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One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility.

In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24.

A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups.

Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).

To determine the proportion of Australian adolescent girls who experience menstrual pain (dysmenorrhea); to assess associations of dysmenorrhea and period pain severity with adolescents missing regular activities because of their periods.

Severity of period pain during the preceding three months (very, quite, a little, or not at all painful); number of activity types missed because of periods; relationship between missing activities and period pain severity.

Of the 1835 participating female members of the LSAC Kinder cohort at waves 6 to 8, 1600 (87%) responded to questions about menstruation during at least one of waves 6 to 8 of data collection. At wave 6 (14 years), 227 of 644 respondents (35%) reported dysmenorrhea, 675 of 1341 (50%) at wave 6 (16 years), and 518 of 1115 (46%) at wave 8 (18 years). Of the 366 participants who reported period pain severity at all three waves, 137 reported no dysmenorrhea at all three waves (37%), 66 reported dysmenorrhea at all three waves (18%), 89 reported increasing period pain over time (24%), and 38 reported declining pain (10%). At wave 6, 223 of 647 participants reported missing at least one activity because of their periods (34%), 454 of 1341 at wave 7 (34%), and 344 of 1111 at wave 8 (31%). Of the participants who experienced very painful periods, 72% (wave 6), 63% (wave 7), and 65% (wave 8) missed at least one activity type because of their periods, as did 45% (wave 6), 36% (wave 7), and 40% (wave 8) of those who experienced quite painful periods.

A large proportion of adolescent girls in Australia experience period pain that affects their engagement in regular activities, including school attendance. Recognising adolescent period pain is important not only for enhancing their immediate quality of life with appropriate support and interventions, but also as part of early screening for chronic health conditions such as endometriosis.