Progress in cardiovascular diseases最新文献

The management of symptomatic obstructive hypertrophic cardiomyopathy remains a therapeutic clinical challenge. Surgical septal myectomy has long been established as the gold-standard intervention for patients with persistent symptoms despite optimal medical therapy, offering durable symptom relief with low perioperative risk in experienced centers. Recently, the introduction of cardiac myosin inhibitors, such as mavacamten and aficamten, has reshaped the treatment paradigm for obstructive hypertrophic cardiomyopathy. By selectively inhibiting cardiac myosin ATPase activity, these agents reduce hypercontractility and improve myocardial energetic efficiency. Randomized, placebo-controlled trials such as EXPLORER-HCM and SEQUOIA-HCM have demonstrated the efficacy of cardiac myosin inhibitors in reducing left ventricular outflow tract gradients, alleviating symptoms, and enhancing functional capacity in patients with obstructive hypertrophic cardiomyopathy. The growing clinical use of cardiac myosin inhibitors raises critical questions regarding their role relative to surgical intervention. While cardiac myosin inhibitors offer an effective and less invasive alternative for many patients, they do not fully replace surgical myectomy across all clinical settings. This review articles explores the evolving therapeutic landscape of obstructive hypertrophic cardiomyopathy, focusing on the comparative advantages and limitations of cardiac myosin inhibitors and surgical myectomy.

Objective: LIFECARD is a community-based longitudinal cohort in Pakistan investigating how anthropometric, environmental, and mental health factors (anxiety and depression) and lifestyle behaviors in low middle income country settings influence cardiovascular -kidney-metabolic (CKM) syndrome risk trajectories in individuals aged 10 to 45 years old.

Methods and analysis: This 10-year longitudinal study will enroll approximately 4000 participants: 2000 adolescents (10-20 years) and 2000 young adults (21-45 years) from Karachi (peri-urban) and Matiari (rural) districts of Sindh. A multistage sampling design will be employed. Clusters of 200 households will be selected first in each area, followed by random selection of 75 households per cluster. One eligible participant per household will be enrolled to minimize clustering. Baseline assessments include sociodemographic data, clinical and family history, obstetric history (married women aged 15-45), tobacco/alcohol consumption, anxiety and depression screening, dietary intake, physical activity, and air quality measurements (personal, indoor, and outdoor). Anthropometric measurements and laboratory investigations (HbA1c, lipid profile) will be performed. These baseline variables will be captured every 2 years. Blood specimens will be bio-banked for future biomarkers and genomic analyses. Carotid intima-media thickness (cIMT) and plaque assessment via ultrasound will be conducted at baseline and every 5 years.

Conclusion: LIFECARD will be Pakistan's first cohort investigating contextual risk factors for premature CKM from early adolescence (10 years) through adulthood (45 years). These insights will identify critical windows for early interventions to prevent disease initiation and progression.

Background and aims: The prognostic significance of global calcium burden-including coronary artery (CAC), mitral annular (MAC), aortic valve (AVC), and thoracic aortic calcification (TAC)-as assessed by cardiac computed tomography (CCT), remains incompletely understood in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR). This study aimed to evaluate the prognostic impact of overall calcification burden in patients with severe AS undergoing AVR.

Methods: A retrospective analysis of 313 patients with severe AS undergoing CCT before AVR between 2016 and 2019 was conducted. MAC, CAC, AVC were quantified using established scoring methods. For TAC, a total thoracic aortic (TTA) score was developed by evaluating calcifications in the ascending, descending and aortic arch. MAC, CAC, AVC, and TTA were integrated into a comprehensive scoring system, the New Total Calcium (NTC) score, using Random Forest models. Outcomes considered included MACE, all-cause mortality, and non-cardiovascular mortality over a 60-month follow-up.

Results: Among 313 patients (mean age 81 years), 93% underwent transcatheter AVR. Severe CAC and MAC were observed in 11% and 7.7% of patients, respectively. During follow-up, 48% of patients died, with non-cardiovascular deaths accounting for 34% and MACE occurring in 43%. In this predominantly TAVR population, the TTA score predicted MACE (p = 0.01), all-cause mortality (p = 0.01), and non-cardiovascular mortality (p = 0.005). The NTC score demonstrated high prognostic accuracy for MACE at 1-, 2-, and 3-years, with AUC values of 0.91, 0.80, and 0.81, respectively. Validation in an external cohort of 100 patients confirmed its robustness.

Conclusions: In this predominantly transcatheter AVR cohort, the NTC score is a promising tool for risk stratification in patients with severe AS. These findings are primarily applicable to transcatheter AVR patients, and further validation in SAVR populations is warranted.

Background: Mitral annular calcification (MAC) can be complicated by mitral regurgitation (MR). However, data on outcomes of severe MR caused by MAC are limited. This study evaluated outcomes of severe MR due to MAC and the prognostic significance of frailty and comorbidities in guiding management.

Methods: In this single-center, retrospective cohort study, we reviewed our echocardiographic database to identify patients with isolated severe MR due to severe MAC. The primary endpoint was all-cause mortality. The Society of Thoracic Surgeons (STS) risk score, Charlson Comorbidity Index (CCI), and a 3-point frailty index (hemoglobin, albumin, inactivity) were calculated. Echocardiographic parameters were recorded.

Results: Between January 2010 and August 2023, out of 10,061 patients with severe MAC on echocardiography, 128 patients with severe MR due to severe MAC were identified, and followed for a median of 134 days (IQR: 33-1812). Median age was 81 years; 72.7% were female. Forty-five patients (35.2%) underwent mitral valve (MV) intervention, and 83 (64.8%) received conservative management. During follow-up, 63 patients (49.2%) died. MV intervention improved survival, even after propensity score matching (p < 0.001). Higher frailty scores predicted poorer outcomes in the entire cohort (p = 0.004) and the conservative subgroup (p = 0.014) but not the surgical group (p = 0.406). CCI did not influence mortality when stratified by treatment.

Conclusion: Patients with severe MR due to MAC were frail with multiple comorbidities and often managed conservatively. Frailty is associated with all-cause mortality, and MV intervention improves survival regardless of frailty status.

Objective: To examine the association between handgrip strength asymmetry and the risk of all-cause and cardiovascular mortality.

Methods: This cohort study analyzed participants aged 50 years and older from the SHARE study (2004-2022) across 28 countries. Handgrip strength asymmetry was assessed using a dynamometer, and mortality outcomes (all-cause and cardiovascular) were determined through proxy interviews. Using time-varying Cox regression models, we examined the association between handgrip asymmetry and mortality risk, adjusting for multiple covariates.

Results: The study included 107,256 participants (54.9 % women, 45.1 % men). Over a mean follow-up of 7.3 years, 11,574 deaths (10.8 %) from all causes and 4274 (3.98 %) from cardiovascular causes were recorded. The analysis revealed a non-linear relationship. For handgrip strength asymmetries of 4-5 kg, both all-cause mortality risk (HR: 1.06; 95 % CI: 1.01-1.10) and cardiovascular mortality risk (HR: 1.15; 95 % CI: 1.07-1.24) increased significantly. A more pronounced increase was observed from 10 kg of asymmetry, with a 32 % increased risk of all-cause mortality (HR: 1.32; 95 % CI: 1.22-1.43) and a 39 % increased risk of cardiovascular mortality (HR: 1.39; 95 % CI: 1.22-1.59). For asymmetries ≥15 kg, the risk of all-cause mortality increased by 39 % (HR: 1.39; 95 % CI: 1.19-1.61) and by 58 % for cardiovascular mortality (HR: 1.58; 95 % CI: 1.24-2.02).

Conclusions: Even minor handgrip strength asymmetry is significantly linked to higher mortality. This finding suggests that handgrip strength asymmetry may have potential clinical relevance as an additional marker for mortality risk assessment, though further research is needed to evaluate its discriminative value beyond established risk factors.

Background: Left ventricular wall thickness (LVWT) is a key echocardiographic parameter in the diagnosis of cardiac amyloidosis (CA), yet its measurement is prone to variability, and traditional thresholds may miss early disease. We aimed to characterize the spectrum of LVWT and derived parameters in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis.

Methods: In this retrospective study, we included 1845 patients treated for CA at a tertiary amyloidosis center from 2006 to 2024. Echocardiographic data were analyzed to assess LVWT, relative wall thickness (RWT), and left ventricular mass index (LVMi). Sex differences and inter-/intra-observer variability were also examined.

Results: A significant subset of patients presented with normal or mildly increased LVWT ({less than or equal to}1.2 cm), including 13 % of AL-CA and 6.5 % of ATTR-CA patients. Conversely, 12.2 % of AL-CA patients exhibited markedly elevated LVWT (>2.0 cm). Women had significantly lower LVWT. Despite low LVWT, 68 % of patients with IVST and PWT {less than or equal to}1.2 cm had RWT >0.42. RWT was more sensitive than LVMi in identifying CA and showed no sex difference. Measurement variability was substantial, with a standard error of ∼1.5 mm.

Conclusions: CA presents across a wide range of LVWT values, including within normal limits, especially in women. RWT offers greater sensitivity and may enhance early disease detection. Significant observer variability underscores the need for standardization and incorporation of derived metrics in echocardiographic interpretation. These findings highlight the limitations of echocardiography and support the use of complementary parameters for improved diagnostic accuracy.

Ischemic stroke is a significant global health challenge, accounting for approximately 66 % of all strokes worldwide. Recent data indicates that stroke was the third leading cause of death (10.7 % of all deaths), following ischemic heart disease and COVID-19. In 2021, nearly 94 million people were living with the consequences of a stroke, and about 12 million new cases were reported. Major risk factors for stroke include high systolic blood pressure, exposure to ambient particulate matter, smoking, and elevated levels of low-density lipoprotein cholesterol (LDL-C), with LDL-C contributing to nearly one-third of all ischemic strokes. In primary prevention, many at-risk individuals have undiagnosed or poorly managed lipid disorders, including elevated lipoprotein(a). The challenge persists in secondary prevention, where up to 40 % of individuals at risk of recurrent ischemic stroke experience a recurrence within five years. A key reason for this is the inadequate diagnosis and management of lipid disorders, underscoring the necessity for early and intensive (upfront) combination lipid-lowering therapy (LLT) to meet treatment goals promptly after an event. Unfortunately, data indicates that up to 40 % of post-stroke patients receive no LLT, and many more receive inadequate treatment. Additionally, existing guidelines for LLT in both primary and secondary stroke prevention are often inconsistent and outdated. Similarly, the understanding of the effects of LDL-C and LLT on the risks of haemorrhagic stroke and dementia remains limited, emphasizing the need for clear and practical guidance. Thus, within this Consensus Paper we aimed to provide consistent, easy-to-follow, and practical guidance on lipid targets, along with clear pathways for effectively treating patients with lipid disorders who are at risk for stroke and those who have experienced one. This approach is intended to help reduce the risk of recurrent ischemic strokes and their associated complications.