Valvular Heart Disease Research Articles

Newly detected atrial fibrillation after stroke (AFDAS) is a specific type of AF and have a different pathophysiology compared to patients with previously known AF before a stroke (KAF). However, the characteristics and outcomes between AFDAS and KAF have not been well studied. We aimed to further explore the clinical characteristics and long-term functional outcomes between AFDAS and KAF. We retrospectively analyzed acute ischemic stroke patients admitted to our hospital between 2010 and 2017, who was also diagnosed with AF. The poor outcome was defined by the combination of death and any disability as scored by the modified Rankin Scale (mRS) score at 3 months and 12 months. Among the final sample of 698 patients, 370 (53%) were classified into KAF and 328 (47%) were AFDAS. Compared to KAF, patients with AFDAS had a lower prevalence of hypertension (P = 0.01), previous stroke (P = 0.02), higher prevalence of valvular heart disease (P = 0.02), less prescribed with anticoagulants during the hospitalization (P < 0.01), and higher mortality at 3 months (OR 1.77, 95%CI 1.07-2.92, P = 0.03). Patients with AFDAS had an increased trend of mRS score compared to KAF (3 months, OR 1.37, 95% CI 1.04-1.81, P = 0.02; 12 months, OR 1.32, 95%CI 1.01-1.75, P = 0.04). Patients with AFDAS had a higher risk of death and an increased trend of mRS score compared to KAF. Lower utilization of anticoagulation may be a major reason of worse outcome in AFDAS. Further investigation is required to identify whether the differences of the outcomes between AFDAS and KAF is confounded by pre-existing anticoagulation.

Calcific aortic valve disease (CAVD) is characterized by a fibrocalcific remodeling of the aortic valve. This pathology is the most prevalent valvular heart disease worldwide and is associated with a poor prognosis. Despite extensive research, no pharmacological treatments are available to slow or reverse valvular degeneration, making aortic valve replacement the only current therapeutic option. This lack of clinical success may stem from an incomplete understanding of the disease's mechanisms and the limitations of current preclinical models, which do not fully replicate the complexity of CAVD and its associated risk factors and comorbidities. Indeed, while existing models offer valuable insights, a deeper understanding of CAVD requires incorporating comorbidities, gender-specific mechanisms, and dynamic cellular and tissue-level changes. This review aims to provide the reader with an overview of preclinical models developed in recent years to study CAVD, assessing their strengths and limitations. We review how these models can be used to mimic and/or investigate the cellular and molecular mechanisms involved in CAVD development, and highlight how key risk factors and comorbidities can be incorporated to enhance the translational potential of research. We hope that this approach will help guide researchers in selecting the most appropriate model for their studies, with the goal of advancing the identification of effective therapeutic candidates.

Rheumatic heart disease is a chronic valvular disorder resulting from acute rheumatic fever, predominantly affecting the mitral valve and characterized by progressive fibrotic thickening. Although the initial insult is driven by autoimmune responses triggered by Group A Streptococcus infection, the sustained progression of valvular fibrosis involves a complex interplay of persistent immune activation, chronic inflammation, and, critically, long-term mechanical stress. Mechanical forces arising from altered hemodynamics and structural valve deformation perpetuate valvular interstitial cell activation, endothelial-to-mesenchymal transition, and extracellular matrix remodeling, thereby driving fibrosis even after acute inflammation resolves. Current therapeutic options to halt or reverse mitral valve fibrosis are limited, with surgical repair or replacement remaining the primary interventions for advanced disease. Advancing mechanistic understanding through physiologically relevant models, coupled with early diagnostic strategies and multitargeted antifibrotic approaches, holds promise for preserving valve function. Integrating molecular insights with scalable public health measures may ultimately mitigate the global burden of rheumatic heart disease and improve outcomes for affected populations.

Background: Pulmonary hypertension is common in left-sided heart valve disease, with historical studies reporting mortality rates up to 31% in severe cases undergoing mitral valve surgery. This study evaluates the impact of severe pulmonary hypertension on outcomes of mechanical mitral valve replacement with posterior leaflet preservation by comparing results with patients having mild-to-moderate pulmonary hypertension. Methods: Prospective analysis of 86 patients with mitral valve disease undergoing mechanical valve replacement with posterior leaflet preservation from March 2015 to September 2016 was conducted. Patients were stratified by pulmonary artery pressure: severe (≥60 mmHg, n = 19) versus mild–moderate (35–59 mmHg, n = 67). Primary outcomes included mortality, complications, and functional recovery at 1, 6, and 12 months. Results: The cohort included 67 patients (77.9%) with mild–moderate pulmonary hypertension and 19 patients (22.1%) with severe pulmonary hypertension. Severe pulmonary hypertension patients demonstrated higher NYHA functional class (73.7% class III vs. 46.2%, p = 0.03), larger left atrial diameter (56.3 ± 9.8 vs. 49.5 ± 6.7 mm, p = 0.01), and higher mean pressure gradients (14.4 ± 5.3 vs. 11.3 ± 5.0 mmHg, p = 0.025). Mortality was 5.3% in the severe group versus 0% in the mild–moderate group (p = 0.331). Patients with severe pulmonary hypertension required longer ICU stays (6.3 ± 3.7 vs. 4.7 ± 2.2 days, p = 0.024) but showed no significant differences in ventilation time, reoperation rates, or major complications. At the 12-month follow-up, both groups achieved equivalent outcomes in pulmonary artery pressures, left ventricular function, and cardiac dimensions. Conclusion: In this study with a relatively small sample size, severe pulmonary hypertension was associated with significantly longer intensive care unit stay but not with higher mortality compared to mild–moderate pulmonary hypertension, with both groups attaining comparable functional and hemodynamic parameters at 12 months after mechanical mitral valve replacement with posterior leaflet preservation.

Background: The genetic architectures of valvular heart disease (VHD) and its subtypes have yet to be fully elucidated. Aims: We aimed to clarify the genetic architectures of VHD and its subtypes and to gain insights into VHD biology. Methods: We performed deep-phenotyping by analyzing detailed medical records and echocardiographic data from BioBank Japan. We classified VHD subtypes from stenosis to regurgitation and other abnormalities in the mitral, aortic, tricuspid, and pulmonary valves and the septum, followed by conducting East Asian-specific genome-wide association studies (GWASs). Then, we also performed GWASs in the UK Biobank, applying deep-phenotyping using ICD-10 codes. In addition, we utilized other available GWAS summary statistics, mainly from FinnGen and VA’s Million Veteran Program. Finally, we conducted cross-ancestry meta-analyses. Results: An East Asian-specific GWAS for VHD with 10,358 cases and 128,008 controls identified five genome-wide significant loci, while GWASs for VHD subtypes identified an additional 14 loci. Of the identified 19 loci, 14 had not been previously reported in GWASs for any valve diseases, whereas 12 exhibited very low allele frequencies (&lt;0.001) in other ancestries. Moreover, cross-ancestry meta-analysis for VHD, which involves 93,584 cases and 1,619,230 controls, revealed 89 loci. Then, meta-analyses for VHD subtypes identified an additional 68 loci, totaling 157 loci, including 83 novel loci. Valve regurgitation and stenosis shared only a few loci, suggesting different etiologies. Interestingly, all regurgitation subtypes shared a locus prioritized for PITX2 with relatively high absolute betas (&gt; 0.1), indicating a pivotal role of PITX2 . Pathway analysis revealed that genes associated with VHD were enriched for heart morphogenesis. Additionally, VHD exhibited a significant genetic correlation with atrial fibrillation (AF), congestive heart failure (CHF), and blood pressure (BP), while Mendelian randomization analysis indicated a causal role of BP in VHD. Furthermore, the polygenic risk score (PRS) for VHD stratified the risk of cardiovascular mortality in the other controls in BBJ. The combination of PRS for CHF or AF with that for VHD outperformed original PRS in the prediction of CHF or AF, suggesting VHD as a genetically independent factor. Conclusion: We conducted the first systematic GWASs for VHD and its subtypes, which elucidated the distinct genetic architectures of different VHD subtypes.

Introduction: Air and noise pollution are recognized public health concerns. However, their long-term impact on valvular heart disease (VHD) remains unclear. Methods: This study analyzed 453,413 participants from the UK Biobank. Air pollution was quantified using the air pollution score based on PM 2.5 , PM 2.5-10 , PM 10 , NO x , and NO 2 levels. Road traffic noise (L den and L night ) exposure was estimated based on baseline residential addresses. Participants were categorized into quintiles (Q1-Q5) of exposure. VHD diagnoses were identified from hospitalization and cause-of-death records. Multivariable Cox proportional hazard models were used to assess the association between pollution exposures and VHD risk, presented as hazard ratios (HR) with 95% confidence intervals (CI). Results: During a median follow-up of 13.9 years, 18,806 cases of VHD were recorded. Participants exposed to the highest levels of pollution exposures had a significantly increased risk of developing VHD compared to those in the lowest exposure group (Q5 vs. Q1: air pollution score [HR 1.73, 95% CI 1.61-1.87], PM 2.5 [HR 1.69, 95% CI 1.57-1.82], PM 2.5-10 [HR 1.43, 95% CI 1.34-1.53], PM 10 [HR 1.29, 95% CI 1.22-1.36], NO 2 [HR 1.59, 95% CI 1.47-1.71], NO X [HR 1.64, 95% CI 1.53-1.77], L den [HR 1.66, 95% CI 1.56-1.77], and L night [HR 1.67, 95% CI 1.57-1.78]). These associations persisted significantly regardless of the genetic risk to VHD and extended across all VHD subtypes, including non-rheumatic, rheumatic, aortic, mitral, tricuspid, and pulmonary valve diseases. Conclusion: This study demonstrates a significantly positive association between long-term exposure to air and noise pollution and increased VHD risk.

Introduction Valvular heart disease and chronic kidney disease are significant causes of mortality in the U.S. Their evolving trends remain underexplored in recent decades. We aim to analyze the mortality trends of valvular heart disease and chronic kidney disease from 1999-2020. Research Question: What are the temporal trends in mortality from valvular heart disease and chronic kidney disease in the United States from 1999 to 2020 across demographic and geographic subgroups? Methods: Death certificates from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research) database were examined from 1999 to 2020. Crude mortality rate (CMR) and age adjusted mortality rate (AAMR) per 1,000,000 were calculated and stratified by sex, race/ethnicity, age groups, regions, and states. Temporal trends were described by calculating annual percent change (APC) and average APC (AAPC) in the rates using Joinpoint regression analysis Results: From 1999-2020, a total of 50319 deaths related to valvular diseases and chronic kidney disease among adults aged 25+. An overall increasing mortality trend was observed from 7.13 in 1999 to 13.57 in 2020 (AAPC: 3.33; 95% CI: 2.11 to 4.77; p &lt;0.000001). Males had a higher overall AAMR (14.38) than females (8.17). Highest AAMR was observed in NH Black/African American (11.98), followed by NH American Indians (10.98), NH White (10.54), Hispanics/Latinos (7.83), and NH Asians (7.78). Among regions, highest mortality rate was found in West (12.25), followed by Midwest (11.57), Northeast (10.63), and South (8.78). States in the top 90 th percentile were Oregon (20.07), followed by Vermont (19.26), Washington (19.18), Minnesota (18.21), and Wisconsin (15.07). Rural had a higher AAMR (11.12) than urban (10.42). Highest number of deaths took place in Medical Facility- inpatient (49.64%). Highest CMR was observed in 85+ years. Conclusion There has been a significant increase in mortality associated with both valvular heart disease and chronic kidney disease. These trends highlight the urgent need for ongoing surveillance and targeted public health strategies to reduce the burden of these chronic cardiovascular and renal conditions.

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardiovascular benefits in randomized trials, including reductions in mortality and heart failure hospitalizations. However, real-world evidence on their effectiveness across the population with valvular heart disease (VHD) remains limited. Methods: We analyzed two matched cohorts from a federated health research network. We identified all the population VHD (excluding those who have received valve replacement or repair, those with congenital heart disease, and those with systolic heart failure). Then we divided them into those with SGLT2i prescription (n = 107,607) and those without (n = 107,607). Propensity score matching was performed on 38 variables encompassing demographics, comorbidities, medications, and laboratory covariates. Outcomes were assessed between 30 and 365 days post-index SGLT2i prescription, and those with outcomes prior to the analysis were excluded. Risk estimates, Kaplan-Meier survival analysis, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Results: SGLT2i use was associated with a significantly lower risk of all-cause mortality (2.8% vs. 5.7%; HR: 0.433, 95% CI: 0.414–0.452; p&lt;0.001). Survival at one year was higher in the SGLT2i group (96.93% vs. 93.12%). No significant differences were observed for atrial fibrillation (4.3% vs. 3.6%; HR: 1.014, 95% CI: 0.965–1.065; p=0.586) or ED visits (7.5% vs. 6.3%; HR: 1.036, 95% CI: 0.992–1.083; p=0.111). Rates of hospital admissions (0.01% vs. 0.01%; HR: 2.638, 95% CI: 0.714–9.746; p=0.459), ICU admissions (0.09% vs. 0.10%; HR: 0.845, 95% CI: 0.640–1.117; p=0.415), and cardiogenic shock (0.20% vs. 0.21%; HR: 0.836, 95% CI: 0.693–1.009; p=0.08) were similar between groups. Conclusion: Among the population with VHD, SGLT2i use was associated with a 57% relative reduction in all-cause mortality. Other outcomes, including atrial fibrillation, ED visits, ICU admissions, and cardiogenic shock, showed no significant differences. These findings support the need for further research.

Introduction: Valvular heart disease (VHD) poses a growing global burden, particularly in aging populations. While transcatheter interventions have expanded rapidly over the past two decades, the extent to which trial populations reflect real-world demographics—especially age and sex—is unclear. Understanding enrollment trends and representation gaps is essential to ensure equitable, generalizable evidence for clinical decision-making. Methods: We systematically reviewed VHD interventional trials (2000–2024) indexed in PubMed. Surgical and percutaneous trials across aortic, mitral, tricuspid, and pulmonic valves were included. Trial characteristics, demographics, and interventions were analyzed using descriptive and nonparametric statistics. Results: We included 487 trials enrolling 87,412 participants (45% women). Median trial size increased over time (z = 4.98, p &lt; 0.01), and the mean age of participants also rose significantly (z = 10.08, p &lt; 0.01). Trials involving percutaneous (11% to 45%), bioprosthetic (22% to 53%), aortic valve (27% to 62%), and multinational (2% to 16%) interventions increased over time. Older participants were more commonly enrolled in percutaneous, industry-funded, multinational, bioprosthetic, and aortic valve trials. Female representation remained unchanged across time (median 47%, z = -0.48, p = 0.63), but trials enrolling older participants tended to include more women (ρ = 0.196, p &lt; 0.01). Female representation was highest in mitral (59%) and tricuspid (59%) valve trials, and more common in percutaneous (52%) than surgical (42%) interventions. Conclusion: Over the past two decades, VHD trials have expanded in size and geographic scope, with increased enrollment of older adults, particularly in percutaneous and industry-sponsored studies. However, sex disparities and demographic variability persist. Future trials should prioritize inclusive designs to ensure equitable, generalizable evidence for evolving valve interventions.

Background: Extraction of data from transthoracic echocardiography (TTE) reports is critical for cardiovascular research, particularly in valvular heart disease. While machine learning (ML) and large language models (LLMs) offer automated solutions, they remain computationally intensive, opaque and cost-prohibitive for many health systems. The AHA highlights the need for scalable and interpretable informatics tools to bridge these gaps. Objective: Building on our prior work demonstrating high-accuracy extraction from TTE reports, we developed and validated an enhanced rule-based natural language processing (NLP) pipeline that emphasizes the extraction of valvular heart disease variables including aortic valve (AV) stenosis from structured and free-text sections. Methods: We analyzed 1,405 adult TTE reports (1000 for all parameters with an additional 405 for AV parameters) between 09/2020–03/2023 from a tertiary academic center. Using iteratively refined regular expressions in R, we extracted and structured 20 variables across demographic, functional and structural domains, with a focus on AV parameters, including degree of stenosis, AV area, gradients and velocities. Improving on our prior model, this pipeline parses unstructured narrative text to extract manually typed variables relevant to valvular disease. Performance was validated via comparison to manually extracted data. The pipeline was further evaluated on 7,800 reports for computational performance on a single-core central processing unit (CPU). Results: Overall mean extraction accuracy was 99.8% and 16 of 20 variables demonstrated 100% precision (PPV). AV area (PPV 99.5%, false positives [FP] 2) and AV peak velocity (PPV 99.6%, FP 2) showed slightly lower precision, whereas AV peak gradient (sensitivity [SN] 97.2%, false negatives [FN] 5) and AV dimensionless index (SN 97.4%, FN 6) showed lower sensitivity primarily due to formatting inconsistencies in free-text sections rather than extraction failure. An overall run-time of 14.5 mins for 7,800 reports, average inference time of 111.5 ms/report, throughput of 9 reports/second and max RAM usage of 47 MB per 1,000 reports. Conclusion: This rule-based NLP pipeline achieves near-perfect accuracy in extracting structured and free text variables from TTE reports, without the energy consumption, cost, or opacity of ML. This pipeline is scalable, interpretable and energy-efficient, making it an effective solution for real-world clinical data environments.

Background: While sex differences have been observed in various valvular heart diseases, data on rheumatic mitral stenosis, the most common form globally, remain limited. Objective: We sought to determine sex differences in rheumatic mitral stenosis (MS). Methods: From the 3,140 patients in the Multicenter MitrAl STEnosis with Rheumatic etiology (MASTER) registry in South Korea between January 2001 and December 2020, 2,631 patients who were diagnosed with moderate or severe rheumatic MS were included, after excluding those who had undergone prior mitral valve (MV) intervention. Patients were categorized by sex, and we compared demographics, echocardiographic data, and clinical outcomes, including all-cause death, heart failure hospitalization, MV intervention, and ischemic stroke. Results: Among the total population (n=2,631), 74.1% (n=1,950) were women. Compared to men, women were older (60.4 ± 13.0 vs. 58.5 ± 12.2, p&lt;0.001), had a lower prevalence of atrial fibrillation (AF) (50.6 vs. 63.1%, p&lt;0.001), a lower mean diastolic pressure gradient (6.8 ± 3.7 vs. 7.3 ± 4.1 mmHg, p=0.009), and a smaller left ventricular mass index (96.5 ± 29.0 vs. 107.1 ± 34.0 ml/m 2 ). All-cause mortality, heart failure hospitalization, and MV intervention rates were similar between the sexes. However, women had a significantly higher incidence of ischemic stroke compared to men (log-rank p=0.007, Figure 1 ). This finding remained consistent in propensity-matched analysis (p=0.007, Figure 2 ) after adjusting for clinical and echocardiographic variables, including AF. Conclusion: Women with moderate to severe MS had a higher risk of ischemic stroke compared with men. These findings might suggest the need for sex-specific anticoagulation strategies in the management of rheumatic MS.

Introduction: Sydenham chorea (SC) is a form of acquired chorea of childhood and is linked to Acute Rheumatic Fever (ARF), which is an autoimmune response to infection with Group A Streptococcus (GAS). Historically called St Vitus Dance, SC is reported in some patients with ARF and forms part of the major criteria for ARF in the Jones Criteria. Case Presentation: A 12 years old female presented with 10-day history involuntary movements. She suffered sudden, involuntary, irregular twitching of the right upper, lower limbs and facial mouthing or grimacing. She developed irritability, restlessness, easy crying, anger over minor events, deteriorating handwriting and slurring of speech. A thorough history was taken from patient and family, it was discovered that she had recurrent episodes of sore throat in the last one year, last episode being 1.5 months before the onset of chorea. Her throat infections were never treated by a qualified doctor. Physical examination revealed spooning sign of the hands, milkmaid grip sign, pronator sign of the arms and darting tongue sign. Tonsillar hypertrophy grade I was also noted. Pansystolic murmur was present over apex, 2D Echo was performed which showed moderate MR and mild AR, LVEF was 65%. Blood work showed highly elevated Anti Streptolysin O levels of &gt;650 IU/ml. MRI of the brain didn’t detect any abnormality. Based on the history and findings, a diagnosis of Acute Rheumatic Fever with Sydenham chorea and valvular heart disease was made. The patient was started on Phenoxymethyl Penicillin, Carbamazepine and Pantoprazole after which her choreiform movements started to ameliorate significantly. Discussion: Despite progress in earlier diagnosis and treatment of streptococcal infection, Sydenham Chorea is still an essential feature of acute rheumatic fever in developing nations. The exact pathophysiology of SC hasn’t been understood, various theories have been suggested for the same. Most accepted theory of SC is an autoimmune one, which occurs in response to the group A streptococcal infection. These antibodies are created against streptococcal antigens and react with neuronal protein tissues particularly in the basal ganglia that account for choreiform movements made by SC patients. Carditis is another severe manifestation of ARF. The cardiac lesion frequently encountered in ARF is mitral regurgitation, aortic regurgitation is the other frequently observed valvular disease.

Background: Calcific aortic valve disease (CAVD) is a leading cause of heart failure and cardiovascular mortality worldwide. While disruption of circadian rhythm by means of shift work has been associated with cardiovascular disease in humans, its role in CAVD remains unclear. Objective: To explore the correlation between shift work and CAVD, elucidate the mechanism of circadian rhythm disruption caused by shift work in promoting aortic valve calcification, and discover new strategies for the treatment of CAVD. Methods and results: The cohort study including 263 910 participants without valvular heart disease at baseline in the UK Biobank demonstrated that shift work exposure was associated with a higher risk of aortic stenosis (AS) [hazard ratio (HR) 1.21, 95% confidence interval (Cl) 1.06-1.38]. ApoE -/- mice were exposed to either regular light-dark cycles or weekly alternating light-dark cycles (12 hours shifts), as a well-established model for shift work. After 24-week high fat diet feeding, more severe aortic valve calcification was observed in mice exposed to alternating light-dark cycles, with increased transvalvular flow velocity, thickened valve leaflets, and elevated collagen fiber and calcium deposition within the valves. Alternate of the light-dark cycle disrupted the expression of circadian clock genes, particularly leading to downregulation of Bmal1 (brain and muscle Arnt-like protein 1). Genetic knockout of Bmal1 in mice markedly exacerbated aortic valve calcification, which was not influenced by light conditions. In parallel, silencing of BMAL1 promoted osteogenic differentiation of human aortic valve interstitial cells. Mechanistically, BMAL1 functioned as a transcription factor driving SEMA6D expression. Under the influence of downregulation of BMAL1 expression, the BMAL1-SEMA6D-PPARγ axis was inhibited, which promoted the progression of aortic valve calcification. Besides, SR8278 restored BMAL1 expression, attenuating calcification in vivo and inhibiting TNF-α-induced osteogenesis in vitro. Conclusion: Shift work exposure is associated with increased AS risk. Activation of TNF signaling pathway and downregulation of BMAL1 expression promotes aortic valve calcification by inhibiting the BMAL1-SEMA6D- PPARγ axis under weekly alternating light-dark cycles. The BMAL1 agonist SR8278 may serve as a potential adjuvant therapy for CAVD. Keywords: Calcific aortic valve disease, Circadian rhythm, shift work, TNF signaling, BMAL1

Background: Understanding cardiovascular mortality is key for shaping public health priorities. Two major sources in the U.S.—CDC WONDER and the Global Burden of Disease (GBD) study—report mortality differently. While CDC WONDER reflects death certificate data, GBD employs modeling techniques and redistributes ill-defined ("garbage") codes to improve cause of death attribution. Prior comparisons have focused on ischemic heart disease and stroke, but other cardiovascular conditions remain understudied. Methods: We examined trends in valvular heart disease (I34.0-I37.9), hypertensive heart disease (I11.0, I11.9), peripheral arterial disease (I70.2), infective endocarditis (I38), and aortic aneurysm (I71) using both databases from 1999–2020. Annual U.S. mortality data from GBD and CDC WONDER were analyzed. For each condition, absolute deaths and crude mortality rates (CMRs) per 100,000 population were extracted. Percent change from 1999 to 2020 was calculated. CMRs were reported with 95% uncertainty intervals (UI) for GBD and 95% confidence intervals (CI) for CDC WONDER. Results: Substantial differences were found between the databases. Valvular heart disease deaths rose by 38.8% (GBD) and 32.2% (CDC). CMRs increased from 7.15 (UI: 7.62–6.18) to 8.33 (9.12–6.74) in GBD and from 11.8 (CI: 11.7–11.9) to 13.2 (13.1–13.4) in CDC. Hypertensive heart disease exhibited the most pronounced increase where deaths rose by 147.2% (GBD) and 474.7% (CDC). GBD CMRs rose from 10.6 (11.2–9.46) to 22.0 (23.62–19.21); CDC from 8.9 (9.2–8.9) to 43.8 (44.3–43.8). Peripheral arterial disease deaths rose 20.9% (GBD) but fell 50.4% (CDC). CMRs changed from 3.21 (3.45–2.82) to 3.26 (3.55–2.78) in GBD and from 0.6 (0.6–0.7) to 0.3 (0.3–0.3) in CDC. Infective endocarditis deaths increased by 41.9% (GBD) and 36.4% (CDC). CMRs rose from 2.4 (2.53–2.17) to 2.86 (3.07–2.50) in GBD and from 3.3 (3.4–3.3) to 3.8 (3.9–3.8) in CDC. Aortic aneurysm deaths declined 31.6% (GBD) and 18.9% (CDC). GBD CMRs fell from 6.19 (6.45–5.63) to 3.55 (3.76–3.15); CDC from 7.9 (8.0–7.8) to 5.4 (5.5–5.3). Conclusion: Cardiovascular mortality trends varied significantly between GBD and CDC WONDER. Differences were especially striking in hypertensive heart disease and peripheral arterial disease, likely due to methodological variation in death coding and redistribution. Awareness of these discrepancies is crucial for interpreting national mortality data and informing policy.

Introduction: Diffuse alveolar hemorrhage (DAH) is characterized by hemoptysis, anemia, and diffuse pulmonary infiltrates due to alveolar bleeding. Common causes include vasculitides, coagulopathy, infections, and valvular heart disease. DAH secondary to severe hypertension is extremely rare. We present a case of DAH in a patient with poorly controlled hypertension. Case Description: A 58-year-old man with diabetes and poorly controlled hypertension presented with three days of hemoptysis. He denied other episodes of overt bleeding, chest pain, arthralgias, weight loss, or fever. He had a prior history of treated latent tuberculosis. He traveled to Las Vegas and noted a blow of moldy dust which he recalled as the only significant recent exposure. On arrival, BP was elevated at 206/131 mm Hg, but he was otherwise hemodynamically stable. Troponin was mildly elevated but later normalized. CBC and BMP were unremarkable. Inflammatory markers were minimally elevated (CRP: 3 mg/L, ESR: 10 mm/hr). CT chest showed diffuse bilateral ground-glass opacities. Bronchoscopy with BAL revealed friable mucosa and progressively bloody aliquots, confirming DAH. There was no evidence of malignancy or infection from BAL analysis. Extensive workup for DAH, including ANA, ANCA, cryoglobulins, anti-GBM, QuantiFERON, AFB smears and cultures, Leptospira, Legionella, Strongyloides, fungal, and bacterial cultures, was negative. TTE demonstrated normal EF and moderate LV hypertrophy; there was no valvular abnormality. With no alternate etiology, severely uncontrolled hypertension was deemed the most likely cause of DAH, supported by a few published case reports. The patient was started on nifedipine 60 mg and losartan 50 mg daily. With improved blood pressure for the remainder of his hospital stay, hemoptysis gradually resolved. At the post-hospital visit, he remained asymptomatic with good blood pressure control and complete resolution of lung opacities on imaging. Conclusion: Severe hypertension can cause end-organ damage, affecting the heart, brain, and kidneys; however, DAH is a poorly recognized complication. Proposed mechanisms include alveolar capillary stress failure, microvascular endothelial injury, and pulmonary venous hypertension. While DAH is a rare presentation of severe hypertension with very few cases reported in the literature, our case highlights this unique complication and the importance of strict blood pressure control in its management.

Introduction: In patients with type 2 diabetes (T2D) at high cardiovascular risk, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have been shown to reduce major adverse cardiovascular events. However, patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), have been largely excluded from randomized trials. Hypothesis: We investigated whether GLP1-RA use is associated with improved one-year cardiovascular outcomes in patients with T2D undergoing TAVI. Methods: We conducted a retrospective cohort study using the TriNetX network. Adults (≥18 years) with T2D who underwent TAVI between 2015 and 2023 were included and stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). The primary outcome was a composite of all-cause mortality or hospitalization at 1 year. Secondary outcomes included acute heart failure (HF) exacerbation, acute myocardial infarction (AMI), cardiac arrest, and ischemic stroke. Outcomes were assessed from 1 month to 1 year after TAVI. Survival probabilities were estimated using Kaplan-Meier analysis, and hazard ratios (HRs) were calculated with Cox proportional hazards models. Results: Among 20,454 patients with T2D undergoing TAVI from 2015-2023, 937 received GLP1-RAs. After PSM, 930 patients were included in each cohort, with a mean age of 73 years and 37% female. The mean follow-up duration was 342 days for GLP1-RA users and 325 days for non-users. GLP1-RA cohort exhibited a higher 1-year survival probability (93.8%) compared to non-users (89.5%) (HR 0.573 [95% CI, 0.410-0.801]; p=0.001). GLP1-RA use was also associated lower rates of all-cause hospitalization (HR 0.762 [95% CI, 0.652-0.891]; p=0.001), acute HF exacerbation (HR 0.687 [95% CI, 0.566-0.834]; p&lt;0.001), and cardiac arrest (HR 0.452 [95% CI, 0.213-0.960]; p=0.034). No differences were observed in AMI (HR 1.033 [95% CI, 0.750-1.423]; p=0.844), or ischemic stroke (HR 0.875 [95% CI, 0.659-1.162]; p=0.356). Conclusions: In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiovascular outcomes, including reductions in acute HF exacerbation, all-cause hospitalization, and cardiac arrest. These findings highlight the need for prospective clinical trials to confirm these results.

Introduction: Ventricular arrhythmias are prevalent in patients with both ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) and are associated with increased mortality. Multi-modality imaging may aid in characterization of Ventricular Tachycardia (VT) substrate. We evaluate the utility of pre-procedural cardiac computed tomography (CT) in predicting substrate for ventricular arrhythmias in patients with ICM and NICM within the Emory healthcare system. Methods: Patients who underwent VT or PVC ablation were identified via retrospective chart review from October 2022 through May 2024. Patients with ICM or NICM along with pre-procedural Cardiac CT were included. Results: A total of 298 ablations were reviewed. Among these, 14 patients (average age 62 ± 15 years; 64% male) had pre-procedural cardiac CT that identified potential VT or PVC substrate. Of these patients, 36% (n=5) had documented ICM, 64% (n=9) had NICM. Notably, 14% (n=2) of the CT findings showed evidence of scar, 14% (n=2) indicated subepicardial fat, and all 14 patients (100%) exhibited various wall motion abnormalities (see figure). Mapping and ablation locations were consistent with pre-procedural CT imaging in 64% (n=9) of the cases. The 36% (n=5) of mismatches were primarily found in patients undergoing ablation in papillary muscles or those with bundle branch reentry, areas that are known to be poorly visualized on CT. Conversely, all matched patients (n=9) had CT findings of wall motion abnormalities, scar, or subepicardial fat corresponding to ablation sites. 21% (n=3) of patients exhibited mid-diastolic potentials on mapping that aligned with pre-procedural CT imaging. 43% (n=6) of patients exhibited late potentials on mapping that aligned with pre-procedural CT imaging. Of note, one patient’s CT findings did not match the location of ablation though did align with late potentials on mapping. Conclusions: While there are no clear guidelines on obtaining pre-procedural cardiac CT for VT ablations, our single academic institution experience suggests excellent localization of VT substrate in patients with ICM and NICM by imaging. The few patients with imaging who did not correlate with ablation targets, were those with ablations in papillary muscles, valvular heart disease, or bundle branch reentry, which are challenging to visualize with CT. These results support the potential role of cardiac CT in enhancing the accuracy of VT substrate characterization.

Background: Rhythm control with catheter ablation (CA) of atrial fibrillation (AF) leads to reverse remodeling of AF substrate. Comorbidities may impact this process and outcomes. Sparse cardiovascular (CV) guidelines address comorbidities and rhythm control practices after CA. We characterized incident comorbidities after index CA that may impact outcomes, reablation, or antiarrhythmic drug (AAD) practices after CA in the ARRC-AF study. Methods: 2,429,863 patients in Optum’s deidentified Market Clarity Data (Market Clarity ® ) newly diagnosed with AF (2007–2021) were followed until disenrollment, death, or study end; 23,323 patients underwent index CA. Comorbidity status before CA and comorbidity event rates after CA were analyzed. We examined these before and during intervening periods between CAs and while receiving medical therapy. Results: Among the 23,323 patients who underwent index CA (median follow-up: 3.2 years; 44.6% prescribed AADs), baseline comorbidities included hypertension (51.8%), coronary artery disease (17.9%), obstructive sleep apnea (14.4%), diabetes (11.7%), heart failure (10.5%), chronic obstructive pulmonary disease (8.9%), peripheral vascular disease (5.4%), valvular heart disease (4.9%), and chronic kidney disease (1.1%). During follow up, 19,461 patients (83.4%) had no further CA; 3,862 patients (46.7% prescribed AADs) had ≥1 reablation (1 reablation, 14.2%; 2 reablations, 2.0%; ≥3 reablations, 0.4%; interval between Cas of 539, 536, and 458 days, respectively). Individual comorbidity event rates after CA ranged from 0 to 4.7% in the 3 cohorts with ≥1 comorbidity/patient ( Table ). Conclusion: After CA, new comorbidities continue to emerge at a modest rate. In general, comorbidity event rates increased as the number of reablations increased. Both CV and non-CV comorbidities need to be assessed before reablation (with and without long-term AAD therapy) for potential impact on endpoints and need best practice management. Co-morbidities can impact outcomes and need to be considered for their impact on sample sizes, study endpoints, morbidity, and mortality in AF ablation trials. Optimizing management of comorbidities could potentially improve results of AF interventions

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder caused by dominant mutations in either the PKD1 or PKD2 genes. Both mutations contribute to disease progression; however, mutations in PKD1 are linked to more severe clinical outcomes. While ADPKD is primarily characterized by the development of renal cysts and fibrosis leading to end-stage renal failure, it is increasingly recognized as a systemic disorder with significant cardiovascular involvement. Common cardiac manifestations of ADPKD include left ventricular hypertrophy, systolic and diastolic dysfunction, and valvular heart disease. Goal: Given the systemic nature and cardiovascular risks associated with ADPKD, we sought to investigate the progression of cardiac dysfunction in a mouse model carrying the Pkd1 R3277C (RC) mutation. This mouse model recapitulates human ADPKD disease progression with renal failure by 9 months of age. Methods: Echocardiographic assessment of the left ventricle was performed in anesthetized mice (9-14 months old) using long- and short-axis view recordings acquired with a Vevo 2100 system and MS400 transducer. M-mode and strain were analyzed using Vevo analysis software. Results: We performed histology and morphometry on kidneys and hearts from wild-type (WT), heterozygous (Het), and homozygous (RC) mice. As expected, extensive cyst formation and double kidney weight over tibia length were observed in RC mice (1 year old). Additionally, our data show no macroscopic changes in heart weight or chamber dimensions. Short-axis echocardiographic analysis revealed a preserved ejection fraction (EF) and normal left ventricle (LV) mass, despite a reduction in the estimated LV volume. A parasternal long-axis view obtained with B-mode echocardiography and analyzed with Vevo Strain software showed decreased cardiac output, stroke volume, and end-diastolic volume (EDV). Moreover, global longitudinal strain (GLS) was significantly reduced in RC mice compared to wild-type controls. Conclusions: Our findings suggest the presence of subclinical cardiac dysfunction in this Pkd1 mouse model. Further studies are warranted to comprehensively evaluate diastolic function and to elucidate the underlying mechanisms of cardiovascular involvement in ADPKD.

Background: The current guidelines recommend at least 3 months of optimal guideline-directed medical therapy (GDMT) for patients with heart failure and left bundle branch block (LBBB) before implantation of the beneficial biventricular pacemaker and cardiac resynchronisation therapy (CRT). Research Question: This study evaluated the impact of GDMT and CRT on ventricular function and volumes in patients with heart failure and LBBB, and whether this effect is dependent on mechanical dyssynchrony. Methods: This retrospective cohort study included all patients from the North Denmark Region with a diagnosis of heart failure between January 1 st , 2015, and December 31 st, 2021, and selected patients with LBBB using the validated Marquette 12SL algorithm. Salient exclusion criteria included prior cardiac device, valve disease, and cardiac revascularization without a post-procedural echocardiogram. Patients were grouped based on whether they displayed a typical two-dimensional strain pattern by echocardiogram, indicating a specific dyssynchrony pattern. The typical pattern mandates early activation of a mid-ventricular or basal segment of the septal or anteroseptal wall with peak shortening before 70% of the ejection phase and early stretching of opposing wall segments with peak contraction after the aortic valve closes. Patients without this pattern were in the non-typical pattern group. Results: A total of 381 patients were included. Baseline left ventricular ejection fraction (LVEF) was 26 [IQR 21-31] and 28 [IQR 25-33] in the typical and non-typical pattern groups, respectively. The typical pattern group improved LVEF by 3.5% points (95%CI, 2.6-4.4) versus 11.3% points (95%CI, 9.6-13.0) in the non-typical pattern group during the median titration time of 160 days. In total 24/284 (8.5%) of patients with a typical pattern recovered LVEF &gt; 35% after titration of GDMT, compared to 68/97 (70.1%) in the non-typical pattern group. A total of 175 patients in the typical pattern group had CRT. Resynchronization improved LVEF by 17.3% (CI 95%, 16.2-18.6) and significantly reduced LVEDV by 46.2mL (±50.4) and LVESV by 56.2mL (±43.4), resulting in 136/168 (81.0%) recovering LVEF &gt; 35%. Conclusion: Patients with heart failure, left bundle branch block, and a typical pattern show clinically insignificant improvements in LVEF by GDMT. However, these patients had a five-fold increase in LVEF after CRT. These patients may benefit from early treatment with CRT.