Over the last 2 decades, mounting evidence has highlighted differences between women and men in the manifestation of common cardiovascular diseases (CVDs). A prevailing perception is that women are affected by the same types of CVD that affect men, albeit with delayed onset and often atypical symptoms. However, with respect to ischemic heart disease (IHD) and heart failure (HF), it is now increasingly recognized that women are more likely than men to develop coronary microvascular dysfunction (CMD) and HF with preserved ejection fraction (HFpEF), especially in the setting of vascular risk factors such as hypertension.^1-3 In effect, the broadening clinical experience of managing CVD conditions that manifest differently between women and men, combined with the accumulating data on sex-specific CVD presentations, suggest that cardiovascular pathophysiology is likely to be fundamentally different between the sexes. If true, then intrinsic sexual dimorphism in cardiovascular pathophysiology must plausibly extend from sexual dimorphism in cardiovascular physiology. To better understand how sex differences in earlier-life cardiovascular physiology may precede sex differences in later-life cardiovascular pathophysiology, we used population-based multicohort data to conduct a comprehensive sex-specific analysis of blood pressure (BP) trajectories over the life course, given that measures of BP elevation in the community represent the single most accessible metric of vascular aging as well as the largest contributor to IHD and HF risk in both women and men.^4-7

In a cohort of BNT162b2 (Pfizer–BioNTech) mRNA vaccine recipients (n = 1,090), we observed that spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228). Post-vaccine symptoms were more prominent for those with prior infection after the first dose, but symptomology was similar between groups after the second dose.

Artificial intelligence (AI) has been developed for echocardiography^1–3, although it has not yet been tested with blinding and randomization. Here we designed a blinded, randomized non-inferiority clinical trial (ClinicalTrials.gov ID: NCT05140642; no outside funding) of AI versus sonographer initial assessment of left ventricular ejection fraction (LVEF) to evaluate the impact of AI in the interpretation workflow. The primary end point was the change in the LVEF between initial AI or sonographer assessment and final cardiologist assessment, evaluated by the proportion of studies with substantial change (more than 5% change). From 3,769 echocardiographic studies screened, 274 studies were excluded owing to poor image quality. The proportion of studies substantially changed was 16.8% in the AI group and 27.2% in the sonographer group (difference of −10.4%, 95% confidence interval: −13.2% to −7.7%, P < 0.001 for non-inferiority, P < 0.001 for superiority). The mean absolute difference between final cardiologist assessment and independent previous cardiologist assessment was 6.29% in the AI group and 7.23% in the sonographer group (difference of −0.96%, 95% confidence interval: −1.34% to −0.54%, P < 0.001 for superiority). The AI-guided workflow saved time for both sonographers and cardiologists, and cardiologists were not able to distinguish between the initial assessments by AI versus the sonographer (blinding index of 0.088). For patients undergoing echocardiographic quantification of cardiac function, initial assessment of LVEF by AI was non-inferior to assessment by sonographers.

Despite rapidly advancing developments in targeted therapeutics and genetic sequencing,^1,2 persistent limits in the accuracy and throughput of clinical phenotyping has led to a widening gap between the potential and the actual benefits realized by precision medicine. This conundrum is exemplified by current approaches to assessing morphologic alterations of the heart.^3,4 If reliably identified, misdiagnoses of certain cardiac diseases (eg, cardiac amyloidosis and hypertrophic cardiomyopathy [HCM]) could be avoided, and specific targeted therapies could be initiated efficiently. Systematic screening paradigms, including through imaging and automated medical record feature review, have shown the opportunity to identify patients with underdiagnosed diseases that are increasingly recognized as more prevalent than was previously thought.^5-9 The ability to reliably distinguish between cardiac disease types with similar morphologic features but different causes would also enhance specificity for linking genetic risk variants and determining mechanisms.

Although physical activity is widely recommended for reducing cardiovascular and all-cause mortality risks, female individuals consistently lag behind male individuals in exercise engagement. The goal of this study was to evaluate whether physical activity derived health benefits may differ by sex. In a prospective study of 412,413 U.S. adults (55% female, age 44 ± 17 years) who provided survey data on leisure-time physical activity, we examined sex-specific multivariable-adjusted associations of physical activity measures (frequency, duration, intensity, type) with all-cause and cardiovascular mortality from 1997 through 2019. During 4,911,178 person-years of follow-up, there were 39,935 all-cause deaths including 11,670 cardiovascular deaths. Regular leisure-time physical activity compared with inactivity was associated with 24% (HR: 0.76; 95% CI: 0.73-0.80) and 15% (HR: 0.85; 95% CI: 0.82-0.89) lower risk of all-cause mortality in women and men, respectively (Wald F = 12.0, sex interaction P < 0.001). Men reached their maximal survival benefit of HR 0.81 from 300 min/wk of moderate-to-vigorous physical activity, whereas women achieved similar benefit at 140 min/wk and then continued to reach a maximum survival benefit of HR 0.76 also at ∼300 min/wk. Sex-specific findings were similar for cardiovascular death (Wald F = 20.1, sex interaction P < 0.001) and consistent across all measures of aerobic activity as well as muscle strengthening activity (Wald F = 6.7, sex interaction P = 0.009). Women compared with men derived greater gains in all-cause and cardiovascular mortality risk reduction from equivalent doses of leisure-time physical activity. These findings could enhance efforts to close the "gender gap" by motivating especially women to engage in any regular leisure-time physical activity.