Wang, Yi

Abstract Aims Our aim was to assess the clinical and prognostic significance of the left ventricular (LV) hypercontractile phenotype (HP) in hypertrophic cardiomyopathy (HCM), which until now remains unclear. Methods and results We enrolled 1533 HCM patients (age 51 ± 15 years, 965 males, 63%) with ejection fraction (EF) ≥ 50%, referred for rest transthoracic echocardiography (TTE) in 27 laboratories from 13 countries. Two-dimensional volumetric TTE assessment included LV outflow tract gradient (LVOTG), LV EF, and LV force (systolic blood pressure + LVOTG/ESV, mmHg/mL). HP was defined as the highest quartile of the force (> 7.32 mmHg/mL). Survival analysis was performed in a subset of 1200 patients with follow-up information. Compared with non-HP patients, HP showed higher heart rate (72 ± 14 vs. 67 ± 14 beats per minute, P < 0.001), lower stroke volume (50 ± 22 vs. 67 ± 22 mL, P < 0.001), larger left atrial volume index (44 ± 16 vs. 40 ± 16 mL/m2, P = 0.011) and higher coronary flow velocity in the mid-distal left anterior descending artery (n = 325, 41 ± 12 vs. 37 ± 14 cm/s, P = 0.021). Force was moderately related to LV EF (r = 0.48, P < 0.001) and weakly to LVOTG (r = 0.36, P < 0.001). During a median follow-up of 87 months (interquartile range 45–143 months), 131 all-cause deaths occurred. At multivariable Cox analysis, a force > 7.32 mmHg (the fourth quartile for analyzed patients) was associated with a hazard ratio of 1.44 (95% Confidence intervals 1.00–2.07) for all-cause death, independently of LVOTG and LV EF. Conclusion HP in HCM is associated with a disadvantageous systemic, cardiac and coronary hemodynamic profile as well as lower survival in the long-term.

Over the past decade, stress echocardiography has evolved from a test for assessing epicardial artery stenosis to a comprehensive functional test, targeting multiple cardiovascular parameters. The new approach includes several structured steps: (a) evaluating regional wall motion abnormalities to detect epicardial artery stenosis or vasospasm; (b) assessing pulmonary congestion and diastolic function via B-lines with lung ultrasound; (c) gauging preload and contractile reserve with volumetric echocardiography; (d) measuring coronary microvascular reserve using Doppler-based coronary flow velocity in the middistal left anterior descending artery; and (e) determining cardiac sympathetic reserve by tracking heart rate reserve on an ECG. This evolution was supported extensively by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), which played a key role in five areas: (1) developing the initial, curiosity-driven project; (2) disseminating protocols and results at national and international conferences, supporting logistic infrastructure and publication expenses; (3) establishing a digital platform (customized Redcap) for data entry and storage; (4) facilitating patient recruitment across 19 Italian centers; and (5) offering formal endorsement through six presidencies, adding credibility and reach beyond any single institution. The protocol quickly advanced from concept to high-impact publications, earning inclusion in 2024 specialty guidelines. Initially Italian-led, the study now includes 50 centers across 20 countries (e.g. USA and China). Beyond the 50 peer-reviewed papers published in 2016–2024, this study offers a novel, sustainable approach to cardiac stress testing, providing more information at lower costs, with zero radiation and minimal environmental impact. SIECVI’s endorsement was instrumental in amplifying the study’s rigor and outreach.

Abstract Background Hypercontractile phenotype (HP) of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS) or heart failure (HF), but its clinical recognition remains difficult. Objectives To assess the clinical variables associated with the HP. Methods In a prospective, observational, multicenter study, we recruited 5,122 patients (age 65 ± 11 years, 2974 males, 58%) with CCS and/or HF with preserved ejection fraction (EF). Systolic blood pressure (SBP) was measured. We assessed wall motion score index (WMSI), LV end-diastolic volume (EDV), end-systolic volume (ESV), EF, force (SBP/ESV), stroke volume (SV), arterial elastance (SBP/SV), and ventricular-arterial coupling (VAC, as SV/ESV). Univariable and multivariable logistic regression analysis assessed independent factors associated with the highest force sextile. Results For all the studied patients, force was 4.51 ± 2.11 mmHg/ml, with the highest sextile (Group 6) > 6.36 mmHg/ml. By multivariable logistic regression model, the highest sextile of force was associated with age > 65 years (OR 1.62, 95% CI 1.36–1.93, p < 0.001), hypertension (OR 1.76, 95% CI 1.40–2.21, p < 0.001), female sex (OR 4.52, 95% CI 3.77–5.42, p < 0.001), absence of beta-blocker therapy (OR 1.41, 95% CI 1.16–1.68), rest SBP ≥ 160 mmHg (OR 2.81, 95% CI 2.21–3.56, p < 0.001), high heart rate (OR 2.08, 95% CI 1.61–2.67, p < 0.001), and absence of prior myocardial infarction (OR 1.34, 95% CI 1.07–1.68, p = 0.012). Patients in the highest sextile of force showed lower values of WMSI, SV, EDV, and ESV, and higher values of arterial elastance and VAC. Conclusions HP of the LV with high force was clinically associated with advanced age, female sex, high resting SBP, and the absence of 𝛽-blocker therapy. By transthoracic echocardiography, HP was associated with a small heart with reduced EDV, reduced SV despite high EF, and higher arterial elastance.

Abstract For reasons largely unknown, Caucasian women are at a significantly higher risk of developing breast cancer than Asian women. Over a decade ago, mutations in BRCA1/2 were identified as genetic risk factors; however, the discovery of additional breast cancer genes and genes contributing to racial disparities are lacking. We report a functional germline mutation (polymorphism) in the galectin-3 gene at position 191 (rs4644) substituting proline with histidine (P64H), which results in susceptibility to matrix metalloproteinase cleavage and acquisition of resistance to drug-induced apoptosis. This substitution correlates with incidence of breast cancer and racial disparity. Genotype analysis of 338 Caucasian (194 disease free and 144 breast cancer patients) and 140 Asian (79 disease free and 61 breast cancer patients) women showed that the allele homozygous for H64 exists in disease free Caucasian and Asian women at a frequency of 12% and 5%, respectively, versus 37% and 82% in breast cancer patients. The data indicate that H/H allele is associated with increased breast cancer risk in both races. The data implicate galectin-3 H64 in breast cancer and explain, in part, the noted racial disparity, thus providing a novel target for diagnosis and treatment. [Cancer Res 2008;68(24):10045–50]