Journal of the American Heart Association最新文献

Background: Long-term survivors of breast cancer (BC) treated with doxorubicin and trastuzumab-based chemotherapy are at increased risk of developing cardiovascular disease. However, the physiological mechanisms associated with increased cardiovascular disease risk are completely unknown. We hypothesized that long-term survivors of BC, compared with controls, exhibit sympathetic neural hyperactivity, vascular dysfunction, cardiac morphofunctional changes, exercise intolerance, and alterations in the circulating milieu.

Methods: Twenty-three survivors of BC (age: 48.9±1.3 years; body mass index: 25.2±0.8 kg/m²) and 18 (age: 46.4±1.3 years; body mass index: 26.8±0.8 kg/m²) well-matched controls were studied. Muscle sympathetic nerve activity (microneurography), brachial artery flow-mediated dilation (ultrasound-Doppler), carotid-femoral pulse wave velocity (tonometry), left ventricular ejection fraction and global longitudinal strain (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), endothelial cell-derived extracellular vesicles (flow cytometry), and plasma metabolome (mass spectrometry) were assessed. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects.

Results: Survivors of breast cancer were tested ⁓8 years after cancer treatment completion. Muscle sympathetic nerve activity was higher and brachial artery flow-mediated dilation and peak oxygen uptake were lower in survivors than controls. Survivors of breast cancer exhibited higher circulating endothelial cell-derived extracellular vesicles, higher reactive oxygen species bioactivity, and lower acetylcholine-evoked nitrics oxide production in plasma-treated human umbilical vein endothelial cells. Twenty-eight plasma metabolites differed in survivors versus controls. Peak oxygen uptake was inversely related to muscle sympathetic nerve activity or positively to brachial artery flow-mediated dilation. No differences in carotid-femoral pulse wave velocity, left ventricular ejection fraction, and left ventricular global longitudinal strain were observed.

Conclusions: Our findings demonstrate that long-term survivors of breast cancer exhibit sympathetic overdrive, vascular dysfunction, and exercise intolerance, which may contribute to increased cardiovascular disease risk in this population.

Background: Cardiac resynchronization therapy with defibrillation (CRT-D) improves outcomes in heart failure. The long-term impact of CRT-D on hospitalizations remains unknown.

Methods: We analyzed the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) trial post hoc to assess the effects of CRT-D versus implantable cardioverter-defibrillator (ICD) on cardiovascular, heart failure (HF), and noncardiovascular hospitalizations. Hospitalization rates, length of stay, and mortality were compared during extended follow-up.

Results: Patients receiving CRT-D had lower rates of hospitalization compared with ICD (37.9 events per 100 patient-years versus 44.3 events per 100 patient-years, P=0.033). Rates of cardiovascular hospitalizations (20.8 versus 28.3 events per 100 patient-years; P<0.001) and heart failure hospitalizations (6.8 versus 11.6 events per 100 patient-years; P<0.001) were lower with CRT-D. There was no difference in noncardiovascular hospitalizations in the CRT-D group compared with ICD (17 versus 16 events per 100 patient-years, P=0.368). The average length of stay for cardiovascular hospitalizations was shorter in the CRT-D group versus the ICD group (6.7±0.89 versus 7.7±0.68 days; P<0.001), as was the length of stay for heart failure hospitalizations (4.2±0.79 versus 4.8±0.58 days; P<0.001). No difference was observed in the length of stay for noncardiovascular hospitalizations (8.1 versus 7.0 days; P=0.082). Hospitalization of any type was associated with a markedly increased risk of death (hazard ratio, 8.97 [95% CI, 6.17-13.05]; P<0.0001).

Conclusions: Among patients in MADIT-CRT, CRT-D was associated with lower rates and shorter durations of all cardiovascular hospitalizations, including heart failure hospitalizations compared with ICD alone. Hospitalization, regardless of cause, was strongly associated with increased mortality.

Registration: https://clinicaltrials.gov/study/NCT00180271.

Background: The loss of physiological nocturnal blood pressure (BP) decline is a major contributor to cardiovascular risk, yet its endocrine underpinnings in primary aldosteronism (PA) remain underexplored. This study aimed to elucidate the dose-dependent relationship between aldosterone excess and circadian BP rhythm disruption and assess whether targeted aldosterone suppression could ameliorate nocturnal dipping.

Methods: We prospectively analyzed 24-hour ambulatory BP data from 681 patients with confirmed PA, stratified by plasma aldosterone concentration. A subset of 99 patients with adrenal vein sampling-confirmed unilateral PA received targeted, minimally invasive vascular intervention for aldosterone suppression and were evaluated for changes in BP rhythm on the basis of treatment response.

Results: In multivariable-adjusted models, both log-transformed plasma aldosterone concentration and aldosterone-to-renin ratio were inversely associated with the proportion of nocturnal systolic BP decline (log plasma aldosterone concentration: β=-0.054 [95% CI, -0.087 to -0.020]; P=0.002; log aldosterone-to-renin ratio: β=-0.016 [95% CI, -0.025 to -0.006]; P=0.001). In patients achieving biochemical remission after selective suppression, nighttime systolic BP decreased significantly (mean reduction=-33 mm Hg; Cohen's d_z=2.113). The prevalence of the dipper pattern increased from 14.5% to 39.1% (P<0.001), while no rhythm improvement was observed in nonresponders. Multivariable regression confirmed biochemical success as an independent predictor of nocturnal dip amelioration (P=0.045), irrespective of adrenal imaging phenotype.

Conclusions: Aldosterone excess contributes directly to circadian BP rhythm disruption in PA. Selective hormonal suppression can ameliorate physiological BP dipping in responsive patients. These findings highlight the value of rhythm-based end points and support aldosterone-targeted modulation as a strategic goal in PA management. Registration: URL: https://www.chictr.org.cn/; Unique Identifier: ChiCTR2200057297.

Background: Medical treatment decisions are often based on estimated global risk scores. When heterogeneity in treatment effects exists, assigning treatment according to estimated individualized treatment rules (ITRs) instead has the potential to improve mean outcomes. This article aims to investigate racial and ethnic group differences in treatment rates when comparing antihypertensive medication recommendations from an estimated ITR with a risk score approach.

Methods: Data were simulated to emulate observational data with underlying treatment effect heterogeneity in survival times. An ITR and risk score approach were compared to illustrate how the resulting recommendations may disagree. An ITR for prescribing antihypertensives was estimated from 3281 adults from MESA (Multi-Ethnic Study of Atherosclerosis), an observational longitudinal cohort study, and compared with the risk-based approach recommended by cardiovascular care guidelines. Hypothetical treatment rates under each "rule" were computed. In the simulation study, the proportion of individuals treated optimally under each rule was calculated. Using MESA, a Chi-square test of independence was performed to determine whether treatment rates differed across racial and ethnic groups.

Results: Two benefits of ITRs were shown: they (1) maximize expected survival times and (2) may mitigate racial disparities when treatment effect heterogeneity is expected. Using MESA, the ITR recommended treatment to more participants than the risk score approach across all racial and ethnic groups. A Chi-square test suggested that treatment rates for different "rules" differed significantly across racial and ethnic groups (P<0.001).

Conclusions: Treatment recommendations varied substantially when assigning treatment using an ITR versus a risk-based approach.

Background: Myocardial fibrosis (MF) is a common pathological manifestation of end-stage cardiovascular diseases such as hypertension. Hypertension increases cardiac afterload and induces fibrotic myocardial remodeling, ultimately progressing to heart failure. DDR1 (discoidin domain receptor 1), a collagen-activated receptor, plays a pivotal role in multiorgan fibrosis progression. However, its specific mechanistic role in hypertension-induced MF remains to be investigated.

Methods: A pressure overload-induced MF model was established in male spontaneously hypertensive rats, and cardiac fibroblasts were stimulated with angiotensin II to induce a fibrotic phenotype. Cardiac function and fibrosis were assessed through echocardiography combined with histological/cellular staining. Western blotting, quantitative reverse transcription polymerase chain reaction, immunoprecipitation, and ubiquitination assays were used to investigate molecular mechanisms.

Results: Results demonstrated upregulated DDR1 expression in both activated cardiac fibroblasts and fibrotic hearts of spontaneously hypertensive rats. DDR1 inhibition improved cardiac structure and function in spontaneously hypertensive rats, while reducing the fibrotic phenotype of cardiac fibroblasts and attenuating MF progression. Mechanistically, DDR1 enhances direct interaction with SP1 (specificity protein 1), suppressing its ubiquitination and degradation. SP1 binds to the ROCK1 (rho-associated protein kinase 1) gene promoter to strengthen transcriptional regulation, thereby upregulating ROCK1 and downstream profibrotic signaling pathways.

Conclusions: In summary, this study demonstrates that DDR1 is a pivotal driver of MF progression, establishing both a theoretical foundation and an experimental basis for DDR1-targeted therapy in MF.

Background: Although current cardiopulmonary resuscitation guidelines recommend administering epinephrine at 3- to 5-minute intervals during advanced life support (ALS), scientific evidence for the optimal dosing interval for enhancing hemodynamic parameters remains limited. Therefore, we compared the hemodynamic effects of 1-, 3-, and 5-minute epinephrine dosing intervals on blood pressure augmentation in a porcine ventricular fibrillation cardiac arrest model.

Methods: Forty-two pigs were randomly assigned to 1-, 3-, and 5-minute epinephrine dosing-interval groups. After ventricular fibrillation induction and a 2-minute downtime, basic life support was initiated with a 30:2 compression-to-ventilation ratio for 8 minutes, followed by 30 minutes of ALS, including asynchronous ventilation at a rate of a single ventilation every 6 seconds, with oxygen delivered at 15 L/min. Epinephrine (0.02 mg/kg) was administered at predetermined intervals of 1, 3, or 5 minutes. We compared the pressure-time integrals for mean blood pressure, coronary perfusion pressure, and diastolic blood pressure among the groups over the 30-minute ALS period.

Results: The mean blood pressure (P<0.001), coronary perfusion pressure (P=0.001), and diastolic blood pressure pressure-time integrals (P=0.005) were significantly higher in the 1-minute group than in the 3- and 5-minute groups. Crucially, mean blood pressure and coronary perfusion pressure pressure-time integrals remained positive in the 1-minute group but became negative in the 3- and 5-minute groups during ALS. The diastolic blood pressure pressure-time integral also remained positive for a longer duration in the 1-minute group.

Conclusions: A 1-minute epinephrine dosing interval may be significantly more effective in augmenting blood pressure and critical hemodynamic parameters during ALS than are the currently recommended 3- or 5-minute intervals.

Background: Truncating TTN variants (TTNtv) are the main genetic cause of dilated cardiomyopathy (DCM) and are independently associated with atrial fibrillation (AF). In DCM, AF usually arises from left atrial (LA) remodeling attributable to left ventricular systolic dysfunction. Whether TTNtv are linked to primary LA dysfunction independent of left ventricular systolic dysfunction remains unclear.

Methods: This retrospective, multicenter study evaluated atrial function by strain echocardiography in TTNtv carriers across the left ventricular ejection fraction (LVEF) spectrum and its relationship with AF. Individuals with TTNtv and LVEF ≥50% (TTNtv+/DCM-) were compared with matched healthy controls, and those with LVEF <50% (TTNtv+/DCM+) were compared with matched patients with idiopathic, variant-negative DCM (iDCM).

Results: Among 460 participants, 153 carried a TTNtv (87 with LVEF ≥50%, 66 with LVEF <50%). All LA strain parameters were significantly lower in TTNtv+/DCM- than in controls (P<0.001). In TTNtv+/DCM+, only LA contractile strain was reduced compared with iDCM (P<0.001). LA contractile strain correlated with LVEF only when LVEF was <50% (TTNtv+/DCM+, r=0.50, P<0.001; iDCM, r=0.47, P<0.001). In TTNtv+/DCM-, all LA strain parameters except contractile strain correlated with LV strain. AF incidence was higher in TTNtv+/DCM+ (3.15/100 person-years) than in TTNtv+/DCM- (1.48) and iDCM (2.27), though cumulative incidence was not significantly different (P=0.200).

Conclusions: LA myopathy, detected by strain imaging, appears early in TTNtv+/DCM- individuals and may represent an early phenotypic marker independent of left ventricular systolic dysfunction. When LVEF declines below 50%, atrial dysfunction worsens in parallel. AF was more frequent in TTNtv carriers, supporting further research on LA strain for AF risk stratification within this population.

Background: Postoperative acute ischemic stroke remains a critical complication of coronary artery bypass grafting. This study aimed to develop a novel Total Cerebral Atherosclerosis Burden (TCAB) score for predicting the risk of AIS post-coronary artery bypass grafting.

Methods: A prospective cohort of patients undergoing coronary artery bypass grafting was enrolled. The TCAB score was calculated by summing stenosis severity grades (0: <50%, 1: 50-69%, 2: 70-99%, 3: 100%) across all intracranial and extracranial artery segments. Primary outcome was in-hospital ischemic stroke. Multivariable logistic regression models adjusted for key clinical covariates were used to evaluate the association between TCAB and clinical outcomes.

Results: Among 909 included patients, the mean TCAB score was significantly higher in patients with in-hospital ischemic stroke compared with those without (8 versus 2, P < 0.001). A TCAB score >3 predicted in-hospital ischemic stroke with an area under the curve of 0.756. Across all 3 multivariable models, higher TCAB scores remained independently associated with in-hospital ischemic stroke (Model 3: odds ratio [OR]=1.089, P=0.011), 1-year ischemic stroke (OR=1.093, P=0.011), and 1-year major adverse cardiovascular and cerebrovascular events (OR=1.068, P=0.020). The gradient boosting machine achieved the most stable predictive ability (area under the curve=0.8736 for in-hospital ischemic stroke; 0.8575 for 1-year ischemic stroke; 0.7475 for 1-year major adverse cardiovascular and cerebrovascular events).

Conclusions: The TCAB score, enhanced by machine learning, effectively predicted in-hospital ischemic stroke, 1-year ischemic stroke, and 1-year major adverse cardiovascular and cerebrovascular events post-coronary artery bypass grafting. It offers a practical tool for guiding preoperative revascularization and intraoperative embolic protection.

Background: During the COVID-19 pandemic, the Centers for Medicare and Medicaid Services created a waiver to reimburse telemedicine services. It is important to understand factors that facilitate incorporation of telemedicine into ongoing cardiovascular practice.

Methods: This was a retrospective cohort study of telemedicine and office visits delivered by cardiologists between January 1, 2022, and December 31, 2023, for Medicare beneficiaries. We calculated the adjusted incidence rate ratio (aIRR) of telemedicine visits, representing the proportion of a physician's visits delivered by telemedicine, to identify factors associated with telemedicine use.

Results: There were 23 334 physicians in our cohort; they were predominantly men (84.8%) and affiliated with a hospital (93.5%), and the majority were general cardiologists (66.1%). During 2022 and 2023, 3.4% of visits were delivered by telemedicine. In a regression model adjusted for beneficiary and provider characteristics, several physician-level factors were associated with increased telemedicine: female sex (aIRR, 1.48 [95% CI, 1.41-1.57]), electrophysiology specialty (aIRR, 1.57 [95% CI, 1.47-1.67] compared with general cardiology), and caring for a high proportion of beneficiaries living in areas of social vulnerability (quartile 3 aIRR, 1.22 [95% CI, 1.12-1.32]; quartile 4 aIRR, 1.27 [95% CI, 1.16-1.39]). Caring for more beneficiaries residing in a rural area (aIRR, 0.71 [95% CI, 0.66-0.76]) or the South (aIRR, 0.61 [95% CI, 0.55-0.66]) and for beneficiaries aged >85 years (aIRR, 0.77 [95% CI, 0.73-0.81] were associated with lower use of telemedicine).

Conclusions: Telemedicine is used relatively sparsely among cardiologists. Physician factors, including sex; specialty; and the vulnerability, rurality, and age of beneficiary panels, impact the degree to which telemedicine is a major part of clinical practice.