Papanastasiou CA, Kampaktsis PN, Papalamprakopoulou Z
… +14 more, Gossios T, Panagiotidis T, Bazmpani MA, Zegkos T, Kokkinidis DN, Votsis S, Tziatzios I, Parcharidou D, Kamperidis V, Efthimiadis G, Giannopoulos AA, Tsapas A, Ziakas A, Karamitsos TD
Am J Cardiol
· 2026 May · PMID 42107501
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Cardiac magnetic resonance (CMR) has gained ground in the assessment of mitral valve prolapse (MVP) patients. In this meta-analysis, we assessed the prognostic value of key CMR-derived imaging biomarkers -late gadolinium...Cardiac magnetic resonance (CMR) has gained ground in the assessment of mitral valve prolapse (MVP) patients. In this meta-analysis, we assessed the prognostic value of key CMR-derived imaging biomarkers -late gadolinium enhancement (LGE), mitral annular disjunction (MAD), and systolic curling- in patients with MVP. We also aimed to define the clinical and imaging features of patients with LGE on CMR. A total of 15 studies comprising 1,994 patients with MVP were included in this systematic review. All 3 MVP-related imaging biomarkers were significantly associated with increased risk of arrhythmic events (pooled RRs: 1.8, 95% CI 1.4 to 2.2, I: 43% for LGE; 1.5, 95% CI 1.2 to 1.9, I: 49% for MAD; 1.8, 95% CI 1.1 to 2.9, I: 40% for curling). LGE demonstrated good predictive performance (Area under curve [AUC]: 0.76, 95% CI 0.72 to 0.80), with pooled sensitivity 0.75 (95% CI 0.57 to 0.87) and specificity 0.63 (95% CI 0.41 to 0.81) for life-threatening ventricular arrhythmias and sudden cardiac death. Additionally, according to our study, patients with LGE were older, had greater mitral regurgitation and more commonly MAD and bileaflet prolapse than those without LGE. In conclusion, CMR is an important tool for the risk stratification of patients with MVP; however, future studies should focus on clinical management pathways for LGE-positive patients with MVP.
Am J Cardiol
· 2026 May · PMID 42107500
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Estimated glomerular filtration rate (eGFR) is a key metric for assessing and monitoring kidney function. In heart failure management, guideline-directed medical therapy (GDMT) medications such as renin-angiotensin-aldos...Estimated glomerular filtration rate (eGFR) is a key metric for assessing and monitoring kidney function. In heart failure management, guideline-directed medical therapy (GDMT) medications such as renin-angiotensin-aldosterone system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors can initially cause a transient decrease in eGFR due to hemodynamic changes, such as a reduction in systemic and glomerular hypertension, reversal of hyperfiltration, and vasodilation in the glomerular vasculature. Despite the initial drop, long-term use of GDMT slows eGFR decline and, in the long-term, lowers the risk of developing chronic kidney disease. However, a significant decline in eGFR (≥20% to 30% reduction) may require closer monitoring and treatment adjustments. Additionally, the combined effect of these agents on eGFR, whether administered concurrently or sequentially, is not clearly understood and should be carefully considered. In conclusion, this review highlights the need for a collaborative approach between nephrologists and cardiologists to closely monitor and manage eGFR changes following GDMT initiation. Prompt alerts to clinicians via the electronic health record, patient education, regular assessment, and clinical review for sustained reduction in eGFR are strategies to maximize the use and subsequent reno-protective effect of GDMT in heart failure.
Zidan A, El-Sururi M, Belbase A
… +6 more, Saleh Y, Kalasipudi R, Al-Rawi R, Malik A, Gupta S, Perez MV
Am J Cardiol
· 2026 May · PMID 42106063
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Large language models (LLMs) are increasingly integrated into healthcare, yet their clinical reliability depends not only on accuracy but also on confidence calibration. General-purpose models have demonstrated strong pe...Large language models (LLMs) are increasingly integrated into healthcare, yet their clinical reliability depends not only on accuracy but also on confidence calibration. General-purpose models have demonstrated strong performance on medical knowledge tasks, while medical-specific models are designed to offer domain alignment. Whether specialization improves clinically meaningful reliability remains unclear. Cardiology, with its complex case-based reasoning, provides a high-stakes test domain. To compare general-purpose and medical-specific LLMs on a standardized cardiology knowledge benchmark, with emphasis on diagnostic accuracy, confidence calibration, uncertainty, and fidelity. A total of 365 text-based questions from the Adult Clinical Cardiology Self-Assessment Program (ACCSAP) were evaluated after exclusion of image-dependent items. ChatGPT-4o and Gemini 2.5 Pro represented general-purpose models, while MedGemma 27B served as a medically fine-tuned comparator. Models received a standardized structured prompt eliciting stepwise reasoning, final answer selection, and self-reported confidence, uncertainty, and fidelity. Statistical comparisons included chi-square testing, nonparametric analyses, correlation coefficients, and Brier scores for calibration. Accuracy differed significantly by model (chi-square = 58.26, p < 0.001): Gemini achieved 87% (95% CI 84% to 91%), ChatGPT 85% (81% to 89%), and MedGemma 67% (62% to 71%). All models reported high confidence, but calibration was modest. Mean confidence differed only slightly between correct and incorrect responses (absolute differences <3%). Brier scores indicated imperfect calibration (Gemini 0.115, ChatGPT 0.137, MedGemma 0.262). ChatGPT demonstrated the strongest confidence-accuracy correlation (r = 0.80, p = 0.005), while Gemini and MedGemma showed weak or nonsignificant alignment. MedGemma exhibited higher uncertainty and lower fidelity across categories. Performance varied by subspecialty, with generalist models outperforming in integrative domains. General-purpose LLMs outperformed a medical-specific model on text-based cardiology assessment, suggesting that large-scale general training may confer advantages in complex clinical reasoning. However, all models showed clinically limited confidence calibration, indicating that self-reported certainty is an unreliable indicator of correctness. Until uncertainty estimation improves, LLM use in cardiology should remain supportive and clinician-supervised.
Park EJ, Kang DO, Lee JS
… +6 more, Lee J, Kim YH, Lim SY, Ahn JC, Song WH, Kim S
Am J Cardiol
· 2026 May · PMID 42103203
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Lifelong antiplatelet maintenance therapy is required after drug-eluting stent (DES) implantation. Although recent randomized studies have suggested potential benefits of clopidogrel monotherapy over aspirin, evidence fr...Lifelong antiplatelet maintenance therapy is required after drug-eluting stent (DES) implantation. Although recent randomized studies have suggested potential benefits of clopidogrel monotherapy over aspirin, evidence from unselected real-world populations remains limited. Using a randomly sampled 20% representative cohort from the Korean National Health Insurance Service database, we identified patients who underwent percutaneous coronary intervention (PCI) with DES between 2002 and 2018. Among patients who remained event-free for 3 years after PCI, thereby defining a stable late chronic maintenance phase, treatment groups were defined by the prescribed antiplatelet agent within 30 days before the event or censoring. After 1:1 propensity score matching, 18,168 patients were analyzed. The primary endpoint was a composite of all-cause death, myocardial infarction (MI), ischemic stroke, and major bleeding during follow-up of up to 10 years. Secondary endpoints comprised 2 composite outcomes: an ischemic composite (MI, repeated revascularization, ischemic stroke, and cardiovascular death) and a hemorrhagic composite (intracranial hemorrhage and major bleeding). The primary composite endpoint did not differ between clopidogrel and aspirin groups (adjusted hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.94 to 1.09; p = 0.85). Ischemic and hemorrhagic composite outcomes were also comparable (adjusted HR 0.94 [0.84 to 1.05] and 1.03 [0.92 to 1.14], respectively). No significant differences were observed in individual endpoints except for MI (adjusted HR 0.71 [0.58 to 0.87]; p = 0.001), favoring clopidogrel. In conclusion, in this nationwide real-world cohort of event-free survivors 3 years after DES PCI, aspirin, and clopidogrel showed comparable long-term efficacy and safety during the chronic maintenance phase over 10 years of follow-up, without a broad net clinical advantage of either strategy.
Severe symptomatic tricuspid regurgitation is associated with a poor prognosis, and many patients are ineligible for surgical intervention. Transcatheter tricuspid valve intervention (TTVI) has emerged as a less invasive...Severe symptomatic tricuspid regurgitation is associated with a poor prognosis, and many patients are ineligible for surgical intervention. Transcatheter tricuspid valve intervention (TTVI) has emerged as a less invasive alternative, but its impact on clinical outcomes compared with optimal medical therapy (OMT) remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies comparing TTVI (transcatheter edge-to-edge repair or valve replacement) with OMT. Databases were searched from inception through December 31, 2025. Outcomes included all-cause and cardiovascular mortality, heart failure hospitalization, myocardial infarction, stroke, bleeding, and new permanent pacemaker or implantable cardioverter-defibrillator implantation. Random-effects models were used to calculate pooled odds ratios. Thirteen studies encompassing 6,732 patients (3,240 TTVI; 3,492 OMT) were included. In pooled analyses of randomized and observational studies, TTVI was associated with a significant reduction in all-cause mortality compared with OMT (odds ratios 0.70; p = 0.009). However, this benefit was not observed in an RCT-only analysis. No significant differences were noted in cardiovascular mortality, heart failure hospitalization, myocardial infarction, severe bleeding, or stroke. A nonsignificant trend toward increased permanent pacemaker/implantable cardioverter-defibrillator implantation (p = 0.06) was primarily driven by valve replacement devices. In symptomatic tricuspid regurgitation, TTVI was associated with reduced all-cause mortality in pooled analyses incorporating both randomized and observational data; however, this benefit was not confirmed in RCT-only analyses, likely reflecting residual confounding in nonrandomized studies which may overestimate treatment effects. These findings support TTVI as an effective therapeutic option for appropriately selected high-risk patients.
Lundgren SW, Diederich T, Lyden E
… +4 more, Nohl J, Alonso W, Pozehl B, Burdorf AF
Am J Cardiol
· 2026 May · PMID 42103201
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Guidance on the use of neurohormonal antagonists (NHA) following left ventricular assist device (LVAD) implantation remains scant despite studies showing that use may reduce morbidity and mortality. We evaluated the impa...Guidance on the use of neurohormonal antagonists (NHA) following left ventricular assist device (LVAD) implantation remains scant despite studies showing that use may reduce morbidity and mortality. We evaluated the impact of a 12-week clinic designed to optimize NHA post-LVAD on medication use and outcomes. A multidisciplinary clinic enrolled patients' postimplantation. The clinic consisted of 6 visits and included medication optimization, nutrition, and pharmacy counseling. Not-enrolled patients served as the comparison group. A total of 44 patients completed the VAD optimization clinic, the comparison group included 71 patients. Enrolled patients averaged 56.1 (±11.4) years of age, 14 (31.8%) were female, 42 (95.5%) patients were HeartMate 3, and the average time to enrollment was 46 (±20) days postimplant. At the end of OPTIMIZE, there was a significant improvement in quadruple NHA utilization compared to controls. Fewer patients in our optimization group experienced recurrent (2 or more) hospitalizations within 6 months of LVAD implant compared to controls (p = 0.02). There was a trend toward reduction in right ventricle failure (p = 0.09) and 2-year mortality (p = 0.12) in those who completed the OPTIMIZE clinic. An optimization clinic post-LVAD improves NHA use and may lead to improved outcomes. Randomized, fully powered studies are needed to better understand how NHA optimization influences post-LVAD outcomes.
Ali Akbar U, Mondal A, Vorla M
… +7 more, Alruwaili W, Lacoste J, Thyagaturu H, Shafique N, Shakeel S, Taha A, Balla S
Am J Cardiol
· 2026 May · PMID 42103200
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The Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) trial demonstrated cardiovascular benefits of semaglutide in patients with obesity without diabetes; however, the real-worl...The Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) trial demonstrated cardiovascular benefits of semaglutide in patients with obesity without diabetes; however, the real-world effect across multiple glucagon-like peptide-1 receptor agonist (GLP-1 RA) agents in patients with established atherosclerotic cardiovascular disease (ASCVD) and overweight or obesity without diabetes mellitus remains unknown. We conducted a target trial emulation using data from the TriNetX US Collaborative Network (January 1, 2010, to December 1, 2025) in adults aged ≥45 years with established ASCVD (history of myocardial infarction, stroke, or coronary or peripheral revascularization), BMI ≥27 kg/m², and without type 2 diabetes. New initiation of any GLP-1 RA (liraglutide, semaglutide, dulaglutide, or exenatide) was compared with no GLP-1 RA use. The primary outcome was all-cause mortality; secondary outcomes were acute myocardial infarction, stroke, and heart failure hospitalization over 5 years, analyzed using Cox proportional hazards and Fine-Gray subdistribution hazard models to account for the competing risk of death. Among 14,844 propensity-matched patients without diabetes (7,422 per group; median age 63 [interquartile range 55 to 71] years; 64% women), GLP-1 RA use was associated with lower all-cause mortality (hazard ratio [HR] 0.68; 95% CI 0.53 to 0.88; p = 0.003), acute myocardial infarction (subdistribution HR [sHR] 0.63; 95% CI 0.41 to 0.98; p = 0.040), and heart failure hospitalization (sHR 0.61; 95% CI 0.39 to 0.95; p = 0.028); no significant association was observed for stroke (sHR 0.76; 95% CI 0.52 to 1.10; p = 0.146). Findings were consistent in landmark and age subgroup analyses; a sensitivity analysis including patients with diabetes (N = 31,910 matched pairs) showed similar associations. In conclusion, these real-world findings are broadly directionally consistent with the SELECT trial and provide complementary observational evidence across multiple GLP-1 RA agents in patients with established ASCVD and overweight or obesity without diabetes mellitus, though causal inference cannot be established from observational data alone.
Am J Cardiol
· 2026 May · PMID 42097264
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Obesity represents a pandemic, independent and modifiable cardiovascular risk factor, distinct from other well-known risk factors such as hypertension, hypercholesterolemia, and diabetes mellitus. The impact of this cond...Obesity represents a pandemic, independent and modifiable cardiovascular risk factor, distinct from other well-known risk factors such as hypertension, hypercholesterolemia, and diabetes mellitus. The impact of this condition on cardiovascular outcomes is remarkably potentiated when obesity is associated with hypertension. These include the development and progression of left ventricular hypertrophy, endothelial dysfunction, sympathetic activation to the heart and peripheral vessels, impaired arterial distensibility, pro-atherogenic vascular alterations, and kidney dysfunction and failure. On the clinical ground, these alterations favor the development and progression of cardiovascular complications, such as coronary artery disease, chronic heart failure, life-threatening cardiac arrhythmias, cerebrovascular disease, and sleep apnea syndrome. In conclusion, the present paper will provide a comprehensive in-depth pathophysiological background, clinical consequences, and therapeutic implications of the obesity-related hypertensive phenotype.
Lim LC, Al-Jarshawi M, Chew NWS
… +6 more, Shepherd T, Partington R, Sabouret P, Al-Alwany A, Ray KK, Mamas MA
Am J Cardiol
· 2026 May · PMID 42097262
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Lipoprotein(a) [Lp(a)] is a genetically determined and likely causal independent risk factor for cardiovascular (CV) outcomes and mortality, with levels >50 mg/dL considered risk-enhancing. Over 90% of variation in level...Lipoprotein(a) [Lp(a)] is a genetically determined and likely causal independent risk factor for cardiovascular (CV) outcomes and mortality, with levels >50 mg/dL considered risk-enhancing. Over 90% of variation in levels is genetically determined, with levels varying by race/ethnicity. Evidence on whether Lp(a) risk thresholds vary by race/ethnicity, and remains inconsistent. This study examines whether the association between Lp(a) and mortality differs by race/ethnicity. We analyzed survey-weighted data from a nationally representative muti-ethnic cohort of US adults from NHANES III with mortality follow-up through 2019. Participants were stratified into non-Hispanic White, non-Hispanic Black, or Mexican-American. Associations between Lp(a) and mortality outcomes were estimated using multivariable Cox and Fine-Gray competing risk models. Lp(a) were analyzed as continuous variables, logarithmically transformed, and divided into three groups (<50, 50 to 75, and >75 mg/dL). A total of 50,519,751 survey-weighted records were included. Mean follow-up was 22.6 years. Median Lp(a) concentrations were higher among non-Hispanic Black participants (36 mg/dL, IQR 22 to 66) than non-Hispanic White (12 mg/dL, IQR 3 to 30) and Mexican-American (8 mg/dL, IQR 2 to 22) participants. Mexican American participants with Lp(a) >75 mg/dL had a higher risk of CV mortality that persisted after multivariable adjustment (sHR 2.93, 95% confidence intervals 1.01 to 8.56, p value 0.049). Among non-Hispanic Black participants, higher Lp(a) was linked to all-cause and CV mortality in unadjusted models but not after adjustment. No significant association was detected in non-Hispanic White participants. In conclusion, Lp(a) distributions and their relationship with clinical outcomes vary by race/ethnicity. Our findings suggest that prognostic thresholds for Lp(a) may differ, supporting the need to define and validate race/ethnicity-specific cut-offs that best predict CV outcomes and improve risk stratification.
Paradoxical low-flow, low-gradient aortic stenosis (pLF-LG AS) represents a distinct phenotype of severe aortic stenosis characterized by a reduced aortic valve area with low transvalvular gradients despite preserved lef...Paradoxical low-flow, low-gradient aortic stenosis (pLF-LG AS) represents a distinct phenotype of severe aortic stenosis characterized by a reduced aortic valve area with low transvalvular gradients despite preserved left ventricular ejection fraction and reduced forward flow. It is associated with concentric remodeling, impaired longitudinal systolic function, and diastolic dysfunction, resulting in reduced stroke volume and potential underestimation of disease severity. This state-of-the-art review synthesizes evidence from registries, observational studies, randomized trial subgroup analyses, guideline recommendations, and mechanistic investigations. Diagnosis requires an integrative multimodality approach combining Doppler echocardiography, low-dose dobutamine stress echocardiography, and computed tomography-based aortic valve calcium scoring to differentiate true-severe from pseudo-severe disease. In symptomatic patients with confirmed severe pLF-LG AS, aortic valve replacement is associated with improved survival, although the magnitude of clinical benefit remains variable. Transcatheter aortic valve implantation represents an effective treatment option in selected patients; however, phenotype-specific comparative data versus surgical valve replacement remain limited. Overall, pLF-LG AS requires accurate diagnostic confirmation and individualized, heart team-guided management to optimize clinical outcomes.
Cau R, Luetkens J, Pontone G
… +25 more, Muscogiuri G, Faletti R, Montisci R, Arcari L, Normant S, Catapano F, D'Angelo T, Bischoff L, Esposito A, Palmisano A, Meloni A, Ciolina F, Negri F, Lisi C, Imazio M, Marchetti MF, Galea N, Volpe A, Blandino A, Pambianchi G, Clemente A, Dacher JN, Gatti M, Saba L, EVOLUTION Group
Takotsubo syndrome (TS) is characterized by transient left ventricular dysfunction accompanied by dynamic changes in myocardial tissue; however, differences in cardiac magnetic resonance (CMR) findings across disease pha...Takotsubo syndrome (TS) is characterized by transient left ventricular dysfunction accompanied by dynamic changes in myocardial tissue; however, differences in cardiac magnetic resonance (CMR) findings across disease phases remain incompletely characterized, particularly in large multicenter cohorts. This retrospective analysis from the multicenter EVOLUTION registry included 439 consecutive patients with TS (400 females; mean age 70.01 ± 11.59 years), stratified according to the time from symptom onset to CMR into acute (1 to 72 hours), subacute (4 to 21 days), and late (≥22 days) acquisition groups. Among these, 146 (33%) were classified as acute, 266 (60%) as subacute, and 27 (6%) as late. Biventricular systolic function was higher in patients imaged at later time points (both p = 0.001). Myocardial edema and late gadolinium enhancement (LGE) were more prevalent and extensive in patients imaged earlier and less evident in those imaged later. In multivariable analysis, T2-mapping Z-score and LGE extent were independently associated with earlier timing of CMR. T2-mapping Z-score decreased by approximately 0.22 units per day, corresponding to an average relative decline of 3% to 4% per day. In conclusion, cross-sectional CMR assessment in TS demonstrates that patients imaged at later time points exhibit more preserved systolic function and lower prevalence of myocardial edema and LGE, supporting the dynamic and reversible nature of myocardial injury in this condition; however, longitudinal studies with serial imaging are needed to confirm these findings.
Bruton tyrosine kinase inhibitors (BTKis) are foundational therapies for B-cell malignancies but are associated with clinically important cardiovascular toxicities. Ibrutinib has been linked to atrial fibrillation/flutte...Bruton tyrosine kinase inhibitors (BTKis) are foundational therapies for B-cell malignancies but are associated with clinically important cardiovascular toxicities. Ibrutinib has been linked to atrial fibrillation/flutter (AF/AFL), bleeding, and ventricular arrhythmias, whereas second-generation BTKis such as Zanubrutinib may confer improved cardiovascular safety. In this study, we aimed to compare adverse cardiovascular outcomes between zanubrutinib and ibrutinib in a large real-world cohort. We conducted a retrospective, multicenter cohort study using the TriNetX Global Collaborative Network. Adults aged ≥18 years with chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, waldenström macroglobulinemia, or marginal zone lymphoma initiating a BTKi were included. Patients with AF/flutter before starting BTKi were excluded. Propensity score matching (1:1) was done across 41 covariates. Outcomes were assessed within 12 months of beginning the BTKi. The Cox-proportional model was used to calculate hazard ratios (HR), and a p-value <0.05 was considered significant. Propensity matching yielded 3,447 balanced pairs. The mean age was 71 years, with 40% females in each cohort. Compared to Ibrutinib users, Zanubrutinib users experienced significantly lower risks of incident AF/AFL (HR = 0.47; 95% CI: 0.38 to 0.58; p <0.001), major bleeding (HR = 0.79; 95% CI: 0.68 to 0.91; p = 0.001), and all-cause mortality (HR = 0.27; 95% CI: 0.15 to 0.48; p <0.001). There was no significant difference between the 2 cohorts in terms of intracranial hemorrhage, ischemic stroke, myocardial infarction, ventricular arrhythmias, incident heart failure, and incident hypertension. In conclusion, Zanubrutinib was associated with a lower risk of AF/AFL, major bleeding, and all-cause mortality compared with Ibrutinib. These findings support the preferential use of Zanubrutinib when cardiovascular safety is a key consideration in patients with B-cell malignancies.
Functional mitral regurgitation (FMR) includes atrial (aFMR), ventricular (vFMR), or combined atrial and ventricular (avFMR) phenotypes. This study evaluated differences in clinical, echocardiographic, and invasive hemod...Functional mitral regurgitation (FMR) includes atrial (aFMR), ventricular (vFMR), or combined atrial and ventricular (avFMR) phenotypes. This study evaluated differences in clinical, echocardiographic, and invasive hemodynamic features among aFMR, vFMR, and avFMR in patients undergoing transcatheter edge-to-edge repair (TEER). We retrospectively analyzed patients who underwent TEER for significant FMR at the Cleveland Clinic from 2019 to 2023. FMR was diagnosed in patients with structurally normal mitral leaflets and regurgitation secondary to atrial or ventricular remodeling. aFMR was defined by isolated left atrial (LA) dilation (left atrial volume index ≥40 mL/m²) without left ventricular (LV) dysfunction; vFMR by LV dysfunction without LA dilation; and avFMR by both. A total of 127 patients were included. Mean age was 71.7 years, and 59% were male. Thirty patients (24%) had aFMR, 23 (18%) had vFMR, and 74 (58%) had avFMR. aFMR patients had higher lateral/septal e' and lower E/e'. LV volumes, LVEF, and LV global longitudinal strain were more impaired in vFMR/avFMR. aFMR patients had lower baseline LA mean pressure (p = 0.031) and V-wave (p = 0.012). After TEER, all groups demonstrated significant reductions in LA pressures, with no adjusted differences in postprocedural LA mean pressure (p = 0.140) or V-wave (p = 0.238). Procedural success (MR ≤2+) was high across groups (94%). In conclusion, FMR phenotype is associated with differences in echocardiographic and hemodynamic profiles, with lower baseline LA pressures in aFMR. All subtypes showed favorable reductions in LA pressures and V-waves after TEER, with high procedural success, supporting TEER as an effective therapy across FMR subtypes.
While triglyceride-rich lipoproteins and small dense low-density lipoprotein (sdLDL) are associated with accelerated coronary atherosclerosis, their relationship with peripheral artery disease (PAD) is less clear. Fifty-...While triglyceride-rich lipoproteins and small dense low-density lipoprotein (sdLDL) are associated with accelerated coronary atherosclerosis, their relationship with peripheral artery disease (PAD) is less clear. Fifty-five male subjects were enrolled from a vascular surgery clinic, including 46 patients with symptomatic PAD (Rutherford categories 3-6) undergoing lower extremity intervention and 9 controls without PAD symptoms and with normal ankle-brachial indices or palpable pedal pulses. Fasting lipid panels and LDL subfraction analysis using the Lipoprint assay were obtained. Clinical characteristics and lipid parameters were compared between groups. The mean age was 68.5 ± 8.9 years in the PAD group and 63.3 ± 15.6 years in controls (p = 0.09). Total cholesterol and LDL-C levels were similar between the PAD and control groups. Patients with PAD demonstrated higher levels of very-low-density lipoprotein cholesterol and triglycerides, though these differences did not reach statistical significance. During 3 years of follow-up, patients with PAD experienced substantially higher rates of major adverse cardiovascular and limb events. In this pilot cohort, traditional lipid parameters did not differ between patients with and without PAD; however, there was a trend toward higher levels of triglyceride-rich lipoproteins in patients with PAD. These findings support further investigation of triglyceride-associated lipoprotein fractions in PAD pathophysiology.
Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention in atrial fibrillation (AF). While reduced-dose regimens are frequently prescribed for elderly or comorbid patients, evidence on long-term s...Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention in atrial fibrillation (AF). While reduced-dose regimens are frequently prescribed for elderly or comorbid patients, evidence on long-term safety and effectiveness remains inconsistent. We evaluated outcomes associated with dose-stratified DOAC therapy in a large, real-world AF cohort. We aimed to describe long-term all-cause mortality, stroke, and bleeding rates stratified by DOAC dose and class. We conducted a retrospective observational cohort study using a large AF registry from the Alfred Hospital. Adults with AF who were prescribed a DOAC were categorized as receiving a standard dose, a guideline-based reduced dose, or a non-guideline-based reduced dose. The primary outcomes were all-cause mortality, with secondary outcomes of major bleeding and stroke/systemic embolism rates. Cox proportional hazards models were adjusted for all significant covariates. Among 3,729 patients, 2,722 (73.0%) received standard dose, 462 (12.4%) guideline-reduced, and 547 (14.7%) non-guideline-reduced DOACs. The non-guideline-reduced dose group was associated with higher mortality compared with the full-dose DOAC group (hazard ratios [HR] 1.42, 95% CI 1.12-1.81; p <0.01), but the guideline-reduced dose group was not (HR 1.19, 95% CI 0.92-1.50; p = 0.2). Guideline-reduced dosing was associated with increased stroke/systemic embolism (HR 3.32, 95% CI 1.19-9.23; p = 0.02), while non-guideline-based dosing showed a borderline association (HR 2.22, 95% CI 0.82-5.96; p = 0.11) compared to full-dose DOAC. There was no association between major bleeding and dose groups. In conclusion, dose-adjusted DOACs were associated with a significantly higher mortality and thromboembolic risk, with no association observed between dose reduction and major bleeding. These findings suggest that dose-adjusted regimens are being selected for patients with particularly high residual risk.