CHA2DS2-VASc Score as a Predictor of Adverse Outcomes after Ischemic Stroke in Patients without Atrial Fibrillation.

BACKGROUND: Ischemic stroke is associated with increased risk of morbidity and mortality in future vascular events. OBJECTIVES: To investigate whether CHA2DS2-VASc scores aid in risk stratification of middle-aged patients without atrial fibrillation (AF) experiencing ischemic stroke. METHODS: We analyzed data of 2628 patients, aged 40-65 years with no known AF who presented with acute ischemic stroke between January 2020 and February 2022. We explored the association between CHA2DS2-VASc scores categorized by subgroups (score 2-3, 4-5, or 6-7) with major adverse cardiac and cerebrovascular events (MACCE) including recurrent stroke, myocardial infarction, coronary revascularization, or all-cause death during a median follow-up of 19.9 months. RESULTS: Mean age was 57 years (30% women); half were defined as low socioeconomic status. Co-morbidities included hypertension, diabetes, obesity, and smoking in 40-60% of the patients. The incidence rate of MACCE per 100 person-years was 6.7, 12.2, and 21.2 in those with score 2-3, 4-5, and 6-7, respectively. In a multivariate cox regression model, compared to patients with score 2-3 (reference group), those with score 4-5 and 6-7 had an adjusted hazard ratio (95% confidence interval [95%CI]) for MACCE of 1.74 (95%CI 1.41-2.14) and 2.87 (95%CI 2.10-3.93), respectively. The discriminative capacity of CHA2DS2-VASc score for overall MACCE was modest (area under curve 0.63; 95%CI 0.60-0.66), although better for myocardial infarction 0.69 (95% CI 0.61-0.77). CONCLUSIONS: CHA2DS2-VASc score may predict future MACCE in middle-aged patients with ischemic stroke and no history of AF.

[DIAGNOSIS AND TREATMENT OF ELEVATED LIPOPROTEIN(A) IN ISRAEL: CONSENSUS STATEMENT FROM THE ISRAEL SOCIETY FOR RESEARCH, PREVENTION AND TREATMENT OF ATHEROSCLEROSIS AND ISRAEL SOCIETY FOR CLINICAL LABORATORY SCIENCES].

INTRODUCTION: Lipoprotein(a) [Lp(a)] is composed of 2 major protein components, a low-density lipoprotein (LDL) cholesterol-like particle containing apolipoprotein B (apo B) that is covalently bound to apolipoprotein(a). Its level is predominantly genetically determined, and it is estimated that 20% to 25% of the population have Lp(a) levels that are associated with increased cardiovascular risk. Elevated Lp(a) is related to increased vascular inflammation, calcification, atherogenesis and thrombosis, and is considered an independent and potentially causal risk factor for atherosclerotic cardiovascular diseases and calcified aortic valve stenosis. Recent data demonstrate that Lp(a) testing has the potential to reclassify patients' risk and improve cardiovascular risk prediction, and therefore could inform clinical decision-making regarding risk management. Statins and ezetimibe are ineffective in lowering Lp(a) levels, whereas proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have a modest effect on Lp(a) reduction. Nevertheless, RNA interference-based therapies with potent Lp(a)-lowering effects are in advanced stages of development, and clinical trials are underway to confirm their benefit in reducing cardiovascular events. This scientific consensus document was developed by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, and the Israeli Society for Clinical Laboratory Sciences, in order to create uniformity in Lp(a) measurement methods, indications for testing and reporting of the results, aiming to improve the diagnosis and management of elevated Lp(a) in clinical practice.

Totally Percutaneous Transfemoral Transcatheter Aortic Valve Replacement Despite Failure to Deploy a Vascular Closure Device: A Single-Centre Case Series.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is preferably performed as a completely percutaneous procedure via transfemoral access. Suture-mediated vascular closure devices are deployed prior to sheath insertion (pre-closure). Inability to perform pre-closure may necessitate surgical vascular repair of the femoral artery. Patients at increased risk of vascular surgery complications may benefit from a percutaneous method for achieving access site haemostasis. Stent graft implantation is commonly used for treating access site injury following TAVR. This study assessed the feasibility of a strategy of planned stent graft implantation within the femoral artery for achieving access site haemostasis in patients undergoing transfemoral TAVR and in whom vascular pre-closure was not possible. METHODS: A prospective institutional TAVR registry was retrospectively analysed and a cohort of patients were identified who were selected for transfemoral valve delivery and in whom pre-closure failed and access site haemostasis was achieved by stent graft implantation. RESULTS: This strategy was used for achieving access site haemostasis in 11 patients (1.5% of 744 patients undergoing transfemoral TAVR). These patients were considered to be at increased risk of vascular surgery complications due to advanced age, frailty, comorbidities, or immobility. Stent graft implantation achieved access site haemostasis in all patients. During follow-up, 30-day mortality was zero, 1-year mortality was 27%, and none of the patients required additional vascular interventions. CONCLUSION: The preliminary data suggest that planned stent graft implantation within the femoral artery may achieve access site haemostasis and enable a totally percutaneous TAVR procedure, despite failure to perform pre-closure with a suture-based vascular closure device.

Transbrachial Secondary Vascular Access in Transcatheter Aortic Valve Replacement Procedures: A Single-Centre Retrospective Analysis.

BACKGROUND: Transfemoral transcatheter aortic valve replacement (TAVR) procedures require secondary vascular access for inserting accessory catheters and performing percutaneous repair of femoral artery injury. Use of the transbrachial approach for secondary vascular access in TAVR procedures has not been reported. METHODS: This study identified 48 patients at the current institution who had undergone transfemoral TAVR utilising transbrachial secondary vascular access. Efficacy and safety of this strategy for achieving a successful totally percutaneous procedure were examined. Study endpoints were occurrence of vascular complications and bleeding related to transbrachial access, as well as periprocedural and 1-year mortality. RESULTS: Mean patient age was 80±7 years and Society of Thoracic Surgeons Predicted Risk of Mortality score was 10.6±3.1. Sizes of sheaths inserted into the brachial artery were 6 Fr (85%), 8 Fr (2%), and 9 Fr (13%). Transbrachial access was used for delivering stent grafts to the femoral artery in 13% of the patients, inflation of an occlusive balloon within the iliac artery in 10%, and treatment of iatrogenic femoral artery stenosis in 2%. Successful valve replacement was achieved in all cases. Brachial sheaths were removed by manual compression following administration of protamine sulfate. There were no major access site complications or VARC-3 type ≥2 bleeding related to the brachial vascular access. Brachial artery occlusion occurred in two patients (4%) who underwent surgical vascular repair. Two (2) additional patients developed mild arm ischaemia, which was treated conservatively. Periprocedural mortality was 0% and early mortality was 8%. CONCLUSIONS: Transbrachial secondary access in TAVR procedures was feasible and enabled percutaneous vascular repair in cases of femoral artery injury.

Assessment of Low LDL Cholesterol in Patients Treated by PCSK9 Inhibition: Comparison of Martin/Hopkins and Friedewald Estimations.

PURPOSE: Recent guidelines recommend further reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk populations. The use of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) enables many patients to achieve profound reduction in LDL-C. However, in patients with low cholesterol, the commonly used Friedewald equation tends to underestimate LDL-C, which may result in undertreatment. We aimed to compare Friedewald LDL-C estimation with the more novel Martin/Hopkins method in PCSK9i-treated patients achieving low LDL-C. METHODS: We investigated high-risk patients treated by PCSK9i in whom Friedewald LDL-C levels were < 70 mg/dL and triglycerides ≤ 300 mg/dL. LDL-C was additionally assessed by the Martin/Hopkins method. The compatibility between estimations was evaluated using methods of concordance and reclassification between LDL-C categories (< 25, 25-40, 40-55, 55-70 mg/dL) and according to triglyceride strata. RESULTS: Mean age was 65 ± 10 years. The correlation coefficient between LDL-C estimations was r = 0.898. Martin/Hopkins reclassified 269 of the 608 patients (44%) to a higher LDL-C category, with 14% of the patients reaching LDL-C > 70 mg/dL. Of the 390 patients achieving Friedewald LDL-C < 55 mg/dL, 113 (29%) were estimated to have LDL-C ≥ 55 mg/dL by the Martin/Hopkins equation. The magnitude of discordance between LDL-C estimates was more pronounced in hypertriglyceridemic patients in whom LDL-C reclassification from < 55 to ≥ 55 mg/dL was observed in 48%. CONCLUSIONS: In real-world practice of high-risk patients achieving low LDL-C under PCSK9i, Martin/Hopkins algorithm displayed significant proportion of LDL-C upward discordance compared to the Friedewald equation, particularly observed in patients with elevated triglycerides, identifying patients that may need treatment intensification.

Value of addition of coronary artery calcium to risk scores in the prediction of major cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The increased risk for cardiovascular events in diabetics is heterogeneous and contemporary clinical risk score calculators have limited predictive value. We therefore examined the additional value of coronary artery calcium score (CACS) in outcome prediction in type 2 diabetics without clinical coronary artery disease (CAD). METHODS: The study examined a population-based cohort of type 2 diabetics (n = 735) aged 55-74 years, recruited between 2006 and 2008. Patients had at least one additional risk factor and no history or symptoms of CAD. Risk assessment tools included Pooled Cohort Equations (PCE) and Multi-Ethnic Study of Atherosclerosis (MESA) 10-year risk score calculators and CACS. The occurrence of myocardial infarction (MI), stroke or cardiovascular death (MACE) was assessed over 10-years. RESULTS: Risk score calculators predicted MACE and MI and cardiovascular death individually but not stroke. Increasing levels of CACS predicted MACE and its components independently of clinical risk scores, glycated hemoglobin and other baseline variables: hazard ratio (95% confidence interval) 2.92 (1.06-7.86), 6.53 (2.47-17.29) and 8.3 (3.28-21) for CACS of 1-100, 101-300 and > 300 Agatston units respectively, compared to CACS = 0. Addition of CACS to PCE improved discrimination of MACE [AUC of PCE 0.615 (0.555-0.676) versus PCE + CACS 0.696 (0.642-0.749); p = 0.0024]. Coronary artery calcium was absent in 24% of the study population and was associated with very low event rates even in those with high estimated risk scores. CONCLUSIONS: CACS in asymptomatic type 2 diabetics provides additional prognostic information beyond that obtained from clinical risk scores alone leading to better discrimination between risk categories.

Impact of Modifiable Risk Factors on Long-Term Outcomes after Coronary Artery Bypass Surgery.

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 < 0.001) were independent predictors of future coronary events after CABG; they also displayed a progressive stepwise increment in the risk of long-term coronary events when cumulatively present. 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.

[UPDATED ISRAELI GUIDELINES FOR THE TREATMENT OF DYSLIPIDEMIA 2020].

INTRODUCTION: Despite the impressive decline in mortality from atherosclerotic cardiovascular diseases (ASCVD), these diseases still account for a large proportion of the overall morbidity and mortality worldwide. A vast amount of research has demonstrated the key role played by circulating lipoproteins, and especially low-density lipoprotein (LDL), in the etiology of atherosclerosis, and numerous studies have proven the efficacy of interventions that lower the atherogenic lipoproteins in reducing morbidity and mortality from ASCVD. While previous guidelines placed an emphasis on the use HMG-CoA reductase inhibitors (statins) for the treatment of dyslipidemia, recent studies have shown that other LDL cholesterol lowering drugs, including ezetimibe and the PCSK9 inhibitors, can provide additional benefit when used in combination with (and in certain cases instead of) statins. These studies have also shown that blood LDL cholesterol levels lower than previously recommended targets provide additional benefit, without evidence of a threshold beyond which the benefit ceases and without excess adverse effects. The updated guidelines were formulated by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, the Israel Society of Internal Medicine, the Israeli Heart Association, the Israeli Neurology Association and the Israel Association of Family Medicine. They provide recommendations for revised risk stratification of patients, novel target goals, and the use of evidence-based treatment and follow-up strategies with reference to specific patient sub-groups.

Survival of Patients with Chronic Total Occlusion of the Right Coronary Artery.

BACKGROUND: The impact of revascularization of coronary chronic total occlusion (CTO) on survival is unknown. Several studies, which included subjects with varied coronary anatomy, suggested that CTO revascularization improved survival. However, the contribution of CTO revascularization to improved outcome is unclear since it was more commonly achieved in subjects with fewer co-morbidities and less extensive coronary disease. OBJECTIVES: To study the association between CTO revascularization and survival in patients with uniform coronary anatomy consisting of isolated CTO of the right coronary artery (RCA). METHODS: A registry of 16,832 coronary angiograms was analyzed. We identified 278 patients (1.7%) with isolated CTO of the RCA who did not have lesions within the left coronary artery for which revascularization was indicated. Survival of 52 patients (19%) who underwent successful percutaneous coronary intervention was compared to those who did not receive revascularization. RESULTS: Revascularized patients were younger (60.2 vs. 66.3 years, P = 0.001), had higher creatinine clearance (106 vs. 83 ml/min, P < 0.0001), and had fewer co-morbidities than those who did not receive revascularization. Lack of CTO revascularization was a univariable predictor of mortality (hazard ratio [HR] = 2.65, 95% confidence interval [95%CI] 1.06-6.4) over 4.3 ± 2.5 years of follow-up. On multivariable analysis, the only predictors of mortality were increased age (HR 1.04, 95%CI 1.01-1.07), reduced creatinine clearance (HR 1.02, 95%CI 1.01-1.03), and ejection fraction below 55% (HR 2.24, 95%CI 1.22-4.11). CONCLUSIONS: Among patients with isolated RCA CTO who underwent extended follow-up, revascularization was not an independent predictor of increased survival.

Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure Long-Term Registry.

Aim: To investigate the characteristics long-term prognostic implications (up to ∼2.2 years) of atrial fibrillation (AF) compared to sinus rhythm (SR), between acute and chronic heart failure (HF) with reduced (HFrEF < 40%), mid-range (HFmrEF 40-49%), and preserved (HFpEF ≥ 50%) ejection fraction (EF). Methods and results: Data from the observational, prospective, HF long-term registry of the European Society of Cardiology were analysed. A total of 14 964 HF patients (age 66 ± 13 years, 67% male; 53% HFrEF, 21% HFmrEF, 26% HFpEF) were enrolled. The prevalence of AF was 27% in HFrEF, 29% in HFmrEF, and 39% in HFpEF. Atrial fibrillation was associated with older age, lower functional capacity, and heightened physical signs of HF. Crude rates of mortality and HF hospitalization were higher in patients with AF compared to SR, in each EF subtype. After multivariable adjustment, the hazard ratio of AF for HF hospitalizations was: 1.036 (95% CI 0.888-1.208, P = 0.652) in HFrEF, 1.430 (95% CI 1.087-1.882, P = 0.011) in HFmrEF, and 1.487 (95% CI 1.195-1.851, P < 0.001) in HFpEF; and for combined all-cause death or HF hospitalizations: 0.957 (95% CI 0.843-1.087, P = 0.502), 1.302 (95% CI 1.055-1.608, P = 0.014), and 1.365 (95% CI 1.152-1.619, P < 0.001), respectively. In patients with HFrEF, AF was not associated with worse outcomes in those presenting with either an acute or a chronic presentation of HF. Conclusions: The prevalence of AF increases with increasing EF but its association with worse cardiovascular outcomes, remained significant in patients with HFpEF and HFmrEF, but not in those with HFrEF.

Retrograde Femoral Artery Stent-Graft Implantation for Treatment of Access-site Bleeding Following Transcatheter Aortic Valve Implantation.

BACKGROUND: Access-site bleeding is a common complication of transfemoral transcatheter aortic valve implantation (TAVI). Percutaneous stent-graft implantation within the femoral artery may achieve hemostasis and avert the need for more invasive surgical vascular repair; however, failure to advance a guidewire antegradely via the injured vessel may preclude stent delivery. While retrograde stent-graft delivery from the distal vasculature may potentially enable percutaneous control of bleeding, this approach has not been reported. OBJECTIVES: To assess the feasibility of a retrograde approach for stent-graft implantation in the treatment of access-site bleeding following transfemoral TAVI. METHODS: A prospective TAVI registry was analyzed. Of 349 patients who underwent TAVI, transfemoral access was used in 332 (95%). Access-site injury requiring stent-graft implantation occurred in 56 (17%). In four patients (7%), antegrade wiring across the site of vascular injury was not possible and a retrograde approach for stent delivery was used. RESULTS: Distal vascular access was achieved via the superficial femoral or profunda artery. Retrograde advancement of a polymer-coated 0.035" wire to the abdominal aorta, followed by stent-graft delivery to the common femoral artery, achieved hemostasis in all cases. During a median (interquartile range) follow-up period of 198 (618) days (range 46-2455) there were no deaths and no patient required additional vascular interventions. CONCLUSIONS: A retrograde approach for stent-graft delivery is feasible and allows percutaneous treatment of a common femoral artery injury following TAVI in patients who are not suitable for the conventional antegrade approach.

Immobilization of captive Persian fallow deer (Dama dama mesopotamica) using medetomidine-ketamine or medetomidine-midazolam.

OBJECTIVE: To establish and compare the effectiveness of two medetomidine-based immobilization protocols in Persian fallow deer (Dama dama mesopotamica). STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: A group of 31 captive Persian fallow deer. METHODS: Deer scheduled for translocation were immobilized with a combination of medetomidine (76 ± 11 µg kg-1) and ketamine (1.0 ± 0.2 mg kg-1) (MK; n = 15) or medetomidine (77 ± 11 µg kg-1) and midazolam (0.10 ± 0.01 mg kg-1) (MM; n = 16) administered intramuscularly. An observer unaware of group assignments recorded times to immobilization and recovery, monitored physiologic variables and scored the quality of induction, immobilization and recovery (scale 1-5: 1, poor; 5, excellent). Atipamezole was administered for reversal. Data analysis was performed using the t test, the Mann-Whitney U test, the chi-square test and the Fisher's exact test. Significance was set at p < 0.05. RESULTS: Data are presented as mean ± standard deviation or median (range). Time to induce immobilization was 9 ± 4 and 10 ± 4 minutes in the MK and MM groups, respectively. Immobilization quality score was 5 (1-5) following both combinations. Hemoglobin oxygen saturation (SpO2) was significantly lower in the MK (80 ± 8%) than in the MM group (87 ± 8%) although respiratory frequency did not differ between MK and MM (11 ± 5 and 10 ± 2 breaths minute-1, respectively). Recovery times were 13 ± 6 (MK) and 14 ± 7 minutes (MM) and did not differ between groups. No morbidities or mortalities were recorded during 1 month after immobilization. CONCLUSIONS AND CLINICAL RELEVANCE: The MK and MM combinations produced sufficient immobilization in captive Persian fallow deer for short nonpainful procedures. Based on the SpO2 values, the MM combination may be associated with less respiratory depression; nevertheless, both combinations may result in a decrease in SpO2.

Impact of diabetes and early revascularization on the need for late and repeat procedures.

BACKGROUND: Coronary artery disease often progresses more rapidly in diabetics, but the integrated impact of diabetes and early revascularization status on late or repeat revascularization in the contemporary era is less clear. METHODS: Coronary angiography was performed in 12,420 patients between the years 2000-2015 and early revascularization status [none, percutaneous coronary intervention (PCI) or bypass surgery (CABG)] was determined. Subsequent revascularization procedures were recorded over a median follow-up of 67 months and its relation to diabetic and baseline revascularization status was studied. RESULTS: Early revascularization status was none in 5391, PCI in 5682 and CABG in 1347 patients. Late revascularization rates were 10, 26 and 11.1% respectively. Diabetes was present in 37%; a stepwise relationship of diabetic status with late revascularization was observed: no diabetes (reference) 14.4%, non-insulin treated diabetes 21% (adjusted HR 1.35, 95% CI 1.23-1.49, p < 0.001) and insulin-treated diabetes 32.8% (adjusted HR 2.20, 95% CI 1.91-2.54, p < 0.001), which was similar in magnitude for each early revascularization state (none, PCI or CABG). Further revascularizations (≥ 2) were also significantly more common in diabetics, in particular if insulin-treated. Glycosylated hemoglobin level was moderately associated with late revascularization in diabetics after early PCI but not following diagnostic catheterization or CABG. CONCLUSIONS: Diabetic status graded by treatment, and in particular insulin therapy, is a strong predictor for late or repeat revascularization irrespective of early revascularization status. The high rate of repeat revascularization in diabetics following PCI remains a challenging issue.

Characterization of Coronary Artery Disease in Young Adults and Assessment of Long-term Outcomes.

BACKGROUND: Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited. OBJECTIVES: To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography. METHODS: A retrospective analysis (2000-2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted. RESULTS: Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15-5.99) and revascularization (HR 4.30, 95%CI 2.01-9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal < 70 mg/dl. CONCLUSIONS: CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.

Clinical Features and Gaps in the Management of Probable Familial Hypercholesterolemia and Cardiovascular Disease.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease (ASCVD). The introduction of potent therapeutic agents underlies the importance of improving clinical diagnosis and treatment gaps in FH.Methods and Results:A regional database of 1,690 adult patients with high-probability FH based on age-dependent peak-low-density lipoprotein cholesterol (LDL-C) cut-offs and exclusion of secondary causes of severe hypercholesterolemia, was examined to explore the clinical manifestations and current needs in the management of ASCVD, which was present in 248 patients (15%), of whom 83% had coronary artery disease (CAD); 19%, stroke; and 13%, peripheral artery disease. ASCVD was associated with male gender, higher peak LDL-C, lower high-density lipoprotein cholesterol (HDL-C), and traditional risk factor burden. Despite high-intensity statin (prescribed in 83% and combined with ezetimibe in 42%), attainment of LDL-C treatment goals was low, and associated with treatment intensity and drug adherence. Multivessel CAD (adjusted hazard ratios (HR), 3.05; 95% CI: 1.65-5.64), myocardial infarction, and the presence of ≥1 traditional risk factor (HR, 2.59; 95% CI: 1.42-4.71), were associated with repeat coronary revascularizations, in contrast with peak LDL-C >300 mg/dL (HR, 1.13; 95% CI: 0.66-1.91). CONCLUSIONS: Main manifestations of ASCVD in FH patients were premature, multivessel CAD with need for recurrent revascularization, associated with classical cardiovascular risk factors but not with peak LDL-C. In spite of intensive therapy with lipid-lowering agents, treatment gaps were significant, with low attainment of LDL-C treatment goals.

Cardiac Computed Tomography Angiographic Findings as Predictors of Late Heart Failure in an Asymptomatic Diabetic Cohort: An 8-Year Prospective Follow-Up Study.

OBJECTIVES: Predictive models for heart failure (HF) in heterogeneous populations have had limited success. We examined cardiac computed tomography angiography (CTA) predictors of HF or cardiovascular death (HF-CVD) in a prospective study of asymptomatic diabetics undergoing baseline assessment by CTA. METHODS: The subjects (n = 735, aged 55-74 years, 51.2% women) had no clinical history of cardiovascular disease at study entry. Coronary artery calcium (CAC) score, CTA-defined coronary atherosclerosis, cardiac chamber volumes, and clinical data were collected and late outcome events recorded over 8.4 ± 0.6 years (range 7.3-9.3). RESULTS: HF-CVD occurred in 41 (5.6%) subjects, with HF occurring mostly (19/23, 82.6%) in subjects without preceding myocardial infarction. Baseline univariate clinical outcome predictors of HF-CVD included older age (p = 0.027), the duration of diabetes (p = 0.004), HbA1c (p < 0.0001), microvascular disease (retinopathy, microalbuminuria) (p < 0.0001), and systolic blood pressure (p = 0.035). Baseline univariate CTA predictors included CAC score (p = 0.004), coronary stenosis (p = 0.047), and a CTA-defined left/right atrial (LA/RA) volume ratio >1 (p < 0.0001). Independent predictors were an LA/RA volume ratio >1, microvascular disease, and systolic blood pressure (model C-statistic 0.792, 95% CI 0.758-0.824). Measures of the extent of coronary artery disease (CAD) were not independent predictors of HF-CVD. CONCLUSIONS: In a low- to moderate-risk asymptomatic diabetic population, CTA LA enlargement (LA/RA volume ratio) but not the extent of CAD had independent prognostic value for HF-CVD in addition to the clinical variables.

The Management and Outcome of Hospitalized and Ambulatory Israeli Heart Failure Patients Compared to European Heart Failure Patients: Results from the ESC Heart Failure Long-Term Registry.

BACKGROUND: The treatment of patients hospitalized with heart failure (HHF) and ambulatory chronic heart failure (CHF) differs in various countries. OBJECTIVES: To evaluate the management and outcomes of patients with HFF and CHF in Israel compared to those in other European countries who were included in the ESC-HF Long-Term Registry. METHODS: From May 2011 to April 2013, heart failure patients - 467 Israelis and 11,973 from other countries - were evaluated. The Israeli patients included 178 with HHF and 289 with CHF. One year outcomes, including all-cause and cardiovascular mortality as well as HHF, were evaluated. RESULTS: The HHF Israeli patients were older than their CHF Israeli counterparts, had more co-morbidities, included more women, and were treated less frequently with medications suggested by European guidelines. The Israeli HHF patients had similar all-cause 1 year mortality rates compared to HHF patients from other participating countries, but their cardiovascular (CV) mortality was lower, while a significantly higher rate of all-cause and HHF was noted. The Israeli CHF patients were older, suffered from more co-morbidities and had prior cardio-electronic implantable devices. In addition, they had higher mortality rates, especially non-CV, and were more frequently hospitalized, compared to CHF patients from other countries. CONCLUSIONS: The Israeli patients with heart failure differed in their baseline characteristics and the therapeutic approach. Despite high usage of treatments recommended by official guidelines, especially among CHF patients, mortality, particularly in HHF patients, remained high.

An Intervention to Reduce the Time Interval Between Hospital Entry and Emergency Coronary Angiography in Patients with ST-Elevation Myocardial Infarction.

BACKGROUND: Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of < 90 minutes. OBJECTIVES: To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes. METHODS: In March 2013 the authors launched a seven-component intervention program:  Direct patient evacuation by out-of-hospital emergency medical services to the coronary intensive care unit or catheterization laboratory Education program for the emergency department staff Dissemination of information regarding the urgency of the PPCI decision Activation of the catheterization team by a single phone call Reimbursement for transportation costs to on-call staff who use their own cars Improvement in the quality of medical records Investigation of failed cases and feedback. RESULTS: During the 14 months prior to the intervention, initiation of catheterization occurred within 90 minutes of hospital arrival in 88/133 patients(65%); during the 18 months following the start of the intervention, the rate was 181/200 (90%) (P < 0.01). The respective mean/median times to treatment were 126/67 minutes and 52/47 minutes (P < 0.01). Intervention also resulted in shortening of the time interval from hospital entry to PPCI on nights and weekends. CONCLUSIONS: Following implementation of a comprehensive intervention, the time from hospital admission to PPCI of STEMI patients shortened significantly, as did the proportion of patients treated within 90 minutes of hospital arrival.

Endothelial nitric oxide synthase polymorphism and prognosis in systolic heart failure patients.

BACKGROUND: The endothelial nitric oxide synthase (eNOS) gene single nucleotide polymorphism G894T is associated with thrombotic vascular diseases. However, its functional significance is controversial and data are scarce concerning its influence in heart failure (HF). METHODS: We studied 215 patients with chronic systolic HF. DNA was analyzed for eNOS gene G894T polymorphism using PCR and DNA sequencing. Evaluation of clinical characteristics and analysis of factors associated with 2-year mortality were performed for the homozygous G-allele G894T variant (GG), relative to the TT and GT variants. RESULTS: The genotype distributions of eNOS G894T alleles were: GG 135 patients (63%) and TT/GT 80 (37%). Two-year mortality was significantly higher in the GG variant (48%) than the combined TT/GT group (32%). The usage of nitrates was associated with increased 2-year mortality (HR 2.0, 95% CI 1.28-3.17; p = 0.003), which was most significant in the GG group treated with nitrates (73.5%) in comparison to the TT/GT group not treated with nitrates (34%); HR 2.75, 95% CI 1.57-4.79, P < 0.001. CONCLUSIONS: Homozygosity for the G allele of the eNOS G894T polymorphism was associated with worse survival in systolic HF patients, especially in those treated with nitrates. ENOS polymorphism may result in different mechanistic interactions in HF than in thrombotic vascular diseases, suggesting that overexpression of NO may be associated with deleterious effects in systolic HF.