@article{690546,

title = {Prognostic Impact of Cardiovascular versus Noncardiovascular Hospitalizations in Heart Failure with Preserved Ejection Fraction: Insights from TOPCAT},

author = {Ebrahim Barkoudah and Brian L Claggett and Eldrin F Lewis and Eileen O’Meara and Nadine Clausell and Rafael Diaz and Jerome L Fleg and Bertram Pitt and Jean L Rouleau and Scott D Solomon and Marc A Pfeffer and Akshay S Desai},

doi = {10.1016/j.cardfail.2022.05.004},

issn = {1532-8414},

year  = {2022},

date = {2022-05-01},

journal = {J Card Fail},

abstract = {BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) are commonly admitted to the hospital for both cardiovascular (CV) and noncardiovascular (non-CV) reasons. The prognostic implications of non-CV hospitalizations in this population are not well understood. In this study, we aimed to examine the prognostic implications of hospitalizations due to CV and non-CV reasons in a HFpEF population. METHODS AND RESULTS: The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) randomized 3,445 stable outpatients with chronic HF with left ventricular ejection fraction >=45% and either prior hospitalization for HF or elevated natriuretic peptides to treatment with spironolactone or placebo. Hospitalizations for any cause were reported by investigators during study follow-up and characterized according to prespecified category causes. This analysis focused on the subset of TOPCAT participants enrolled in the Americas (N=1,767), in which 2,973 hospitalizations were observed in 1,062 subjects (60%) over a mean follow-up of 3.3 years of study follow-up, of which 1,474 (49%) were ascribed to CV causes. Among 1,056 first hospitalizations, 478 (45%) were for CV reasons and 578 (55%) for non-CV reasons. Mortality rates were lowest for participants not hospitalized during the trial (3.2 per 100 patient-years (PY)), but similarly elevated following first hospitalization for CV and non-CV reasons (11.0 per 100 PY vs. 12.6 per 100 PY, respectively},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{690548,

title = {Occam’s Razor for Severe B12 Deficiency},

author = {Carson Moss and Deepa T Patil and Nathan T Connell and Rebecca L Zon and Ebrahim Barkoudah},

doi = {10.1016/j.amjmed.2022.01.039},

issn = {1555-7162},

year  = {2022},

date = {2022-02-01},

journal = {Am J Med},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{690547,

title = {Utilization of a National Writing Challenge to Promote Scholarly Work: A Pilot Study},

author = {Angela Keniston and Maria Frank and Lauren McBeth and Ebrahim Barkoudah and Juliessa Pavon and Nidhi Rohatgi and Valerie Vaughn and Sanjay Bhandari and Marisha Burden},

doi = {10.7759/cureus.21935},

issn = {2168-8184},

year  = {2022},

date = {2022-02-01},

journal = {Cureus},

volume = {14},

number = {2},

pages = {e21935},

abstract = {Background Hospitalists value mentorship and scholarly work, yet often struggle to find time and mentors amid busy clinical workloads. Objective To help catalyze writing for hospitalists nationally, we created a Writing Challenge, where we asked hospitalists to commit to the goal of writing 400 words a day, four days a week, for four weeks. Methods Prospective, programmatic evaluation with daily logs followed by a survey at the completion of the project.~The four-week Writing Challenge occurred between June 7 and July 5, 2021.~Email invitations to participate in the challenge were disseminated to peer networks, and the challenge was promoted using social media.~Participants agreed to attempt to write 400 words per day, four days per week, for four weeks. Results Seventy-four individuals from 28 institutions registered for the Writing Challenge, with 36 (49%) participating in the challenge by logging their writing.~Participants wrote an average of 4,372~+/- 4,324 words during the challenge. Sixty-eight percent of the participants reported that their amount of writing increased during the challenge and 50% of the participants stated they planned to publish their work, though many participants (46%) reported struggling to write each day. Conclusions The Writing Challenge is one way to generate increased writing and may result in increased scholarly output for academic hospitalists.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{684252,

title = {Application of optical coherence tomography angiography macular analysis for systemic hypertension. A systematic review and meta-analysis},

author = {Rita Anjos and André Ferreira and Ebrahim Barkoudah and Brian Claggett and Luis Abegão Pinto and Ana Miguel},

doi = {10.1093/ajh/hpab172},

issn = {1941-7225},

year  = {2021},

date = {2021-10-01},

journal = {Am J Hypertens},

abstract = {BACKGROUND: Microvascular rarefaction due to hypertension has been linked to disease severity and end-organ complications. Optical coherence tomography angiography (OCTA) has been explored as a potential tool to evaluate the retinal microvascular network in hypertensive patients. 

METHODS: PubMed, Scopus, Web of Science and Cochrane were systematically searched to 10th of September of 2021, along with a manual search. Studies that used OCTA as a primary diagnostic method to evaluate the macular microvasculature of hypertensive patients were included. Meta-analysis was performed using a random-effects model. Primary outcomes were macular vessel density and foveal avascular zone at the superficial and deep capillary plexus. RESULTS: Of 947 screened articles, 9 were found eligible for qualitative and for quantitative analysis. Vessel density in hypertensive patients was reduced when compared to controls in the fovea (0.93, 95% CI 0.87 to 0.99},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669784,

title = {Increased short-term risk of cardiovascular events in inflammatory rheumatic diseases: results from a population-based cohort},

author = {Vital Da Silva Domingues and Ana M Rodrigues and Sara S Dias and Luís Delgado and Ebrahim Barkoudah and Jaime Branco and Helena Canhão},

doi = {10.1007/s00296-020-04754-7},

issn = {1437-160X},

year  = {2021},

date = {2021-02-01},

journal = {Rheumatol Int},

volume = {41},

number = {2},

pages = {311-318},

abstract = {Cardiovascular diseases represent the first cause of death globally. Inflammatory rheumatic disease (IRMD) patients, due to their lifelong inflammatory status, are at increased risk of developing premature cardiovascular disease. We aimed to assess the risk for cardiovascular events (CVE) in a population-based study. We followed 10,153 adults from the EpiDoC Cohort, a large Portuguese population-based prospective study (2011-2016). IRMD patients were identified at baseline and followed during 5~years. CVE were defined as a composite of self-reported myocardial infarction or angina pectoris, arrhythmias, valvular disease, stroke or transient ischemic attack and peripheral artery disease. Statistical analysis was performed by utilizing multivariate logistic regression and goodness-of-fit and area under ROC curve. At baseline, IRMD patients had similar age as the non-IRMD participants (mean age 55 vs 53~years-old; 72.1% female); dyslipidaemia and sedentary lifestyle were more common (40.7% vs 31.4%},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669780,

title = {Perianal warts as a risk marker for anal high-risk-human papillomavirus (HPV) detection and HPV-associated diseases},

author = {A Cerejeira and S Cunha and R Coelho and G Macedo and E Barkoudah and F Azevedo and C Lisboa},

doi = {10.1111/jdv.16834},

issn = {1468-3083},

year  = {2020},

date = {2020-11-01},

journal = {J Eur Acad Dermatol Venereol},

volume = {34},

number = {11},

pages = {2613-2619},

abstract = {BACKGROUND: Genital warts are the most common sexually transmitted infection (STI) and are caused by human papillomavirus (HPV). Persistent anal infection by oncogenic genotypes of HPV is a determinant for anal cancer. Currently, anal cancer screening is not widely implemented. 

OBJECTIVES: Our aim is to evaluate the role of perianal warts as a risk marker for anal high-risk (HR) HPV detection and anal dysplasia. 

METHODS: In this observational, retrospective, cohort study of attendees of a STI outpatient clinic between January 2010 and June 2018, all human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) who performed anal cytology, anal HPV DNA detection and anoscopy were included. A comparison was made between patients with and without perianal warts. Primary endpoint: proportion of patients with an abnormal anal cytology. Secondary endpoints: proportion of patients with (i) anal HR-HPV detection; (ii) anal HPV 16 detection; (iii) abnormal anal biopsy; and (iv) anal high-grade squamous intraepithelial lesion (HSIL). RESULTS: Seventy-eight individuals were included: 39 with perianal warts and 39 without perianal warts. Subjects with perianal warts more frequently had an abnormal anal cytology (71.8% vs. 38.5%; P~=~0.003). This group also had a higher rate of anal HPV 16 detection (38.5% vs. 12.8%; P~=~0.01). No differences were detected in the proportion of patients with anal HR-HPV detection, with an abnormal anal biopsy or with anal HSIL. Perianal warts was an independent risk factor for an abnormal anal cytology (OR: 7.2) and for anal HPV 16 detection (OR: 6.7). 

CONCLUSION: Given the high risk of anal cancer in HIV-positive MSM, effective screening strategies are greatly needed. This study suggests that the presence of perianal warts is a suitable risk marker for anal HPV 16 detection and anal dysplasia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669779,

title = {Perianal warts as a risk marker for anal high-risk-human papillomavirus (HPV) detection and HPV-associated diseases},

author = {A Cerejeira and S Cunha and R Coelho and G Macedo and E Barkoudah and F Azevedo and C Lisboa},

doi = {10.1111/jdv.16834},

issn = {1468-3083},

year  = {2020},

date = {2020-11-01},

journal = {J Eur Acad Dermatol Venereol},

volume = {34},

number = {11},

pages = {2613-2619},

abstract = {BACKGROUND: Genital warts are the most common sexually transmitted infection (STI) and are caused by human papillomavirus (HPV). Persistent anal infection by oncogenic genotypes of HPV is a determinant for anal cancer. Currently, anal cancer screening is not widely implemented. 

OBJECTIVES: Our aim is to evaluate the role of perianal warts as a risk marker for anal high-risk (HR) HPV detection and anal dysplasia. 

METHODS: In this observational, retrospective, cohort study of attendees of a STI outpatient clinic between January 2010 and June 2018, all human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) who performed anal cytology, anal HPV DNA detection and anoscopy were included. A comparison was made between patients with and without perianal warts. Primary endpoint: proportion of patients with an abnormal anal cytology. Secondary endpoints: proportion of patients with (i) anal HR-HPV detection; (ii) anal HPV 16 detection; (iii) abnormal anal biopsy; and (iv) anal high-grade squamous intraepithelial lesion (HSIL). RESULTS: Seventy-eight individuals were included: 39 with perianal warts and 39 without perianal warts. Subjects with perianal warts more frequently had an abnormal anal cytology (71.8% vs. 38.5%; P~=~0.003). This group also had a higher rate of anal HPV 16 detection (38.5% vs. 12.8%; P~=~0.01). No differences were detected in the proportion of patients with anal HR-HPV detection, with an abnormal anal biopsy or with anal HSIL. Perianal warts was an independent risk factor for an abnormal anal cytology (OR: 7.2) and for anal HPV 16 detection (OR: 6.7). 

CONCLUSION: Given the high risk of anal cancer in HIV-positive MSM, effective screening strategies are greatly needed. This study suggests that the presence of perianal warts is a suitable risk marker for anal HPV 16 detection and anal dysplasia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669766,

title = {COVID-19 and Rhabdomyolysis},

author = {Nicholas R Chedid and Swalpa Udit and Zhabiz Solhjou and Maria Y Patanwala and Alice M Sheridan and Ebrahim Barkoudah},

doi = {10.1007/s11606-020-06039-y},

issn = {1525-1497},

year  = {2020},

date = {2020-10-01},

journal = {J Gen Intern Med},

volume = {35},

number = {10},

pages = {3087-3090},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669767,

title = {Caught in a Flare},

author = {Alisa A Mueller and Anand Vaidya and Laura L Tarter and Joshua P Klein and Ebrahim Barkoudah},

doi = {10.1056/NEJMimc2003325},

issn = {1533-4406},

year  = {2020},

date = {2020-08-01},

journal = {N Engl J Med},

volume = {383},

number = {7},

pages = {e48},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669773,

title = {Forensic Medical Evaluation of Children Seeking Asylum: A Guide for Pediatricians},

author = {Matthew G Gartland and Roya Ijadi-Maghsoodi and Minal Giri and Sarah Messmer and Katherine Peeler and Ashley Barkoudah and Sural Shah},

doi = {10.3928/19382359-20200421-01},

issn = {1938-2359},

year  = {2020},

date = {2020-05-01},

journal = {Pediatr Ann},

volume = {49},

number = {5},

pages = {e215-e221},

abstract = {Applications for asylum in the United States have increased significantly in the past decade, including those by children fleeing persecution. Pediatricians may serve as a resource for children seeking asylum by participating in specialized training and performing forensic medical evaluations for use in the legal process. A forensic medical evaluation comprises an interview to elicit a narrative of reported abuse, a psychological assessment, and/or a medical assessment. Evaluators document an impression of the consistency of medical and psychological findings with the trauma, which forms the legal basis for a child’s asylum claim. This article provides guidance to pediatrician evaluators with an emphasis on an age- and development-specific approach to a forensic medical evaluation of children seeking asylum. Collaboration with primary care pediatricians and community partners about asylum evaluations is important to building support for immigrant children who have experienced trauma. [Pediatr Ann. 2020;49(5):e215-e221.].},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669771,

title = {The Many Shades of Dyspnea},

author = {Ebrahim Barkoudah and Christopher L Roy},

doi = {10.1016/j.amjmed.2017.08.031},

issn = {1555-7162},

year  = {2018},

date = {2018-01-01},

journal = {Am J Med},

volume = {131},

number = {1},

pages = {e5-e6},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532946,

title = {Maximum renal responses to renin inhibition in healthy study participants: VTP-27999 versus aliskiren},

author = {Ebrahim Barkoudah and Bibi S Thiel and Naomi DL Fisher and Richard A Gregg and A. H. Jan Danser and George V Moukarbel and Norman K Hollenberg},

doi = {10.1097/HJH.0000000000000860},

issn = {1473-5598},

year  = {2016},

date = {2016-05-01},

journal = {J Hypertens},

volume = {34},

number = {5},

pages = {935-41},

abstract = {BACKGROUND: Renin inhibition with aliskiren induced the largest increases in renal plasma flow (RPF) in salt-depleted healthy volunteers of all renin-angiotensin system (RAS) blockers. However, given its side-effects at doses higher than 300 mg, no maximum effect of renin inhibition could be established. We hypothesized that VTP-27999, a novel renin inhibitor without major side-effects at high doses, would allow us to establish this. 

METHODS AND RESULTS: The effects of escalating VTP-27999 doses (75-600 mg) on RPF, glomerular filtration rate (GFR), and plasma RAS components were compared with those of 300 mg aliskiren in 22 normal volunteers on a low-sodium diet. VTP-27999 dose-dependently increased RPF and GFR; its effects on both parameters at 600 mg (increases of 18 ±â€Š4 and 20 ±â€Š4%, respectively) were equivalent to those at 300 mg, indicating that a maximum had been reached. The effects of 300 mg aliskiren (increases of 13 ±â€Š5 and 8 ±â€Š6%, respectively; P < 0.01 vs. 300 and 600 mg VTP-27999) resembled those of 150 mg VTP-27999. VTP-27999 dose-dependently increased renin, and lowered plasma renin activity and angiotensin II to detection limit levels. The effects of aliskiren on RAS components were best comparable to those of 150 mg VTP-27999. 

CONCLUSION: Maximum renal renin blockade in healthy, salt-depleted volunteers, requires aliskiren doses higher than 300 mg, but can be established with 300 mg VTP-27999. To what degree such maximal effects (exceeding those of angiotensin-converting enzyme inhibitors and AT1-receptor blockers) are required in patients with renal disease, given the potential detrimental effects of excessive RAS blockade, remains to be determined.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532951,

title = {Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure},

author = {John JV McMurray and Henry Krum and William T Abraham and Kenneth Dickstein and Lars V Køber and Akshay S Desai and Scott D Solomon and Nicola Greenlaw and M Atif Ali and Yanntong Chiang and Qing Shao and Georgia Tarnesby and Barry M Massie},

doi = {10.1056/NEJMoa1514859},

issn = {1533-4406},

year  = {2016},

date = {2016-04-01},

journal = {N Engl J Med},

volume = {374},

number = {16},

pages = {1521-32},

abstract = {BACKGROUND: Among patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. 

METHODS: After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTS: After a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532956,

title = {Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction: Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial},

author = {Søren L Kristensen and David Preiss and Pardeep S Jhund and Iain Squire and José Silva Cardoso and Bela Merkely and Felipe Martinez and Randall C Starling and Akshay S Desai and Martin P Lefkowitz and Adel R Rizkala and Jean L Rouleau and Victor C Shi and Scott D Solomon and Karl Swedberg and Michael R Zile and John JV McMurray and Milton Packer},

doi = {10.1161/CIRCHEARTFAILURE.115.002560},

issn = {1941-3297},

year  = {2016},

date = {2016-01-01},

journal = {Circ Heart Fail},

volume = {9},

number = {1},

abstract = {BACKGROUND: The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND RESULTS: We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: < 6.0% [< 42 mmol/mol], 6.0%-6.4% [42-47 mmol/mol; pre-diabetes mellitus], and >= 6.5% [>= 48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n = 2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P < 0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre-diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, > 6.5%) and known diabetes mellitus compared with those with HbA1c < 6.0% was 1.39 (1.17-1.64); P < 0.001 and 1.64 (1.43-1.87); P < 0.001, respectively. Patients with pre-diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10-1.47]; P < 0.001) compared with those with HbA1c < 6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. 

CONCLUSIONS: In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre-diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c < 6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. 

CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532961,

title = {Screening for Type 2 Diabetes Mellitus},

author = {Ebrahim Barkoudah and Larry A Weinrauch},

doi = {10.7326/L15-5153},

issn = {1539-3704},

year  = {2015},

date = {2015-11-01},

journal = {Ann Intern Med},

volume = {163},

number = {9},

pages = {726},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532966,

title = {Getting lost among the guidelines: the difference between patient-focused treatment and population management},

author = {Larry A Weinrauch and Ebrahim Barkoudah},

doi = {10.1016/j.amjmed.2014.12.023},

issn = {1555-7162},

year  = {2015},

date = {2015-10-01},

journal = {Am J Med},

volume = {128},

number = {10},

pages = {e73},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532971,

title = {Letter by Weinrauch and Barkoudah Regarding Article, "Lack of concordance between empirical scores and physician assessments of stroke and bleeding risk in atrial fibrillation. Results from the Outcomes Registry for Better Informed Treatment of Atrial Fib},

author = {Larry A Weinrauch and Ebrahim Barkoudah},

doi = {10.1161/CIRCULATIONAHA.114.011869},

issn = {1524-4539},

year  = {2015},

date = {2015-02-01},

journal = {Circulation},

volume = {131},

number = {5},

pages = {e335},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532976,

title = {Angiotensin-neprilysin inhibition versus enalapril in heart failure},

author = {John JV McMurray and Milton Packer and Akshay S Desai and Jianjian Gong and Martin P Lefkowitz and Adel R Rizkala and Jean L Rouleau and Victor C Shi and Scott D Solomon and Karl Swedberg and Michael R Zile},

doi = {10.1056/NEJMoa1409077},

issn = {1533-4406},

year  = {2014},

date = {2014-09-01},

journal = {N Engl J Med},

volume = {371},

number = {11},

pages = {993-1004},

abstract = {BACKGROUND: We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients. 

METHODS: In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes. RESULTS: The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P<0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P<0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P<0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P<0.001) and decreased the symptoms and physical limitations of heart failure (P=0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group. 

CONCLUSIONS: LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. (Funded by Novartis; PARADIGM-HF ClinicalTrials.gov number, NCT01035255.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532981,

title = {Spironolactone for heart failure with preserved ejection fraction},

author = {Bertram Pitt and Marc A Pfeffer and Susan F Assmann and Robin Boineau and Inder S Anand and Brian Claggett and Nadine Clausell and Akshay S Desai and Rafael Diaz and Jerome L Fleg and Ivan Gordeev and Brian Harty and John F Heitner and Christopher T Kenwood and Eldrin F Lewis and Eileen O’Meara and Jeffrey L Probstfield and Tamaz Shaburishvili and Sanjiv J Shah and Scott D Solomon and Nancy K Sweitzer and Song Yang and Sonja M McKinlay},

doi = {10.1056/NEJMoa1313731},

issn = {1533-4406},

year  = {2014},

date = {2014-04-01},

journal = {N Engl J Med},

volume = {370},

number = {15},

pages = {1383-92},

abstract = {BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. 

METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532991,

title = {Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial},

author = {Mihai Gheorghiade and Michael Böhm and Stephen J Greene and Gregg C Fonarow and Eldrin F Lewis and Faiez Zannad and Scott D Solomon and Fabio Baschiera and Jaco Botha and Tsushung A Hua and Claudio R Gimpelewicz and Xavier Jaumont and Anastasia Lesogor and Aldo P Maggioni},

doi = {10.1001/jama.2013.1954},

issn = {1538-3598},

year  = {2013},

date = {2013-03-01},

journal = {JAMA},

volume = {309},

number = {11},

pages = {1125-35},

abstract = {IMPORTANCE: Hospitalizations for heart failure (HHF) represent a major health burden, with high rates of early postdischarge rehospitalization and mortality. 

OBJECTIVE: To investigate whether aliskiren, a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular (CV) death or HF rehospitalization among HHF patients. DESIGN, SETTING, AND PARTICIPANTS: International, double-blind, placebo-controlled study that randomized hemodynamically stable HHF patients a median 5 days after admission. Eligible patients were 18 years or older with left ventricular ejection fraction (LVEF) 40% or less, elevated natriuretic peptides (brain natriuretic peptide [BNP] >= 400 pg/mL or N -terminal pro-BNP [NT-proBNP] >= 1600 pg/mL), and signs and symptoms of fluid overload. Patients were recruited from 316 sites across North and South America, Europe, and Asia between May 2009 and December 2011. The follow-up period ended in July 2012. 

INTERVENTION: All patients received 150 mg (increased to 300 mg as tolerated) of aliskiren or placebo daily, in addition to standard therapy. The study drug was continued after discharge for a median 11.3 months. MAIN OUTCOME MEASURES Cardiovascular death or HF rehospitalization at 6 months and 12 months. RESULTS: In total, 1639 patients were randomized, with 1615 patients included in the final efficacy analysis cohort (808 aliskiren, 807 placebo). Mean age was 65 years; mean LVEF, 28%; 41% of patients had diabetes mellitus, mean estimated glomerular filtration rate, 67 mL/min/1.73 m2. At admission and randomization, median NT-proBNP levels were 4239 pg/mL and 2718 pg/mL, respectively. At randomization, patients were receiving diuretics (95.9%), β-blockers (82.5%), angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (84.2%), and mineralocorticoid receptor antagonists (57.0%). In total, 24.9% of patients receiving aliskiren (77 CV deaths, 153 HF rehospitalizations) and 26.5% of patients receiving placebo (85 CV deaths, 166 HF rehospitalizations) experienced the primary end point at 6 months (hazard ratio [HR], 0.92; 95% CI, 0.76-1.12; P = .41). At 12 months, the event rates were 35.0% for the aliskiren group (126 CV deaths, 212 HF rehospitalizations) and 37.3% for the placebo group (137 CV deaths, 224 HF rehospitalizations; HR, 0.93; 95% CI, 0.79-1.09; P = .36). The rates of hyperkalemia, hypotension, and renal impairment/renal failure were higher in the aliskiren group compared with placebo. 

CONCLUSION AND RELEVANCE: Among patients hospitalized for HF with reduced LVEF, initiation of aliskiren in addition to standard therapy did not reduce CV death or HF rehospitalization at 6 months or 12 months after discharge. 

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00894387.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532986,

title = {Treatment of anemia with darbepoetin alfa in systolic heart failure},

author = {Karl Swedberg and James B Young and Inder S Anand and Sunfa Cheng and Akshay S Desai and Rafael Diaz and Aldo P Maggioni and John JV McMurray and Christopher O’Connor and Marc A Pfeffer and Scott D Solomon and Yan Sun and Michal Tendera and Dirk J Veldhuisen},

doi = {10.1056/NEJMoa1214865},

issn = {1533-4406},

year  = {2013},

date = {2013-03-01},

journal = {N Engl J Med},

volume = {368},

number = {13},

pages = {1210-9},

abstract = {BACKGROUND: Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia. 

METHODS: In this randomized, double-blind trial, we assigned 2278 patients with systolic heart failure and mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter) to receive either darbepoetin alfa (to achieve a hemoglobin target of 13 g per deciliter) or placebo. The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure. RESULTS: The primary outcome occurred in 576 of 1136 patients (50.7%) in the darbepoetin alfa group and 565 of 1142 patients (49.5%) in the placebo group (hazard ratio in the darbepoetin alfa group, 1.01; 95% confidence interval, 0.90 to 1.13; P=0.87). There was no significant between-group difference in any of the secondary outcomes. The neutral effect of darbepoetin alfa was consistent across all prespecified subgroups. Fatal or nonfatal stroke occurred in 42 patients (3.7%) in the darbepoetin alfa group and 31 patients (2.7%) in the placebo group (P=0.23). Thromboembolic adverse events were reported in 153 patients (13.5%) in the darbepoetin alfa group and 114 patients (10.0%) in the placebo group (P=0.01). Cancer-related adverse events were similar in the two study groups. 

CONCLUSIONS: Treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Our findings do not support the use of darbepoetin alfa in these patients. (Funded by Amgen; RED-HF ClinicalTrials.gov number, NCT00358215.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{77201,

title = {Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial.},

author = {Greene SJ Böhm M Gheorghiade M},

year  = {2013},

date = {2013-01-01},

journal = {JAMA},

volume = {309},

number = {11},

pages = {1125-35},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{77196,

title = {Treatment of anemia with darbepoetin alfa in systolic heart failure.},

author = {Anand IS Young JB Swedberg K},

year  = {2013},

date = {2013-01-01},

journal = {N Engl J Med},

volume = {28},

number = {368(13)},

pages = {1210-9},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{532996,

title = {Mortality rates in trials of subjects with type 2 diabetes},

author = {Ebrahim Barkoudah and Hicham Skali and Hajime Uno and Scott D Solomon and Marc A Pfeffer},

doi = {10.1161/JAHA.111.000059},

issn = {2047-9980},

year  = {2012},

date = {2012-02-01},

journal = {J Am Heart Assoc},

volume = {1},

number = {1},

pages = {8-15},

abstract = {BACKGROUND: In randomized controlled trials (RCTs) of subjects with type 2 diabetes mellitus, mortality rates vary substantially. We sought to examine the inclusion and exclusion criteria of these RCTs to explore relationships with mortality. METHODS AND RESULTS: MEDLINE database was searched from August 1980 through March 2011. Selection criterion included published RCTs of adults with type 2 diabetes mellitus of at least 1000 patients, reporting all-cause mortality and having follow-up duration of at least 1 year. Twenty-two trials were eligible. Annualized mortality rates were derived. Inclusion and exclusion criteria were tabulated for each trial. Trials were categorized in 4 groups according to annual mortality rates: <1, >=1 to <2, >=2 to <4, and >=4 per 100 patient-years. The analysis cohort included 91842 patients and 6837 deaths. Mortality rates ranged from 0.28 to 8.24 per 100 patient-years. Patients enrolled in the highest mortality category were more likely to be older and had longer diabetes duration and higher blood pressure. The selection for hypertension was common in the low- as well as high-mortality trials. Although the mortality rates were higher in RCTs with prior cardiovascular morbidity, the selection for chronic kidney disease-defined by either higher serum creatinine or lower estimated glomerular filtration rate and/or the presence of proteinuria-was associated with the highest mortality rates. 

CONCLUSIONS: In this analysis of RCTs of type 2 diabetes mellitus, a 29-fold difference in annualized mortality was observed. In these RCTs, selection for renal disease, defined by either decline in renal function or presence of proteinuria, portends important mortality risk. (J Am Heart Assoc. 2012;1:8-15.) 

CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00303979.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{37055,

title = {Management of Palpitations in Urgent Care},

author = {Ebrahim Barkoduah and Jeffery P Collins},

year  = {2012},

date = {2012-01-01},

journal = {Journal of Urgent Care Medicine},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{37054,

title = {Mortality Rates in Trials of Subjects With Type 2 Diabetes.},

author = {Ebrahim Barkoudah and Hicham Skali and Hajime Uno and Scott D Solomon and Marc A Pfeffer},

year  = {2012},

date = {2012-01-01},

journal = {Journal of the American Heart Association},

volume = {1},

pages = {8-18},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{533001,

title = {Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients?},

author = {Norman K Hollenberg and Naomi DL Fisher and Juerg Nussberger and George V Moukarbel and Ebrahim Barkoudah and A. H. Jan Danser},

doi = {10.1097/HJH.0b013e32834c627a},

issn = {1473-5598},

year  = {2011},

date = {2011-12-01},

journal = {J Hypertens},

volume = {29},

number = {12},

pages = {2454-61},

abstract = {OBJECTIVE: Activation of the renal renin-angiotensin system in patients with diabetes mellitus appears to contribute to the risk of nephropathy. Recently, it has been recognized than an elevation of prorenin in plasma also provides a strong indication of risk of nephropathy. This study was designed to examine renin-angiotensin system control mechanisms in the patient with diabetes mellitus. 

METHODS: We enrolled 43 individuals with type 2 diabetes mellitus. All individuals were on a high-salt diet to minimize the contribution of the systemic renin-angiotensin system. After an acute exposure to captopril (25 mg), they were randomized to treatment with either irbesartan (300 mg) or aliskiren (300 mg) for 2 weeks. 

RESULTS: All agents acutely lowered blood pressure and plasma aldosterone, and increased renal plasma flow and glomerular filtration rate. Yet, only captopril and aliskiren acutely increased plasma renin and decreased plasma angiotensin II, whereas irbesartan acutely affected neither renin nor angiotensin II. Plasma renin and angiotensin II subsequently did increase upon chronic irbesartan treatment. When given on day 14, irbesartan and aliskiren again induced the above hemodynamic, renal and adrenal effects, yet without significantly changing plasma renin. Irbesartan at that time did not affect plasma angiotensin II, whereas aliskiren lowered it to almost zero. 

CONCLUSION: The relative resistance of the renal renin response to acute (irbesartan) and chronic (irbesartan and aliskiren) renin-angiotensin system blockade supports the concept of an activated renal renin-angiotensin system in diabetes, particularly at the level of the juxtaglomerular cell, and implies that diabetic patients might require higher doses of renin-angiotensin system blockers to fully suppress the renal renin-angiotensin system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{533006,

title = {Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOS},

author = {Henry Krum and Barry Massie and William T Abraham and Kenneth Dickstein and Lars Kober and John JV McMurray and Ashkay Desai and Claudio Gimpelewicz and Albert Kandra and Bernard Reimund and Henning Rattunde and Juergen Armbrecht},

doi = {10.1093/eurjhf/hfq212},

issn = {1879-0844},

year  = {2011},

date = {2011-01-01},

journal = {Eur J Heart Fail},

volume = {13},

number = {1},

pages = {107-14},

abstract = {AIMS: The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS ’escape’. Direct renin inhibitors (DRIs) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo. The aim of the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril monotherapy, or the combination. The primary endpoints of ATMOSPHERE are (i) whether the aliskiren/enalapril combination is superior to enalapril monotherapy in delaying time to first occurrence of cardiovascular death or HF hospitalization and (ii) whether aliskiren monotherapy is superior or at least non-inferior to enalapril monotherapy on this endpoint. Perspective The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{533011,

title = {Rationale and design of the multicentre, randomized, double-blind, placebo-controlled Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT)},

author = {Mihai Gheorghiade and Mazen Albaghdadi and Faiez Zannad and Gregg C Fonarow and Michael Böhm and Claudio Gimpelewicz and Jaco Botha and Shelley Moores and Eldrin F Lewis and Henning Rattunde and Aldo Maggioni},

doi = {10.1093/eurjhf/hfq209},

issn = {1879-0844},

year  = {2011},

date = {2011-01-01},

journal = {Eur J Heart Fail},

volume = {13},

number = {1},

pages = {100-6},

abstract = {BACKGROUND: Hospitalizations for acute heart failure syndromes (AHFS) are associated with high post-discharge mortality and readmission rates in spite of available therapies. Renin-angiotensin-aldosterone system (RAAS) antagonists improve outcomes in outpatients with heart failure (HF) and reduced ejection fraction, however these therapies have not been tested in AHFS. Aliskiren is a direct renin inhibitor (DRI) that is known to enhance RAAS inhibition, which may result in improved clinical outcomes in AHFS. The aim of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) study is to evaluate the effect of aliskiren on cardiovascular death and HF in AHFS patients. METHODS: ASTRONAUT will be an event-driven trial with an estimated enrolment of 1782 patients hospitalized with worsening chronic HF, a left ventricular ejection fraction <=40%, and an estimated glomerular filtration rate >=40 mL/min/1.73 m(2). Patients will be randomized 1:1 in a double-blind fashion to receive aliskiren or placebo, in addition to standard HF therapy. The primary endpoint will be a composite of time to either cardiovascular death or first occurrence of HF re-hospitalization. 

PERSPECTIVE: Aliskiren is a DRI with a favourable neurohormonal and haemodynamic profile that may benefit patients hospitalized with worsening HF. Given the neurohormonal abnormalities that are present during and after hospitalization for AHFS, it is hypothesized that adding aliskiren to standard therapy will reduce post-discharge mortality and re-hospitalization. NCT00894387.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{37061,

title = {Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE},

author = {B. ; Abraham H.; Massie Krum},

year  = {2011},

date = {2011-01-01},

journal = {European Journal of Heart Failure},

number = {13},

pages = {107-114},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{37060,

title = {Rationale and design of the multicentre, randomized, double-blind, placebo-controlled Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT)},

author = {M. ; Zannad M.; Albaghdadi Gheorghiade},

year  = {2011},

date = {2011-01-01},

journal = {European Journal of Heart Failure},

number = {13},

pages = {100–106},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{37058,

title = {Renal responses to three types of renin–angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients?},

author = {Norman K Hollenberg and Naomi DL Fisher and Juerg Nussbergerc and George V Moukarbel and Ebrahim Barkoudah and A. H. Jan Danser},

year  = {2011},

date = {2011-01-01},

journal = {Journal of Hypertension},

number = {29},

pages = {2454–2461},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{533016,

title = {Pathogenesis of sudden unexpected death in a clinical trial of patients with myocardial infarction and left ventricular dysfunction, heart failure, or both},

author = {Anne-Catherine Pouleur and Ebrahim Barkoudah and Hajime Uno and Hicham Skali and Peter V Finn and Steven L Zelenkofske and Yuri N Belenkov and Viacheslav Mareev and Eric J Velazquez and Jean L Rouleau and Aldo P Maggioni and Lars Køber and Robert M Califf and John JV McMurray and Marc A Pfeffer and Scott D Solomon},

doi = {10.1161/CIRCULATIONAHA.110.940619},

issn = {1524-4539},

year  = {2010},

date = {2010-08-01},

journal = {Circulation},

volume = {122},

number = {6},

pages = {597-602},

abstract = {BACKGROUND: The frequency of sudden unexpected death is highest in the early post-myocardial infarction (MI) period; nevertheless, 2 recent trials showed no improvement in mortality with early placement of an implantable cardioverter-defibrillator after MI. METHODS AND RESULTS: To better understand the pathophysiological events that lead to sudden death after MI, we assessed autopsy records in a series of cases classified as sudden death events in patients from the VALsartan In Acute myocardial infarctioN Trial (VALIANT). Autopsy records were available in 398 cases (14% of deaths). We determined that 105 patients had clinical circumstances consistent with sudden death. On the basis of the autopsy findings, we assessed the probable cause of sudden death and evaluated how these causes varied with time after MI. Of 105 deaths considered sudden on clinical grounds, autopsy suggested the following causes: 3 index MIs in the first 7 days (2.9%); 28 recurrent MIs (26.6%); 13 cardiac ruptures (12.4%); 4 pump failures (3.8%); 2 other cardiovascular causes (stroke or pulmonary embolism; 1.9%); and 1 noncardiovascular cause (1%). Fifty-four cases (51.4%) had no acute specific autopsy evidence other than the index MI and were thus presumed arrhythmic. The percentage of sudden death due to recurrent MI or rupture was highest in the first month after the index MI. By contrast, after 3 months, the percentage of presumed arrhythmic death was higher than recurrent MI or rupture (chi(2)=23.3, P<0.0001). 

CONCLUSIONS: Recurrent MI or cardiac rupture accounts for a high proportion of sudden death in the early period after acute MI, whereas arrhythmic death may be more likely subsequently. These findings may help explain the lack of benefit of early implantable cardioverter-defibrillator therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{37057,

title = {Pathogenesis of Sudden Unexpected Death in a Clinical Trial of Patients With Myocardial Infarction and Left Ventricular Dysfunction, Heart Failure, or Both},

author = {Anne-Catherine Pouleur and Ebrahim Barkoudah and Hajime Uno and Hicham Skali and Peter V Finn and Steven L Zelenkofske and Yuri N Belenkov and Viacheslav Mareev and Eric J Velazquez and Jean L Rouleau and Aldo P Maggioni and Lars Køber and Robert M Califf and John JV McMurray and Marc A Pfeffer and Scott D Solomon},

year  = {2010},

date = {2010-01-01},

journal = {Circulation},

number = {122},

pages = {597-602},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{533021,

title = {Design of the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF): a Phase III, anaemia correction, morbidity-mortality trial},

author = {John JV McMurray and Inder S Anand and Rafael Diaz and Aldo P Maggioni and Christopher O’Connor and Marc A Pfeffer and Krishna R Polu and Scott D Solomon and Yan Sun and Karl Swedberg and Michal Tendera and Dirk J Veldhuisen and Scott M Wasserman and James B Young},

doi = {10.1093/eurjhf/hfp098},

issn = {1879-0844},

year  = {2009},

date = {2009-08-01},

journal = {Eur J Heart Fail},

volume = {11},

number = {8},

pages = {795-801},

abstract = {BACKGROUND: Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. 

OBJECTIVE: The Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF; Clinical Trials.gov NCT 003 58215) was designed to evaluate the effect of the long-acting erythropoietin-stimulating agent darbepoetin alfa on mortality and morbidity (and quality of life) in patients with HF and anaemia. METHODS: Approximately 2600 patients with New York Heart Association class II-IV, an ejection fraction < or =40%, and a haemoglobin (Hb) consistently < or =12.0 g/dL but > or =9.0 g/dL will be enrolled. Patients are randomized 1:1 to double-blind subcutaneous administration of darbepoetin alfa or placebo. Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL (but not exceeding 14.5 g/dL) with sham adjustments of the dose of placebo. The primary endpoint is the time to death from any cause or first hospital admission for worsening HF, whichever occurs first. The study will complete when approximately 1150 subjects experience a primary endpoint.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{37062,

title = {Design of the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF): a Phase III, anaemia correction, morbidity-mortality trial},

author = {I. S. ; Diaz J.J.; Anand McMurray},

year  = {2009},

date = {2009-01-01},

journal = {European Journal of Heart Failure},

number = {11},

pages = {795–801},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{533026,

title = {The permissive role of endothelial NO in CO-induced cerebrovascular dilation},

author = {Ebrahim Barkoudah and Jonathan H Jaggar and Charles W Leffler},

doi = {10.1152/ajpheart.00369.2004},

issn = {0363-6135},

year  = {2004},

date = {2004-10-01},

journal = {Am J Physiol Heart Circ Physiol},

volume = {287},

number = {4},

pages = {H1459-65},

abstract = {Carbon monoxide (CO) and nitric oxide (NO) are important paracrine messengers in the newborn cerebrovasculature that may act as comessengers. Here, we investigated the role of NO in CO-mediated dilations in the newborn cerebrovasculature. Arteriolar branches of the middle cerebral artery (100-200 microm) were isolated from 3- to 7-day-old piglets and cannulated at each end in a superfusion chamber, and intravascular pressure was elevated to 30 mmHg, which resulted in the development of myogenic tone. Endothelium removal abolished dilations of pressurized pial arterioles to bradykinin and to the CO-releasing molecule Mn(2)(CO)(10) [dimanganese decacarbonyl (DMDC)] but not dilations to isoproterenol. With endothelium intact, N(omega)-nitro-l-arginine (l-NNA), 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), or tetraethylammonium chloride (TEA(+)), inhibitors of NO synthase (NOS), guanylyl cyclase, and large-conductance Ca(2+)-activated K(+) (K(Ca)) channels, respectively, also blocked dilation induced by DMDC. After inhibition of NOS, a constant concentration of sodium nitroprusside (SNP), a NO donor that only dilated the vessel 6%, returned dilation to DMDC. The stable cGMP analog 8-bromo-cGMP also restored dilation to DMDC in endothelium-intact, l-NNA-treated, or endothelium-denuded arterioles, and this effect was blocked by TEA(+). Similarly, in the continued presence of ODQ, 8-bromo-cGMP restored DMDC-induced dilations. These findings suggest that endothelium-derived NO stimulates guanylyl cyclase in vascular smooth muscle cells and, thereby, permits CO to cause dilation by activating K(Ca) channels. Such a requirement for NO could explain the endothelium dependency of CO-induced dilation in piglet pial arterioles.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{37056,

title = {The permissive role of endothelial NO in CO-induced cerebrovascular dilation},

author = {Ebrahim Barkoudah and Jonathan H Jaggar and Charles W Leffler},

year  = {2004},

date = {2004-01-01},

journal = {Am J Physiol Heart Circ Physio},

volume = {287},

number = {4},

pages = {H1459-65},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{684254,

title = {Application of Optical Coherence Tomography Angiography Macular Analysis for Systemic Hypertension. A Systematic Review and Meta-analysis},

author = {Rita Anjos and André Ferreira and Ebrahim Barkoudah and Brian Claggett and Luis Abegão Pinto and Ana Miguel},

doi = {10.1093/ajh/hpab172},

issn = {1941-7225},

journal = {Am J Hypertens},

volume = {35},

number = {4},

pages = {356-364},

abstract = {BACKGROUND: Microvascular rarefaction due to hypertension has been linked to disease severity and end-organ complications. Optical coherence tomography angiography (OCTA) has been explored as a potential tool to evaluate the retinal microvascular network in hypertensive patients. 

METHODS: PubMed, Scopus, Web of Science, and Cochrane were systematically searched to 10th of September of 2021, along with a manual search. Studies that used OCTA as a primary diagnostic method to evaluate the macular microvasculature of hypertensive patients were included. Meta-analysis was performed using a random-effects model. Primary outcomes were macular vessel density (VD) and foveal avascular zone (FAZ) at the superficial and deep capillary plexus. RESULTS: Of 947 screened articles, 9 were found eligible for qualitative and quantitative analysis. VD in hypertensive patients was reduced when compared with controls in the fovea (0.93, 95% confidence interval [CI] 0.87-0.99},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{684250,

title = {Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction},

author = {Marc A Pfeffer and Brian Claggett and Eldrin F Lewis and Christopher B Granger and Lars Køber and Aldo P Maggioni and Douglas L Mann and John JV McMurray and Jean-Lucien Rouleau and Scott D Solomon and Philippe G Steg and Otavio Berwanger and Maja Cikes and Carmine G De Pasquale and Cara East and Alberto Fernandez and Karola Jering and Ulf Landmesser and Roxana Mehran and Béla Merkely and Freny Vaghaiwalla Mody and Mark C Petrie and Ivo Petrov and Morten Schou and Michele Senni and David Sim and Peter Meer and Martin Lefkowitz and Yinong Zhou and Jianjian Gong and Eugene Braunwald},

doi = {10.1056/NEJMoa2104508},

issn = {1533-4406},

journal = {N Engl J Med},

volume = {385},

number = {20},

pages = {1845-1855},

abstract = {BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. 

METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. 

CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{684249,

title = {Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction},

author = {Marc A Pfeffer and Brian Claggett and Eldrin F Lewis and Christopher B Granger and Lars Køber and Aldo P Maggioni and Douglas L Mann and John JV McMurray and Jean-Lucien Rouleau and Scott D Solomon and Philippe G Steg and Otavio Berwanger and Maja Cikes and Carmine G De Pasquale and Cara East and Alberto Fernandez and Karola Jering and Ulf Landmesser and Roxana Mehran and Béla Merkely and Freny Vaghaiwalla Mody and Mark C Petrie and Ivo Petrov and Morten Schou and Michele Senni and David Sim and Peter Meer and Martin Lefkowitz and Yinong Zhou and Jianjian Gong and Eugene Braunwald},

doi = {10.1056/NEJMoa2104508},

issn = {1533-4406},

journal = {N Engl J Med},

volume = {385},

number = {20},

pages = {1845-1855},

abstract = {BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. 

METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. 

CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{684255,

title = {Beta Cell Function as a Baseline Predictor of Weight Loss After Bariatric Surgery},

author = {Marta Borges-Canha and João Sérgio Neves and Fernando Mendonça and Maria Manuel Silva and Cláudia Costa and Pedro M Cabral and Vanessa Guerreiro and Rita Lourenço and Patrícia Meira and Daniela Salazar and Maria João Ferreira and Jorge Pedro and Ebrahim Barkoudah and Ana Sande and Eva Lau and Selma B Souto and John Preto and Paula Freitas and Davide Carvalho},

doi = {10.3389/fendo.2021.714173},

issn = {1664-2392},

journal = {Front Endocrinol (Lausanne)},

volume = {12},

pages = {714173},

abstract = {Background: Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain. 

Aim: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity. 

Methods: Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery). Results: There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (β = -1.04 [-1.82 to -0.26], p<0.01; β = -1.16 [-2.13 to -0.19]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{684258,

title = {Clinical course and outcome among patients with acute pancreatitis and COVID-19},

author = {Vivek Kumar and Ebrahim Barkoudah and Daniel A T Souza and David X Jin and Julia McNabb-Baltar},

doi = {10.1097/MEG.0000000000002160},

issn = {1473-5687},

journal = {Eur J Gastroenterol Hepatol},

volume = {33},

number = {5},

pages = {695-700},

abstract = {BACKGROUND: The data on clinical course and outcome of acute pancreatitis among patients with coronavirus disease 2019 (COVID-19) are sparse. In this study, we analyzed the clinical profiles of patients with COVID 19 and acute pancreatitis. 

METHODS: This retrospective study was conducted on Research Patient Data Registry data which was pooled from five Mass General Brigham Healthcare Network hospitals. We extracted data on demographics, symptoms, ICU transfer, mechanical ventilation, laboratories’ profiles, imaging findings, and patient outcomes. 

RESULT: Of 985 screened adult patients, 17 were eligible for the study, 9 (52.9%) were admitted primarily for respiratory failure and developed acute pancreatitis after a median of 22.5 days (13-76 days) from the onset of COVID-19 symptoms. On contrary, eight patients presented with typical symptoms and were diagnosed with acute pancreatitis, the majority with mild severity (62.5%) on admission. Patients who were admitted primarily with severe COVID-19 illness were younger (median age 57 vs. 63 years), females (55.6 vs. 25%), of Hispanic ethnicity (55.6 vs. 25%), and obese (88.9 vs. 37.5%). The median peak lipase, C reactive protein, ferritin, lactate dehydrogenase, D-dimer were higher among patients who developed acute pancreatitis later during hospitalization. Patients who developed acute pancreatitis later also experienced higher episodes of necrotizing pancreatitis (11.1% vs. 0), thromboembolic complications (55.6 vs. 12.5%), and higher mortality (37.5 vs. 12.5%). 

CONCLUSION: Acute pancreatitis is not common among patients with COVID-19. Patients with COVID-19 who had acute pancreatitis on admission had more benign course and overall better outcome as compared to the patients who developed acute pancreatitis during hospitalization.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{684248,

title = {Mode of Death in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF Trial},

author = {Akshay S Desai and Muthiah Vaduganathan and John G Cleland and Brian L Claggett and Ebrahim Barkoudah and Peter Finn and Finnian R Mc Causland and Mehmet B Yilmaz and Martin Lefkowitz and Victor Shi and Marc A Pfeffer and John JV McMurray and Scott D Solomon},

doi = {10.1161/CIRCHEARTFAILURE.121.008597},

issn = {1941-3297},

journal = {Circ Heart Fail},

volume = {14},

number = {12},

pages = {e008597},

abstract = {BACKGROUND: Patients with heart failure (HF) and preserved left ventricular ejection fraction comprise a heterogeneous group including some with mildly reduced EF. We hypothesized that mode of death differs by EF in ambulatory patients with HF and preserved left ventricular ejection fraction. METHODS: PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) compared clinical outcomes in 4796 patients with chronic HF and EF >=45% randomly assigned to sacubitril/valsartan or valsartan. We examined the mode of death in relation to baseline EF in logistic regression models and the effect of randomized treatment on cause-specific death in Cox regression models. Nonlinear relationships with continuous EF were modelled using quadratic and cubic terms. 

RESULTS: Of 691 deaths during the trial, 416 (60%) were ascribed to cardiovascular, 220 (32%) to noncardiovascular, and 55 (8%) to unknown causes. Of cardiovascular deaths, 154 (37%) were due to sudden death, 118 (28%) were due to HF, 35 (8%) to stroke, 27 (6%) to myocardial infarction, and 82 (20%) to other cardiovascular causes. Rates of all-cause, cardiovascular, and sudden death were higher in those with lower left ventricular ejection fraction (all P<0.001), while rates of non-cardiovascular death were greater in patients with higher EF. Sacubitril/valsartan did not reduce overall death, cardiovascular death, or sudden death compared with valsartan, irrespective of baseline EF (all P for interaction >0.30). 

CONCLUSIONS: Among patients with HF and preserved left ventricular ejection fraction enrolled in PARAGON-HF, the proportion of cardiovascular and sudden death were higher in those with lower left ventricular EF, and the proportion of noncardiovascular death rose with EF. Regardless of EF, sacubitril/valsartan did not reduce death from any cause compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{684257,

title = {Worsening Heart~Failure Episodes Outside a Hospital Setting in Heart~Failure With Preserved Ejection Fraction: The PARAGON-HF Trial},

author = {Muthiah Vaduganathan and Jonathan W Cunningham and Brian L Claggett and Finnian Mc Causland and Ebrahim Barkoudah and Peter Finn and Faiez Zannad and Marc A Pfeffer and Adel R Rizkala and Shalini Sabarwal and John JV McMurray and Scott Solomon and Akshay S Desai},

doi = {10.1016/j.jchf.2021.01.014},

issn = {2213-1787},

journal = {JACC Heart Fail},

volume = {9},

number = {5},

pages = {374-382},

abstract = {OBJECTIVES: This study sought to evaluate the frequency and prognostic implications of urgent heart failure (HF) visits in a large global clinical trial of HF with preserved ejection fraction (HFpEF). 

BACKGROUND: Episodes of worsening HF managed without hospitalization are common and prognostically important in HF with reduced ejection fraction (EF). The significance of these ambulatory worsening HF events in HFpEF is uncertain. METHODS: PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) randomly assigned 4,796 patients with HFpEF (>=45%) to treatment with sacubitril/valsartan vs. valsartan with a primary composite endpoint of total HF hospitalizations and cardiovascular death. Urgent ambulatory HF visits requiring intravenous diuretic treatment were prospectively collected and adjudicated by a blinded committee. We examined the effect of study treatment on a prespecified expanded composite of cardiovascular death and worsening HF events (including HF hospitalizations and urgent HF visits) and the effect of each type of HF event on subsequent mortality. RESULTS: Of 884 first worsening HF events, 66 (7.5%) were urgent HF visits. Patients whose first episode of worsening HF event was an urgent visit had similar age, comorbidities, baseline N-terminal prohormone of B-type natriuretic peptide, and Meta-Analysis Global Group in Chronic Heart~Failure risk scores to those in whom the first HF event was a hospitalization (all comparisons p > 0.05). Regardless of the treatment setting, patients with a first episode of worsening HF had higher rates of subsequent death (19.2 per 100 patient-years; 95% confidence interval [CI]: 16.9 to 21.8 for HF hospitalization and 10.1 per 100 patients-years; 95%~CI: 5.4 to 18.7 for urgent HF visit) compared with those who did not experience worsening HF (death rate 4.0 per 100 patient-years; 95%~CI: 3.6 to 4.4). Including total urgent HF visits in the composite study endpoint added 95 total events and would have shortened the trial duration needed for event accrual. The addition of urgent HF visits in a prespecified composite endpoint reinforced the treatment efficacy of sacubitril/valsartan compared with valsartan (rate ratio 0.86; 95%~CI: 0.75 to 0.99; p~=~0.040). 

CONCLUSIONS: Like HF hospitalizations, worsening HF events treated in the ambulatory setting are prognostically important in HFpEF. Inclusion of these events in the composite primary endpoint underscores the benefit of sacubitril/valsartan compared with valsartan in PARAGON-HF. (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669768,

title = {Cardiovascular and Renal Outcomes of~Mineralocorticoid Receptor Antagonist~Use in PARAGON-HF},

author = {Karola S Jering and Faiez Zannad and Brian Claggett and Finnian R Mc Causland and João Pedro Ferreira and Akshay Desai and Ebrahim Barkoudah and John JV McMurray and Marc A Pfeffer and Scott D Solomon},

doi = {10.1016/j.jchf.2020.08.014},

issn = {2213-1787},

journal = {JACC Heart Fail},

volume = {9},

number = {1},

pages = {13-24},

abstract = {OBJECTIVES: This study sought to evaluate the efficacy and safety of sacubitril/valsartan in patients with heart failure with preserved ejection fraction (HFpEF) according to background mineralocorticoid receptor antagonist (MRA) therapy. 

BACKGROUND: Current guidelines recommend consideration of MRAs in selected patients with HFpEF. This study assessed cardiovascular outcomes, renal outcomes, and safety of sacubitril/valsartan compared with valsartan in patients with HFpEF according to background MRA treatment. METHODS: PARAGON-HF (Prospective Comparison of ARNI [angiotensin receptor-neprilysin inhibitor] with ARB [angiotensin-receptor blockers] Global Outcomes in HF with Preserved Ejection Fraction) randomized 4,796 patients with HFpEF to sacubitril/valsartan or valsartan. In a pre-specified subgroup analysis, the effect of sacubitril/valsartan versus valsartan was evaluated according to baseline MRA use on the primary study composite of total heart failure hospitalizations and cardiovascular death using semiparametric proportional rates methods, as well as the renal composite of~>=50% decrease in estimated glomerular filtration rate, development of end-stage renal disease, or death from renal causes using Cox proportional hazards regression models. Annual decline in estimated glomerular filtration rate was analyzed with repeated-measures mixed-effect models. Key safety outcomes included incidence of hypotension, hyperkalemia, and elevations in serum creatinine above predefined thresholds. RESULTS: Patients treated with MRAs at baseline (n~=~1,239, 26%), compared with MRA nonusers (n~=~3,557, 74%), were younger (72 vs. 73 years), more often male (52% vs. 47%), had lower left ventricular ejection fraction (57% vs. 58%), and a higher proportion of prior HF hospitalization (59% vs. 44%) (all p~<~0.001). Efficacy of sacubitril/valsartan compared with valsartan with regard to the primary cardiovascular (for MRA users: rate ratio: 0.73; 95% confidence interval [CI]: 0.56 to 0.95; vs. for MRA nonusers: rate ratio: 0.94; 95%~CI: 0.79 to 1.11; pinteraction~=~0.11) and renal endpoints (for MRA users: hazard ratio: 0.31; 95%~CI: 0.13 to 0.76; vs. for MRA non-users: HR: 0.59; 95%~CI: 0.36 to 0.95; pinteraction~=~0.21) did not significantly vary by baseline MRA use. The incidence of key safety outcomes including hypotension and severe hyperkalemia (K > 6.0~mmol/l) did not vary by baseline MRA use. However, annual decline in estimated glomerular filtration rate was less with the combination of MRA and sacubitril/valsartan (for MRA users: absolute difference favoring sacubitril/valsartan:~+1.2~ml/min/1.73~m2 per year; 95%~CI: 0.6 to 1.7; vs. for MRA nonusers:~+0.4; 95%~CI: 0.1 to 0.7; pinteraction~=~0.01). 

CONCLUSIONS: Clinical efficacy of sacubitril/valsartan compared with valsartan with regard to predefined cardiorenal composite outcomes in PARAGON-HF was consistent in patients treated and not treated with MRA at baseline. Addition of sacubitril/valsartan rather than valsartan alone to MRA appears to be associated with a lesser decline in renal function and no increase in severe hyperkalemia. These data support possible added value of combination treatment with sacubitril/valsartan and MRA in patients with HFpEF. (Prospective Comparison of ARNI [angiotensin receptor -neprilysin inhibitor] with ARB [angiotensin-receptor blockers] Global Outcomes in HF with Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669777,

title = {Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients: An NATF Anticoagulation Action Initiative},

author = {Ebrahim Barkoudah and Gregory Piazza and Todd E H Hecht and Paul Grant and Steven Deitelzweig and Margaret C Fang and John Fanikos and Cheng-Kai Kao and Geoffrey D Barnes and Thomas Chen and Téa Ramishvili and Jeffrey L Schnipper and Jennifer N Goldstein and Christian T Ruff and Scott Kaatz and Aviva Schwartz and Jean M Connors and Samuel Z Goldhaber},

doi = {10.1016/j.amjmed.2019.12.001},

issn = {1555-7162},

journal = {Am J Med},

volume = {133 Suppl 1},

pages = {1-27},

abstract = {Hospitalized patients with acute medical illnesses are at risk for venous thromboembolism (VTE) during and after a hospital stay. Risk factors include physical immobilization and underlying pathophysiologic processes that activate the coagulation pathway and are still present after discharge. Strategies for optimal pharmacologic VTE thromboprophylaxis are evolving, and recommendations for VTE prophylaxis can be further refined to protect high-risk patients after hospital discharge. An early study of extended VTE prophylaxis with a parenteral agent in medically ill patients yielded inconclusive results with regard to efficacy and bleeding. In the Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial, extended use of betrixaban halved symptomatic VTE, decreased hospital readmission, and reduced stroke and major adverse cardiovascular events compared with standard enoxaparin prophylaxis. Based on findings from APEX, the Food and Drug Administration approved betrixaban in 2017 for extended VTE prophylaxis in acute medically ill patients. In the Reducing Post-Discharge Venous Thrombo-Embolism Risk (MARINER) study, extended use of rivaroxaban halved symptomatic VTE in high-risk medical patients compared with placebo. In 2019, rivaroxaban was approved for extended thromboprophylaxis in high-risk medical patients, thus making available a new strategy for in-hospital and post-discharge VTE prevention. To address the critical unmet need for VTE prophylaxis in medically ill patients at the time of hospital discharge, the North American Thrombosis Forum (NATF) is launching the Anticoagulation Action Initiative, a comprehensive consensus document that provides practical guidance and straightforward, patient-centered recommendations for VTE prevention during hospitalization and after discharge.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669776,

title = {Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients: An NATF Anticoagulation Action Initiative},

author = {Ebrahim Barkoudah and Gregory Piazza and Todd E H Hecht and Paul Grant and Steven Deitelzweig and Margaret C Fang and John Fanikos and Cheng-Kai Kao and Geoffrey D Barnes and Thomas Chen and Téa Ramishvili and Jeffrey L Schnipper and Jennifer N Goldstein and Christian T Ruff and Scott Kaatz and Aviva Schwartz and Jean M Connors and Samuel Z Goldhaber},

doi = {10.1016/j.amjmed.2019.12.001},

issn = {1555-7162},

journal = {Am J Med},

volume = {133 Suppl 1},

pages = {1-27},

abstract = {Hospitalized patients with acute medical illnesses are at risk for venous thromboembolism (VTE) during and after a hospital stay. Risk factors include physical immobilization and underlying pathophysiologic processes that activate the coagulation pathway and are still present after discharge. Strategies for optimal pharmacologic VTE thromboprophylaxis are evolving, and recommendations for VTE prophylaxis can be further refined to protect high-risk patients after hospital discharge. An early study of extended VTE prophylaxis with a parenteral agent in medically ill patients yielded inconclusive results with regard to efficacy and bleeding. In the Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial, extended use of betrixaban halved symptomatic VTE, decreased hospital readmission, and reduced stroke and major adverse cardiovascular events compared with standard enoxaparin prophylaxis. Based on findings from APEX, the Food and Drug Administration approved betrixaban in 2017 for extended VTE prophylaxis in acute medically ill patients. In the Reducing Post-Discharge Venous Thrombo-Embolism Risk (MARINER) study, extended use of rivaroxaban halved symptomatic VTE in high-risk medical patients compared with placebo. In 2019, rivaroxaban was approved for extended thromboprophylaxis in high-risk medical patients, thus making available a new strategy for in-hospital and post-discharge VTE prevention. To address the critical unmet need for VTE prophylaxis in medically ill patients at the time of hospital discharge, the North American Thrombosis Forum (NATF) is launching the Anticoagulation Action Initiative, a comprehensive consensus document that provides practical guidance and straightforward, patient-centered recommendations for VTE prevention during hospitalization and after discharge.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{669772,

title = {A retrospective study of adult patients with noncirrhotic hyperammonemia},

author = {Andrew B Stergachis and Kris M Mogensen and Charbel C Khoury and Alexander P Lin and Roy Wa Peake and Joshua J Baker and Ebrahim Barkoudah and Inderneel Sahai and David A Sweetser and Gerard T Berry and Joel B Krier},

doi = {10.1002/jimd.12292},

issn = {1573-2665},

journal = {J Inherit Metab Dis},

volume = {43},

number = {6},

pages = {1165-1172},

abstract = {Adult-onset noncirrhotic hyperammonemia (NCH) is poorly understood and has a high morbidity and mortality. To elucidate the etiology and management of NCH, we performed a retrospective analysis of 23 adults (median age 51) with NCH treated between 2014 and 2020 at two academic medical centers. Hyperammonemia was diagnosed in all cases during the evaluation of altered mental status, with 22% presenting with seizures. Peak ammonia levels were >200 μmol/L in 70% of cases. Defects in ammonia metabolism were assessed using urea cycle biochemical testing, germline genetic testing, and testing for urease-producing infectious agents. Ammonia metabolism defects in these cases appear attributable to four major sources: (a) infection with urease-producing organism (n = 5); (b) previously undiagnosed inborn errors of metabolism (IEMs) (n = 4); (c) clinical exposures causing acquired urea cycle dysfunction (n = 6); and (d) unexplained acquired urea cycle dysfunction (uaUCD) (n = 8), as evidenced by biochemical signatures of urea cycle dysfunction without a genetic or clinical exposure. Severe protein malnutrition appeared to be a reversible risk factor for uaUCD. Overall, 13% of our cohort died prior to resolution of hyperammonemia, 26% died after hyperammonemia resolution, 57% survived after having reversible neurological changes, and 4% survived with irreversible neurological changes. Renal replacement therapy for ammonia clearance was often utilized for patients with an ammonia level above 250 μmol/L and patients were frequently empirically treated with antibiotics targeting urea-splitting organisms. Our study demonstrates that acquired urea cycle dysfunction, IEMs and urease-producing infections are major sources of adult-onset NCH and highlights successful management strategies for adult-onset NCH.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}