Cardiology

Mogensen, U. M., L. Kober, S. L. Kristensen, P. S. Jhund, J. Gong, M. P. Lefkowitz, A. R. Rizkala, J. L. Rouleau, V. C. Shi, K. Swedberg, M. R. Zile, S. D. Solomon, M. Packer and J. J. V. McMurray (2017). “The effects of sacubitril/valsartan on coronary outcomes in paradigm-hf.” Am Heart J 188: 35-41.

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BACKGROUND: Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. METHODS AND RESULTS: We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization. At baseline, of 8399 patients, 3634 (43.3%) had a prior MI and 4796 (57.1%) had a history of any coronary artery disease. Among all patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73-0.87], P<.001), the broader composite (HR 0.83 [0.76-0.90], P<.001) and the coronary composite (HR 0.83 [0.75-0.92], P<.001). Although each of the components of the coronary composite occurred less frequently in the sacubitril/valsartan group, compared with the enalapril group, only CV death was reduced significantly. CONCLUSIONS: Compared with enalapril, sacubitril/valsartan reduced the risk of both the primary endpoint and a coronary composite outcome in PARADIGM-HF. Additional studies on the effect of sacubitril/valsartan on atherothrombotic outcomes in high-risk patients are merited.

Levitsky, J., R. N. Formica, R. D. Bloom, M. Charlton, M. Curry, J. Friedewald, J. Friedman, D. Goldberg, S. Hall, M. Ison, T. Kaiser, D. Klassen, G. Klintmalm, J. Kobashigawa, A. Liapakis, K. O’Conner, P. Reese, K. Shelat, D. Stewart, N. Terrault, N. Theodoropoulos, J. Trotter, E. Verna and M. Volk (2017). “The american society of transplantation consensus conference on the use of hepatitis c viremic donors in solid organ transplantation.” Am J Transplant: 2017 May [Epub ahead of print].

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The availability of direct acting antiviral agents for the treatment of hepatitis C virus (HCV) has resulted in a profound shift in the approach to the management of this infection. These changes have impacted the practice of solid organ transplantation by altering the framework by which patients with end stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provide the opportunity to explore their use in the setting of transplanting organs from HCV viremic patients into HCV non-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waiting list. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of utilizing organs for hepatitis C infected donors. In response to this rapidly changing practice and the need for both urgent scientific study and consensus on how these investigations should proceed, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the future study of utilizing HCV viremic organs in solid organ transplantation.

Jetelina, K. K., J. M. Reingle Gonzalez, C. V. R. Brown, M. L. Foreman and C. Field (2017). “Acute alcohol use, history of homelessness, and intent of injury among a sample of adult emergency department patients.” Violence Vict: 2017 May [Epub ahead of print].

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BACKGROUND: The literature is clear that adults who are currently homeless also have higher rates of intentional injuries, such as assault and suicide attempts. No study has assessed whether intentional injuries are exacerbated because of substance use among adults with a history of homelessness. METHODS: Data were obtained from a cohort of adults admitted to 3 urban emergency departments (EDs) in Texas from 2007 to 2010 (N = 596). Logistic regression analyses were used to determine whether a history of homelessness was associated with alcohol use at time of injury in intentional violent injuries (gunshot, stabbing, or injury consistent with assault). RESULTS: 39% adults with a history of homelessness who were treated at trauma centers for a violent injury. Bivariate analyses indicated that adults who had ever experienced homelessness have 1.67 increased odds, 95% confidence interval (CI) [1.11, 2.50], of any intentional violent injury and 1.95 increased odds (95% CI [1.12, 3.40]) of a stabbing injury than adults with no history of homelessness. CONCLUSIONS: Adults who experienced homelessness in their lifetime were more likely to visit EDs for violencerelated injuries. Given our limited knowledge of the injuries that prompt ED use by currently homeless populations, future studies are needed to understand the etiology of injuries, and substance-related injuries specifically, among adults with a history of homelessness.

Howden, E. J., C. East, J. S. Lawley, A. S. L. Stickford, M. Verhees, Q. Fu and B. D. Levine (2017). “Integrative blood pressure response to upright tilt post renal denervation.” Am J Hypertens 30(6): 632-641.

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BACKGROUND: Whether renal denervation (RDN) in patients with resistant hypertension normalizes blood pressure (BP) regulation in response to routine cardiovascular stimuli such as upright posture is unknown. We conducted an integrative study of BP regulation in patients with resistant hypertension who had received RDN to characterize autonomic circulatory control. METHODS: Twelve patients (60 +/- 9 [SD] years, n = 10 males) who participated in the Symplicity HTN-3 trial were studied and compared to 2 age-matched normotensive (Norm) and hypertensive (unmedicated, HTN) control groups. BP, heart rate (HR), cardiac output (Qc), muscle sympathetic nerve activity (MSNA), and neurohormonal variables were measured supine, and 30 degrees (5 minutes) and 60 degrees (20 minutes) head-up-tilt (HUT). Total peripheral resistance (TPR) was calculated from mean arterial pressure and Qc. RESULTS: Despite treatment with RDN and 4.8 (range, 3-7) antihypertensive medications, the RDN had significantly higher supine systolic BP compared to Norm and HTN (149 +/- 15 vs. 118 +/- 6, 108 +/- 8 mm Hg, P < 0.001). When supine, RDN had higher HR, TPR, MSNA, plasma norepinephrine, and effective arterial elastance compared to Norm. Plasma norepinephrine, Qc, and HR were also higher in the RDN vs. HTN. During HUT, BP remained higher in the RDN, due to increases in Qc, plasma norepinephrine, and aldosterone. CONCLUSION: We provide evidence of a possible mechanism by which BP remains elevated post RDN, with the observation of increased Qc and arterial stiffness, as well as plasma norepinephrine and aldosterone levels at approximately 2 years post treatment. These findings may be the consequence of incomplete ablation of sympathetic renal nerves or be related to other factors.

Nasir, J. M., W. Pomeroy, A. Marler, M. Hann, T. Baykaner, R. Jones, R. Stoll, K. Hursey, A. Meadows, J. Walker and S. Kindsvater (2017). “Predicting determinants of atrial fibrillation or flutter for therapy elucidation in patients at risk for thromboembolic events (predate af) study.” Heart Rhythm: 2017 May [Epub ahead of print].

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BACKGROUND: Atrial fibrillation (AF) is the most common clinically significant cardiac rhythm disorder. There is considerable interest in screening for AF, as it is a leading cause of stroke, and oral anticoagulants (OACs) have been shown to significantly reduce the risk of stroke in patients with AF. Improved screening for AF with subsequent treatment may help improve long-term outcomes, but the optimal patient population and screening intensity are unknown. OBJECTIVES: In this study, we prospectively evaluated the use of the CHA2DS2-VASc score for the prediction of new-onset AF using insertable cardiac monitors (ICMs) and examined whether this screening led to the initiation of OAC therapy. METHODS: We enrolled 245 subjects with no history of AF and CHA2DS2-VASc score >/=2 to be screened for AF with an ICM. The ICMs were programmed to record AF episodes >/=6 minutes in duration. Subjects were followed for 18 months with monthly remote interrogations and all events adjudicated by cardiologists. In subjects diagnosed with AF, medical records were reviewed to determine subsequent care. RESULTS: During a mean follow-up of 451 +/- 185 days, the incidence of AF was 22.4% (95% confidence interval 17.2%-27.7%) with a mean time to detection of 141.3 +/- 139.5 days. Among subjects newly diagnosed with AF, 76.4% were prescribed anticoagulation with either a novel OAC (n = 38) or warfarin (n = 4). CONCLUSION: In this large prospective cohort of subjects with CHA2DS2-VASc scores >/=2, 22.4% were newly diagnosed with AF and the majority of these subjects were given OACs, suggesting a potential role of ICMs in AF screening.