Artificial Intelligence Assessment of Biological Age from Transthoracic Echocardiography: Discrepancies to Chronologic Age Predict Significant Excess Mortality.

BACKGROUND: Age and sex can be estimated by artificial intelligence based on various sources. OBJECTIVES: We aimed to test whether convolutional neural networks could be trained to estimate the age and predict the sex using standard transthoracic echocardiography (TTE), and to evaluate its prognostic implications. METHODS: The algorithm was trained on 76,342 patients, validated in 22,825 patients, and tested in 20,960 patients. It was then externally validated using data from a different hospital (N=556). Finally, a prospective cohort of handheld point-of-care ultrasound (POCUS) devices (N=319; ClinicalTrials.Gov NCT05455541) was used to confirm the findings. Multivariate Cox regression model was used to investigate the association between age-estimation and chronological age with overall survival. RESULTS: The mean average error in age estimation was 4.9 years, with a Pearson correlation coefficient of 0.922. The probabilistic value of sex had an overall accuracy of 96.1% and an area under the curve (AUC) of 0.993. External validation and prospective study cohorts yielded consistent results. Finally, survival analysis demonstrated that age prediction ≥ 5 years of chronological age was associated with an independent 34% increased risk of death during follow-up (p<0.001). CONCLUSIONS: Applying artificial intelligence to the standard TTE allows prediction of sex and estimation of age. Machine-based estimation is an independent predictor of overall survival and, with further evaluation, can be used for risk stratification and estimation of biological age.

Low cardiorespiratory fitness is associated with elevated intraocular pressure among apparently healthy adults.

PURPOSE: To evaluate the association of cardiorespiratory fitness with elevated intraocular pressure (IOP) in healthy adults. METHODS: In this cross-sectional study, we evaluated 17,990 asymptomatic self-referred adults free of diabetes or cardiovascular disease who were screened in a preventive healthcare setting. All subjects underwent measurement of IOP and completed a maximal exercise stress test according to the Bruce protocol. Fitness was categorized into age and sex-specific quintiles according to the treadmill time and dichotomized to low (lowest quintile) and non-low fitness groups. Elevated IOP was defined as ≥ 21 mmHg. RESULTS: Median age was 45 (IQR 39-52) years and 12,073 (67%) were men. There were 3,351 (19%) subjects in the low fitness group. Median IOP was 14 mmHg (IQR 12-16) with elevated IOP documented in 188 (1%) subjects. Univariate binary logistic regression model demonstrated that compared with non-low fitness group, subjects in the low fitness group were 2.2 times more likely to have elevated IOP (95% CI 1.598-2.95, p<0.001). Multivariate binary logistic regression with adjustment to known cardiovascular risk factors (age, sex, hypertension, smoking, overweight, regular physical activity, low HDL cholesterol, high triglycerides, and fasting glucose levels) successfully demonstrated that lower fitness was independently and significantly associated with a 90% increased likelihood of elevated IOP (95% CI 1.37-2.61, p<0.001). Subgroup analysis revealed that the association was more pronounced among women compared with men (OR 3.8 vs. 1.6, p for interaction = 0.069). CONCLUSIONS: Low cardiorespiratory fitness is independently associated with increased IOP among apparently healthy adults.

Non-Interventional Weight Changes Are Associated with Alterations in Serum Uric Acid Levels.

Background/Objectives: Serum uric acid is an established cardiovascular risk factor. Higher serum uric acid levels are associated with overweight and obesity. We assessed whether non-interventional weight changes affect serum uric acid levels. Methods: We performed a retrospective analysis of 19,193 participants referred to annual medical screening. Body mass index (BMI) and serum uric acid were measured annually. Subjects were divided into five groups according to changes in BMI between visits: large reduction (reduction of more than 5% in BMI), moderate reduction (reduction of more than 2.5% and 5% or less in BMI), unchanged (up to 2.5% change in BMI), moderate increase (increase of more than 2.5% and 5% or less in BMI), and large increase (increase of more than 5% in BMI). The primary outcome was serum uric acid level changes between visits. Results: A decrease in serum uric acid levels was evident as BMI decreased and an increase in serum uric acid levels was associated with an increase in BMI. The proportion of patients whose serum uric acid levels were increased by at least 10% between visits increased with the relative increase in BMI, while the proportion of patients whose serum uric acid levels were reduced by at least 10% decreased with the relative decrease in BMI. Conclusions: Non-interventional weight changes, even modest, are associated with significant alterations in serum uric acid levels. Our findings may aid in better risk stratification and the primary prevention of cardiovascular morbidity and mortality.

Amyloid Typing in Cardiac Amyloidosis Using Western Blotting.

BACKGROUND: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA). OBJECTIVES: To demonstrate the utility of the Western blotting (WB)-based amyloid typing method in patients diagnosed with cardiac amyloidosis where the type of amyloid was not obvious based on the clinical context. METHODS: Congo red positive endomyocardial biopsy specimens were studied in patients where the type of amyloid was uncertain. Amyloid proteins were extracted and identified by WB. Mass spectrometry (MS) of the electrophoretically resolved protein-in-gel bands was used for confirmation of WB data. RESULTS: WB analysis allowed differentiation between AL, AA, and ATTR in cardiac biopsies based on specific immunoreactivity of the electrophoretically separated proteins and their characteristic molecular weight. The obtained results were confirmed by MS. CONCLUSIONS: WB-based amyloid typing method is cheaper and more readily available than the complex and expensive gold standard techniques such as MS analysis or immunoelectron microscopy. Notably, it is more sensitive and specific than the commonly used immunohistochemical techniques and may provide an accessible diagnostic service to patients with amyloidosis in Israel.

Non-Interventional Weight Changes Are Associated with Alterations in Lipid Profiles and in the Triglyceride-to-HDL Cholesterol Ratio.

BACKGROUND: Obesity is associated with dyslipidemia, and weight loss can improve obese patients' lipid profile. Here, we assessed whether non-interventional weight changes are associated with alterations in lipid profile, particularly the triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C). METHODS: In this retrospective analysis of subjects referred to medical screening, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), TG, and HDL-C levels were measured annually. Patients were divided according to BMI changes between visits. The primary outcomes were the changes in LDL-C, TG, HDL-C, and the TG/HDL-C ratio between visits. RESULTS: The final analysis included 18,828 subjects. During the year of follow-up, 9.3% of the study population lost more than 5% of their weight and 9.2% gained more than 5% of their weight. The effect of weight changes on TG and on the TG/HDL-C ratio was remarkable. Patients with greater BMI increases showed greater increases in their TG/HDL-C ratio, and conversely, a decreased BMI level had lower TG/HDL-C ratios. This is true even for moderate changes of more than 2.5% in BMI. CONCLUSIONS: Non-interventional weight changes, even modest ones, are associated with significant alterations in the lipid profile. Understanding that modest, non-interventional weight changes are associated with alterations in the TG/HDL-C ratio may aid in better risk stratification and primary prevention of CV morbidity and mortality.

The safety of sodium glucose transporter 2 inhibitors and trends in clinical and hemodynamic parameters in patients with left ventricular assist devices.

BACKGROUND: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2-I) in patients with left ventricular assist devices (LVAD) are unknown. METHODS: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2-I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2-I. RESULTS: SGLT2-I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2-I initiation was 108 days, IQR (26-477). Following SGLT2-I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2-38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7-4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23-11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2-I initiation (p > 0.2 for all). No adverse events were recorded during median follow-up of 354 days, IQR (206-786). CONCLUSION: SGLT2-I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP.

Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation.

BACKGROUND: Electroporation is a promising nonthermal ablation method for cardiac arrhythmia treatment. Although initial clinical studies found electroporation pulsed-field ablation (PFA) both safe and efficacious, there are significant knowledge gaps concerning the mechanistic nature and electrophysiological consequences of cardiomyocyte electroporation, contributed by the paucity of suitable human in vitro models. Here, we aimed to establish and characterize a functional in vitro model based on human-induced pluripotent stem cells (hiPSCs)-derived cardiac tissue, and to study the fundamentals of cardiac PFA. METHODS: hiPSC-derived cardiomyocytes were seeded as circular cell sheets and subjected to different PFA protocols. Detailed optical mapping, cellular, and molecular characterizations were performed to study PFA mechanisms and electrophysiological outcomes. RESULTS: PFA generated electrically silenced lesions within the hiPSC-derived cardiac circular cell sheets, resulting in areas of conduction block. Both reversible and irreversible electroporation components were identified. Significant electroporation reversibility was documented within 5 to 15-minutes post-PFA. Irreversibly electroporated regions persisted at 24-hours post-PFA. Per single pulse, high-frequency PFA was less efficacious than standard (monophasic) PFA, whereas increasing pulse-number augmented lesion size and diminished reversible electroporation. PFA augmentation could also be achieved by increasing extracellular Ca2+ levels. Flow-cytometry experiments revealed that regulated cell death played an important role following PFA. Assessing for PFA antiarrhythmic properties, sustainable lines of conduction block could be generated using PFA, which could either terminate or isolate arrhythmic activity in the hiPSC-derived cardiac circular cell sheets. CONCLUSIONS: Cardiac electroporation may be studied using hiPSC-derived cardiac tissue, providing novel insights into PFA temporal and electrophysiological characteristics, facilitating electroporation protocol optimization, screening for potential PFA-sensitizers, and investigating the mechanistic nature of PFA antiarrhythmic properties.

Echocardiography vs hemodynamic assessment of diastolic dysfunction.

OBJECTIVES: Ostial CTOs can be challenging to revascularize. We aim to describe the outcomes of ostial chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of 8788 CTO PCIs performed at 35 US and non-US centers between 2012 and 2022. In-hospital major adverse cardiac events (MACE) included death, myocardial infarction, urgent repeat target-vessel revascularization, tamponade requiring pericardiocentesis or surgery, and stroke. RESULTS: Ostial CTOs constituted 12% of all CTOs. Patients with ostial CTOs had higher J-CTO score (2.9 ± 1.2 vs 2.3 ± 1.3; P less than .01). Ostial CTO PCI had lower technical (82% vs. 86%; P less than .01) and procedural (81% vs. 85%; P less than .01) success rates compared with non-ostial CTO PCI. Ostial location was not independently associated with technical success (OR 1.03, CI 95% 0.83-1.29 P =.73). Ostial CTO PCI had a trend towards higher incidence of MACE (2.6% vs. 1.8%; P =.06), driven by higher incidence of in-hospital death (0.9% vs 0.3% P less than.01) and stroke (0.5% vs 0.1% P less than .01). Ostial lesions required more often use of the retrograde approach (30% vs 9%; P less than .01). Ostial CTO PCI required longer procedure time (149 [103,204] vs 110 [72,160] min; P less than .01) and higher air kerma radiation dose (2.3 [1.3, 3.6] vs 2.0 [1.1, 3.5] Gray; P less than .01). CONCLUSIONS: Ostial CTOs are associated with higher lesion complexity and lower technical and procedural success rates. CTO PCI of ostial lesions is associated with frequent need for retrograde crossing, higher incidence of death and stroke, longer procedure time and higher radiation dose.

Modifiers of the Association between E/e' Ratio and Survival among Patients with No Apparent Structural or Functional Cardiac Abnormality.

BACKGROUND: The ratio between early mitral flow wave to early diastolic mitral annulus velocity (E/e' ratio) varies according to age and sex and is associated with mortality in heart failure. We sought to describe the association between E/e' and mortality in patients with no apparent structural or functional cardiac abnormality and explore possible modifiers of this association. METHODS: A retrospective study of 104,315 patients who underwent echocardiographic evaluation during 2009-2021 in the largest tertiary center in Israel. Patients with cancer, ventricular dysfunction, significant valvular or structural heart disease, or evidence of pulmonary hypertension were excluded. RESULTS: The final analysis included 32,836 patients with a median age of 56 (43-66) years, and 13,547 (41%) were female. The median E/e' was 8.3 (6.8-10.3), and 9,306 (28%) had an E/e' >10. During a median follow-up of 5.7 (3.3-8.5) years, 2,396 (7.3%) individuals died. E/e' >10 was associated with mortality (adjusted hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.07-1.27, p<0.001). The mortality risk associated with E/e' >10 was significantly higher in those aged ≤70 (HR 1.26, 95% CI 1.12-1.42, p<0.001), males (HR 1.34, 95% CI 1.19-1.49, p<0.001), a normal left ventricular mass (HR 1.13, 95% CI 1.02-1.24, p = 0.017), and pulmonary artery pressure <30 mmHg (HR 1.18, 95% CI 1.06-1.30, p = 0.003). CONCLUSION: An elevated E/e' is associated with mortality, specifically in younger individuals, males, and those with a normal left ventricular mass and lower pulmonary artery pressure. This suggests that an elevated E/e' might be a marker of subclinical risk in these subgroups. Further studies are needed to identify whether an elevated E/e' is useful in shared decision-making regarding the management of cardiovascular risk factors.

Evaluation of coronary disease among patients undergoing transcatheter aortic valve implantation: propensity score matching analysis.

BACKGROUND: Chronic coronary syndrome (CCS) is common among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). Current guidelines recommend performance of percutaneous coronary intervention (PCI) of any > 70% proximal coronary lesions prior to TAVI. AIMS: To evaluate the outcomes of two diagnostic approaches for CCS clearance pre-TAVI and to determine the reduction in the need of invasive angiography (IA). METHODS: We investigated 2219 patients undergoing TAVI for severe aortic stenosis at two large centers with different pre-procedural strategies for CCS assessment: pre-TAVI computed tomography angiography (CTA) with selective invasive angiography according to CTA results or mandatory IA. We preformed propensity score matching analysis using a 1:1 ratio. The final study cohort included 870 matched patients. Peri-procedural complications were documented according to the VARC-2 criteria. Mortality rates were prospectively documented. RESULTS: Mean age of the study population was 82 ± 7, of whom 55% were female. Patients in the IA group had significantly higher rates of pre-TAVI PCI compared to the CTA group (39% vs. 22%, p < 0.001). Following TAVI, peri-procedural myocardial infarction (MI) rates were similar between the two groups (0.3% vs. 0.7%, p value = 0.41), but spontaneous MI were significantly lower among the IA group (0% vs. 1.3%, p value = 0.03). Kaplan-Meier's survival analysis found that the cumulative probability of 1-year morality was similar between the two groups (p value log rank = 0.65). Cox regression analysis did not find association between CCS clearance strategy and outcome. CONCLUSIONS: In elderly patients, CTA-driven approach for CCS evaluation pre-TAVI is a valid strategy with similar outcome as compared to invasive approach. CTA strategy significantly reduces invasive procedures rates without compromising patient's outcome.

Comparison of MANTA versus Perclose Prostyle large-bore vascular closure devices during transcatheter aortic valve implantation.

BACKGROUND: New vascular closure devices (VCD) are being introduced for achieving hemostasis after transcatheter aortic valve implantation (TAVI). However, no safety or efficacy data have been published compared to other contemporary VCD. AIM: To compare the safety and efficacy of suture-based Perclose Prostyle as compared to plug-based MANTA device. METHODS: A total of 408 consecutive TAVI patients from two high volume TAVI centers were included in the present study. Patients were grouped according to VCD: Prostyle versus MANTA. Propensity score matching (PSM) and multivariable analysis were utilized to compare clinical endpoints between the two groups. The primary endpoint was any vascular complication (VC) according to VARC-3 criteria. RESULTS: After PSM, a total of 264 patients were analyzed, of them 132 in each group. Overall baseline characteristics of the two groups were comparable. Primary end-point was similar between MANTA as compared to Prostyle (16.7% vs. 15.3% respectively, p = 0.888). The main driver for VC among MANTA group were minor vascular complications (15.2%). Conversely, minor and major VC contributed equally to the primary endpoint among Prostyle group (7.6%) (p = 0.013). No outcome predictors were identified in multivariate analysis. CONCLUSIONS: VCD for transfemoral TAVI using the new-generation Prostyle device or the MANTA device achieved comparable VARC-3 VC rates.

Mild renal impairment is associated with increased cardiovascular events and all-cause mortality following cancer diagnosis.

BACKGROUND: The association between mildly decreased renal function and cardiovascular (CV) outcomes in cancer patients remains unestablished. AIMS: We sought to explore this association in asymptomatic self-referred healthy adults. METHOD: We followed 25, 274 adults, aged 40-79 years, who were screened in preventive healthcare settings. Participants were free of CV disease or cancer at baseline. The estimated glomerular filtration rate (eGFR) was calculated according to the CKD Epidemiology Collaboration equation and categorized into groups [≤59, 60-69, 70-79, 80-89, 90-99, ≥100 (ml/min/1.73 m²)]. The outcome included a composite of death, acute coronary syndrome, or stroke, examined using a Cox model with cancer as a time-dependent variable. RESULTS: Mean age at baseline was 50 ±â€…8 years and 7973 (32%) were women. During a median follow-up of 6 years (interquartile range: 3-11), 1879 (7.4%) participants were diagnosed with cancer, of them 504 (27%) develop the composite outcome and 82 (4%) presented with CV events. Multivariable time-dependent analysis showed an increased risk of 1.6, 1.4, and 1.8 for the composite outcome among individuals with eGFR of 90-99 [95% confidence interval (CI): 1.2-2.1 P = 0.01], 80-89 (95% CI: 1.1-1.9, P = 0.01) and 70-79 (95% CI: 1.4-2.3, P < 0.001), respectively. The association between eGFR and the composite outcome was modified by cancer with 2.7-2.9 greater risk among cancer patients with eGFR of 90-99 and 80-89 but not among individuals free from cancer ( Pinteraction < 0.001). CONCLUSION: Patients with mild renal impairment are at high risk for CV events and all-cause mortality following cancer diagnosis. eGFR evaluation should be considered in the CV risk assessment of cancer patients.

Transcatheter edge-to-edge mitral valve repair in patients with acute decompensated heart failure due to severe mitral regurgitation.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair (TEER) has been established as a therapy for severe symptomatic mitral regurgitation (MR) in stable patients, and it has recently emerged as a reasonable option for acutely ill patients. The aim of this study was to evaluate the safety and efficacy of TEER in hospitalized patients with acute decompensated heart failure (ADHF) and severe MR that was deemed to play a major role in their deterioration. METHODS: We included 31 patients who underwent emergent TEER for MR ≥ 3+ from 2012 to 2022 at Sheba Medical Center. Outcomes included procedural safety, procedural success, all-cause mortality, heart failure readmission, and functional improvement. Outcomes were evaluated at 3 months and at 1 year. Data were obtained retrospectively by chart review. RESULTS: Implantation of a TEER device was achieved in 97% of patients, and reduction in MR severity of at least two grades and final MR ≤ 2+ at discharge was achieved in 74%. No intra-procedural mortality or life-threatening complications were noted. Mortality at 30 days was 23%. No excess mortality occurred beyond 6 months, with a total mortality of 41%. At 1 year all survivors had MR ≤ 2+, all were free of heart failure hospitalizations, and 88% were at New York Heart Association class ≤ II. CONCLUSIONS: Mitral valve TEER for patients with ADHF and significant MR is safe, feasible, and achieves substantial reduction in MR severity. Despite high early mortality, procedural success is associated with good long-term clinical outcomes for patients surviving longer than 6 months.

Levetiracetam Interaction with Direct Oral Anticoagulants: A Pharmacovigilance Study.

BACKGROUND: Levetiracetam is widely used in post-stroke epilepsy. However, it is suspected to possess P-glycoprotein (P-gp) induction properties, and therefore, a potentially significant interaction with direct oral anticoagulants (DOACs). We aimed to search for ischemic stroke signals with levetiracetam and the DOACs. METHODS: In this retrospective pharmacovigilance study, we used the FAERS database to identify ischemic stroke events associated with DOACs and concomitant use of levetiracetam. We evaluated disproportionate reporting by the adjusted reporting odds ratio (adjROR) and the lower bound of the shrinkage 95% confidence interval. When shrinkage is positive, an increased risk of a specific adverse event occurrence is emphasized over the sum of the individual risks when these same drugs are used separately. RESULTS: We identified 1841 (1.5%), 3731 (5.3%), 338 (4.9%), and 1723 (1.3%) ischemic stroke reports with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. The adjROR of the interaction effect was 3.57 (95% CI 2.81-4.58) between DOACs and levetiracetam. The shrinkage analysis detected an interaction between each of the DOACs and levetiracetam. The logistic model and shrinkage analysis failed to detect an interaction when queried for hemorrhagic stroke. A significant signal in the classical enzyme inducer, carbamazepine, strengthened our results (adjROR; 8.47, 95% CI 5.37-13.36). CONCLUSIONS: Our study shows a strong signal for the levetiracetam interaction with the DOACs. Our findings suggest implementation of a drug monitoring strategy.

Serum Magnesium Is Associated with Long-Term Survival of Non-ST-Elevation Myocardial Infarction Patients.

BACKGROUND: Low serum magnesium (sMg) is associated with cardiovascular risk factors and atherosclerotic disease. OBJECTIVE: To evaluate the association between sMg levels on admission and clinical outcomes in hospitalized non-ST-elevation myocardial infarction (NSTEMI) patients. METHODS: A retrospective analysis of all patients admitted to a single tertiary center with a primary diagnosis of NSTEMI. Patients with advanced chronic kidney disease were excluded. Clinical data were collected and compared between lower sMg quartile patients (Q1; sMg < 1.9 mg/dL) and all other patients (Q2-Q4; sMg ≥ 1.9 mg/dL). RESULTS: The study cohort included 4552 patients (70% male, median age 69 [IQR 59-79]) who were followed for a median of 4.4 (IQR 2.4-6.6) years. The median sMg level in the low sMg group was 1.7 (1.6-1.8) and 2.0 (2.0-2.2) mg/dL in the normal/high sMg group. The low sMg group was older (mean of 72 vs. 67 years), less likely to be male (64% vs. 72%), and had higher rates of comorbidities, including diabetes, hypertension, and atrial fibrillation (59% vs. 29%, 92% vs. 85%, and 6% vs. 5%; p < 0.05 for all). Kaplan-Meier survival analysis demonstrated significantly higher cumulative death probability at 4 years in the low sMg group (34% vs. 22%; p log rank <0.001). In a multivariable analysis model adjusted for sex, significant comorbidities, coronary interventions during the hospitalization, and renal function, the low sMg group exhibited an independent 24% increased risk of death during follow up (95% CI 1.11-1.39; p < 0.001). CONCLUSIONS: Low sMg is independently associated with higher risk of long-term mortality among patients recovering from an NSTEMI event.

Guess What We Can Hear-Novel Voice Biomarkers for the Remote Detection of Disease.

The advancement of digital biomarkers and the provision of remote health care greatly progressed during the coronavirus disease 2019 global pandemic. Combining voice/speech data with artificial intelligence and machine-based learning offers a novel solution to the growing demand for telemedicine. Voice biomarkers, obtained from the extraction of characteristic acoustic and linguistic features, are associated with a variety of diseases and even coronavirus disease 2019. In the current review, we (1) describe the basis on which digital voice biomarkers could facilitate "telemedicine," (2) discuss potential mechanisms that may explain the association between voice biomarkers and disease, (3) offer a novel classification system to conceptualize voice biomarkers depending on different methods for recording and analyzing voice/speech samples, (4) outline evidence revealing an association between voice biomarkers and a number of disease states, and (5) describe the process of developing a voice biomarker from recording, storing voice samples, and extracting acoustic and linguistic features relevant to training and testing deep and machine-based learning algorithms to detect disease. We further explore several important future considerations in this area of research, including the necessity for clinical trials and the importance of safeguarding data and individual privacy. To this end, we searched PubMed and Google Scholar to identify studies evaluating the relationship between voice/speech features and biomarkers and various diseases. Search terms included digital biomarker, telemedicine, voice features, voice biomarker, speech features, speech biomarkers, acoustics, linguistics, cardiovascular disease, neurologic disease, psychiatric disease, and infectious disease. The search was limited to studies published in English in peer-reviewed journals between 1980 and the present. To identify potential studies not captured by our database search strategy, we also searched studies listed in the bibliography of relevant publications and reviews.

Baseline renal function and the risk of cancer among apparently healthy middle-aged adults.

BACKGROUND: The association between mildly impaired renal function with all-site and site-specific cancer risk is not established. We aim to explore this association among apparently healthy adults. METHODS: We followed 25,073 men and women, aged 40-79 years, free of cancer or cardiovascular disease at baseline who were screened annually in preventive healthcare settings. The estimated glomerular filtration rate (eGFR) was calculated using the CKD Epidemiology Collaboration equation (CKD-EPI) and classified into four mutually exclusive groups: <60, 60-74, 75-89, ≥90 (mL/min/1.73 m²). The primary outcome was all-site cancer while the secondary outcome was site-specific cancer. Cancer data was available from a national registry. RESULTS: Mean age at baseline was 50 ± 8 years and 7973 (32 %) were women. During a median follow-up of 9 years (IQR 3-16) and 256,279 person years, 2045 (8.2 %) participants were diagnosed with cancer. Multivariable Cox model showed a 1.2 (95 %CI: 1.0-1.4 p = 0.05), 1.2 (95 %CI: 1.0-1.4 p = 0.02), and 1.4 (95 %CI: 1.1-1.7 p = 0.003) higher risk for cancer with eGFR of 75-89, 60-74, and < 60, respectively. Site-specific analysis demonstrated a 1.8 (95 %CI: 1.2-2.6 p = 0.004), 1.7 (95 %CI: 1.2-2.6 p = 0.004) and 2.2 (95 %CI: 1.3-3.6 p = 0.002) increased risk for prostate cancer with eGFR of 75-89, 60-74, and < 60, respectively. eGFR< 60 was associated with a 2.0 (95 %CI: 1.1-3.7 p = 0.03) and 3.7 (95 %CI: 1.1-13.1 p = 0.04) greater risk for melanoma and gynecological caner respectively. CONCLUSIONS: CKD stage 2 and worse is independently associated with higher risk for cancer incidence, primarily prostate cancer. Early intervention and screening are warranted among these individuals in order to reduce cancer burden.

Investigation of cardiac arrhythmia events in patients treated with lamotrigine: FDA adverse event reporing system analysis.

OBJECTIVES: In October 2020 and March 2021, the U.S. Food and Drug Administration (FDA) classified lamotrigine as a class IB antiarrhythmic, announcing an increased risk of heart rhythm problems. We sought to investigate the nature of the arrhythmia signal with lamotrigine use compared to anticonvulsants with sodium-blocking and non-sodium-blocking mechanisms. METHODS: This retrospective pharmacovigilance case-non-case study used disproportionality analysis to detect signals of adverse reaction of interest reported with lamotrigine to the FDA Adverse Event Reporting System (FAERS) between 1998 and 2022. Our regression model adjusted for interacting concomitant medications. Sensitivity analyses included stratifying by indication and publication date. RESULTS: Overall, 2917 cases of heart rhythm problems with anticonvulsants were analyzed (1557 female [58.4%] and 1109 male [41.6%]). The mean age ± standard deviation (SD) was 43 ± 19, the groups did not differ significantly by age. Forty cases (7.91%) in the epileptic indication included more than one concomitant medication that influences cardiac conduction. The disproportionality signal for cardiac arrest did not differ for lamotrigine compared with other anticonvulsants, adjusted reporting odds ratio (adj.ROR, .88; 95% CI, .59-1.29) in the epileptic indication. A significantly lower reporting risk for bradyarrhythmia was identified with lamotrigine users in the epileptic population, (adj.ROR, .45; 95% confidence interval [CI], .29-.68). The psychiatric indication demonstrated a sixfold reporting risk for cardiac arrest compared to the epileptic indication. Concomitant medications that affect cardiac conduction, as well as reports on overdose and suicide attempts, were significant variables in psychiatric patients (ROR, 2.45; 95% CI, 2.21-2.71) and (ROR, 1.44; 95% CI, 1.34-1.55), respectively. SIGNIFICANCE: Our results do not support a significant difference in the reporting risk for cardiac arrest, syncope, tachyarrhythmia, and bradyarrhythmia with lamotrigine in the epileptic indication. Signals of cardiac arrest in lamotrigine could be explained by confounding factors in the psychiatric indication, such as greater concomitant use of medications with cardiac adverse events, and greater reports on overdose and suicide attempts. We recommend that patients with polypharmacy undergo clinical and electrocardiographic monitoring. We illustrate the importance of examining signals for separate indications.

Atrial fibrillation in young hospitalized patients: Clinical characteristics, predictors of new onset, and outcomes.

BACKGROUND: Atrial fibrillation (AF) in young adults is an uncommon and not well studied entity. METHODS: Consecutive patients aged 18-45 years admitted to internal or cardiology services in a large tertiary medical center (January 1, 2009 through December 31, 2019) were included. Clinical, electrocardiographic, and echocardiographic data were compared between patients with and without AF at baseline. Predictors of new-onset AF in the young were identified using multivariate Cox regression model among patients free of baseline AF. RESULTS: Final cohort included 16,432 patients with median age of 34 (IQR 26-41) years of whom 8914 (56 %) were men. Patients with AF at baseline (N = 366; 2 %) were older, more likely to be men, and had higher proportion of comorbidities and electrocardiographic conduction disorders. Male sex, increased age, obesity, heart failure, congenital heart disease (CHD) and the presence of left or right bundle branch block were all independently associated with baseline AF in a multivariate model (p < 0.001 for all). Sub-analysis of 10,691 (98 %) patients free of baseline AF identified 85 cases of new-onset AF during a median follow up of 3.5 (IQR 1.5-6.5) years. Multivariate model identified increased age, heart failure, and CHD as independent predictors of new-onset AF. Finally, the CHARGE-AF risk score outperformed the CHA2DS2-VASc score in AF prediction [AUC of ROC 0.75 (0.7-0.8) vs. 0.56 (0.48-0.65)]. CONCLUSIONS: AF among hospitalized young adults is not rare. Screening for new-onset AF in young post hospitalization patients may be guided by specific clinical predictors and the CHARGE-AF risk score.

The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study.

BACKGROUND: As indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults. METHODS: A retrospective, pharmacovigilance study of the FDA's global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (< 75 years) and older adults (≥ 75), we performed a disproportionality analysis using the sex-adjusted reporting odds ratio (adj.ROR). RESULTS: We identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 [IQR: 51-68] years, 2,339 [9.6%] aged ≥ 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR = 355.1 [95%CI: 258.8 - 487.3] vs adj.ROR = 250.2 [79.3 - 789.5]), Fournier gangrene (adj.ROR = 45.0 [34.5 - 58.8] vs adj.ROR = 88.0 [27.0 - 286.6]), diabetic ketoacidosis (adj.ROR = 32.3 [30.0 - 34.8] vs adj.ROR = 23.3 [19.2 - 28.3]), genitourinary infections (adj.ROR = 10.3 [9.4 - 11.2] vs adj.ROR = 8.6 [7.2 - 10.3]), nocturia (adj.ROR = 5.5 [3.7 - 8.2] vs adj.ROR = 6.7 [2.8 - 15.7]), dehydration (adj.ROR = 2.5 [2.3 - 2.8] vs adj.ROR = 2.6 [2.1 - 3.3]), and fractures (adj.ROR = 1.7 [1.4 - 2.1] vs adj.ROR = 1.5 [1.02 - 2.1]) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (Pinteraction threshold of 0.05). Acute kidney injury was associated with SGLT2i in adults (adj.ROR = 1.97 [1.85 - 2.09]) but not in older adults (adj.ROR = 0.71 [0.59 - 0.84]). Falls, hypotension, and syncope were not associated with SGLT2i among either adults or older adults. CONCLUSION: In this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted.