Cardiac Tamponade in Patients Treated with Direct Oral Anticoagulants.

BACKGROUND: Direct oral anticoagulants (DOACs) are the treatment of choice for patients with non-valvular atrial fibrillation; however, bleeding risk remains significant. We reported a single-center experience with 11 patients who presented with hemorrhagic cardiac tamponade while treated with DOACs. OBJECTIVES: To evaluate the characteristics and clinical outcomes of patients under DOACs with cardiac tamponade. METHODS: We retrospectively identified 11 patients treated with DOACs admitted with pericardial tamponade in our cardiology unit during 2018-2021. RESULTS: The mean age was 84 ± 4 years; 7 males. Atrial fibrillation was the indication for anticoagulation in all cases. DOACs included apixaban (8 patients), dabigatran (2 patients), and rivaroxaban (1 patient). Urgent pericardiocentesis via a subxiphoid approach under echocardiography guidance was successfully performed in 10 patients. One patient was treated with urgent surgical drainage with a pericardial window. Reversal of anticoagulation using prothrombin complex concentrate and idarucizumab was given before the procedure to 6 patients treated with apixaban and one patient treated with dabigatran. One patient, initially treated with urgent pericardiocentesis, underwent pericardial window surgery due to re-accumulation of blood in the pericardium. The pericardial fluid analysis demonstrated hemopericardium. Cytology tests were negative for malignant cells in all cases. Discharge diagnoses regarding the cause of hemopericardium included pericarditis (3 patients) and idiopathic (8 patients). Medical therapy included non-steroidal anti-inflammatory drugs (1 patient), colchicine (3 patients), and steroids (3 patients). No patient died during hospitalization. CONCLUSIONS: Hemorrhagic cardiac tamponade is a rare complication of DOACs. We found good short-term prognosis following pericardiocentesis.

Effect of aspirin on primary prevention of cardiovascular disease and mortality among patients with chronic kidney disease.

Chronic kidney disease is associated with an increased risk for cardiovascular and bleeding events. Data regarding the effectiveness and risks of aspirin therapy for primary prevention in the high-risk group of patients with chronic kidney disease are scant and controversial. This retrospective study included patients with chronic kidney disease. Participants were divided according to aspirin use. Outcomes included non-fatal cardiovascular events, major bleeding events and all-cause mortality. Among 10,303 patients, 2169 met the inclusion criteria and 1818 were included after 1:1 propensity-score matching. Our final cohort included patients with mean age of 73.4 ± 11.6 years, estimated glomerular filtration rate of 31.5 ± 10.5 ml/min/1.73m2 with follow up of 4.9 ± 1.5 years. There were no significant differences in all-cause mortality and bleeding events (odds ratio = 1.03, confidence interval [0.62, 1.84], p = .58 and odds ratio = 1.09, confidence interval [0.65, 1.72], p = .87 respectively). The incidence of cardiovascular events was higher in aspirin users versus non-users on univariate analysis (p < 0.01) and was comparable after controlling for possible risk-factors (OR = 1.05, CI [0.61, 3.14], p = .85). Chronic aspirin use for primary prevention of cardiovascular disease was not associated with lower mortality, cardiovascular events or increased bleeding among patients with chronic kidney disease. Those results were unexpected and should prompt further research in this field.

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

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

Temporal Trends in the Characteristics, Treatment, and Outcomes of Conservatively Managed Patients With Non-ST Elevation Acute Coronary Syndrome (from the ACSIS Registry 2000 to 2016).

Despite advances in percutaneous coronary interventions (PCI), a subgroup of acute coronary syndrome (ACS) patients are still managed medically by a conservative approach. We sought to characterize a contemporary, large-scale, real-world cohort of ACS patients treated conservatively via pharmacological management, without PCI. Data was gathered from the ACS Israeli Survey (ACSIS) between 2000 and 2016, encompassing all consecutive patients admitted to cardiology wards with an ACS diagnosis. Included were 3,543 conservatively managed patients with non-ST elevation ACS (NSTE-ACS). Patients with ST elevation MI or those who underwent any coronary revascularization (PCI or bypass surgery) were excluded. Primary endpoints were 30-day major adverse cardiovascular events (MACE) and 1-year mortality. The study cohort was divided to 4 time-periods. Over 2 decades, medically managed NSTE-ACS patients remained of similar age (67 ± 13 years, p = 0.78), but had more atherosclerotic risk-factors and comorbidities. During time, patients were more often referred to diagnostic angiography and treated with statins, ACE-I/ARBs, and P2Y12 inhibitors (p < 0.001 for each). Over time, there were less in-hospital complications such as kidney injury and heart failure. The rate of 30-day MACE decreased (from 20.7% to 10.3%, earliest to latest period, p < 0.001). Compared with the earliest period, the latest period was associated with a reduction in 1-year mortality (14.7% to 11.6%; adjusted HR 0.65, 95% CI 0.47 to 0.90). In conclusion, Over 2 decades, in medically managed NSTE-ACS patients, short term prognosis has significantly improved while 1-year mortality demonstrated improvement only recently, likely due to incremental benefits of medical management.

Sex-specific contemporary trends in incidence, prevalence and survival of patients with non-valvular atrial fibrillation: A long-term real-world data analysis.

INTRODUCTION: Atrial fibrillation (AF) is a major increasing public health problem worldwide, with clinical and epidemiological differences between men and women. However, contemporary population-level data on incidence and survival are scarce. AIM: To evaluate sex-specific contemporary trends in the incidence, prevalence, and long-term survival of non-valvular AF in a real-world setting. METHODS: AF patients diagnosed between 2007-2015, insured by a large, state-mandated health organization in Israel (Maccabi Healthcare Services) were included. AF was diagnosed based on registered diagnoses. Patients with valvular disease, active malignancy, cardiac surgery ≤ 6 months, or recent pregnancy, were excluded. Annual incidence rate, period prevalence, and 5-year survival for each calendar year during the study period, were calculated. RESULTS: A total of 15,409 eligible patients (8,288 males, 7,121 females) were identified. Males were more likely to be younger, have higher rates of underlying diseases (ischemic heart disease, heart failure, and chronic obstructive pulmonary disease), but with lower rates of hypertension and chronic kidney diseases as compared to female patients. During the study period, age-adjusted incidence decreased both in men: (-0.020/1,000-person year, p-for trend = 0.033) and, women (-0.025/1,000 person-year p = 0.009). The five-year survival rate was significantly higher among men vs. women (77.1% vs. 71.5%, respectively, p<0.001). Age-adjusted prevalence increased significantly among men (+0.102 per year, p-for trend<0.001) yet decreased among women (-0.082 per year, p-for trend = 0.005). A significant trend toward improved long-term survival was observed in women and not in men. CONCLUSIONS: The current study shows significant sex-related disparities in the incidence, prevalence, and survival of AF patients between 2007-2015; while the adjusted incidence of both has decreased over-time, prevalence and mortality decreased significantly only in women.

ECG changes after non-cardiac surgery: a prospective observational study in intermediate-high risk patients.

BACKGROUND: Efforts to mitigate the risk for perioperative cardiac events focus on both patient's and operation's risk and often include a preprocedural electrocardiogram (ECG). The merits of postprocedural ECG for detection of occult cardiac events occurring during surgery are unknown. We aim to explore the incidence of pre, and new postprocedural ECG pathologies in an intermediate-high risk population undergoing non-cardiac surgery. METHODS: This single-center, prospective, observational study, included patients older than 18 years with at least two cardiovascular risk factors who were scheduled for non-cardiac surgery. All patients had pre, and postprocedural ECG. The ECG was analyzed and coded according to the Minnesota criteria. A multivariable logistic regression analysis was performed for indices associated with new postoperative ECG pathologies. RESULTS: A total of 217 patients were enrolled. Preoperative pathologic ECG changes were recorded in 62.2% of the patients. Postoperatively, new ECG pathologies were documented in 49.8% of patients, most commonly T-wave changes (36.4% of changes). Pathologic ECG changes at baseline (OR 3.15, 95% CI [1.61-6.17]; P<0.01), diabetes (OR 1.93, 95% CI [1.02-3.64]; P=0.04), history of ischemic heart disease (OR 2.14, 95% CI [1.03-4.47]; P=0.04), higher volumes of fluid replacement (OR 1.70, 95% CI [1.10-2.61]; P=0.01) and higher levels of preoperative hemoglobin (OR 1.24, 95% CI [1.04-1.47]; P=0.01) were all independently associated with postoperative ECG changes. CONCLUSIONS: Pre-, but most importantly, postoperative ECG changes are common in intermediate-high risk surgical patients. Postoperative ECG may be valuable to disclose silent cardiovascular events that occurred during surgery.

Non-coronary cardiac calcifications and outcomes in patients with heart failure.

BACKGROUND: Calcium deposits on heart valves are considered a local manifestation of atherosclerosis and are associated with poor cardiovascular outcomes. The clinical significance of cardiac calcifications among heart failure (HF) patients, as assessed by echocardiography, is unknown. This study evaluated associations of cardiac calcifications with mortality and hospital admissions in this specific population. METHODS: Medical records of all patients who initiated ambulatory surveillance at our HF clinic during 2011-2018 were reviewed. Calcifications in the aortic valve, aortic root, or the mitral valve were evaluated. Patients with moderate to severe regurgitation or stenosis of the aortic or mitral valves were excluded. The primary endpoint was the composite of long-term all-cause mortality and HF hospitalizations. Secondary endpoints were long-term all-cause mortality and more than one hospitalization due to HF. RESULTS: This retrospective study included 814 patients (mean age 70.9 ± 13 years, 63.2% male). Of the total cohort, 350 (43%) had no cardiac calcifications and 464 (57%) had at least 1 calcified site. Considering the patients with no calcification as the reference group yielded a higher adjusted odds ratios for the composite endpoint, all-cause death, and recurrent HF hospitalizations, among patients with any cardiac calcification (OR = 1.68, 95%CI = 1.1-2.5, p = 0.01, OR=1.61, 95%CI = 1.1-2.3, p < 0.01, and OR = 1.50, 95%CI = 1.1-2.2, p < 0.01, respectively). CONCLUSIONS: We found an independent association between cardiac calcifications and the risk of death and HF hospitalizations among ambulatory HF patients. Cardiac calcifications evaluated during routine echocardiography may contribute to the risk stratification of patients with HF.

Hyperphosphatemia is required for initiation but not propagation of kidney failure-induced calcific aortic valve disease.

High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease (CAVD). However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. The experimental design consisted of administering a uremia-inducing diet, with or without phosphate enrichment, to rats for 7 wk. Forty-two rats were fed with a phosphate-enriched uremic regimen that caused renal insufficiency and hyperphosphatemia. Another 42 rats were fed with a phosphate-depleted uremic regimen, which induces similar severity of renal insufficiency, but without its related mineral disorder. Aortic valves were evaluated at several points during the time of diet administration. In the second part, additional 54 rats were fed a phosphate-enriched diet for various time periods and were then switched to a phosphate-depleted diet to complete 7 wk of uremic diet. Osteoblast-like phenotype, inflammation, and eventually valve calcification were observed only in rats that were fed with a phosphate-enriched regimen. Significant valve calcification was observed only in rats that were fed a phosphate-enriched diet for at least 4 wk. Valve calcification was observed only when the switch to a phosphate-depleted regimen occurred after osteoblast markers and activation of Akt and ERK intracellular signaling pathways had already been found in the valve. Phosphate is essential for the initiation of the calcification process. However, when osteoblast markers are already expressed in valve tissue, phosphate depletion will not halt the disease.NEW & NOTEWORTHY High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease. However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. Our findings indicated that phosphate is essential for the initiation of the process that includes macrophage accumulation and osteoblast phenotype. Furthermore, hyperphosphatemia is dispensable beyond a certain phase of the process, a point of "no return" after which phosphate depletion does not prevent calcification. This point is relatively early in the course of calcification, when no calcification is apparent, but the inflammation, osteoblast markers, and activation of ERK and Akt pathways have already been identified. Our findings emphasize the complexity of the calcification process and suggest that different mediators might be required during different phases and that the role of phosphate precedes the actual calcification.

Impact of Marital Status on the Outcome of Acute Coronary Syndrome: Results From the Acute Coronary Syndrome Israeli Survey.

Background Marriage is one of the common forms of social support. Conflicting evidence exists about the impact of marital status on the outcomes of patients with acute coronary syndrome ( ACS ). It is further not clear if sex disparity exists in the outcome of married and nonmarried patients with ACS. Methods and Results Data from the ACS Israeli Survey, collected between 2004 and 2016, were used to compare baseline characteristics, clinical indexes, and outcomes of married and nonmarried patients with ACS. Cox regression analysis and propensity score matching were used to explore if marital status was independently associated with long-term outcome. Of 7233 patients included with reported marital status, 5643 (78%) were married. Married patients were younger (62.69±12.07 versus 68.47±14.84 years; P<0.001), more frequently men (83.1% versus 54.8%; P<0.001), and less likely to be hypertensive (61.1% versus 69.3%; P<0.001). All-cause mortality incidence at 30 days and at 1 year was lower in married patients (3.1% versus 7.6% [ P<0.001]; and 7.1% versus 15.3% [ P<0.001], respectively). After adjusting for multiple covariates, the hazard ratio for 5-year all-cause mortality for married patients was 0.74 (95% CI , 0.62-0.88). Similar results were observed after propensity score matching. Kaplan-Meier estimates for all-cause mortality at 5 years demonstrated the best prognosis for married men and the worst for nonmarried women. Conclusions Marriage is independently associated with better short- and long-term outcomes across the spectrum of ACS . Attempts to intensify secondary prevention measures should focus on nonmarried patients and especially nonmarried women.

Prognostic implications of small left atria on hospitalized patients.

AIMS: To demonstrate the association between small left atria (LA) and outcome in a relatively large heterogeneous population of hospitalized patients. METHODS AND RESULTS: In a single-centre retrospective study, all inpatients that underwent an echocardiographic assessment between 2011 and 2016 and had an available left atrial volume index (LAVI) measurement were included. The cohort consisted of 17 343 inpatients who had an available LAVI measurement, 288 with small LA (LAVI <16 mL/m2), 7531 patients had LAVI within normal limits (16-34 mL/m2) divided into low normal (16-24.9 mL/m2; n = 2636) and high normal (25-34 mL/m2; n = 4895), 4720 patients had large LAVI (34.1-45 mL/m2) and 4804 had very large LAVI (>45 mL/m2). Median follow-up time was 2.4 years. After adjustments for age, gender, and baseline characteristics with a P-value <0.2 in univariable analyses (body mass index, haemoglobin, ischaemic heart disease, valvulopathy, atrial fibrillation, diabetes mellitus, hypertension, hyperlipidaemia, smoking, renal dysfunction, lung disease, and malignancy) small LA was associated with a higher risk for in-hospital mortality (odds ratio 2.9, 95% confidence interval (CI) 1.4-5.7; P = 0.002] and all-cause mortality [hazard ratio (HR) 2.1, 95% CI 1.6-2.8; P < 0.001] compared with high normal LA. For every mL/m2 decrease below high normal LA size the risk for in-hospital and long-term all-cause mortality increased by 10% (HR 1.1, 95% CI 1.02-1.18; P = 0.005) and 8% (HR 1.08, 95% CI 1.05-1.12; P < 0.001), respectively. CONCLUSION: Small LA are independently associated poorer short- and long-term mortality. LA volume should be referred to as J-shaped in terms of mortality. HELSINKI COMMITTEE APPROVAL NUMBER: 0170-17-TLV.

Managing Anti-Platelet Therapy in Thrombocytopaenic Patients with Haematological Malignancy: A Multinational Clinical Vignette-Based Experiment.

Data on anti-platelet therapy (APT) for prevention of atherothrombotic events in thrombocytopaenic cancer patients is lacking. We aimed to identify patient and physician characteristics associated with APT management in thrombocytopaenic patients with haematological malignancy. A clinical vignette-based experiment was designed. Eleven haematologists were interviewed, identifying five variable categories. Next, 18 hypothetical vignettes were generated. Each physician received three vignettes and chose to: hold all APT; continue APT without platelet transfusion support; or continue APT with platelet transfusion support. The survey was distributed to haematologists and thrombosis specialists in three countries. Multivariate cluster robust Poisson regression models were used to calculate relative risks (RRs) of using one management option (over the other) for each variable in comparison to a reference variable. A total of 145 physicians answered 434 cases. Clinicians were more likely to hold APT in case of 20,000/µL platelets (vs. 40,000/µL; RR for continuing: 0.82 [95% confidence interval: 0.75-0.91]), recent major gastrointestinal bleeding (vs. none; RR 0.81 [0.72-0.92]) and when the physician worked at a university-affiliated community hospital (vs. non-academic community hospital; RR 0.84 [0.72-0.98]). Clinicians were more likely to continue APT in ST elevation myocardial infarction with dual APT (vs. unstable angina with single APT; RR 1.31 [1.18-1.45]) and when there were institutional protocols guiding management (vs. none; RR 1.15 [1.03-1.27]). When APT was continued, increased platelet transfusion targets were used in 34%. In summary, the decision process is complex and affected by multiple patient and physician characteristics. Platelet transfusions were frequently chosen to support APT, although no evidence supports this practice.

Thrombosis, anticoagulation and outcomes in malignant superior vena cava syndrome.

Anticoagulation is often used in superior vena cava syndrome (SVCS) associated with cancer (i.e malignant SVCS), even without thrombosis, but its effect on outcomes has not been reported. We aimed to determine factors and outcomes associated with thrombosis and anticoagulation in malignant SVCS. Patients with malignant SVCS diagnosed on computerized tomography (CT) were retrospectively included, indexed at diagnosis and followed for 6 months using medical records. The cohort included 183 patients with malignant SVCS of which 153 (84%) were symptomatic. Thirty of the 127 patients (24%) with a reviewable baseline CT had thrombosis of the SVC or tributaries at diagnosis. Patients with baseline thrombosis more often had symptomatic SVCS (p < 0.01). 70% (21/30) of patients with thrombosis and 52% (49/97) of those without thrombosis at baseline received anticoagulation, most often at therapeutic doses. Thrombosis occurred in 5/39 patients with anticoagulation (13%) compared to 2/18 (11%) of those without, during follow-up (p = 0.85). Anticoagulation was associated with a reduction in risk of SVC stent placement during follow-up that did not reach statistical significance (HR 0.47, 95% CI 0.2-1.13, p = 0.09). Major bleeding occurred in 7 (4%) patients, six of whom received anticoagulation (four therapeutic and two intermediate dose). Neither thrombosis nor anticoagulation affected survival. Anticoagulation is commonly used as primary prevention but its benefit remains to be proven. The role of reduced-dose anticoagulation in non-thrombotic malignant SVCS should be prospectively assessed.

Physical Training in a Medical Fitness Room for Patients with Chronic Diseases: Functional and Metabolic Outcomes.

BACKGROUND: Physical inactivity is a pivotal factor in the development and progression of various chronic diseases. However, most fitness facilities exclude unhealthy individuals. Therefore, an exercise program that admits such patients is imperative. OBJECTIVES: To evaluate the effectiveness of a fitness facility that admits adult subjects with multiple chronic diseases. METHODS: We conducted a retrospective screening of patient records from the Medical Fitness Facility at Meir Medical Center, Israel. Intake of subjects was done by a multidisciplinary team. For each individual, personalized diet and exercise plans were developed and patients attended the facility twice a week. Each participant was evaluated at enrolment and after 4 months for well-being, metabolic parameters, exercise capacity, and laboratory blood tests. RESULTS: A total of 838 individuals were enrolled, mean age 57 years. Their medical conditions included dyslipidemia (48.8%), hypertension (37.6%), and diabetes mellitus (24.9%), followed by musculoskeletal problems (arthropathy 19%, lower back pain 16.1%) and ischemic heart disease (13.4%). Less common diagnoses were vascular diseases, pulmonary diseases, and malignancy. Only 40.5% of participants adhered to the regimen with advanced age being the best predictor for adherence. At the follow-up visit, body mass index was lower (31.2 vs. 30.2 kg/m2, P <0.0001), exercise capacity increased (measured as maximal MET; 7.1 vs. 8.1, P < 0.0001), and well-being improved (measured by Short Form Survey [SF-36]; 69.3 vs. 76.0, P <0.0001). CONCLUSIONS: We show that a fitness program for patients with multiple chronic diseases is feasible and effective in improving prognostic parameters, albeit significantly challenged by adherence limitations.

Mean platelet volume and risk of thrombotic and bleeding complications in patients with Philadelphia chromosome negative myeloproliferative neoplasms.

: Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) are associated with increased thrombosis and bleeding risk. Mean platelet volume (MPV) is associated with thrombosis in nonmalignant settings. This study evaluates the association between MPV and thrombosis and bleeding in MPN. Patients with MPN without prior thrombosis, nonhematologic malignancy or anticoagulant use were included in this retrospective analysis. The primary endpoint was arterial or venous thrombosis. The secondary endpoints were any bleeding and major bleeding. MPV was measured at diagnosis and during the index episode. A total of 135 MPN patients met the inclusion criteria. Over a median follow-up of 6.6 years, 23 patients (15.6%) experienced thrombosis. There was no difference in MPV at diagnosis (8.47 vs. 8.73 fl, P = 0.4) or during the index event between patients with or without thrombosis. Twelve patients (8.9%) had a bleeding event, whereas seven (5.2%) had major bleeding. MPV was significantly higher among patients with major bleeding, both at diagnosis (10.04 vs. 8.61, P = 0.005) and during the bleeding episode. There was no association after regression analysis of variables associated with MPV at diagnosis. MPV is not associated with thrombotic events in MPN. The study generates the hypothesis that MPV may be an indirect marker of bleeding in MPN.

Ultra-Low Contrast Volume for Patients with Advanced Chronic Kidney Disease Undergoing Coronary Procedures.

BACKGROUND/AIMS: Contrast induced nephropathy (CIN) is associated with adverse clinical outcomes in patients undergoing coronary interventions, particularly in patients with advanced chronic kidney. The study was aimed to assess the real-life feasibility and safety of ultra-low volume coronary procedures in patients with advanced chronic kidney disease. METHODS: A prospective study that included patients with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2) was conducted. Coronary procedures were performed using an ultra-low contrast volume technique. RESULTS: The 30 patients had a mean eGFR of 31.8(±8) mL/min/1.73 m2. Indications for coronary angiography were non-ST elevation myocardial infarction (63.3%), unstable (20%), and stable angina pectoris (16.7%). Median contrast volume for diagnostic coronary angiography was 13 mL (interquartile ranges [IQR] 12-14.9), and an additional 13 mL (IQR 8.8-14.3) for percutaneous coronary intervention (PCI). In 3 patients (10%), a ≥25% increase was demonstrated in serum cystatin C levels 48 h following the procedure. None of the patients demonstrated a ≥25% increase in serum creatinine levels at 48 h. Following 6 months, no patient required renal replacement therapy or unplanned coronary intervention. CONCLUSIONS: In patients with advanced chronic kidney disease, the ultra-low contrast technique is feasible and effective and can be used safely without a significant deterioration in renal function. This technique may increase the utilization of PCI in high-risk coronary patients with chronic kidney disease.

The Effect of Combined Aspirin and Clopidogrel Treatment on Cancer Incidence.

BACKGROUND: Multiple studies have shown an association between aspirin treatment and a reduction in newly diagnosed cancer. Conversely, there are conflicting clinical and laboratory data on the effect of combined clopidogrel and aspirin therapy on cancer incidence, including analyses suggesting an increased cancer risk. No large-scale cohort study has been performed to address this issue in a heterogeneous real-world scenario. We investigated the effect of clopidogrel and aspirin on cancer incidence compared with aspirin alone and no antiplatelet therapy. METHODS: A population-based historical cohort study of subjects aged ≥50 years covered by Clalit Health Services, an Israeli health maintenance organization, was performed. Patients treated with the newer antiplatelet drugs, prasugrel or ticagrelor, which, like clopidogrel, inhibit adenosine diphosphate receptors, and those with prior cancer were excluded. Prescription records of antiplatelet medication were retrieved. RESULTS: The cohort included 183,912 subjects diagnosed with 21,974 cancer cases based upon the International Classification of Diseases, Ninth Revision. Dual aspirin and clopidogrel was prescribed in 9.6%, while 49% received aspirin alone and 41% used neither. Compared with nonusers, there was a lower risk of cancer in subjects exposed to aspirin with (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.44-0.49) or without clopidogrel (HR 0.54; 95% CI, 0.52-0.56), on long-term follow-up. Combined treatment was associated with a lower cancer risk than the aspirin-only group (HR 0.92; 95% CI, 0.86-0.97). CONCLUSIONS: Dual clopidogrel and aspirin treatment is safe regarding the cancer risk. This study generates the hypothesis that clopidogrel may reduce cancer incidence.

Long-term Follow-up of Coronary Artery Bypass Patients With Preoperative and New Postoperative Native Coronary Artery Chronic Total Occlusion.

BACKGROUND: Chronic total occlusions (CTOs) of native coronary arteries are a frequent finding among patients who are referred for surgical revascularization with coronary artery bypass grafting (CABG). The long-term clinical significance of native coronary artery CTO identified at baseline and 1 year after CABG is unknown. METHODS: All patients who underwent 1-year follow-up angiography as part of the multicentre Radial Artery Patency Study (RAPS) were assessed for late clinical events. RESULTS: At a mean follow-up of 7.3 ± 2.9 years, the study group of 388 patients had the following outcomes: 39 (10%) deaths, 6 (1.5%) cases of nonfatal myocardial infarction, and 19 (4.9%) cases of percutaneous coronary intervention (PCI). CTO of ≥ 1 native coronary artery in the baseline preoperative coronary angiogram was demonstrated in 240 (61.9%) patients. The composite of all-cause death, nonfatal myocardial infarction, and PCI occurred significantly more often in patients with at least 1 preoperative CTO than in patients without a preoperative CTO (20% vs 11%; P = 0.048). A new native coronary artery CTO 1 year after surgery occurred in 169 (43.6%) patients. The composite of all-cause death, nonfatal myocardial infarction, and PCI occurred significantly more often in patients with a new CTO 1 year after CABG compared with those without a new CTO (21.3% vs 12.8%; P = 0.028). CONCLUSIONS: In patients undergoing CABG, both preoperative CTOs and new CTOs that develop 1 year after surgery are associated with adverse long-term clinical outcomes.

Incidence and Expression of Circulating Cell Free p53-Related Genes in Acute Myocardial Infarction Patients.

AIM: The circulating RNA levels are predictive markers in several diseases. We determined the levels of circulating p53-related genes in patients with acute ST-segment elevation myocardial infarction (STEMI), indicating major heart muscle damage. METHODS: Plasma RNA was extracted from the patients (n=45) upon their arrival to the hospital (STEMI 0h) and at four hours post-catheterization (STEMI 4h) as well as from controls (n=34). RESULTS: Of 18 circulating p53-related genes, nine genes were detectable. A significantly lower incidence of circulating p21 (p ＜ 0.0001), Notch1 (p=0.042) and BTG2 (p ＜ 0.0001) was observed in the STEMI 0h samples in comparison to the STEMI 4h and control samples. Lower expression levels (2.1-fold) of circulating BNIP3L (p=0.011), p21 (3.4-fold, p=0.005) and BTG2 (6.3-fold, p=0.0001) were observed in the STEMI 0h samples in comparison to the STEMI 4h samples, with a 7.4-fold lower BTG2 expression (p ＜ 0.001) and 2.6-fold lower p21 expression (p=0.034) compared to the control samples. Moreover, the BNIP3L expression (borderline significance, p=0.0655) predicted the level of peak troponin, a marker of myocardial infarction. In addition, the BNIP3L levels on admission (p=0.0025), at post-catheterization (p=0.020) and the change between the groups (p=0.0079) were inversely associated with troponin. The BNIP3L (p=0.0139) and p21 levels (p=0.0447) were also associated with a longer time to catheterization. CONCLUSIONS: Our results suggest that circulating downstream targets of p53 are inhibited during severe AMI and subsequently re-expressed after catheterization, uncovering possible novel death-or-survival decisions regarding the fate of p53 in the heart and the potential use of its target genes as prognostic biomarkers for oxygenation normalization.

Native coronary artery patency after coronary artery bypass surgery.

OBJECTIVES: The aim of the study was to determine native coronary artery patency 1 year after coronary artery bypass grafting and to identify clinical and angiographic predictors for the development of a chronic total occlusion (CTO). BACKGROUND: In contrast to the large body of information regarding graft patency, data regarding atherosclerosis progression and vessel patency in surgically bypassed native coronary arteries are less clear. METHODS: Of the 440 patients who underwent 1-year follow-up angiography as part of the multicenter RAPS (Radial Artery Patency Study), included in our study were 388 patients (88%) for whom angiograms were available for review. Angiograms were reviewed for native coronary artery patency in an independent blinded manner. RESULTS: On the pre-operative angiogram, CTO of at least 1 native coronary vessel was demonstrated in 240 patients (61.9%) having 305 occluded vessels. At 1 year after coronary artery bypass grafting, at least 1 new native coronary artery CTO occurred in 169 patients (43.6%). In 7.5% of patients, the native artery and the graft supplying that territory were both occluded. A new CTO was almost 5 times more likely to occur in coronary vessels with a pre-operative proximal stenosis >90% compared with vessels with proximal stenosis <90% (45.5% vs. 9.5%, respectively, p < 0.001). Patients with a new CTO had significantly more baseline Canadian Cardiovascular Society class 4 angina compared with patients without a new CTO. A new CTO was less likely to occur in the left anterior descending artery (18.4%), supplied by the left internal thoracic artery. When comparing radial artery and saphenous vein grafts, neither the type of graft nor graft patency had any association with native coronary artery occlusion. CONCLUSIONS: CTO of surgically bypassed coronary arteries 1 year after coronary artery bypass grafting is extremely common.

Comparison of mortality in patients with coronary or peripheral artery disease following the first vascular intervention.

OBJECTIVES: Patients with peripheral artery disease (PAD) less frequently achieve secondary prevention goals compared with patients with coronary artery disease (CAD). We aimed to compare mortality rates in patients with PAD and CAD following first vascular intervention. PATIENTS AND METHODS: Patients 18 years of age or older without a history of cardiovascular disease, who underwent first coronary or lower limb vascular intervention between 2002 and 2010, were included in this study. The primary endpoint was all-cause mortality. RESULTS: Of the 9950 participants, 8242 (82.8%) underwent first coronary revascularization and 1708 (17.2%) received first peripheral vascular intervention. During a mean follow-up period of 5.6±2.3 years, 1283 (12.9%) participants died. Compared with CAD patients, patients with PAD had significantly worse long-term prognosis with an increased risk for all-cause mortality (hazard ratio=2.95, 95% confidence interval 2.6-3.3, P<0.0001). This association remained statistically significant following a multivariable analysis (hazard ratio=1.86, 95% confidence interval 1.6-2.1, P<0.0001). Furthermore, PAD patients were less frequently treated with cardioprotective medications including statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, aspirin, and clopidogrel (P<0.001). CONCLUSION: Patients with PAD have worse outcome compared with patients with CAD, even in the specific group of patients following first vascular intervention. These findings demand more effort to improve secondary prevention guidelines in all patients with cardiovascular diseases, but especially in PAD patients.