Clinical outcomes among patients with mitral valve regurgitation undergoing Impella-supported high-risk PCI.

BACKGROUND: Mitral valve regurgitation (MR) is associated with worse outcomes in patients undergoing percutaneous coronary intervention (PCI). We sought to evaluate outcomes of Impella-supported high-risk PCI (HRPCI) patients according to MR severity. METHODS: Patients from the PROTECT III study undergoing Impella-supported HRPCI were stratified into 4 groups according to MR severity: No or trace MR, mild MR, moderate MR, and severe MR. Immediate PCI-related complications, major adverse cardiovascular and cerebrovascular events (MACCE: all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization) at 90 days and death at 1-year were assessed. RESULTS: From March 2017 to March 2020, 631 patients who underwent Impella-supported HRPCI in the PROTECT III study had evaluable MR severity at baseline. Patients with severe MR had lower body mass indices, lower left ventricular ejection fractions (LVEFs), and were more frequently diagnosed with heart failure. The incidence of immediate PCI-related complications was similar between groups. Unadjusted 90-day MACCE and 1-year mortality rates were numerically higher in patients with severe MR compared to the other study groups yet without reaching statistical significance. In multivariable analyses, there was no significant association between the presence of severe MR for 90-day MACCE or 1-year mortality compared with other degrees of MR (adj. HR = 1.71, 95% CI [0.73, 3.98], p = 0.21; adj. HR = 1.79, 95% CI [0.86, 3.74], p = 0.12, respectively). CONCLUSIONS: Impella-supported HRPCI patients with moderate or severe MR exhibited a higher prevalence of heart failure, lower LVEF, and longer hospital stays. Patients with severe MR showed numerically higher unadjusted rates of 90-day MACCE and 1-year mortality compared to other groups, however these differences did not reach statistical significance even after adjustment for potential confounders. CLINICAL TRIAL INFORMATION: Trial Name: The Global cVAD Study (cVAD) ClinicalTrial.govIdentifier:NCT04136392 URL: https://clinicaltrials.gov/ct2/show/NCT04136392?term=cvad&draw=2&rank=2.

Implications of anemia in patients undergoing PCI with Impella-support: insights from the PROTECT III study.

Background: Anemia is prevalent among patients with cardiovascular disease and is associated with adverse outcomes. However, data regarding the impact of anemia in high-risk percutaneous coronary intervention (HRPCI) are limited. Objectives: This study aimed to evaluate the impact of anemia in patients undergoing Impella-supported HRPCI in the PROTECT III study. Methods: Patients undergoing Impella-supported HRPCI in the multicenter PROTECT III study were assessed for anemia based on baseline hemoglobin levels according to World Health Organization criteria. Patients were stratified into three groups, namely, no anemia, mild anemia, and moderate or severe anemia. Major adverse cardiovascular and cerebrovascular events (MACCE: all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization) at 30 and 90 days, and major bleeding events were compared across groups. Results: Of 1,071 patients with baseline hemoglobin data, 37.9% had no anemia, 43.4% had mild anemia, and 18.7% had moderate or severe anemia. Anemic patients were older and more likely to have comorbidities. Anemia was associated with higher MACCE rates at 30 days (moderate to severe, 12.3%; mild, 9.8%; no anemia, 5.4%; p = 0.02) and at 90 days (moderate to severe, 18.7%; mild, 14.6%; none, 8.3%; p = 0.004). These differences persisted after adjustment for potential confounders at 30 and 90 days, and sensitivity analysis excluding dialysis showed similar results. Major bleeding at 30 days was also higher in anemic patients (5.5% vs. 1.2%, p = 0.002). Conclusion: Baseline anemia in Impella-supported HRPCI is common and independently associated with MACCE and major bleeding, emphasizing its significance as a prognostic factor. Specific management strategies to reduce anemia-associated MACCE risk after HRPCI should be examined. Clinical Trial Information Trial Name: The Global cVAD Study (cVAD)ClinicalTrial.gov Identifier: NCT04136392URL: https://clinicaltrials.gov/ct2/show/NCT04136392?term=cvad&draw=2&rank=2.

Association of Preprocedural SYNTAX Score With Outcomes in Impella-Assisted High-Risk Percutaneous Coronary Intervention.

Background: Patients with complex coronary artery disease, as defined by high SYNTAX scores, undergoing percutaneous coronary intervention (PCI) have poorer outcomes when compared with patients with lower SYNTAX I scores. This study aimed to assess if mechanical circulatory support using Impella mitigates the effect of the SYNTAX I score on outcomes after high-risk percutaneous coronary intervention (HRPCI). Methods: Using data from the PROTECT III study, patients undergoing Impella-assisted HRPCI between March 2017 and March 2020 were divided into 3 cohorts based on SYNTAX I score-low (≤22), intermediate (23-32), and high (≥33). Procedural and clinical outcomes out to 90 days were compared between groups. Multivariable regression analysis was used to assess the impact of SYNTAX I score on major adverse cardiovascular and cerebrovascular events (MACCE) at 90 days. Results: A total of 850 subjects with core laboratory-adjudicated SYNTAX I scores were identified (low: n = 310; intermediate: n = 256; high: n = 284). Patients with high SYNTAX I scores were older than those with low or intermediate SYNTAX I scores (72.7 vs 69.7 vs 70.1 years, respectively; P < .01). After adjustment for covariates, high SYNTAX I score remained a significant predictor of 90-day MACCE (hazard ratio [HR], 2.14; 95% CI, 1.42-3.69; P < .01 vs low), whereas intermediate SYNTAX I score was not (HR, 0.92; 95% CI, 0.47-1.77; P = .80 vs low). These findings persisted after adjustment for post-PCI SYNTAX I score. Conclusions: A high SYNTAX I score was associated with higher rates of 90-day MACCE in patients who underwent Impella-assisted HRPCI. Further research is needed to understand the patient and procedural factors driving this finding.

Angiographic Characteristics and Clinical Outcomes in Patients With Chronic Kidney Disease Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention: Insights From the cVAD PROTECT III Study.

BACKGROUND: Prior studies have found that patients with chronic kidney disease (CKD) have worse outcomes following percutaneous coronary intervention (PCI). There are no data about patients with advanced CKD undergoing Impella-supported high-risk PCI. We, therefore, aimed to evaluate angiographic characteristics and clinical outcomes in patients with CKD who received Impella-supported high-risk PCI as part of the catheter-based ventricular assist device PROTECT III study (A Prospective, Multi-Center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump [IABP] in Patients Undergoing Non Emergent High Risk PCI). METHODS: Patients enrolled in the PROTECT III study were analyzed according to their baseline estimated glomerular filtration rate (eGFR). The primary outcome was 90-day major adverse cardiovascular and cerebrovascular events (the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization). RESULTS: Of 1237 enrolled patients, 1052 patients with complete eGFR baseline assessment were evaluated: 586 with eGFR ≥60 mL/min per 1.73 m2, 190 with eGFR ≥45 to <60, 105 with eGFR ≥30 to <45, and 171 with eGFR <30 or on dialysis. Patients with lower eGFR (all groups with eGFR <60) were more frequently females and had a higher prevalence of hypertension, diabetes, anemia, and peripheral artery disease. The baseline Synergy Between PCI With Taxus and Cardiac Surgery score was similar between groups (28.2±12.6 for all groups). Patients with lower eGFR were more likely to have severe coronary calcifications and higher usage of atherectomy. There were no differences in individual PCI-related coronary complications between groups, but the rates of overall PCI complications were less frequent among patients with lower eGFR. Major adverse cardiovascular and cerebrovascular events at 90 days and 1-year mortality were significantly higher among patients with eGFR <30 mL/min per 1.73 m2 or on dialysis. CONCLUSIONS: Patients with advanced CKD undergoing Impella-assisted high-risk PCI tend to have higher baseline comorbidities, severe coronary calcification, and higher atherectomy usage, yet CKD was not associated with a higher rate of immediate PCI-related complications. However, 90-day major adverse cardiovascular and cerebrovascular events and 1-year mortality were significantly higher among patients with eGFR<30 mL/min per 1.73 m2 or on dialysis. Future studies of strategies to improve intermediate and long-term outcomes of these high-risk patients are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136392.

Clinical characteristics and outcomes of patients requiring prolonged mechanical circulatory support after high-risk percutaneous coronary intervention.

BACKGROUND: There are limited data on the clinical characteristics and outcomes of patients who require prolonged mechanical circulatory support (MCS) after Impella-supported high-risk percutaneous coronary intervention (HR-PCI). AIMS: The aim of this study is to describe the contemporary clinical characteristics, outcomes, and predictors associated with prolonged MCS support after assisted HR-PCI. METHODS: Patients enrolled in the prospective, multicentre, clinical endpoint-adjudicated PROTECT III study who had undergone HR-PCI using Impella were evaluated. Patient and procedural characteristics and outcomes for those who received prolonged MCS beyond the duration of their index procedure were compared to those in whom MCS was successfully weaned and explanted at the conclusion of the index PCI. RESULTS: Among 1,155 patients who underwent HR-PCI with Impella between 2017 and 2020 and had sufficient data to confirm the duration of Impella support, 16.5% received prolonged MCS (mean duration 25.2±31.1 hours compared with 1.8±5.8 hours for those who only received intraprocedural MCS). Patients receiving prolonged support presented with more urgent indications (e.g., acute coronary syndromes [ACS], lower ejection fraction [EF], elevated baseline heart rate and lower systolic blood pressure). Use of the Impella CP, intraprocedural complications, periprocedural complications and in-hospital mortality were all more common amongst the prolonged MCS group. Prolonged MCS was associated with increased rates of major adverse cardiovascular and cerebrovascular events, cardiovascular death, and all-cause mortality at 90-day follow-up. CONCLUSIONS: Patients receiving prolonged MCS after Impella-supported HR-PCI presented with more ACS, reduced EF and less favourable haemodynamics. Additionally, they were more likely to experience intraprocedural and periprocedural complications as well as increased in-hospital and post-discharge mortality.

Prevalence of Cardiac Sarcoidosis in Middle-Aged Adults Diagnosed with High-Grade Atrioventricular Block.

INTRODUCTION: Atrioventricular block may be idiopathic or a secondary manifestation of an underlying systemic disease. Cardiac sarcoidosis is a significant underlying cause of high-grade atrioventricular block, posing diagnostic challenges and significant clinical implications. This study aimed to assess the prevalence and clinical characteristics of cardiac sarcoidosis among younger patients presenting with unexplained high-grade atrioventricular block. METHODS: We evaluated patients aged between 18 and 65 years presenting with unexplained high-grade atrioventricular block, who were systematically referred for cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, prior to pacemaker implantation. Subjects with suspected cardiac sarcoidosis based on imaging findings were further referred for tissue biopsy. Cardiac sarcoidosis diagnosis was confirmed based on biopsy results. RESULTS: Overall, 30 patients with high-grade atrioventricular block were included in the analysis. The median age was 56.5 years (interquartile range 53-61.75, years). In 37%, cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, were suggestive of cardiac sarcoidosis, and in 33% cardiac sarcoidosis was confirmed by tissue biopsy. Compared with idiopathic high-grade atrioventricular block patients, all cardiac sarcoidosis patients were males (100% vs 60%, P = .029), were more likely to present with heart failure symptoms (50% vs 10%, P = .047), had thicker inter-ventricular septum on echocardiography (12.2 ± 2.7 mm vs 9.45 ± 1.6 mm, P = .002), and were more likely to present with right ventricular dysfunction (33% vs 10%, P = .047). CONCLUSIONS: Cardiac sarcoidosis was confirmed in one-third of patients ≤ 65 years, who presented with unexplained high-grade atrioventricular block. Cardiac sarcoidosis should be highly suspected in such patients, particularly in males who present with heart failure symptoms or exhibit thicker inter-ventricular septum and right ventricular dysfunction on echocardiography.

Influence of left ventricular ejection fraction in patients undergoing contemporary pLVAD-supported high-risk PCI.

BACKGROUND: Left ventricular (LV) systolic dysfunction worsens outcomes in patients undergoing percutaneous coronary intervention (PCI). The objective of this study, therefore, was to evaluate outcomes of pLVAD-supported high-risk PCI (HRPCI) patients according to LV ejection fraction (LVEF). METHODS: Patients from the PROTECT III study undergoing pLVAD-supported HRPCI were stratified according to baseline LVEF: severe LV dysfunction (LVEF <30%), mild and moderate LV dysfunction (LVEF ≥30% to <50%), or preserved LV function (LVEF ≥50%). Major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization), and PCI-related complications were assessed at 90 days and mortality was assessed at 1-year. RESULTS: From March 2017 to March 2020, 940 patients had evaluable baseline LVEF recorded in the study database. Patients with preserved LV function were older, more frequently presented with myocardial infarction, and underwent more left main PCI and atherectomy. Immediate PCI-related coronary complications were infrequent (2.7%, overall), similar between groups (P = 0.98), and not associated with LVEF. Unadjusted 90-day MACCE rates were similar among LVEF groups; however, as a continuous variable, LVEF was associated with both 90-day MACCE (adj.HR per 5% 0.89, 95% CI [0.80, 0.98], P = 0.018) and 1-year mortality (adj.HR per 5% 0.84 [0.78, 0.90], P <0.0001). CONCLUSIONS: Patients who underwent pLVAD-supported HRPCI exhibited low incidence of PCI-related complications, regardless of baseline LVEF. However, LVEF was associated with 90-day MACCE and 1-year mortality.

Sex Differences in pLVAD-Assisted High-Risk Percutaneous Coronary Intervention: Insights From the PROTECT III Study.

BACKGROUND: Prior studies have found that female patients have worse outcomes following high-risk percutaneous coronary intervention (HRPCI). OBJECTIVES: The authors sought to evaluate sex-based differences in patient and procedural characteristics, clinical outcomes, and safety of Impella-supported HRPCI in the PROTECT III study. METHODS: We evaluated sex-based differences in the PROTECT III study; a prospective, multicenter, observational study of patients undergoing Impella-supported HRPCI. The primary outcome was 90-day major adverse cardiac and cerebrovascular events (MACCE)-the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization. RESULTS: From March 2017 to March 2020, 1,237 patients (27% female) were enrolled. Female patients were older, more often Black, more often anemic, and had more prior strokes and worse renal function, but higher ejection fractions compared to male patients. Preprocedural SYNTAX score was similar between sexes (28.0 ± 12.3). Female patients were more likely to present with acute myocardial infarction (40.7% vs 33.2%; P = 0.02) and more often had femoral access used for PCI and nonfemoral access used for Impella device implantation. Female patients had higher rates of immediate PCI-related coronary complications (4.2% vs 2.1%; P = 0.004) and a greater drop in SYNTAX score post-procedure (-22.6 vs -21.0; P = 0.04). There were no sex differences in 90-day MACCE, vascular complications requiring surgery, major bleeding, or acute limb ischemia. After adjustment using propensity matching and multivariable regression, immediate PCI-related complications was the only safety or clinical outcome that was significantly different by sex. CONCLUSIONS: In this study, rates of 90-day MACCE compared favorably to prior cohorts of HRPCI patients and there was no significant sex differences. (The PROTECT III Study is a substudy of The Global cVAD Study [cVAD]; NCT04136392).

Significance of Anteroseptal Late Gadolinium Enhancement Among Patients With Acute Myocarditis.

Anteroseptal location of late gadolinium enhancement (LGE) in patients with acute myocarditis (AM) detected by cardiovascular magnetic resonance may indicate an independent marker of unfavorable outcomes according to recent data. We aimed to evaluate the clinical characteristics, management, and inhospital outcomes in patients with AM with positive LGE based on its presence in the anteroseptal location. We analyzed data from 262 consecutive patients hospitalized with a diagnosis of AM with positive LGE within 5 days of hospitalization (n = 425). Patients were divided into 2 groups: those with anteroseptal LGE (n = 25, 9.5%) and those with non-anteroseptal LGE (n = 237, 90.5%). Except for age that was higher in patients with anteroseptal LGE, the demographic and clinical characteristics did not differ significantly between both groups including past medical history, clinical presentation, electrocardiogram parameters, and lab values. Moreover, patients with anteroseptal LGE were more likely to present with reduced left ventricular ejection fraction and to receive congestive heart failure treatments. Although univariate analysis showed that patients with anteroseptal LGE were more likely to have inhospital major adverse cardiac events (28% vs 9%, p = 0.003), there was no difference inhospital outcomes on multivariable analysis between both groups (hazard ratio, 1.17 [95% confidence interval, 0.32 to 4.22], p = 0.81). A higher left ventricular ejection fraction in either echocardiography or cardiovascular magnetic resonance corresponded to better inhospital outcomes regardless of the presence or absence of anteroseptal LGE. In conclusion, the presence of anteroseptal LGE did not confer additional prognostic value for inhospital outcomes.

Pacemaker in patients undergoing mammography: A limitation for breast cancer diagnosis?

INTRODUCTION: A pacemaker may affect the utility of a mammogram in several ways. The aim of this study is to summarize our institution's experience with mammograms among patients with a cardiac pacemaker, focusing on the diagnostic workup among patients with a newly diagnosed ipsilateral breast cancer. METHODS: A retrospective search of all mammography reports between January 2011 and April 2021 was conducted for identifying cases of patients with a pacemaker. Demographic and clinical characteristics as well as mammography-derived quality parameters and findings were categorized and statistically compared. RESULTS: The incidence of pacemaker concurrence in mammographic examination, although apparently slightly under-documented, accounted for 0.33% of cases. Population mean age was 71.7 years, and most patients (79%) had a left-sided pacemaker. The pacemaker was much more likely to be projected on the medio-lateral-oblique (96%) than on the cranio-caudal view (10%), on the axilla rather than the breast, and on the retro-pectoral rather than the pre-pectoral region (P < 0.001 for all). Compression force decreased by up to 23.0% (P < 0.001) and breast thickness increased by up to 9.5% (P < 0.001) for the ipsilateral vs. the contralateral side. Among 11 patients with newly diagnosed ipsilateral breast cancer, the pacemaker partially projected on the tumour region in two cases, and significantly obscured the tumour in another two. CONCLUSION: Although rare, the coexistence of a pacemaker in patients undergoing mammography is associated with reduced image quality due to suboptimal breast visualization and reduced compression, and as a result, this may eventually lead to decreased diagnostic efficacy.

Optical Coherence Tomography-Guided Percutaneous Coronary Intervention: Practical Application.

Optical coherence tomography (OCT) provides high-resolution imaging of coronary arteries and can be used to optimize percutaneous coronary intervention (PCI). Intracoronary OCT, however, has had limited adoption in clinical practice. Novelty and relative complexity of OCT interpretation compared with the more established intravascular ultrasound, lack of a standardized algorithm for PCI guidance, paucity of data from randomized trials, and lack of rebate for intravascular imaging have contributed to the modest practical adoption of OCT. We provide a practical step-by-step guide on how to use OCT in PCI, including device set-up, simplified image interpretation, and an algorithmic approach for PCI. optimization.

The Association between Marital Status and Outcomes of Patients Hospitalized with Heart Failure.

BACKGROUND: Little is known about the association between marital status and long-term outcomes of patients hospitalized with heart failure (HF). We aimed to examine the association between marital status and early as well as long-term outcomes of patients hospitalized with HF. METHOD: We analyzed data of 4089 patients hospitalized with HF and were enrolled in the multicenter national survey in Israel between March and April 2003 and were followed until December 2014. Patients were classified into married (N = 2462, 60%) and unmarried (N = 1627, 40%). RESULTS: Married patients were more likely to be males, younger, and more likely to have past myocardial infarction and previous revascularization. Also, they tended to have higher rates of diabetes mellitus (DM) and dyslipidemia, as well as smokers. Survival analysis showed that unmarried patients had higher mortality rates at 1 and 10 years (33% vs. 25%, at 1 year, 89% vs. 80% at 10 years, all p < 0.001). Consistently, multivariable analysis showed that unmarried patients had independently 44% and 35% higher risk of mortality at 1- and 10-year follow-up respectively (1-year HR = 1.44; 95%CI 1.14-1.81; p = 0.002, 10-year HR = 1.35; 95%CI 1.19-1.53; p ≤ 0.001). Other consistent predictors of mortality at both 1- and 10-year follow-up include age, renal failure, and advanced HF. CONCLUSIONS: Being unmarried is independently associated with worse short- and long-term outcomes, particularly among women. Thus, attempts to intensify secondary preventive measures should focus mainly on unmarried patients and mainly women.

Prevalence and clinical implication of thrombocytopenia and heparin-induced thrombocytopenia in patients who are critically ill with COVID-19.

As the COVID-19 pandemic continues to evolve, different clinical manifestations are better understood and studied. These include various haematologic disorders that have been shown to be associated with increased morbidity and mortality. We studied the prevalence of one unusual manifestation, heparin-induced thrombocytopenia (HIT) and its clinical implications in patients who are severely ill with COVID-19 in a single tertiary centre in Israel. The presence of thrombocytopenia, disseminated intravascular coagulation (DIC) and HIT, and their association with clinical course and outcomes were studied. One-hundred and seven patients with COVID-19 were included. Fifty-seven (53.2%) patients developed thrombocytopenia, which was associated with the worst outcomes (ventilation, DIC and increased mortality). Sixteen (28.0%) patients with thrombocytopenia were positive for HIT, all of which were supported by extracorporeal devices. HIT was independently associated with ventilation days, blood product transfusions, longer hospitalisation and mortality.Platelet abnormalities and HIT are common in patients who are critically ill with COVID-19 and are associated with the worst clinical outcomes. The mechanisms underlying HIT in COVID-19 are yet to be studied; HIT may contribute to the dysregulated immunologic response associated with COVID-19 critical illness and may play a significant part in the coagulopathy seen in these patients. As many patients with COVID-19 require aggressive thromboprophylaxis, further understanding of HIT and the implementation of appropriate protocols are important.

Preparation and characterization of flexible furosemide-loaded biodegradable microneedles for intradermal drug delivery.

Transdermal drug delivery systems are a useful and minimally invasive alternative to other drug administration routes. Biodegradable polymeric microneedles (MNs) are widely used in controlled-release drug delivery due to their tunable properties and ease of patient self-administration. Polylactic-co-glycolic acid (PLGA) is often used for sustained drug release owing to special intrinsic properties including biocompatibility and biodegradability, which offer excellent applicability in preparing MNs. Congestive heart failure (CHF) is characterized by fluid overload during acute exacerbation, necessitating frequent patient hospitalization for continuous intravenous (i.v.) diuretic therapy. In the present study, we incorporated furosemide (FUR) as a model drug into flexible PLGA MN skin patches for potential intradermal delivery to overcome the limitations associated with i.v. diuresis. The MNs were fabricated by a casting-mold technique and consisted of two main parts, PLGA needle tips loaded with varying concentrations of FUR and a flexible backing layer comprising sodium alginate and glycerol. MN formulations were characterized by SEM and exhibited a uniform pyramidal shape. The measured surface pH of all samples suggested that no skin irritation is expected upon application. High encapsulation efficiency was obtained for FUR-MN formulations in which a decrease was noted as the FUR/PLGA ratio decreased. Drug loading content ranged from 19.1 ± 1% to 28.9 ± 1.4%. Successful insertion of MNs into a Parafilm® skin simulant model suggested that MNs will easily penetrate the skin's outermost layer, the stratum corneum, and will permit intradermal delivery of FUR. The MNs were further characterized by analytical methods. Finally, the MNs exhibited an initial burst release followed by a sustained release of FUR. Self-administered FUR-MNs can open new avenues to overcome i.v. drip limitations and increase patient compliance.

Ethnic Disparity in Mortality Among Ischemic Heart Disease Patients. A-20 Years Outcome Study From Israel.

Background: Long-term morbidity and mortality data among ischemic heart disease (IHD) patients of different ethnicities are conflicting. We sought to determine the independent association of ethnicity and all-cause mortality over two decades of follow-up of Israeli patients. Methods: Our study comprised 15,524 patients including 958 (6%) Arab patients who had been previously enrolled in the Bezafibrate Infarction Prevention (BIP) registry between February 1, 1990, and October 31, 1992, and subsequently followed-up for long-term mortality. We compared clinical characteristics and outcomes of Israeli Arabs and Jews. Propensity score matching (PSM) (1:2 ratios) was used for validation. Results: Arab patients were significantly younger (56 ± 7 years vs. 60 ± 7 years; p < 0.001; respectively), and had more cardiovascular disease (CVD) risk factors. Kaplan-Meier survival analysis showed that all-cause mortality was significantly higher among Arab patients (67 vs. 61%; log-rank p < 0.001). Multivariate adjusted analysis showed that mortality risk was 49% greater (HR 1.49; 95% CI: 1.37-1.62; p < 0.001) among Arabs. Conclusions: Arab ethnicity is independently associated with an increased 20-year all-cause mortality among patients with established IHD.

The Utility of 18FDG-PET/CT in Diagnosing Fever of Unknown Origin: The Experience of a Large Tertiary Medical Center.

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18-93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.

Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination.

BACKGROUND: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. METHODS: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. FINDINGS: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. INTERPRETATION: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. FUNDING: none.

Burden of heart failure and underlying causes in 195 countries and territories from 1990 to 2017.

AIMS: To provide the first systematic analysis of the burden and underlying causes of heart failure (HF) in 195 countries and territories from 1990 to 2017. METHODS AND RESULTS: We collected detailed information on prevalence, years lived with disability (YLDs), and underlying causes of HF from the Global Burden of Disease study 2017. Numbers and age-standardized rates of HF prevalence and YLDs were compared by age, sex, socio-demographic index (SDI), and location. The proportions of HF age-standardized prevalence rates due to 23 underlying causes were also presented. Globally, the age-standardized prevalence and YLD rates of HF in 2017 were 831.0 and 128.2 per 100 000 people, a decrease of -7.2% and -0.9% from 1990, respectively. Nevertheless, the absolute numbers of HF prevalent cases and YLDs have increased by 91.9% and 106.0% from 1990, respectively. There is significant geographic and socio-demographic variation in the levels and trends of HF burden from 1990 to 2017. Among all causes of HF, ischaemic heart disease accounted for the highest proportion (26.5%) of age-standardized prevalence rate of HF in 2017, followed by hypertensive heart disease (26.2%), chronic obstructive pulmonary disease (23.4%). CONCLUSION: HF remains a serious public health problem worldwide, with increasing age-standardized prevalence and YLD rates in countries with relatively low SDI. More geo-specific strategies aimed at preventing underlying causes and improving medical care for HF are warranted to reduce the future burden of this condition.