Interventricular septal thickness on cardiac computed tomography as a novel risk factor for conduction disturbances in patients undergoing transcatheter aortic valve replacement.

AIMS: We examined whether thickness of the basal muscular interventricular septum (IVS), as measured by pre-procedural computed tomography (CT), could be used to identify the risk of conduction disturbances following transcatheter aortic valve replacement (TAVR). The IVS is a pivotal region of the electrical conduction system of the heart where the atrioventricular conduction axis is located. METHODS AND RESULTS: Included were 78 patients with severe aortic stenosis who underwent CT imaging prior to TAVR. The thickness of muscular IVS was measured in the coronal view, in systolic phases, at 1, 2, 5, and 10 mm below the membranous septum (MS). The primary endpoint was a composite of conduction disturbance following TAVR. Conduction disturbances occurred in 24 out of 78 patients (30.8%). Those with conduction disturbances were significantly more likely to have a thinner IVS than those without conduction disturbances at every measured IVS level (2.98 ± 0.52 mm vs. 3.38 ± 0.52 mm, 4.10 ± 1.02 mm vs. 4.65 ± 0.78 mm, 6.11 ± 1.12 mm vs. 6.88 ± 1.03 mm, and 9.72 ± 1.95 mm vs. 10.70 ± 1.55 mm for 1, 2, 5 and 10 mm below MS, respectively, P < 0.05 for all). Multivariable logistic regression analysis showed that pre-procedural IVS thickness (<4 mm at 2 mm below the MS) was a significant independent predictor of post-procedural conduction disturbance (adjOR 7.387, 95% CI: 2.003-27.244, P = 0.003). CONCLUSION: Pre-procedural CT assessment of basal IVS thickness is a novel predictive marker for the risk of conduction disturbances following TAVR. The IVS thickness potentially acts as an anatomical barrier protecting the underlying conduction system from mechanical compression during TAVR.

The Association between Multi-Vessel Coronary Artery Disease and High On-Aspirin Platelet Reactivity.

BACKGROUND: Multi-vessel coronary artery disease (MV-CAD) is correlated with worse clinical outcomes compared with single-vessel CAD (SV-CAD). The aim of this study was to evaluate the association between MV-CAD and high on-aspirin platelet reactivity (HAPR) in patients with stable CAD treated with aspirin. METHODS: The current study is an analysis of prospectively enrolled randomly selected patients with known stable CAD, who were taking aspirin (75-100 mg qd) regularly for at least one month, and had undergone coronary angiography at least 3 months prior to the enrollment to the study. EXCLUSION CRITERIA: acute coronary syndrome at the time of platelet function testing, active malignancy, acute infection, active inflammatory/rheumatic disease, major surgery in the past 6 months, chronic liver failure, treatment with oral anticoagulation, non-adherence with Aspirin and thrombocytopenia (<100 K/micl). Blood was drawn from the participants and sent for platelet function testing (VerifyNow, Instrumentation Laboratory Company, Bedford, Massachusetts, United States). MV-CAD was defined as >50% stenosis in ≥2 separate major coronary territories per coronary angiography. HAPR was defined as aspirin reaction units (ARU) >550. RESULTS: Overall, 507 patients were analyzed; age 66.7 ± 11.2, 17.9% women, 223 (44%) had MV-CAD. The rate of HAPR was significantly higher among patients with MV-CAD vs. SV-CAD (14.8% vs. 3.5%, p < 0.001, respectively). Furthermore, a "dose response"-like association was found between the number of stenotic coronary arteries and the rate of HAPR (3.5%, 13.5 and 17.3% for SV-CAD, 2-vessel and 3-vessel disease, respectively). In a multivariate analysis adjusted for potential confounders, MV-CAD was found to be a strong independent predictor of HAPR [OR = 1.8 (95%CI: 1.05-4.7), p = 0.014]. CONCLUSIONS: A significant association between MV-CAD and HAPR was found. Additional studies designed to investigate the mechanisms of HAPR and different therapeutic options for this subset of patients are warranted.

Preoperative evaluation of pulmonary hypertension in lung transplant candidates: echocardiography versus right heart catheterization.

BACKGROUND: Right heart catheterization (RHC) and echocardiography are both routinely used for pulmonary artery systolic pressure (PASP) assessment in lung transplantation (LT) candidates, although this is not mandated by current guidelines. We aimed to explore the performance of echocardiographic PASP as an indicator of pulmonary hypertension in LT candidates, in order to assess the necessity of RHC. METHODS: From a retrospective registry of 393 LT candidates undergoing RHC and echocardiography during 2015-2019, patients were assessed for the presence of pulmonary hypertension (PH), defined as mean pulmonary artery pressure (mPAP) above 20 mmHg, according to two methods-echocardiography and RHC. The primary outcome was the correlation between the PASP estimated by echocardiography to that measured by RHC. Secondary outcomes were the prediction value of the echocardiographic evaluation and its accuracy. RESULTS: The mean value of PASP estimated by echocardiography was 49.5 ± 20.0 mmHg, compared to 42.5 ± 18.0 mmHg measured by RHC. The correlation between the two measurements was moderate (Pearson's correlation: r = 0.609, p < 0.01). Echocardiography PASP measurements were moderately discriminative to diagnose PH, with an area under the curve (AUC) of 0.72 (95% CI 0.66-0.77). Echocardiographic overestimation of PASP of more than 10 mmHg was found in 35.0% of the patients, and underestimation was found in 11.6% of the patients. CONCLUSION: In the pre-surgical evaluation of LT candidates, echocardiographic estimation of PASP had moderate correlation and limited accuracy compared to the PASP measured by RHC. We thus recommend performing routine RHC to all LT candidates, regardless of the echocardiographic estimation of PASP.

Shifting from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: predictors, patterns and temporal trends.

BACKGROUND: Non-Vitamin K antagonist oral anticoagulants (NOACs) emerged as an alternative with comparable or superior efficacy and safety to vitamin K antagonists (VKAs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). OBJECTIVES: The aim of the current study was to investigate the patterns, predictors, timelines and temporal trends of shifting from VKAs to NOACs. METHODS: In this retrospective observational study, the computerized database of a large healthcare provider in Israel, Maccabi Healthcare Services, was searched to identify patients with AF for whom either a VKA or NOAC was prescribed between 2012 and 2015. Time from diagnosis to therapy initiation and to shifting between therapies was evaluated. RESULTS: Out of 6987 eligible AF incident patients, 2338 (33.4%) initiated treatment with a VKA and 2221 (31.7%) with a NOAC. In addition, 5259 prevalent patients were analyzed. During the study period, NOAC prescriptions proportion among the newly diagnosed cases increased from 32 to 68.4% (p for trend <  0.001). The median time from diagnosis to first dispensing was greater in NOAC than VKA and decreased among patients treated with NOAC during the study period (2012: 1.9 and 0.3 months, 2015: 0.7 and 0.2 months, respectively). During follow-up, 3737 (49%) patients (54.3% and 47.1% of the incident and prevalent cases, respectively), shifted from a VKA to a NOAC, after a median of 22 months and 39 months in the incident and prevalent cases, respectively, decreasing throughout the study period. Female gender, younger age, southern district, higher CHADS2 and CHA2DS2-VASC score, non-smoking, and treatment with antiplatelets were associated with a greater likelihood for therapy shift. Shifting from a NOAC to a VKA decreased over time from 8 to 4.5% in 2012 to 0.5% and 0.7% in 2015 in the incident and prevalent groups, p <  0.001 respectively. CONCLUSIONS: Shifting from VKA to NOAC occurred in 50% of the cases, more frequently among incident cases, and younger patients with greater stroke risk. Shifting from a NOAC to a VKA was much less frequent, yet it occurred more often in incident cases and decreased over time. A socially and economically sensitive program to optimize the initiation of OAC therapy upon diagnosis is warranted.

Sex and Ethnic Disparities in Health-Related Outcomes Following Acute Myocardial Infarction in Israel.

BACKGROUND: Survivors of acute myocardial infarction (AMI) are at increased risk for recurrent cardiac events and tend to use excessive healthcare services, thus resulting in increased costs. OBJECTIVES: To evaluate the disparities in healthcare resource utilization and costs throughout a decade following a non-fatal AMI according to sex and ethnicity groups in Israel. METHODS: A retrospective study included AMI patients hospitalized at Soroka University Medical Center during 2002-2012. Data were obtained from electronic medical records. Post-AMI annual length of hospital stay (LOS); number of visits to the emergency department (ED), primary care facilities, and outpatient consulting clinics; and costs were evaluated and compared according sex and ethnicity groups. RESULTS: A total of 7685 patients (mean age 65.3 ± 13.6 years) were analyzed: 56.8% Jewish males (JM), 26.6% Jewish females (JF), 12.4% Bedouin males (BM), and 4.2% Bedouin females (BF). During the up-to 10-years follow-up (median 5.8 years), adjusted odds ratios [AdjOR] for utilizations of hospital-associated services were highest among BF (1.628 for LOS; 1.629 for ED visits), whereas AdjOR for utilization of community services was lowest in BF (0.722 for primary clinic, 0.782 for ambulatory, and 0.827 for consultant visits), compared with JM. The total cost of BF was highest among the study groups (AdjOR = 1.589, P < 0.01). CONCLUSIONS: Long-term use of hospital-associated healthcare services and total costs were higher among Bedouins (especially BF), whereas utilization of ambulatory services was lower in these groups. Culturally and economically sensitive programs optimizing healthcare resources utilization and costs is warranted.

The Use of Embolic Protection Devices During Transcatheter Aortic Valve Implantation.

BACKGROUND: Aortic stenosis (AS) is a common valvular pathology and is increasing in prevalence. Severe symptomatic AS is associated with serious outcomes if left untreated. Transcatheter aortic valve implantation (TAVI) is an innovative modality, which has revolutionized the treatment of AS. With growing experience and technological upgrades, TAVI has become a valid alternative to surgical valve replacement. However, TAVI is associates with increase non-negligible risks of mortality, stroke, physical disability, and healthcare expenditures. Furthermore, imaging modalities have shown new ischemic lesions in most patients following TAVI (silent strokes), which might be related to worse subsequent neurocognitive function. Embolic protective devices are emerging as a safe, technically feasible implements to reduce the burden of periprocedural thromboembolism, and have shown promising results of improved clinical outcomes.

Characteristics and Long-Term Prognosis of Holocaust Survivors Presenting with Acute Myocardial Infarction.

BACKGROUND: Catastrophic life events are associated with the occurrence of cardiovascular incidents and worsening of the clinical course followirg-such events. OBJECTIVES: To evaluate the characteristics and long-term prognosis of Holocaust survivors presenting with acute myocardial infarction (AMI) compared to non-Holocaust survivors. METHODS: Israeli Jews who were born before 1941 and had been admitted to a tertiary medical center due to AMI during the period 2002-2012 were studied. Holocaust survivors were compared with non-Holocaust survivor controls using individual age matching. RESULTS: Overall 305 age-matched pairs were followed for up to 10 years after AMI. We found a higher prevalence of depression (5.9% vs. 3.3%, P = 0.045) yet a similar rate of cardiovascular risk factors, non-cardiovascular co-morbidity, severity of coronary artery disease, and in-hospital complications in survivors compared to controls. Throughout the follow-up period, similar mortality rates (62.95% vs. 63.9%, P = 0.801) and reduced cumulative mortality (0.9 vs. 0.96, HR = 0.780, 95% CI 0.636-0.956, P = 0.016) were found among survivors compared to age-matched controls, respectively. However, in a multivariate analysis survival was not found to be an independent predictor of mortality, although some tendency towards reduced mortality was seen (AdjHR = 0.84, 95% CI 0.68-1.03, P = 0.094). Depression disorder was associated with a 77.9% increase in the risk for mortality. CONCLUSIONS: Holocaust survivors presenting with AMI were older and had a higher prevalence of depression than controls. No. excessive, and possibly even mildly improved, risk of mortality.was observed in survivors compared with controls presenting with AMI. Possibly, specific traits that are associated with surviving catastrophic events counter the excess risk of such events following AMI.

Lessons learned from the Syrian sarin attack: evaluation of a clinical syndrome through social media.

On the night of 21 August 2013, sarin was dispersed in the eastern outskirts of Damascus, killing 1400 civilians and severely affecting thousands more. This article aims to delineate the clinical presentation and management of a mass casualty event caused by a nerve agent as shown in the social media. Authors searched YouTube for videos uploaded of this attack and identified 210 videos. Of these, 67 met inclusion criteria and were evaluated in the final analysis.These videos displayed 130 casualties; 119 (91.5%) of which were defined as moderately injured or worse. The most common clinical signs were dyspnea (53.0%), diaphoresis (48.5%), and loss of consciousness (40.7%). Important findings included a severe shortage of supporting measures and lack of antidotal autoinjectors. Decontamination, documented in 25% of the videos, was done in an inefficient manner. Protective gear was not noticed, except for sporadic use of latex gloves and surgical masks.This is believed to be the first time that social media was used to evaluate clinical data and management protocols to better prepare against future possible events.

Airway control in case of a mass toxicological event: superiority of second-generation supraglottic airway devices.

INTRODUCTION: Early respiratory support and airway (AW) control with endotracheal intubation (ETI) are crucial in mass toxicology events and must be performed while wearing chemical personal protective equipment (C-PPE). AIM: The aim of this study is to evaluate the efficiency of AW control by using second-generation supraglottic AW devices (SADs) as compared with ETI and first-generation SAD while wearing C-PPE. METHODS: This is a randomized crossover trial involving 117 medical practitioners. Four AW management devices were examined: endotracheal tube, the first-generation SAD, laryngeal mask AW unique and 2 second-generation SAD, the laryngeal tube suction disposable, and supreme laryngeal mask AW (SLMA). Primary end point measured were success or failure, number of attempts, and time needed to achieve successful device insertion. Secondary end point was a subjective appraisal of the AW devices by study population. RESULTS: More attempts were required to achieve AW control with endotracheal tube, with and without C-PPE (P<.001). Time to achieve AW control with ETI was, on average, 88% longer than required with other devices and improved with practice. The mean times to achieve an AW were longer when operators were equipped with C-PPE as compared with standard clothing. Subjectively, difficulty levels were significantly higher for ETI than for all other devices (P<.0001). CONCLUSIONS: When compared with ETI, the use of SADs significantly shortened the time for AW control while wearing C-PPE. Second-generation SAD were superior to laryngeal mask AW unique. These finding suggest that SADs may be used in a mass toxicology event as a bridge, until definite AW control is achieved.

[New treatments for stroke and thromboembolism prevention in atrial fibrillation].

Atrial fibrillation (AF) is the most common sustained arrhythmia in Western countries (prevalence 1-2%). Patients with AF have a 5-fold increased risk of stroke, and 15%-20% of all strokes are attributable to AF. Moreover, mortality, morbidity and economic burden from stroke complicating AF are particularly high. Thus, preventing stroke and thromboembolism is the cornerstone in AF management, with the vitamin K antagonist (VKA) - warfarin as the leading drug for many years. Although warfarin is effective in stroke reduction, only 55% of eligible patients with AF received it, 28% of patients discontinue it by 1-year, rates of major bleeding are higher that 20% and patients remain in the therapeutic range (INR 2-3) only 58% of the time. Warfarin underuse results from its pharmacological properties including: genetic variability in metabolism, multiple drug and food interactions, unpredictable anticoagulant effects, narrow therapeutic window, and the resulting need for inconvenient monitoring. The combination of aspirin and clopidogrel was found to be less effective than warfarin. Hence, new treatments were recently evaluated for AF-related stroke and thromboembolic prevention including: direct thrombin inhibitors (dabigatran etexilate), oral selective factor Xa inhibitors (rivaroxaban and apixaban), and percutaneous left atrial appendage closure. Some of these drugs have demonstrated promising results in clinical studies, they are convenient to use and do not require monitoring. The downsides are lack of antidotes or specific blood assays to monitor the anticoagulant effect and the need for invasive procedure for installation. Herein, we review the new treatments and the available clinical evidence for their use in AF.

[Long-term complications of sulfur mustard exposure: a therapeutic update].

Sulfur mustard (SM) is an alkylating chemical warfare agent with high military significance due to its high toxicity, resistance and availability. SM was widely used in military conflicts, the last being the Iran-Iraq war with more than 100,000 Iranians exposed, one-third of whom are still suffering from late effects. The intensity of the delayed complications correlates to the extent, the area and the route of exposure. The clinical manifestations most commonly involve respiratory, ocular and dermal effects. Respiratory complications include dyspnea, cough and expectorations and various obstructive and restrictive lung diseases. Dermal complications are itching, burning sensation, blisters, dry skin, dermatitis and pigmentary changes. Ocular complications include photophobia, red eye, tearing, corneal ulcers and blindness. Although the picture remains incomplete the major mechanisms responsible for the clinical and pathological effects of SM are: DNA alkylation and cross-linking, protein modification and membrane damage in addition to induction of inflammatory mediators in the target tissues causing extensive necrosis, apoptosis and loss of tissue structure. The current report reviews long-term complications of SM exposure, focusing on new treatments tested in clinical trials conducted on humans. Such treatments include: N-acetyl cysteine, bronchodilators, corticosteroids, Interferon-gamma, furosemide and morphine for the respiratory complications. Ocular complications may entail: Invasive procedures treating corneal complication, limbal ischemia and stem cell deficiency. Treatment for dermatological complications include: anti-depressants, pimercrolimus, Unna's boot, capsaicin, phenol and menthol, Aloe vera and olive oil, curcumin and Interferon-gamma.

An empirical approach for life expectancy estimation based on survival analysis among a post-acute myocardial infarction population.

Background: Practical communication of prognosis is pertinent in the clinical setting. Survival analysis techniques are standardly used in cohort studies; however, their results are not straightforward for interpretation as compared to the graspable notion of life expectancy (LE). The present study empirically examines the relationship between Cox regression coefficients (HRs), which reflect the relative risk of the investigated risk factors for mortality, and years of potential life lost (YPLL) values after acute myocardial infarction (AMI). Methods: This retrospective population-based study included patients aged 40-80 years, who survived AMI hospitalization from January 1, 2002, to October 25, 2017. A survival analysis approach assessed relationships between variables and the risk for all-cause mortality in an up to 21-year follow-up period. The total score was calculated for each patient as the summation of the Cox regression coefficients (AdjHRs) values. Individual LE and YPLL were calculated. YPLL was assessed as a function of the total score. Results: The cohort (n = 6316, age 63.0 ± 10.5 years, 73.4 % males) was randomly split into training (n = 4243) and validation (n = 2073) datasets. Sixteen main clinical risk factors for mortality were explored (total score of 0-14.2 points). After adjustment for age, sex and nationality, a one-point increase in the total score was associated with YPLL of ∼one year. A goodness-of-fit of the prediction model found 0.624 and 0.585 for the training and validation datasets respectively. Conclusions: This functional derivation for converting coefficients of survival analysis into the comprehensible form of YPLL/LE allows for practical prognostic calculation and communication.

Interaction between anemia and renal dysfunction in relation to long-term survival following acute myocardial infarction.

BACKGROUND: Anemia and chronic kidney disease (CKD) adversely affect prognosis following acute myocardial infarction (AMI). We aimed to assess their interaction regarding long-term survival post-AMI. METHODS: This is a single-center, retrospective analysis of consecutive AMI survivors. Stratified by admission-time anemia status and CKD grade, as determined by hemoglobin and creatinine levels, the cohort was evaluated for all-cause mortality at 10 years after hospital discharge. RESULTS: A total of 11,395 patients (69.1% males, mean age 65.8 ± 13.9 years, 49.6% with ST elevation MI) were included, of whom 29.9% had anemia and 15.9% - grade 3b or higher CKD. CKD was more advanced among anemic patients and the prevalence of anemia rose as CKD grade increased (p for trend < 0.001). At 10 years, 47.8% of patients died. Notwithstanding differences in baseline characteristics, presentation, and treatment between those with various anemia status and CKD grades, anemia presence (HR 1.40, 95% CI 1.32-1.49, p < 0.001) and increasing CKD grade (HR 1.10, 95% CI 1.02-1.20, p for trend < 0.001) were independently associated with a higher mortality risk. The incremental hazard imposed by either anemia or more advanced CKD was limited to patients with normal renal function and up to grade 3a (in the total cohort and the conservative treatment subgroup) or 4 (in the invasive revascularization subgroup) CKD. The added risk associated with increasing CKD grade also affected non-anemic individuals irrespective of the specific CKD grade. CONCLUSION: Anemia and more advanced CKD are associated with reduced long-term survival post-AMI, inflicting higher risk when conjoined in lower-grade CKD.

Tricuspid Regurgitation and Kidney Transplant Recipient Outcomes.

Rationale & Objective: Kidney function can be adversely affected by significant tricuspid regurgitation (TR) owing to effects on cardiac output and systemic venous congestion. However, the impact of significant TR on short- and long-term kidney function following a kidney transplant remains uncertain. Study Design: Retrospective observational cohort. Setting & Participants: Kidney transplant recipients from a single center between 2016 and 2019. Exposure: Significant TR, defined by at least moderate regurgitation, on echocardiogram before kidney transplantation. Outcomes: Primary end points included the estimated glomerular filtration rate (eGFR) at the following 3 time points: 2 weeks, 3 months, and 1 year after transplantation. Secondary end points included major adverse cardiac events including nonfatal myocardial infarction, all-cause mortality, and hospitalization owing to cardiovascular disease. Analytical Approach: Propensity score matching was performed in 1:3 ratio between patients treated with significant TR and controls, within a caliper 0.05 standard deviation of the propensity score, to analyze for the primary end point. Results: Among 557 kidney transplant recipients, 26 (5%) exhibited significant TR pretransplantation. According to propensity score matching analysis, with 1:3 ratio between 24 patients with significant TR and 72 controls, the presence of significant TR was associated with a lower eGFR posttransplantation. Specifically, the mean eGFR was 41.2 mL/min/1.73 m2 compared to 53.3 mL/min/1.73 m2 at 2 weeks (P < 0.01), 50.0 mL/min/1.73 m2 versus 60.3 mL/min/1.73 m2 at 3 months (P < 0.01), and 49.4 mL/min/1.73 m2 versus 61.2 mL/min/1.73 m2 at 1 year (P < 0.01). Delayed graft function was observed in 41.7% of the patients with significant TR compared to 12.5% of those without significant TR (P < 0.01). No patients with significant TR required dialysis after 1 year. 1-year major adverse cardiac events were nonsignificantly higher among patients with significant TR (20.8% vs 8.1%; P = 0.16). Limitations: Retrospective design and relatively small TR population. Conclusions: The presence of significant TR among kidney transplant recipients was associated with a lower eGFR at 2 weeks, 3 months, and 1 year following transplant, although all remained dialysis independent at 1 year.

Significant tricuspid regurgitation (TR) is associated with increased mortality rates and kidney failure, but its impact on kidney transplant recipients is poorly investigated. We examined how significant TR diagnosed pretransplantation affects kidney function within the first posttransplant year in a retrospective cohort study. Among 24 patients with significant TR, there was a consistent pattern of lower kidney function at 2 weeks, 3 months, and 1 year following transplantation, compared to 72 matched controls based on a propensity score. Results were statistically significant at all time points within the first year after transplant. These findings suggest that selected individuals with significant TR are able to undergo successful kidney transplantation, although with worse kidney function following transplantation.

Complex left appendage morphology is associated with Embolic Stroke of Undetermined Source.

INTRODUCTION: Variations in the left atrial appendage (LAA) morphology are associated with different embolic risk in patients with atrial fibrillation (AF). Data are scarce regarding the association between LAA morphology and Embolic stroke of undetermined source (ESUS). PATIENTS AND METHODS: Using cardiac computed tomography (CCT) scans, LAA morphology was categorized as either chicken wing (CW), cactus, windsock, or cauliflower. Furthermore, we examined the presence of large secondary lobes arising from the main lobe, considering their existence as indicative of a complex LAA morphology. LAA morphologies were compared between ESUS (n = 134) and AF patients (n = 120); and between ESUS patients with (n = 24) and without (n = 110) subsequent AF diagnosis during long-term follow-up. RESULTS: ESUS patients had a significantly higher prevalence of cauliflower morphology compared to AF group (52% vs 34%, respectively, p = 0.01); however, no significant difference was found between the groups when categorizing LAA morphology to either CW or non-CW. ESUS patients had significantly higher prevalence of large secondary lobes compared with AF patients (50% vs 29%, respectively, p = 0.001). When comparing ESUS patients with and without AF diagnosis during follow-up (20-48 months of follow-up, median 31 months), there were no significant differences in the prevalence of the "classical" morphologies, but large secondary lobes were significantly more prevalent among those without subsequent AF diagnosis. CONCLUSION: ESUS patients have a high prevalence of complex LAA morphology, which might be associated with an increased risk for thrombus formation even in the absence of AF.

Lipoprotein(a): Emerging insights and therapeutics.

The strong association between lipoprotein (a) [Lp(a)] and atherosclerotic cardiovascular disease has led to considerations of Lp(a) being a potential target for mitigating residual cardiovascular risk. While approximately 20 % of the population has an Lp(a) level greater than 50 mg/dL, there are no currently available pharmacological lipid-lowering therapies that have demonstrated substantial reduction in Lp(a). Novel therapies to lower Lp(a) include antisense oligonucleotides and small-interfering ribonucleic acid molecules and have shown promising results in phase 2 trials. Phase 3 trials are currently underway and will test the causal relationship between Lp(a) and ASCVD and whether lowering Lp(a) reduces cardiovascular outcomes. In this review, we summarize emerging insights related to Lp(a)'s role as a risk-enhancing factor for ASCVD, association with calcific aortic stenosis, effects of existing therapies on Lp(a) levels, and variations amongst patient populations. The evolving therapeutic landscape of emerging therapeutics is further discussed.

Artificial Intelligence in Coronary Artery Calcium Scoring Detection and Quantification.

Coronary artery calcium (CAC) is a marker of coronary atherosclerosis, and the presence and severity of CAC have been shown to be powerful predictors of future cardiovascular events. Due to its value in risk discrimination and reclassification beyond traditional risk factors, CAC has been supported by recent guidelines, particularly for the purposes of informing shared decision-making regarding the use of preventive therapies. In addition to dedicated ECG-gated CAC scans, the presence and severity of CAC can also be accurately estimated on non-contrast chest computed tomography scans performed for other clinical indications. However, the presence of such "incidental" CAC is rarely reported. Advances in artificial intelligence have now enabled automatic CAC scoring for both cardiac and non-cardiac CT scans. Various AI approaches, from rule-based models to machine learning algorithms and deep learning, have been applied to automate CAC scoring. Convolutional neural networks, a deep learning technique, have had the most successful approach, with high agreement with manual scoring demonstrated in multiple studies. Such automated CAC measurements may enable wider and more accurate detection of CAC from non-gated CT studies, thus improving the efficiency of healthcare systems to identify and treat previously undiagnosed coronary artery disease.

Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry.

BACKGROUND: Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). METHODS AND RESULTS: This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001). CONCLUSIONS: Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.