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Abstract Background Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood. Objective To investigate the relationship between elevated Lp(a) and DM with CAD outcomes. Methods Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L). Results Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) 90th% − 1.3%; DM and Lp(a) 90th% − 4.7% (p

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.

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

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

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.

We investigated the recovery pattern from acute kidney injury (AKI) following acute myocardial infarction (AMI) and its association with long-term mortality. The retrospective study included AMI patients (2002–2027), who developed AKI during hospitalization. Creatinine (Cr) measurements were collected and categorized into 24 h timeframes up to 7 days from AKI diagnosis. The following groups of recovery patterns were defined: rapid (24–48 h)/no rapid and early (72–144 h)/no early recovery. Specific cut-off points for recovery at each AKI stage and timeframe were determined through receiver operating characteristic (ROC) curves. The probability of long-term (up to 10 years) mortality as a post-AKI recovery was investigated using a survival approach. Out of 17,610 AMI patients, 1069 developed AKI. For stage 1 AKI, patients with a Cr ratio p = 0.010. Among stages 2–3 AKI patients, the risk for long-term mortality was higher among patients who did not recover in the early period: AdjHR = 1.742; 95% CI: 1.085–2.797; p = 0.022. The absence of rapid recovery in stage 1 AKI and lack of early recovery in stages 2–3 AKI are associated with higher long-term mortality.

Abstract Aims This study aimed to characterize the final diagnosis and prognosis of patients with grade 1 myocardial scintigraphy uptake, which is an unequivocal result for the diagnosis of transthyretin cardiac amyloidosis (ATTR‐CA) requiring further invasive investigation with tissue biopsy. Methods and results We retrospectively compared the clinical and imaging parameters of patients suspected for ATTR‐CA (based on clinical and echocardiographic parameters) with grade 1 vs. grades 2/3 technetium pyrophosphate uptake on cardiac scintigraphy. Prospectively, grade 1 patients underwent re‐evaluation for ATTR‐CA at long term. Of the 132 ATTR‐CA suspected patients, 89 (67%) were diagnosed as grade 1 and 43 (33%) as grades 2/3 uptake. Grade 1 vs. grades 2/3 patients were younger and female predominant with lower biomarker levels and left ventricular mass. Based on available imaging and pathology findings, only 6 out of the 89 patients with grade 1 uptake (7%) were finally diagnosed with light‐chain cardiac amyloidosis, whereas no patient was diagnosed with ATTR‐CA. At 2 [interquartile range (IQR) 0.75, 3.25] years of follow‐up, the survival of patients with grade 1 vs. grades 2/3 uptake was significantly better [hazard ratio 0.271 (95% confidence interval 0.130 to 0.563, P = 0.0005)]. Prospectively, 30 patients with grade 1 uptake were re‐evaluated at a median follow‐up of 3.2 (IQR 2.2, 3.9) years. Their New York Heart Association class, biomarker levels, and echocardiography findings remained stable. No patient (0/25) demonstrated grades 2/3 uptake at repeated long‐term scintigraphy. Conclusions Patients with suspected ATTR‐CA and a grade 1 scintigraphy uptake demonstrate a stable clinical, laboratory, imaging, and scintigraphy phenotype along with a benign survival profile at long‐term follow‐up. Larger studies should define the optimal evaluation strategy in this population.

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.

To the best of our knowledge, this is the first published report of anti-immunoglobulin-like transcript 3 (ILT3)-induced myocarditis. A 48-year old female patient with refractory acute myeloid leukemia who was given a single dose of anti-ILT3 monotherapy presented with fever, hypotension, chest pain, and elevated cardiac biomarkers. Systolic bi-ventricular function was in normal limits. The patient was promptly treated with pulse dose steroids with a rapid hemodynamic and clinical improvement and declining levels of cardiac biomarkers. The diagnosis of acute myocarditis was confirmed using cardiac magnetic resonance imaging applying the revised Lake Lewis criteria. While larger-scale data are needed in order to assess the incidence, management and prognosis of anti-ILT-3 induced myocarditis, we believe a high level of suspicion for adverse non-target cardiac effects is required in patients receiving this novel class of drugs.

Abstract 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

IntroductionVaccination-associated myocarditis was reported following COVID-19 vaccine initially among persons aged 16 or older and recently among adolescents aged 12–15.ObjectivesTo describe the clinical and cardiac magnetic resonance (CMR) characteristics of adolescents aged 12–15 with myocarditis following the administration of the BNT162b2 mRNA COVID-19 vaccine.MethodsCMR of adolescents (age 12–15) with a clinical diagnosis of myocarditis within 42 days following the first COVID-19 vaccine were analyzed.ResultsA total of 182,605 adolescent were vaccinated, out of which 9 were diagnosed with clinically adjudicated myocarditis while CMR was performed in 5/9 patients (56%). Median age was 15 years (range 13–15), 4/5 (80%) males. All the patients we previously healthy. The ECG upon presentation was abnormal in 3/5 (60%) of patients. All cases were classified as clinically mild and no patient required inotropes or mechanical circulatory support treatment. The median follow-up time, for the 5-included patients, was 206 (IQR 192–229, range 179–233) days. During the follow-up, no re-admissions, deaths, or any other cardiac events have occurred.The median time between the diagnosis to the CMR was 104 days (range 27–149). The median left ventricular ejection fraction was within normal range 65% (range 62–69). Native T1 was available in four patients, the local T1 value was increased in three of them. T2 values were available in two patients and were all within normal range. The median late gadolinium enhancement (LGE) was 2% (range 0–6%) with inferolateral wall being the most common location (3/5). The patterns of the LGE were as following: (i) mid-wall in 3 patients; (ii) epicardial in 1-patient. LGE in the pericardium was present in 2/5 patients with pericardial effusion present in 4/5 patients with a median diameter of 4 mm (range 3–5 mm) at end-systole.ConclusionsCMR findings and clinical course of adolescents with COVID-19 vaccination associated myocarditis, are similar to those of older patients, being relatively mild and potentially implying favorable outcomes.

AimsNon-invasive coronary assessment using single-photon emission computerized tomography (SPECT) testing for potential cardiac ischemia is an essential part of the evaluation of kidney transplant candidates. We aimed to examine the prognostic value of preoperative SPECT test results in kidney transplanted patients.Methods and resultsWe retrospectively analyzed the pre-surgical nuclear SPECT test results in a registry of kidney transplanted patients. Follow-up at 1 month and 1 year recorded major adverse cardiac events (MACE) including non-fatal myocardial infarction, all-cause mortality and hospitalization due to cardiovascular disease following the renal transplantation. Of 577 patients available for analysis, 408 (70.9%) patients underwent nuclear SPECT test pre-transplant and 83 (20.3%) had abnormal results with either evidence of ischemia or infarct. A significantly higher incidence of post-operative MACE at 1 month was evident among patients with abnormal SPECT test compared to patients with no evidence of ischemia (10.8 vs. 4.3% respectively; P = 0.019). Differences were mostly derived from significantly increased rates of myocardial infarction events (8.4 vs. 1.8%; P = 0.002). Yet, MACE rate was not statistically different at 1 year (20.5 vs. 13.1%; P = 0.88). Importantly, the prognostic impact of an abnormal SPECT was significantly attenuated for all outcomes following multivariable adjusting for conventional cardiovascular risk factors and coronary revascularization.ConclusionPre-surgical cardiac risk assessment of kidney transplant candidates with nuclear SPECT test was found to be predictive of post-operative MACE, yet apparently, its prognostic value was significantly attenuated when adjusted for cardiac risk factors.

Introduction: End-stage renal disease is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered contraindication for kidney transplant, although some patients demonstrate myocardial recovery post-transplant. We aimed to identify and characterize the phenomenon of reverse myocardial remodeling in kidney transplanted patients. Methods: The study is a retrospective cohort of patients undergoing kidney transplants between 2016 and 2019 (n = 604) at Rabin Medical Center. Patients were assessed according to availability of two echocardiographic examinations: pre- and post-kidney transplant. The change in estimated ejection fraction (EF) and possible predictors of myocardial recovery were examined. Results: Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal to or above 5%, whereas 36 (12%) patients had a LVEF improvement of 10% or more post-transplantation. Twenty-five patients (8.5%) had moderate or severe systolic heart failure with LVEF reduced to 40% or less at baseline. 13 of them (52%) had a LVEF improvement of ≥5%, and 10 patients (40%) had an improvement of ≥10% in their EF. Cox regression analyses identified female gender as the only independent variable associated with LVEF improvement of at least 10%. Conclusion: Renal transplantation might lead to improved LV systolic function in some patients. [ABSTRACT FROM AUTHOR]

We investigated the recovery pattern from acute kidney injury (AKI) following acute myocardial infarction (AMI) and its association with long-term mortality. The retrospective study included AMI patients (2002–2027), who developed AKI during hospitalization. Creatinine (Cr) measurements were collected and categorized into 24 h timeframes up to 7 days from AKI diagnosis. The following groups of recovery patterns were defined: rapid (24–48 h)/no rapid and early (72–144 h)/no early recovery. Specific cut-off points for recovery at each AKI stage and timeframe were determined through receiver operating characteristic (ROC) curves. The probability of long-term (up to 10 years) mortality as a post-AKI recovery was investigated using a survival approach. Out of 17,610 AMI patients, 1069 developed AKI. For stage 1 AKI, patients with a Cr ratio <1.5 at 24 h and/or <1.45 at 48 h were defined as 'rapid recovery'; for stages 2–3 AKI, a Cr ratio <2.5 at 96 h was defined as 'early recovery'. Mortality risk in stage 1 AKI was higher among the non-rapidly recovered: AdjHR = 1.407; 95% CI: 1.086–1.824; p = 0.010. Among stages 2–3 AKI patients, the risk for long-term mortality was higher among patients who did not recover in the early period: AdjHR = 1.742; 95% CI: 1.085–2.797; p = 0.022. The absence of rapid recovery in stage 1 AKI and lack of early recovery in stages 2–3 AKI are associated with higher long-term mortality. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

BackgroundMyocarditis has been reported following the first two doses of Pfizer-BNT162b2 messenger RNA (mRNA) COVID-19 vaccination. Administration of a third dose (booster) of the vaccine was initiated recently in Israel.ObjectiveThe aim of this study was to describe the characteristics of patients referred for cardiac magnetic resonance (CMR) imaging with myocarditis following the booster.MethodsPatients referred for CMR imaging with a clinical diagnosis of myocarditis within 21 days following the booster, between July 13 and November 11, 2021, were analyzed.ResultsOverall, 4 patients were included, 3/4 (75%) were men, and the mean age was 27 ± 10 years. The time from booster administration to the onset of symptoms was 5.75 ± 4.8 days (range 2–14). Obstructive coronary artery disease was excluded in 3 of the patients (75%). CMR was performed 34 ± 15 days (range 8-47 days) following the 3rd vaccination. The mean left ventricular ejection fraction was 61 ± 7% (range 53–71%), and regional wall motion abnormalities were present in one of the patients. Global T1 was increased in one of the patients, while focal T1 values were increased in 3 of the patients. Global T2 was increased in one of the patients, while focal T2 values were increased in all the patients. Global ECV was increased in 3 of the patients, while focal ECV was increased in all the patients. Median late gadolinium enhancement (LGE) was 4 ± 3% (range 1–9%), with the inferolateral segment as the most common location (3 of the 4 patients). All the patients met the Updated Lake Louise Criteria.ConclusionsPatient characteristics and CMR imaging findings of myocarditis following the administration of the booster vaccine are relatively mild and consistent with those observed with the first two doses. Although larger-scale prospective studies are necessary, these initial findings are somewhat reassuring.

Abstract Background Acute myocardial infarction (AMI) is associated with greater utilization of healthcare resources and financial expenditure. Objectives To evaluate temporal trends in healthcare resource utilization and costs following AMI throughout 2003–2015. Methods AMI patients who survived the first year following hospitalization in a tertiary medical center (Soroka University Medical Center) throughout 2002–2012 were included and followed until 2015. Length of the in-hospital stay (LOS), emergency department (ED), primary care, outpatient consulting clinic visits and other ambulatory services, and their costs, were evaluated and compared annually over time. Results Overall 8047 patients qualified for the current study; mean age 65.0 (SD = 13.6) years, 30.3% women. During follow-up, LOS and the number of primary care visits has decreased significantly. However, ED and consultant visits as well as ambulatory-services utilization has increased. Total costs have decreased throughout this period. Multivariate analysis, adjusted for potential confounders, showed as significant trend of decrease in LOS and ambulatory-services utilization, yet an increase in ED visits with no change in total costs. Conclusions Despite a decline in utilization of most healthcare services throughout the investigated decade, healthcare expenditure has not changed. Further evaluation of the cost-effectiveness of long-term resource allocation following AMI is warranted. Nevertheless, we believe more intense ambulatory follow-up focusing on secondary prevention and early detection, as well as high-quality outpatient chest pain unit are warranted.

IntroductionAtrial fibrillation (AF) is a major increasing public health problem worldwide, with clinical and epidemiological differences between men and women. However, contemporary population-level data on incidence and survival are scarce.AimTo evaluate sex-specific contemporary trends in the incidence, prevalence, and long-term survival of non-valvular AF in a real-world setting.MethodsAF patients diagnosed between 2007-2015, insured by a large, state-mandated health organization in Israel (Maccabi Healthcare Services) were included. AF was diagnosed based on registered diagnoses. Patients with valvular disease, active malignancy, cardiac surgery ≤ 6 months, or recent pregnancy, were excluded. Annual incidence rate, period prevalence, and 5-year survival for each calendar year during the study period, were calculated.ResultsA total of 15,409 eligible patients (8,288 males, 7,121 females) were identified. Males were more likely to be younger, have higher rates of underlying diseases (ischemic heart disease, heart failure, and chronic obstructive pulmonary disease), but with lower rates of hypertension and chronic kidney diseases as compared to female patients. During the study period, age-adjusted incidence decreased both in men: (-0.020/1,000-person year, p-for trend = 0.033) and, women (-0.025/1,000 person-year p = 0.009). The five-year survival rate was significantly higher among men vs. women (77.1% vs. 71.5%, respectively, pConclusionsThe current study shows significant sex-related disparities in the incidence, prevalence, and survival of AF patients between 2007-2015; while the adjusted incidence of both has decreased over-time, prevalence and mortality decreased significantly only in women.