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Background. Cerebral microinfarcts (CMI) represent covert brain ischemia and were associated with stroke risk and cognitive impairment. Magnetic resonance imaging diffusion-weighted imaging (DWI) hyperintensities have been suggested to represent acute CMI. The relationship between malignancy and CMI is unknown. Aims. We aimed to examine whether CMI is more common in patients with undiagnosed lung cancer, and therefore might serve as a prediction marker for cognitive impairment or cancer-related stroke. Methods. We used the computerized database of Clalit Health Services (the largest healthcare provider in Israel) to identify adults diagnosed with lung cancer who had an MRI brain scan for any indication prior to cancer diagnosis. We analyzed DWI sequences, in order to evaluate CMI incidence in this population, and compared it to control groups of patients with other undiagnosed malignancies and patients without known cancer. Results. Altogether, we reviewed 1822 MRI brain scans, of which 497 scans were taken in patients with undiagnosed lung cancer, 543 scans of noncancer patients, and 793 scans of patients with other undiagnosed malignancies. In the lung cancer group, we found 24 CMI, compared with 4 in the noncancer group ( p = 0.04 ) and 8 in the other cancer group ( p = 0.07 ). Conclusions. CMI is common in undiagnosed lung cancer patients compare to other undiagnosed cancer types or noncancer patients. At the time of lung cancer diagnosis patients may be at risk for future stroke or cognitive decline.

Background Tixagevimab and cilgavimab, a combined monoclonal antibody (Evusheld), was granted emergency use authorization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preexposure prophylaxis in individuals with immunocompromising conditions. In this study we used population-based real-world data to evaluate the effectiveness of Evusheld in immunocompromised patients. Methods Using the computerized database of the largest healthcare provider in Israel, we identified all adult immunocompromised patients who were eligible to receive Evusheld (150 mg tixagevimab and 150 mg cilgavimab) on 15 February 2022. Patients with a documentation of a prior SARS-CoV-2 infection were excluded. A total of 703 patients who received Evusheld were propensity score matched, using a ratio of 1:4, with 2812 patients who had not received Evusheld (control group). Patients were followed through 30 June 2022 for up to 90 days for the first documentation of SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19)–related hospitalization. Results Overall, 72 patients in the Evusheld group and 377 patients in the control group had SARS-CoV-2 infection, reflecting an incidence rate of 4.18 and 5.64 per 100 person-months, respectively. The hazard ratios were 0.75 (95% confidence interval [CI]: .58–.96) for SARS-CoV-2 infection and 0.41 (95% CI: .19–.89) for COVID-19–related hospitalization in the Evusheld group compared to the control group. The magnitude of relative risk reduction of each outcome was greater in nonobese patients (P for interaction = .020 and .045, respectively). Conclusions This study suggests that Evusheld is effective in reducing the risk of SARS-CoV-2 infection and COVID-19 hospitalization in immunocompromised patients. The effectiveness of this dose appears to be greater in nonobese patients.

Background Paxlovid was granted an Emergency Use Authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19), based on the interim analysis of the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real-world data to evaluate the effectiveness of Paxlovid. Methods The database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first-ever positive test for severe acute respiratory syndrome coronavirus 2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28-day hazard ratio (HR) for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable. Results Overall, 180 351 eligible patients were included; of these, only 4737 (2.6%) were treated with Paxlovid, and 135 482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HRs of 0.54 (95% confidence interval [CI], .39–.75) and 0.20 (95% CI, .17–.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction P < .05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status. Conclusions This study suggests that in the era of Omicron and in real-life settings, Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.

Background: Lymphopenia is associated with adverse prognosis in chronic disease states that are related to immune dysregulation. We aimed to determine the association between lymphopenia and mortality in patients presenting to coronary angiography and investigate whether elevated red blood cell distribution width (RDW), an established cardiovascular prognostic marker, further refines risk stratification. Methods: Retrospective analysis of patients undergoing coronary angiography for evaluation or treatment of coronary artery disease between 2003 and 2018. Mortality risk associated with relative (1000–1500/μL) or severe (< 1000/μL) lymphopenia was analyzed using adjusted Cox proportional hazards regression models. Results: Overall, 15,179 patients aged 65 ± 12 years underwent coronary angiography. During a median follow-up of 8 years, 4253 patients died. Compared to normal lymphocyte count, the adjusted hazard ratio (HR) for mortality was 1.31 (95% confidence interval [CI] 1.21–1.41) and 1.97 (95% CI 1.75–2.22) for relative and severe lymphopenia, respectively. The increase in mortality associated with severe lymphopenia was significant in patients presenting in the non-acute setting (HR 2.18, 95% CI 1.74–2.73), ST-segment elevation myocardial infarction (STEMI) (HR 1.59, 95% CI 1.15–2.21), or unstable angina/non-STEMI (HR 2.00, 95% CI 1.70–2.34); p-value for interaction 0.626. The association of lymphopenia with mortality remained significant after additional adjustment to RDW. High RDW (> 14.5%) was associated with reduced survival, and it improved the predictive accuracy of lymphocytes count with an increase in Harrell’s Concordance statistic from 0.634 (SE = 0.005) to 0.672 (SE = 0.005), p < 0.001. Conclusions: lymphopenia is associated with increased risk of mortality during long-term follow-up in patients undergoing coronary angiography, regardless of the coronary presentation. High RDW may enhance the predictive ability of lymphopenia.

Smoking is associated with increased risk for acute ST-elevation myocardial infarction (STEMI) at a young age. Although smoking is a modifiable risk factor, smoking cessation rates after STEMI are suboptimal. We investigated the association between smoking status 1 year after STEMI and adverse events in patients (n = 765) aged ≤60 years. Patients were categorized as: (1) nonsmokers, (2) quit smoking, and (3) continued/resumed smoking. The association between smoking status and risk for major adverse cardiovascular events (MACEs) was analyzed during a median follow-up of 8 years. At presentation with STEMI, the mean age was 51 ± 7 years (88% men) and 427 (56%) were smokers. A year after STEMI, 272 continued smoking, 35 quit but later resumed smoking (summed to a single group; n = 307), and 120 quit smoking. Continued smoking was associated with younger age, male gender, lower weight, and low socioeconomic status. Compared with nonsmokers, the adjusted hazard ratio (95% confidence interval) for myocardial infarction, stroke, unstable angina, death, and MACE was 2.51 (1.67 to 3.73), 2.07 (0.94 to 4.56), 3.73 (1.84 to 7.58), 2.52 (1.53 to 4.13), and 2.40 (1.80 to 3.22), accordingly, in those who continued to smoke. However, the adjusted hazard ratio was not significantly associated with these outcomes in patients who quit smoking (MACE: 1.20 [0.77 to 1.87], p=0.414; nonsignificant for individual end points). In conclusion, the prevalence of smoking in young and middle-aged patients presenting with STEMI is high and smoking cessation rates are low. A year after STEMI, those who continued to smoke had worse cardiovascular outcomes and death compared with nonsmokers; however, the long-term outcomes among those who quit smoking appear to be comparable with nonsmokers. The results highlight the contrast between health benefits of quitting smoking after STEMI and low abstinence rates in clinical practice.

Background The COVID-19 pandemic has had diverse effects on population health and psychology in relation to non-COVID-19 diseases, as well as on COVID-19 infection. Fewer patients with acute myocardial infarction (AMI) sought medical attention during the first lockdown of the pandemic. Methods and results We conducted a retrospective cohort study of Clalit Health Services patients treated in multiple hospitals for AMI. We examined the numbers and characteristics of the patients and 30-day mortality during three 5-week phases of the first wave of the COVID-19 pandemic in Israel: pre-lockdown ( N = 702), lockdown (N = 584), and lockdown-lift (N = 669). We compared data for the same period in 2018 and 2019. We stratified the data by ST-elevation myocardial infarction (STEMI) and non-STEMI. AMI hospitalizations during the lockdown were 17% lower than in the pre-lockdown period (rate ratio-0.83, 95% CI 0.74–0.93), and 22% and 31% lower than in the corresponding periods in 2018 and 2019, respectively. The reduction was mainly attributed to non-STEMI hospitalizations (26% lower than the pre-lockdown period in 2020). Hospitalizations due to both STEMI and non-STEMI were moderately reduced during the post-lockdown period compared to the corresponding periods in 2018 and 2019. Thirty-day mortality rate was similar for all the periods assessed. Conclusions The number of hospitalized patients with AMI during the first COVID-19 lockdown and post-lockdown periods was significantly reduced, without significant changes in 30-day mortality rates.

Hypertension is a well-established risk factor for the onset and progression of atrial fibrillation (AF). Blood pressure (BP) measurements during routine exercise stress testing (EST) may identify subjects at increased risk for developing AF. We performed a retrospective analysis of treadmill EST carried out using the Bruce protocol in patients aged ≥40 years without a history of AF (n = 17,617; 42% women). BP was measured at rest, peak exercise, and 2-min recovery and analyzed for its association with the risk for developing AF. During a mean follow-up of 7 years, AF was documented in 4.5% of the patients. The incidence rate of AF per 1000 person-years increased with the rise in CHA

We sought to assess the effectiveness of oral vancomycin compared to metronidazole on recurrence and mortality among hospitalized patients with non-severe Clostridioides difficile infection (CDI).A single center retrospective cohort study was conducted, including adult patients hospitalized between 2015 and 2020 with a first episode of non-severe CDI, treated with metronidazole or vancomycin as monotherapy for at least 10 days. We assessed recurrence of CDI requiring hospitalization (primary outcome) and all-cause mortality up to 8 weeks, post discharge.Overall, 160 patients were treated with vancomycin and 149 treated with metronidazole. Re-hospitalization within 8 weeks due to CDI occurred in 10 (6.2%) patients in the vancomycin group, and 13 (8.7%) in the metronidazole group (P value = 0.407). Eight-week mortality occurred in 39 patients (26.2%) in the metronidazole group and 46 patients (28.8%) in the vancomycin group (P value = 0.61). After adjusting for age, gender, Ischemic heart disease, white blood cell count, neutrophile count and CRP, there was no significant difference between the two treatments (Re-hospitalization in 8 weeks due to CDI P = 0.5059; In-hospital death P = 0.7950; 4-week mortality P = 0.2988; 8-week mortality P = 0.8237).There is no benefit of using vancomycin compared to metronidazole concerning recurrence rate requiring hospitalization, in-hospital and up to 4- and 8-week mortality rate in non-severe first episode of CDI.

Background The PINNACLE FLX (Protection Against Embolism for Non‐valvular AF [Atrial Fibrillation] Patients: Investigational Device Evaluation of the Watchman FLX LAA [Left Atrial Appendage] Closure Technology) trial evaluated the safety and efficacy of a next‐generation left atrial appendage closure device (WATCHMAN FLX; Boston Scientific, Marlborough, MA). At 1 year, the study met the primary end points of safety and anatomical efficacy/appendage closure. This final report of the PINNACLE FLX trial includes the prespecified secondary end point of ischemic stroke or systemic embolism at 2 years, also making it the first report of 2‐year outcomes with this next‐generation left atrial appendage closure device. Methods and Results Patients with nonvalvular atrial fibrillation with CHA 2 DS 2 ‐VASc score ≥2 (men) or ≥3 (women), with an appropriate rationale for left atrial appendage closure, were enrolled to receive the left atrial appendage closure device at 29 US centers. Adverse events were assessed by an independent clinical events committee, and imaging was assessed by independent core laboratories. Among 395 implanted patients (36% women; mean age, 74 years; CHA 2 DS 2 ‐VASc, 4.2±1.5), the secondary efficacy end point of 2‐year ischemic stroke or systemic embolism was met, with an absolute rate of 3.4% (annualized rate, 1.7%) and an upper 1‐sided 95% confidence bound of 5.3%, which was superior to the 8.7% performance goal. Two‐year rates of adverse events were as follows: 9.3% all‐cause mortality, 5.5% cardiovascular death, 3.4% all stroke, and 10.1% major bleeding (Bleeding Academic Research Consortium 3 or 5). There were no additional systemic embolisms, device embolizations, pericardial effusions, or symptomatic device‐related thrombi after 1 year. Conclusions The secondary end point of 2‐year stroke or systemic embolism was met at 3.4%. In these final results of the PINNACLE FLX trial, the next‐generation WATCHMAN FLX device demonstrated favorable safety and efficacy outcomes.

Background Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance. Methods We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons. Results Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637. Conclusions The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

Pericardial access, predominantly utilized for emergency treatment, has evolved as an important approach for performing cardiac interventions. Accordingly, the complex anatomy and unique physiology...

Background Estimation of kidney function by glomerular filtration rate (eGFR) is affected by age and is important for decision making regarding treatment and prognosis of patients with cardiovascular disease. We investigated the impact of eGFR on long-term cardiovascular outcomes in an elderly population undergoing coronary angiography for evaluation or treatment of coronary artery disease. Methods GFR was estimated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in 3690 elderly patients (aged 70-100 years) undergoing coronary angiography. Patients receiving maintenance dialysis were excluded. The association between eGFR and major adverse cardiovascular events (MACE) including myocardial infarction, ischemic stroke or death, was investigated. GFR was further calculated according to modification of diet in renal disease (MDRD) and the Cockcroft-Gault equations, and compatibility between estimations was analyzed. Results Cardiovascular comorbidities were more prevalent with the reduction in kidney function as was the proportion of patients presenting with acute coronary syndromes. The adjusted hazard ratio (95% confidence interval) for MACE during a mean follow-up of 5 years was 0.95 (0.77-1.16), 1.04 (0.84-1.29), 1.56 (1.16-1.84), 2.22 (1.65-2.97) and 3.74 (2.20-6.38) in patients with eGFR 60-89, 45-59, 30-44, 15-29 and 90 ml/min/1.73m2. Reclassification of eGFR stages by MDRD (upward 23.8%, downward 0.4%) and Cockcroft-Gault (upward 4.3%, downward 28.1%) compared to CKD-EPI estimation, was noted. However, the association between eGFR stages and MACE was similar between equations. Conclusions Kidney function, as manifested by eGFR, has a graded inverse association with the burden of cardiovascular comorbidities and long-term adverse events in elderly patients undergoing coronary angiography.

Permanent pacemaker (PPM) implantation is required in 5% to 10% of patients following transcatheter aortic valve implantation (TAVI). However, there are limited data on the impact of PPM implantation on the incidence of pericardial effusion, cardiac tamponade, and outcomes after TAVI. We identified all hospitalizations in patients ≥18 years of age who underwent TAVI in the years 2016 to 2017 in the Nationwide Readmission Database. The endpoints of the study were pericardial effusion, cardiac tamponade, and percutaneous or surgical drainage of the pericardial cavity in patients that required PPM implantation after TAVI. Multivariable logistic regression determined associations of PPM implantation, pericardial effusion, and tamponade with patient outcomes. A total of 54,317 unweighted hospitalizations for TAVI were identified, of which 5,639 (10.4%) required PPM. The risk of pericardial effusion was significantly greater in patients who required PPM (2.4% vs 1.6%, adjusted odds ratio (aOR) 1.39 (1.15 to 1.70), p

Objectives To analyze urinary stone composition in Israel and determine the effects of demographic parameters, such as gender, age, socioeconomic status, ethnicity, medical history and geographic region, on stone composition. Patients and Methods The stone composition of 10633 consecutive patients from an Israeli database was analyzed between 2014 and 2019 by a central laboratory using the Fouriertransform infrared spectroscopy. Chi-squared test was used to determine associations between stone composition and the different demographic parameters. Results Calcium oxalate (CaOx) monohydrate was the predominant stone type (51.9%). 5776 stones had pure component (54%) and 4,857 (46%) had mixed components. Men had a higher frequency of CaOx stones (89.6% vs. 85.6%), whereas women had a higher frequency of calcium phosphate, infection, and cystine stones (27.2%, 17.7%, and 0.9% vs. 17.2%, 7.5%, and 0.5%, respectively). Cystine stones were more abundant in Arabs (1.2% vs. 0.5% in the Jewish population). Lower socioeconomic status was associated with higher prevalence of calcium phosphate, uric acid, and infectious stones and a lower prevalence of CaOx stones. Uric acid stones were associated with medical conditions, such as diabetes, hypertension, ischemic heart disease, and obesity (28.3%, 24.9%, 25.7%, and 22.6% vs. 9.6%, 8.4%, 12.3%, and 10.3%, respectively). Conclusions The most common stone type was CaOx monohydrate. Stone types are highly influenced by patients’ demographics.

Hypertension, obesity, and low cardiorespiratory fitness (CRF) are known risk predictors for the development of atrial fibrillation (AF) that often interrelate with each other. We examined the interplay of these 3 risk indicators with the occurrence of AF in patients without known cardiovascular disease.A retrospective analysis of 13,042 patients underwent exercise stress testing (EST). The occurrence of AF during the median follow-up period of 6.8 years was investigated in relation to the presence of obesity (body mass index ≥30 kg/mThe mean age of the study population was 58 ± 9 years; 49% were women. AF occurred in 499 patients (3.8%). Obesity [hazard ratio (95% confidence interval)], 1.36 (1.12-1.65), hypertension, 1.47 (1.19-1.82), and low CRF, 1.32 (1.06-1.64), were independent risk predictors for AF after multivariable adjustment, including after adjusting for each other and also when the risk predictors were analyzed as continuous variables. In a combined model, a gradual increase in the risk of AF was observed, reaching an adjusted hazard ratio of 2.53 (1.77-3.62) in those with all 3 compared with neither risk indicators. P-for-interaction between hypertension and obesity, or hypertension and low CRF was nonsignificant.Obesity, low CRF, and hypertension are independently associated with an excess risk of developing AF in patients without known cardiovascular disease, both individually and more so when coexisting together.

Radiofrequency ablation (RFA) is a common treatment of atrial fibrillation. However, current treatment is associated with a greater than 20% recurrence rate, in part due to inadequate monitoring of tissue viability during ablation. Spectral parameters, in particular cyclic variation of integrated backscatter (CVIB), have shown promise as early indicators of myocardial recovery from ischemia. Our aim was to demonstrate the use of spectral parameters to differentiate atrial myocardium before and after radiofrequency ablation. An AcuNav 10 F catheter was used to collect radiofrequency signals from the posterior wall of the left atrium of patients before and immediately after RFA for AF. The normalized power spectrum was obtained and three spectral parameters (integrated backscatter [IB], slope, and intercept) were extracted across two continuous heart cycles. Parameters were gated for ventricular end-diastole and compared before and after ablation. Additionally, the cyclic variation of each of these three parameters was generated as an average of the variation across the two recorded heart cycles. Data from 14 patients before and after ablation demonstrated a significant difference in the magnitude of the cyclic variation of integrated backscatter (9.0 vs. 6.0 dB, p

Background: It is not well understood why some patients with atrial fibrillation (AF) develop significant atrial functional mitral regurgitation (AFMR). We sought to investigate the mechanistic determinants ofAFMR by comparing anatomic and functional characteristics of patients with AFwho develop significant AFMR (≥2+ MR) to those without AFMR. Methods: We screened AF patients referred for cardiac computed tomography (CCT) before pulmonary vein isolation or appendage occlusion between 2017 and 2019. Patients with primary leaflet pathology, prior mitral surgery, left ventricular dysfunction or dilation, and without echocardiography within six months were excluded. We identified 50 patients with ≥2+ MR, and 50 controls were selected based on age and gender propensity matching. Mitral anatomy was compared by CCT, while diastology and strains were compared by echocardiography. Results: Patients with significant AFMR had larger annular and atrial dimensions (all p p p p = NS). On strain analysis, they had lower LA strain (p = 0.001) and LV longitudinal strain (p = 0.001), with shorter deceleration time (DT, p = 0.001) and isovolumetric relaxation time (IVRT, p p = 0.004) with more concomitant significant (≥2+) tricuspid regurgitation (TR, p = 0.006). Conclusions: Patients with significant AFMR have larger atria and annuli with insufficient compensatory leaflet growth but similar tenting height and area with a shallower posterior angle. They also have impaired atrial and ventricular strains and shorter DT and IVRT, with associated higher RVSP and more concomitant TR.

ObjectiveTo examine the association between psoriatic arthritis (PsA) and all-cause mortality from a large population-based database.MethodsPatients with PsA from the Clalit Health Services database were identified between 2003–2018 and matched to 4 controls by age, sex, ethnicity, and index date. Patient demographics, comorbidities, and treatments were extracted. Mortality data were obtained from the Israeli Notification of Death certificate. The proportionate mortality rate (PMR) of the leading causes of death was calculated and compared to that of the general population. Cox proportional hazard regression models were used to estimate the crude and the multivariate adjusted HR for the association between PsA and all-cause mortality and for factors associated with mortality within the PsA group.ResultsThere were 5275 patients with PsA and 21,011 controls included and followed for 7.2 ± 4.4 years. The mean age was 51.7 ± 15.4 years, and 53% were females. Among patients with PsA, 38.2% were on biologics. Four hundred seventy-one (8.9%) patients died in the PsA group compared to 1668 (7.9%) in the control group. The crude HR for the association of PsA and all-cause mortality was 1.16 (95% CI 1.04–1.29) and 1.02 (95% CI 0.90–1.15) on multivariate analysis. Malignancy was the leading cause of death (26%), followed by ischemic heart disease (15.8%); this is in keeping with the leading causes of death in the general population. Older age, male sex, lower socioeconomic status, increased BMI, increased Charlson comorbidity index scores, and history of psoriasis or hospitalization in 1 year prior to entry were positive predictors for mortality.ConclusionNo clinically relevant increase in mortality rate was observed in patients with PsA, and specific PMRs were similar to those of the general population.

Background We sought to examine outcomes of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation with valve repair/replacement. Methods and Results Two atrial fibrillation cohorts from Medicare were identified from 2015 to 2019. They comprised patients who underwent surgical or transcatheter mitral valve repair (MV repair cohort) and surgical aortic or mitral bioprosthetic or transcatheter aortic valve replacement (bioprosthetic cohort). Each cohort was divided into warfarin and DOACs (apixaban, rivaroxaban, and dabigatran) groups. Study outcomes included mortality, stroke, and major bleeding. Inverse probability weighting was used for adjustment between the 2 groups in each cohort. The MV repair cohort included 1178 patients. After a median of 468 days, DOACs were associated with lower risk of mortality (hazard ratio [HR], 0.67 [95% CI, 0.55–0.82], P P =0.05) and bleeding (HR, 0.79 [95% CI, 0.63–0.99], P =0.04) compared with warfarin. The bioprosthetic cohort included 8089 patients. After a median follow‐up of 413 days, DOACs were associated with similar risk of mortality (adjusted HR, 0.93 [95% CI, 0.86–1.01], P =0.08), higher risk of ischemic stroke (adjusted HR, 1.27 [95% CI, 1.13–1.43], P P Conclusions In patients with atrial fibrillation, DOACs are associated with similar mortality, lower bleeding, but higher stroke with bioprosthetic valve replacement and lower risk of all 3 outcomes with MV repair compared with warfarin.

Among patients treated with irinotecan, homozygous carriers of the UGT1A1*28 allele are at increased risk for neutropenia, but UGT1A1 genotype alone does not account for irinotecan-induced toxicity. Our aim was to study the association between single-nucleotide variants in genes encoding for efflux transporters of irinotecan (ABCG2, ABCB1, and ABCC2) and toxicity in real life. The source population was a cohort of patients with colorectal cancer (CRC) in Northern Israel, who had undergone genome-wide association study. From the source population we chose the patients with CRC prescribed irinotecan, and a comparative cohort of patients with CRC treated with other anticancer systemic therapies. Using Clalit Health Services electronic medical records (including laboratory results) we ascertained hematological and gastrointestinal adverse effects and mortality, within 90 days of the first dose, as a composite outcome. There were 601 patients with CRC who received irinotecan, and 756 patients with CRC treated with other anticancer regimens. The minor allele in rs2231142 (ABCG2) was associated with lower incidence of the composite outcome (odds ratio (OR) = 0.54 (0.33, 0.91); P = 0.02) in irinotecan-treated patients with CRC, but not in patients with CRC treated with other regimens. ABCB1 rs1045642 and ABCC2 rs3740066 were not associated with the composite outcome. In a sensitivity analysis, adjusted for UGT1A1 status and for possible demographic and clinical confounders, adjusted OR was 0.56 (0.33, 0.94) for the association between rs2231142 (ABCG2) and the composite outcome. In conclusion, we describe a novel association between the minor allele of rs2231142 in the efflux transporter gene ABCG2 and protection against severe side effects in CRC patients treating with irinotecan.

Background Molnupiravir was granted emergency use authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). In this study, we used population-based real-world data to evaluate the effectiveness of molnupiravir. Methods The database of the largest healthcare provider in Israel was used to identify all adults with first-ever positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) performed in the community during January–February 2022, who were at high risk for severe COVID-19, and had no contraindications for molnupiravir use. Patients were included regardless of SARS-CoV-2 vaccination status. A total of 2661 patients who received molnupiravir were propensity score matched with 2661 patients who have not received molnupiravir (control group). Patients were followed through 10 March 2022 for up to 28 days for the first occurrence of the composite severe COVID-19 or COVID-19-specific mortality. Results The composite outcome occurred in 50 patients in the molnupiravir group and 60 patients in the control group. Molnupiravir was associated with a nonsignificant reduced risk of the composite outcome: hazard ratio, 0.83 (95% confidence interval, .57–1.21). However, subgroup analyses showed that molnupiravir was associated with a significant decrease in the risk of the composite outcome in older patients 0.54 (0.34–0.86), in females 0.41 (0.22–0.77), and in patients with inadequate COVID-19 vaccination 0.45 (0.25–0.82). The results were similar when each component of the composite outcome was examined separately. Conclusions This study suggests that in the era of Omicron and in real-life setting, molnupiravir might be effective in reducing the risk of severe COVID-19 and COVID-19-related mortality, particularly in specific subgroups.

Previous small studies have proposed a higher incidence of acute mastoiditis in Israeli pediatric patients than in other Western countries. The aim of this study was to describe the incidence of acute mastoiditis and its epidemiological features over a decade, in order to identify variables that could possibly affect the incidence.All admitted patients aged18 years diagnosed with acute mastoiditis between 2008 and 2018 at Clalit Healthcare Services were identified and a database was generated.A total of 1189 and 1115 patients met the inclusion criteria, respectively. Acute mastoiditis diagnosis was confirmed in 95.2% of the patients. The incidence was 7.78 cases per 100,000 children-years but was significantly higher in children under 2 years of age (average of 38.31 per 100,000 children-years). No specific pattern was observed in the annualized incidence rate during the study period. Acute mastoiditis was significantly more common in children of Jewish descent than non-Jewish (10.4 vs. 3.03 per 100,000 children-years,A higher incidence of acute mastoiditis was observed in the Israeli population than in other reports. The age-dependent rate was identified along with unique epidemiological features such as seasonality, higher incidence in patients of Jewish descent, or high socioeconomic status. Related parental smoking habits lend further support against the exposure of young children to household smoking.Level of evidence: Individual retrospective cohort study.

AIMS Oral anticoagulants (OACs) are considered the mainstay in preventing stroke in atrial fibrillation (AF). OAC treatment remains suboptimal among AF patients, even after the introduction of direct oral anticoagulants (DOACs). We aimed to assess trends overtime and current implementation of OAC treatment guidelines in AF, using a large dataset of real world data from Israel. METHODS This is a retrospective cohort study that includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed nonvalvular AF between January 2014 and December 2019 with CHA2 DS2 -VASc score ≥2. OAC treatment rates were calculated and multivariate regression models were used to identify predictors of OACs initiation. RESULTS Overall, 46 531 patients were included in the study. The 3-months cumulative OAC treatment rates increased consistently over the years: 46.9% (95% confidence interval, 46.1-47.7%), 54.9% (54.1-55.6%) and 61.7% (60.9-62.4%) during 2014-2015, 2016-2017 and 2018-2019, respectively. DOACs constituted 51.3% of prescribed OACs in 2014-2015 and increased to 95.1% during 2018-2019. On multivariate analyses, the likelihood of OACs initiation among AF patients increased across the years and across higher socioeconomic classes, and was more likely among females, Jews, statins users and patients previously screened for colorectal cancer, but less likely among smokers and patients with impaired renal function. The likelihood of treatment increased with higher CHA2 DS2 -VASc score and decreased with higher HAS-BLED score. CONCLUSION Despite the increasing OAC treatment rates among high-risk AF patients, mainly attributed to the expanding DOAC use, OAC treatment scope is still far from optimal.

Reduced clopidogrel effectiveness in preventing recurrent myocardial ischemia following percutaneous coronary intervention has been demonstrated in CYP2C19 loss-of-function carriers. Less is known about the effect of CYP2C19 genotype on the effectiveness of clopidogrel for stroke prevention, particularly in Caucasians. This is a retrospective cohort study, in which we used the Clalit clinical database to follow genotyped clopidogrel initiators, for up to 3 years. Endpoint was a new primary discharge diagnosis of ischemic stroke; secondary endpoints were new primary discharge diagnoses of coronary angioplasty, myocardial infarction (MI), or a composite endpoint of: stroke, MI, or coronary angioplasty. After 3 years of follow up over 628 clopidogrel initiators, 2 out of 12 (16.7%) poor metabolizers, 9 out of 144 intermediate metabolizers (6.3%), and 29 out of 472 (6.1%) normal/rapid/ultrarapid metabolizers have been newly diagnosed with ischemic stroke. Poor metabolizer status was associated with higher risk for ischemic stroke, marginally significant in univariate analysis and in multivariable models; and higher risk for the composite outcome of stroke, myocardial infarction and coronary angioplasty, HR = 3.32 (1.35-8.17) p = 0.009, 2.86 (1.16-7.06) p = 0.02 (univariate and multivariate analyses, respectively). Poor metabolizer status was associated with higher risk for stroke HR = 5.80 (1.33-25.24) p = 0.019, HR = 4.13 (0.94-18.13) p = 0.06 (univariate and multivariate analyses, respectively) in patients who "survived" the first year, and were in the cohort 1-3 years. Caucasian treated with clopidogrel who are homozygote for the CYP2C19 loss-of function allele might be at increased risk for ischemic stroke, and for the composite outcome of ischemic stroke, myocardial infarction and coronary angioplasty.

Integrative oncology (IO) is increasingly becoming part of palliative cancer care. This study examined the correlation between an IO treatment program and rates of survival among patients with advanced gynecological cancer. Patients were referred by their oncology healthcare professionals to an integrative physician (IP) for consultation and IO treatments. Those undergoing at least 4 treatments during the 6 weeks following the consultation were considered adherence to the integrative care program (AIC), versus non-adherent (non-AIC). Survival was monitored for a period of 3 years, comparing the AIC vs. non-AIC groups, as well as controls who did not attend the IP consultation. A total of 189 patients were included: 71 in the AIC group, 44 non-AIC, and 74 controls. Overall 3-year survival was greater in the AIC group (vs. non-AIC, p = 0.012; vs. controls, p = 0.003), with no difference found between non-AIC and controls (p = 0.954). Multimodal IO programs (≥ 3 modalities) were correlated in the AIC group with greater overall 3-year survival (p = 0.027). Greater rates of survival were also found in the AIC group at 12 (p = 0.004) and 18 months (p = 0.001). When compared with the AIC group, a multivariate analysis found higher crude and adjusted hazard ratios for 3-year mortality in the non-AIC group (HR 95% CI 2.18 (1.2–3.9), p = 0.010) and controls (2.23 (1.35–3.7), p = 0.002). Adherence to an IO treatment program was associated with higher survival rates among patients with advanced gynecological cancer. Larger prospective trials are needed to explore whether the IO setting enhances patients’ resilience, coping, and adherence to oncology treatment.

Paxlovid was granted emergency use authorization for the treatment of mild to moderate COVID-19, based on the interim analysis of EPIC-HR trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real world data to evaluate the effectiveness of Paxlovid.The database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first ever positive test for SARS-CoV-2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28 day HR for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable.Overall, 180,351 eligible were included, of them only 4,737 (2.6%) were treated with Paxlovid, and 135,482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HR 0.54 (95% CI, 0.39-0.75) and 0.20 (95% CI, 0.17-0.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction p-value0.05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status.This study suggests that in the era of omicron and in real life setting Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.

Heart rate response during exercise testing (ET) provides valuable prognostic information. Limited data are available regarding the prognostic interplay of heart rate (HR) measured at rest, exercise and recovery phases of ET, and its ability to predict risk beyond exercise capacity.Retrospective analysis of treadmill ETs was performed by the Bruce protocol in patients aged 35-75 yr without known cardiovascular disease (CVD; n = 13 887; 47% women). Heart rate recovery at 2 min (HRR2; defined abnormal42 beats) and chronotropic index (CI; defined abnormal80%, determined as age-predicted HR reserve) were analyzed in association with the risk of developing myocardial infarction, stroke, or death (major adverse cardiovascular event [MACE]) during median follow-up of 6.5 yr.The HRR242 beats and CI80% were each associated with increased risk of MACE: adjusted hazard ratios with 95% confidence interval 1.47: 1.27-1.72 and 1.66: 1.42-1.93, P.001, respectively, evident also when analyzed as continuous variables. Strength of association of HRR2 and CI with outcome was attenuated but remained significant with further adjustment for exercise duration and metabolic equivalents. Having both HRR2 and CI abnormal compared with only one measure abnormal was associated with hazard ratios with 95% confidence interval of 1.66: 1.38-2.00 and 1.48: 1.22-1.79 for MACE, before and after adjustment for cardiorespiratory fitness (CRF). The degree of CRF (low vs mid/high) did not modify the prognostic effect of HRR2 and CI (P-for-interaction nonsignificant).Both HRR2 and CI provide independent prognostic information beyond CRF in patients without CVD referred for ET. The predictive ability is more pronounced when both abnormal HR measures coexist.

Background Risk factors control and secondary prevention measures are often reported to be suboptimal in patients undergoing coronary artery bypass grafting (CABG) and may lead to worse clinical outcomes. We aimed to examine potentially modifiable risk factors in patients undergoing CABG and investigate their association with long-term coronary events. Methods Cardiovascular risk factors were recorded preoperatively in the setting of a cardiac catheterization laboratory and were analyzed in relation to long-term coronary events, defined as acute coronary syndrome (ACS) or revascularization after CABG. Results Study population included 1,125 patients undergoing CABG without previous revascularization. Modifiable risk factors included hypertension (71%), hyperlipidemia (67%), diabetes (42%), obesity (28%), and smoking (21%). Only 8% did not have any of the five risk factors. During the mean follow-up of 93 ± 52 months after CABG, 179 patients (16%) experienced a coronary event. Incidence rates were higher in patients with than without the presence of each of the modifiable risk factors, except obesity. Active smoking (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: (1.07–2.13); p = 0.020), presence of diabetes (HR: 1.61; 95% CI: 1.18–2.18; p = 0.002), and hyperlipidemia (HR: 2.13; 95% CI: 1.45–3.14; p Conclusions In patients undergoing CABG, diabetes, hyperlipidemia, and smoking, as documented preoperatively, were potentially modifiable risk factors that were independently and cumulatively associated with long-term risk of ACS or coronary revascularization, highlighting the importance of early identification and risk factors control for improving cardiovascular health after CABG.

Subclinical venous injuries are common during transvenous lead extraction (TLE), but their implications for future TLE are unclear. Little is known about whether a prior TLE adds risk or complexity to subsequent extraction procedures.The purpose of this study was to assess procedural profiles and outcomes of TLE based on whether patients had prior extraction procedures.All 3258 consecutive patients undergoing TLE at the Cleveland Clinic (1996-2012) were included. Procedural profiles and outcomes were determined.Of 3258 TLEs, 198 had prior TLE. Median number of leads in place was 2 in both groups, but patients with prior TLE were more likely to have defibrillator leads (47% vs 41%; P = .08) and more likely to be pacemaker-dependent (32% vs 25%; P = .02). The age of oldest lead (median 2134 vs 1902 days; P = .4) and combined age of leads (median 2948 vs 2676 days; P = .6) were comparable. Procedures were longer in those with prior TLE (166 ± 79 minutes vs 149 ± 74 minutes; P = .004) with comparable fluoroscopy times (median 13 vs 11 minutes; P = .07), and successful extraction was more likely to require specialized tools (88% vs 81%; P = .006) with higher likelihood of rescue femoral workstation (12% vs 4%; P.0001). Clinical success rates were comparable in those with prior TLE (99.5% vs 98.9%; P = .8) with similar major (3.0% vs 1.9%; P = .3) and minor (3.0% vs 3.7%; P = .8) complication rates.Extraction procedures were more challenging in patients with prior TLE compared to those without prior TLE but with excellent success and low complication rates.

Objectives This study sought to investigate the association between nonalcoholic fatty liver disease (NAFLD) and arrhythmia recurrence following atrial fibrillation ablation; and to examine the impact of NAFLD stage on outcomes. Background Metabolic derangements, including obesity and diabetes, are associated with incident and recurrent atrial fibrillation (AF), in addition to the development of NAFLD. Methods This was a retrospective study of 267 consecutive patients undergoing AF ablation, 89 of whom were diagnosed with NAFLD prior to ablation and matched in a 2:1 manner based on age, sex, body mass index, ejection fraction, and AF type with 178 patients without NAFLD. Patients were monitored for arrhythmia recurrence during a mean follow-up of 29 months. Results Recurrent arrhythmia was observed in 50 (56%) patients with NAFLD compared with 37 (21%) without NAFLD. Epicardial fat volume was measured on computed tomography and was significantly higher among those with NAFLD (248 ± 125 ml vs. 223 ± 97 ml; p = 0.01). On multivariable models adjusting for sleep apnea, body mass index, heart failure, AF type, and left atrial size, NAFLD was independently associated with increased rates of arrhythmia recurrence (hazard ratio: 3.010; 95% confidence interval: 1.980 to 4.680; p Conclusions NAFLD is associated with significantly increased arrhythmia recurrence rates following AF ablation. Identification and reversal, where possible, may result in improved arrhythmia-free survival.

Cardiorespiratory fitness (CRF) has been shown to correlate with incident atrial fibrillation (AF) and AF burden. In recent years there has been increasing recognition of the pivotal role of modifying risk factors before AF ablation.The purpose of this study was to investigate whether higher baseline CRF measured using exercise stress testing (EST) was associated with improved outcomes after AF ablation.We studied 591 patients who underwent EST within 12 months before AF ablation. Patients were categorized into low (85% predicted), adequate (85%-100% predicted), and high (100% predicted) CRF groups. Outcomes of interest included arrhythmia recurrence, cessation of antiarrhythmic therapy, repeat hospitalization for arrhythmia, repeat rhythm control procedures, and all-cause mortality.During mean follow-up of 32 months after ablation, arrhythmia recurrence was observed in 79% of patients in the low CRF group compared to 54% in the adequate CRF group and 27.5% in the high CRF group (P.0001). Similarly, rates of repeat arrhythmia-related hospitalization, repeat rhythm control procedures, and need for ongoing antiarrhythmic therapy were significantly lower in the high CRF group (P.0001). Death occurred in 2.5% of patients in the high CRF group compared to 4% in the adequate CRF group and 11% in the low CRF group (P.0001). In Cox proportional hazards analyses, high CRF was significantly associated with lower arrhythmia recurrence.Higher CRF is associated with reduced arrhythmia recurrence rates and death among patients undergoing AF ablation. Efforts should be made to enhance CRF before AF ablation.

Background Virtual visits (VVs) are a modality for delivering health care services remotely through videoconferencing tools. Data about patient and physician experience in using VVs are limited. Objective The purpose of this study was to assess patient and physician experience with the use of VVs in cardiac electrophysiology. Methods We performed a prospective survey of cardiac electrophysiology patients and physicians who participated in an outpatient VV from December 2018 to July 2019. Results One-hundred consecutive VVs were included. Sixty-four patients elected to complete a survey. Patients rated their experience as either excellent/very good in scheduling a VV (87%), seeing their physician of choice (100%), transmitting arrhythmia data (88%), rating their physician's ability to communicate (98%), asking all questions (98%), rating the level of care received (98%), paying for the cost of a VV (67%), and rating their overall level of satisfaction (98%). Thirty-eight of 64 patients (59.4%) preferred a VV for their next visit, 12 of 64 (18.8%) preferred an in-office visit, 13 of 64 (20.3%) responded that their decision for a virtual or office visit depended on indication, and 1 of 64 (1.6%) had no preference. A total of 14 cardiac electrophysiologists participated in 100 VVs. Nine visits were not included due to technical difficulty. Physician responses to survey questions were rated as excellent/very good in the ability to communicate (92%), accessing monitoring data (95%), and overall level of satisfaction (98%). Conclusion In our small study population, most patients and physicians prefer VVs. Convenience, cost, and reason for follow-up were important determinants that affected both patient and physician preference.

There is very limited evidence to support the common practice of preparative fasting prior to contrast-enhanced computerized tomography (CT). This study examined the effect of withholding fasting orders, prior to contrast-enhanced CT, on the incidence of aspiration pneumonitis and adverse gastrointestinal symptoms. This randomized controlled trial enrolled hospitalized patients referred for non-emergency, contrast-enhanced CT scan to either at least 4 h of fasting or to an unrestricted consumption of liquids and solids up to the time of CT. The primary outcome was incidence of aspiration pneumonitis and the secondary outcomes were rates of adverse gastrointestinal symptoms (nausea and/or vomiting). After excluding participants with incomplete follow-up, a total of 1080 participants were assigned to the fasting group and 1011 were assigned to the non-fasting group. Aspiration pneumonitis was not identified in either group. The mean time of fasting in the fasting group was 8.4 ± 1.6 h. Rates of nausea and vomiting were not statistically different between the fasting group compared with the non-fasting group, 6.6% vs. 7.6% (p = 0.37) and 2.6% vs. 3.0% (p = 0.58), respectively. A subgroup analysis of patients who were required to drink oral contrast agent (n = 1257) showed that rates of nausea and vomiting were not statistically different between the fasting and non-fasting groups, 6.8% vs. 8.0% (p = 0.42) and 2.6% vs. 3.6% (p = 0.3), respectively. Withholding fasting orders prior to contrast-enhanced CT was not associated with a greater risk of aspiration pneumonitis or a significant increase in rates of adverse gastrointestinal symptoms. ClinicalTrials.gov : NCT03533348 • Is fasting necessary prior to contrast-enhanced computed tomography (CT)? • In this randomized clinical study including 2091 participants referred to non-emergency contrast-enhanced CT scan, withholding preparative fasting was not associated with a greater risk of aspiration pneumonitis or clinically significant increase in rates of adverse gastrointestinal symptoms. • Eating and drinking prior to contrast-enhanced CT can be allowed and are not associated with an increased risk of aspiration pneumonitis.

Objectives This study sought to determine the incidence and prevalence of atrial fibrillation (AF) in transthyretin cardiac amyloidosis (ATTR-CA); to study the factors associated with the development of AF in this population; to study the prognostic implications of AF and maintenance of normal sinus rhythm (NSR) in patients with ATTR-CA; and to determine the impact of ATTR-CA stage on AF prevalence, outcomes, and efficacy of rhythm control strategies. Background AF is common in patients with ATTR-CA. The aim of this study was to determine the predictors, prevalence, and outcomes of AF in patients with ATTR-CA in addition to the efficacy of rhythm control strategies. Methods This was a retrospective cohort study of 382 patients with ATTR-CA diagnosed at our institution between January 2004 and January 2018. Means testing, and univariable and multivariable models were used. Results AF occurred in 265 (69%) patients. Factors associated with the development of AF included older age, advanced ATTR-CA stage, and higher left atrial volume index. Antiarrhythmic therapy (AAT) was used in 35% of patients with AF; cardioversion was performed in 45%, and 5% underwent AF ablation. Rhythm control strategies were substantially more effective when performed earlier in the disease course. During a mean follow-up of 35 months, no difference in mortality between patients with AF and those without AF was observed (65% vs. 49%; p = 0.76). On Cox proportional hazards analyses, maintenance of normal sinus rhythm and tafamidis use were associated with improved survival, whereas advanced ATTR-CA stage and higher New York Heart Association functional class were associated with increased mortality. Conclusions With advancing ATTR-CA stage, AF became more prevalent, occurring in 69% of our entire study cohort. Rhythm control strategies including AAT, direct-current cardioversion, and AF ablation were substantially more effective when performed earlier during the disease course.

Involvement of atherosclerosis in extracardiac vascular territories may identify coronary artery disease (CAD) patients at higher risk for adverse events. We investigated the long-term prognostic implications of polyvascular disease in patients with CAD, and further analyzed lipid goal attainment and its relation to patient outcomes. The study was a retrospective analysis of 10,297 patients who underwent coronary revascularization, categorized as having CAD alone (83.1%) or with multisite artery disease (MSAD) (16.9%) including cerebrovascular disease (CBVD) and/or peripheral artery disease (PAD). Incidence rates and hazard ratios (HR) for major adverse cardiovascular events (MACE) (myocardial infarction, ischemic stroke, or all-cause death) according to vascular territories involved, and in relation to most-recent lipid levels attained, were analyzed. Patients with MSAD were older with higher burden of co-morbidities. The rate of MACE (myocardial infarction, ischemic stroke, or all-cause death) and its individual components increased with the number of affected vascular beds. Adjusted HR (95% confidence interval) for MACE was 1.41 (1.24 to 1.59) in patients with CAD and CBVD, 1.46 (1.33 to 1.62) in CAD and PAD, and 1.69 (1.49 to 1.92) in those with CAD and CBVD and PAD, compared with CAD alone. Most-recent low-density lipoprotein cholesterol (LDL-C) levels55 mg/dl and70 mg/dl were attained by 21.8% and 44.6% of patients with CAD alone, in comparison to 22.7% and 43.3% in MSAD. Compared with patients with most-recent LDL-C100 mg/dl, attaining LDL-C70 mg/dl had an adjusted HR for MACE of 0.52 (0.47 to 0.57) in CAD only patients and 0.66 (0.57 to 0.78) in MSAD patients. In conclusion, the presence of CBVD and/or PAD in patients with CAD is associated with higher burden of co-morbidities and progressive increase in long-term MACE. More than half of CAD patients with or without MSAD do not achieve lipid goals, which are associated with a significantly lower risk for adverse events.

Background Injury to the cardiac venous structures can complicate left ventricular lead placement for cardiac resynchronization therapy (CRT). Little is known about the outcomes of coronary sinus (CS) dissection with or without perforation. Objective The purpose of this study was to determine the outcomes in patients who had a CS injury during CRT implantation. Methods All patients undergoing procedures for CRT implantation at the Cleveland Clinic (2001–2018) were enrolled in a prospectively maintained registry for procedural profiles and complications. All patients with cardiac venous injuries during the procedures were included. Results CS injury occurred in 35 of 5011 patients (0.7%; 6 perforations (17.1%), 29 dissections without perforation (82.9%)). In patients with dissection in the absence of perforation, attempts at CS lead placement after dissection were successful in 21 of 29 patients (72.4%). In those with perforation (n=6, 17.1%), CS lead placement was successful in one of them (16.7%). Cardiac tamponade occurred in 2 patients (5.7%), and the procedure was aborted in both of them. Overall, CS lead placement failed in 13 patients (37%) but 9 (25.7%) underwent subsequent CRT with CS lead placement (n=6, 17.1%; median 58 days later) or epicardial leads (n=3, 8.6%). Three of the remaining 4 patients (8.6%) refused to undergo further procedures, and the fourth (2.9%) died of a complicated course. Conclusion CS injury is not common during CRT implantation procedures and did not preclude successful lead placement in 23 of 35 patients (65.7%) during the index procedure and 6 of 6 (100%) during the subsequent attempted procedures. A low rate of mortality was observed in such patients, but CS injury was associated with increased morbidity.

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized infiltrative cardiomyopathy in which conduction system disease is common. The aim of our study was to define the incidence and prevalence of high-grade atrioventricular (AV) block requiring pacemaker implantation in our quaternary referral center. This was a single-center retrospective cohort study of 369 consecutive patients with ATTR-CA who underwent 12-lead electrocardiogram at the time of ATTR-CA diagnosis. During a mean follow-up of 28 months, serial ECGs and the electronic medical record were examined for the development of high-grade AV block and pacemaker implantation. Wild-type ATTR-CA (wtATTR-CA) was diagnosed in 261 patients and 108 had hereditary ATTR-CA (hATTR-CA). A total of 35 (9.5%) had high-grade AV block requiring pacemaker implantation at the time of diagnosis of ATTR-CA. The most common conduction abnormalities evident on the baseline ECG were a wide QRS complex, present in 51% with wtATTR-CA and 48% with hATTR-CA (p = 0.62), followed by first-degree AV block, which was present in 49% with wtATTR-CA and 43% with hATTR-CA (p = 0.31). During follow-up, high-grade AV block developed in 10% of those with hATTR-CA and 12% of patients with wtATTR-CA (p = 0.64). On multivariable models, high-grade AV block was not significantly associated with increased mortality. More advanced ATTR-CA stage and a history of obstructive coronary artery disease were associated with increased mortality on multivariable models. In conclusion, the incidence and prevalence of high-grade AV block is high in patients with ATTR-CA. Patients with ATTR-CA require close monitoring during follow-up for the development of conduction system disease.