol with a novel injection catheter system. METHODS: Left ventricular lesions were performed in 9 male swine (80-85 pounds); two animals were studied 6 weeks following anterior infarction produced by agarose gel embolization. An 8 Fr deflectable catheter equipped with a 27 gauge adjustable depth, retractable needle was directed to the LV using a retrograde aortic approach. Lesion deployment was guided by fluoroscopy and intracardiac echocardiography (ICE). Lesion characteristics were assessed with ICE imaging and pathologic analysis. RESULTS: Ethanol lesions were confined to the tissue directly adjacent to the injection port. Lesions were intramural with no evidence of overlying thrombus. Lesions delivered with a single port injection needle in normal myocardium (n = 24) averaged 1910 +/- 1066 mm(3) with a depth of 8.9 +/- 3.3 mm. Lesions directed to infarct border zones (n = 4) averaged 929 +/- 882 mm(3) with a depth of 4.3 +/- 2.8 mm. Lesions were immediately evident on ICE imaging, and were visualized by increased echo density and tissue swelling. Pathological analysis revealed homogenous lesions with intramural hemorrhage and contraction band necrosis. CONCLUSIONS: Myocardial catheter ablation using direct ethanol injection is feasible, and relatively large and deep intramural lesions can be delivered, even in the infarct border zone. This technique may prove useful in ablation of arrhythmia substrates that are deep to the endocardial surface.

Multiplane Transesophageal and Intracardiac Echocardiography in Large Swine: Imaging Technique, Normal Values, and Research Applications.

Transthoracic echocardiographic imaging has been difficult to attain in the swine model. This study: (1) compares multiplane transesophageal echocardiography (TEE) with single plane TEE and intracardiac catheter echocardiography (ICE) for imaging of the swine cardiovascular system; and (2) defines normal values using these techniques in a closed chest large swine model (n = 24, body weight 50-114 kg). Multiplane TEE increased success rate over the single plane (the variable plane array only at 0 degrees ) TEE (P < 0.01) for imaging the left ventricular (LV) long-axis view (100% vs 50%), LV outflow tract (100% vs 33%), right atrium and its appendage (79% vs 33%), ascending aorta (100% vs 58%), and aortic arch (100% vs 17%). TEE-derived normal values at end-diastole (ED) and end-systole (ES) were: LV internal diameter (ID) = 49 +/- 3 mm (ED) and 33 +/- 4 mm (ES); LV wall thickness = 7 +/- 1 mm (ED); right ventricular (RV) ID = 24 +/- 4 mm (ED); RV wall thickness = 4 +/- 2 mm (ED); left atrial ID = 48 +/- 6 mm (ES); aortic root ID = 26 +/- 3 mm (ES); LV volume = 157 +/- 49 ml (ED) and 57 +/- 22 ml (ES). Baseline LV ejection fraction (64% +/- 6%), Doppler-derived stroke volume (86 +/- 14 ml), and cardiac index (107 ml/min per kg) were determined. Basal normal values, except for an elevated cardiac index in swine, are comparable to those reported for human adults. Multiplane TEE provided better overall cardiac imaging than did single plane TEE. ICE provided higher resolution imaging of individual cardiac chambers and structures when the ultrasound catheter was introduced into the right or left heart, but whole heart imaging was limited by ultrasound penetration at 12.5 MHz. Normal indices of chamber size and function provide a reference for the physiological significance of induced pathological states in this relevant animal model.