Prognostic relevance of demographic factors in cardiac magnetic resonance-proven acute myocarditis: A cohort study.

Aim: Acute myocarditis (AM) is a heterogeneous condition with variable estimates of survival. Contemporary criteria for the diagnosis of clinically suspected AM enable non-invasive assessment, resulting in greater sensitivity and more representative cohorts. We aimed to describe the demographic characteristics and long-term outcomes of patients with AM diagnosed using non-invasive criteria. Methods and results: A total of 199 patients with cardiac magnetic resonance (CMR)-confirmed AM were included. The majority (n = 130, 65%) were male, and the average age was 39 ± 16 years. Half of the patients were White (n = 99, 52%), with the remainder from Black and Minority Ethnic (BAME) groups. The most common clinical presentation was chest pain (n = 156, 78%), with smaller numbers presenting with breathlessness (n = 25, 13%) and arrhythmias (n = 18, 9%). Patients admitted with breathlessness were sicker and more often required inotropes, steroids, and renal replacement therapy (p < 0.001, p < 0.001, and p = 0.01, respectively). Over a median follow-up of 53 (IQR 34-76) months, 11 patients (6%) experienced an adverse outcome, defined as a composite of all-cause mortality, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) therapy. Patients in the arrhythmia group had a worse prognosis, with a nearly sevenfold risk of adverse events [hazard ratio (HR) 6.97; 95% confidence interval (CI) 1.87-26.00, p = 0.004]. Sex and ethnicity were not significantly associated with the outcome. Conclusion: AM is highly heterogeneous with an overall favourable prognosis. Three-quarters of patients with AM present with chest pain, which is associated with a benign prognosis. AM presenting with life-threatening arrhythmias is associated with a higher risk of adverse events.

Losartan Has No Effect on High Altitude Diuresis or Acute Mountain Sickness in Well-Acclimatizing Individuals.

Delamere, John P., Susie B. Bradwell, Christopher T. Lewis, Alex Clarke, and Arthur R. Bradwell. Losartan has no effect on high altitude diuresis or acute mountain sickness in well-acclimatizing individuals. High Alt Med Biol. 22:96-101, 2021. Introduction: The diuretic response that occurs on ascent to altitude is associated with suppression of aldosterone. We speculated that losartan, an angiotensin II receptor blocker, might further reduce aldosterone activity thereby enhancing the diuresis. Materials and Methods: Twenty subjects (paired for angiotensin converting enzyme genotypes [II:ID:DD] gender and age) were randomized, on a double-blind basis, to either daily losartan, 100 mg, or placebo. During 7 days of motorized ascent from 2,850 to 5,035 m, collections of 24-hour urine output were measured daily with samples taken for sodium (Na+) and potassium (K+) concentrations. In addition, measurements were made of blood gases and aldosterone concentrations. Results: During the main ascent, there were similar progressive increases in 24-hour urine volumes in placebo and losartan groups with no change in Na+ or K+ excretion. There were negative correlations between mean 24-hour urine volumes and PaO2 (r = -0.97, p < 0.03), and the diuretic response and acute mountain sickness scores at 5,053 m (r = -0.51, p < 0.03). There were no significant changes in aldosterone concentrations measured at baseline and at our high point on day 6 within or between the losartan and placebo groups. Conclusion: The high altitude diuretic response was not increased by losartan indicating aldosterone activity was suppressed in individuals on placebo who were acclimatizing well to altitude.

Hypoxia is not the primary mechanism contributing to exercise-induced proteinuria.

INTRODUCTION: Proteinuria increases at altitude and with exercise, potentially as a result of hypoxia. Using urinary alpha-1 acid glycoprotein (α1-AGP) levels as a sensitive marker of proteinuria, we examined the impact of relative hypoxia due to high altitude and blood pressure-lowering medication on post-exercise proteinuria. METHODS: Twenty individuals were pair-matched for sex, age and ACE genotype. They completed maximal exercise tests once at sea level and twice at altitude (5035 m). Losartan (100 mg/day; angiotensin-receptor blocker) and placebo were randomly assigned within each pair 21 days before ascent. The first altitude exercise test was completed within 24-48 hours of arrival (each pair within ~1 hour). Acetazolamide (125 mg two times per day) was administrated immediately after this test for 48 hours until the second altitude exercise test. RESULTS: With placebo, post-exercise α1-AGP levels were similar at sea level and altitude. Odds ratio (OR) for increased resting α1-AGP at altitude versus sea level was greater without losartan (2.16 times greater). At altitude, OR for reduced post-exercise α1-AGP (58% lower) was higher with losartan than placebo (2.25 times greater, p=0.059) despite similar pulse oximetry (SpO2) (p=0.95) between groups. Acetazolamide reduced post-exercise proteinuria by approximately threefold (9.3±9.7 vs 3.6±6.0 µg/min; p=0.025) although changes were not correlated (r=-0.10) with significant improvements in SpO2 (69.1%±4.5% vs 75.8%±3.8%; p=0.001). DISCUSSION: Profound systemic hypoxia imposed by altitude does not result in greater post-exercise proteinuria than sea level. Losartan and acetazolamide may attenuate post-exercise proteinuria, however further research is warranted.

Urinary Alpha-1-Acid Glycoprotein Is a Sensitive Marker of Glomerular Protein Leakage at Altitude.

Talks, Ben J., Susie B. Bradwell, John Delamere, Will Rayner, Alex Clarke, Chris T. Lewis, Owen D. Thomas, and Arthur R. Bradwell. Urinary alpha-1-acid glycoprotein is a sensitive marker of glomerular protein leakage at altitude. High Alt Med Biol. 19:295-298, 2018.-Proteinuria is an established feature of ascent to altitude and may be caused by a loss of negative charges on glomerular capillary walls (GCWs). To test this hypothesis, we measured two similar sized but oppositely charged proteins in urine: negatively charged alpha-1-acid glycoprotein (α1-AGP, 41-43 kDa) and positively charged dimeric lambda free light chains (λ-FLCs, 50 kDa). Twenty-four-hour urinary leakage was compared with albumin, a 66 kDa negatively charged protein. We studied 23 individuals (ages 23-78 years, male = 17) at baseline (140 m) and daily during an expedition to 5035 m. The results showed a significant increase in median urinary leakage of α1-AGP (p < 0.0001; 6.85-fold) and albumin (p = 0.0006; 1.65-fold) with ascent to altitude, but no significant increase in leakage of λ-FLCs (p = 0.39; 1.14-fold). α1-AGP correlated with the daily ascent profile (p = 0.0026) and partial pressure of oxygen (p = 0.01), whereas albumin showed no correlation (p = 0.19). Urinary α1-AGP was a more sensitive marker of altitude proteinuria than urinary albumin and λ-FLCs, and supported the possibility of loss of GCW negative charges at altitude.

Exercise limitation of acetazolamide at altitude (3459 m).

OBJECTIVE: To assess the effect of acetazolamide (Az) on exercise performance during early acclimatization to altitude. METHODS: Az (250 mg twice daily) or placebo was administered for 3 days in a double-blind, randomized manner followed by a rapid ascent to 3459 m in the Italian Alps. Twenty healthy adults (age range, 18-67 years) were tested at 60% of sea-level peak power output for 15 minutes on a bicycle ergometer after 16 to 27 hours of altitude exposure. Exercise performance was measured in relation to peripheral oxygen saturations measured from pulse oximetry (Spo2), Lake Louise acute mountain sickness (AMS) score, and perceived difficulty. RESULTS: At altitude, resting Spo2 was higher in the Az group compared with placebo (P < .001). The highest AMS scores were in 4 of the placebo individuals with the lowest resting Spo2 (P < .05). During the exercise test, Spo2 fell in all but 1 subject (P < .001) and was reduced more in the Az group (P < .01). Four Az and 1 placebo subject were unable to complete the exercise test; 4 of these 5 had the largest fall in Spo2. The perception of exercise difficulty was higher in the Az subjects compared with those taking the placebo (P < .01). There was an age relationship with exercise limitation; 4 of the 9 older than 50 years failed to complete the test whereas only 1 of 11 younger than 50 years failed, and there were no failures in the 6 younger than 30 years (P < .05). CONCLUSIONS: In this study group, and despite higher resting Spo2, Az may have compromised exercise at 3459 m altitude during early acclimatization, particularly in older subjects.