ApoA-I Infusion Therapies Following Acute Coronary Syndrome: Past, Present, and Future.

PURPOSE OF REVIEW: The elevated adverse cardiovascular event rate among patients with low high-density lipoprotein cholesterol (HDL-C) formed the basis for the hypothesis that elevating HDL-C would reduce those events. Attempts to raise endogenous HDL-C levels, however, have consistently failed to show improvements in cardiovascular outcomes. However, steady-state HDL-C concentration does not reflect the function of this complex family of particles. Indeed, HDL functions correlate only weakly with serum HDL-C concentration. Thus, the field has pivoted from simply raising the quantity of HDL-C to a focus on improving the putative anti-atherosclerotic functions of HDL particles. Such functions include the ability of HDL to promote the efflux of cholesterol from cholesterol-laden macrophages. Apolipoprotein A-I (apoA-I), the signature apoprotein of HDL, may facilitate the removal of cholesterol from atherosclerotic plaque, reduce the lesional lipid content and might thus stabilize vulnerable plaques, thereby reducing the risk of cardiac events. Infusion of preparations of apoA-I may improve cholesterol efflux capacity (CEC). This review summarizes the development of apoA-I therapies, compares their structural and functional properties and discusses the findings of previous studies including their limitations, and how CSL112, currently being tested in a phase III trial, may overcome these challenges. RECENT FINDINGS: Three major ApoA-I-based approaches (MDCO-216, CER-001, and CSL111/CSL112) have aimed to enhance reverse cholesterol transport. These three therapies differ considerably in both lipid and protein composition. MDCO-216 contains recombinant ApoA-I Milano, CER-001 contains recombinant wild-type human ApoA-I, and CSL111/CSL112 contains native ApoA-I isolated from human plasma. Two of the three agents studied to date (apoA-1 Milano and CER-001) have undergone evaluation by intravascular ultrasound imaging, a technique that gauges lesion volume well but does not assess other important variables that may relate to clinical outcomes. ApoA-1 Milano and CER-001 reduce lecithin-cholesterol acyltransferase (LCAT) activity, potentially impairing the function of HDL in reverse cholesterol transport. Furthermore, apoA-I Milano can compete with and alter the function of the recipient's endogenous apoA-I. In contrast to these agents, CSL112, a particle formulated using human plasma apoA-I and phosphatidylcholine, increases LCAT activity and does not lead to the malfunction of endogenous apoA-I. CSL112 robustly increases cholesterol efflux, promotes reverse cholesterol transport, and now is being tested in a phase III clinical trial. Phase II-b studies of MDCO-216 and CER-001 failed to produce a significant reduction in coronary plaque volume as assessed by IVUS. However, the investigation to determine whether the direct infusion of a reconstituted apoA-I reduces post-myocardial infarction coronary events is being tested using CSL112, which is dosed at a higher level than MDCO-216 and CER-001 and has more favorable pharmacodynamics.

Most Promising Therapies in Interventional Cardiology.

PURPOSE OF REVIEW: The last 40 years of clinical research in interventional cardiology were extraordinarily innovative. This article will review the most promising up and coming interventional cardiovascular therapies, with a primary focus on the treatment of coronary artery disease. RECENT FINDINGS: From the first stent, to the first transcatheter aortic valve implantation (TAVI), and the left appendage closure technique, percutaneous interventions revolutionized the treatment of multiple diseases and dramatically improved the prognosis of many patients. While these advances have decreased the risk of mortality in some patients (such as ST-elevation myocardial infarction), 15% of acute coronary syndrome (ACS) patients still experience recurrent ischemic events within the first year, challenging us to develop new pharmaceutical targets and new devices. The continued emergence of data supporting inflammation as a risk factor and pharmacologic target as well as data supporting the importance of cholesterol efflux have identified novel therapeutic targets that may play a major role in the improvement of prognosis of patients with coronary artery disease. In addition, novel medical devices are being developed to allow even earlier detection of acute cardiac events and to support high-risk percutaneous coronary interventions. Advances in computing and the ability to analyze large datasets will allow us to use artificial intelligence to augment the clinician patient experience, both in and out of the catheterization laboratory, with live procedural guidance as well as pre- and post-operative prognostication tools.

Safety and efficacy of non-vitamin K oral anticoagulant for atrial fibrillation patients after percutaneous coronary intervention: A bivariate analysis of the PIONEER AF-PCI and RE-DUAL PCI trial.

BACKGROUND: The tradeoff in safety versus efficacy in substituting a non-vitamin K antagonist oral anticoagulant for a vitamin K antagonist (VKA) in the stented atrial fibrillation patient has not been quantitatively evaluated. METHODS: Based on summary data from the PIONEER AF-PCI and RE-DUAL PCI trials, 4 antithrombotic regimens were compared with VKA-based triple therapy: (1) rivaroxaban (riva) 15 mg daily + P2Y12 inhibitor, (2) riva 2.5 mg twice daily + P2Y12 inhibitor + aspirin, (3) dabigatran (dabi) 110 mg twice daily + P2Y12 inhibitor, and (4) dabi 150 mg twice daily + P2Y12 inhibitor. A bivariate model with a noninferiority margin of 1.38 was used to simultaneously assess safety and efficacy. The safety end point was major or clinically relevant nonmajor bleeding by International Society on Thrombosis and Haemostasis definitions. The efficacy end point was a thromboembolic event (myocardial infarction, stroke, or systemic embolism), death, or urgent revascularization. The bivariate outcome, a measure of risk difference in the net clinical outcome, was compared between antithrombotic regimens. RESULTS: All 4 non-vitamin K antagonist oral anticoagulant regimens were superior in bleeding and noninferior in efficacy compared with triple therapy with VKA. Riva 15 mg daily and 2.5 mg twice daily were associated with bivariate combined risk reductions of 5.6% (2.3%-8.8%) and 5.5% (2.1%-8.7%), respectively, and dabi 110 mg twice daily and 150 mg twice daily reduced the bivariate risk by 3.8% (0.5%-7.0%) and 6.3% (2.4%-9.8%), respectively. CONCLUSIONS: A bivariate analysis that simultaneously characterizes both risk and benefit demonstrates that riva- and dabi-based regimens were both favorable over VKA plus dual antiplatelet therapy among patients with atrial fibrillation undergoing PCI.

Total bleeding with rivaroxaban versus warfarin in patients with atrial fibrillation receiving antiplatelet therapy after percutaneous coronary intervention.

Among atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI), rivaroxaban with background antiplatelet therapy significantly reduced the first occurrence of bleeding compared to triple therapy with warfarin. This study hypothesized that total bleeding events, including those beyond the first event, would be reduced with rivaroxaban-based regimens. In the PIONEER AF-PCI trial, 2099 patients in the modified intention-to-treat population were randomized to three groups and followed for 12 months: (1) rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (N = 696); (2) rivaroxaban 2.5 mg twice daily plus dual antiplatelet therapy (DAPT) (N = 706); and (3) dose-adjusted warfarin plus DAPT (N = 697). Descriptive statistics for the number of subjects who experienced one or more bleeding events were calculated. The total number of bleeding events was compared across treatment groups using the Wei, Lin, and Weissfeld method. A total of 514 and 439 events of clinically significant bleeding and bleeding requiring medical attention occurred throughout the study. Compared to triple therapy with warfarin, rivaroxaban-based regimen was associated with a reduction in total events of clinically significant bleeding (Group 1 vs. Group 3: HR 0.64 [95% CI 0.49-0.85], p < 0.001, NNT = 11; Group 2 vs. Group 3: HR 0.62 [95% CI 0.48-0.80], p < 0.001, NNT = 10). Similarly, rivaroxaban reduced the total bleeding events requiring medical attention (Group 1 vs. Group 3: HR 0.66 [95% CI 0.49-0.89], p < 0.001, NNT = 14; Group 2 vs. Group 3: HR 0.64 [95% CI 0.48-0.85], p = 0.002, NNT = 13). Rivaroxaban-based regimen reduced the total bleeding events compared with VKA-based triple therapy in stented AF patients. One clinically significant bleeding event could be prevented with rivaroxaban use for every 10-11 patients treated, and one bleeding requiring medical attention could be prevented with rivaroxaban for every 13-14 patients treated. These data provide evidence that total bleeding events, including those beyond the first event, are reduced with rivaroxaban-based antithrombotic regimens. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01830543 (PIONEER AF-PCI).

A rare cause of retinal artery embolism: Accessory mitral valve tissue.

A 42-year-old female patient was referred our clinic for investigation of a history of acute retinal artery occlusion. Transthoracic echocardiography showed a cyst-like, mobile formation on posterior mitral valve leaflet. 2D and real time 3D transesophageal echocardiography showed a flexible circular mobile structure which was attached to posterior mitral valve leaflet. Echocardiographic appearance and morphological characteristics were suggestive of accessory mitral valve tissue.

[Pericardial effusion predicts mortality in patients with chronic obstructive pulmonary disease]. / Kronik obstrüktif akciger hastaliginda perikart sivi birikimi mortalite öngördürücüsüdür.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is an increasingly important cause of morbidity and mortality worldwide. Pericardial effusion (PE) is a current issue proven to be a mortality predictor, especially in pulmonary arterial hypertension. In this study, we aimed to evaluate the prognostic value of PE in COPD. STUDY DESIGN: The study cohort consisted of 488 COPD patients and a control group of 50 healthy patients. At the start of the study, 37 patients (7.5%) had PE. Mean follow-up time was 12 months (range; 1-16 months). Clinical spirometric and echocardiographic data were compared between patients with PE(+) group (n=37), patients without PE(-) group (n=451) and the healthy control group. RESULTS: Right ventricular functions were more depressed and pulmonary arterial pressure was more elevated in the PE(+) group. Also, Kaplan-Meier survival curve analysis showed that at one-year follow- up, mortality was higher in the PE(+) group: PE(-) group 139 (30.8%), PE(+) group 21 (56.8%) log-Rank p value: 0.009). Age, presence of PE, and oxygen usage were independent predictors of mortality in Cox regression analysis. CONCLUSION: Presence of PE predicts mortality in COPD patients at one-year follow-up.

Left atrial deformation parameters in patients with non-alcoholic fatty liver disease: a 2D speckle tracking imaging study.

The presence of the metabolic syndrome is a strong predictor for the presence of NASH (non-alcoholic steatohepatitis) in patients with NAFLD (non-alcoholic fatty liver disease). In the present study, we assessed LA (left atrial) deformation parameters in patients with NAFLD using 2D-STE (speckle tracking echocardiography) and to investigate if any changes exist between subgroups of the NAFLD. A total of 55 NAFLD patients and 21 healthy controls were included in the study. The diagnosis of NAFLD was based on liver biopsy. After patients were categorized into groups according to histopathological analysis (simple steatosis, borderline NASH, definitive NASH), all patients underwent echocardiography with Doppler examination. In the 2D-STE analysis of the left atrium, LA-Res (peak LA strain during ventricular systole), LA-Pump (peak LA strain during atrial systole), LA-SR(S) (peak LA strain rate during ventricular systole), LA-SR(E) (peak LA strain rate during early diastole) and LA-SR(A) (peak LA strain rate during atrial systole) were obtained. LA-Res, LA-Pump and LA-SR(A) were lower in the NAFLD group than in the control group. LA-Res was found to be significantly lower in NAFLD subgroups compared with healthy subjects (43.9±14.2 in healthy controls compared with 31.4±8.3 with simple steatosis, 32.8±12.8 with borderline NASH and 33.8±9.0 with definitive NASH). LA-Pump was significantly lower in the NAFLD group (18.2±3.1 in healthy controls compared with 13.3±4.7 with borderline NASH and 14.4±4.7 with definitive NASH). There were significant differences in LA-SR(A) between healthy controls compared with simple steatosis and borderline NASH (-1.56±0.36 compared with 1.14±0.38 and 1.24±0.32 respectively). Correlation analysis showed significant correlation of LA-Res values with E (early diastolic peak velocity)/E(m) (early diastolic mitral annular velocity) ratio (r=-0.50, P≤0.001), with LAVI (LA volume index; r=-0.45, P≤0.001) and with V(p) (propagation velocity; r=0.39, P≤0.001). 2D-STE-based LA deformation parameters are impaired in patients with NAFLD with normal systolic function. Although LA-Res and pump function parameters might be useful in estimating LV (left ventricular) filling pressure in the NAFLD patient group, it could not be used for differentiating the subgroups.

Relationship between left ventricular diastolic function and arterial stiffness in patients with bicuspid aortic valve.

BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve (BAV), one of the most common congenital cardiac abnormalities, is the result of abnormal aortic leaflet formation during valvulogenesis. Recent studies have reported BAV to be associated with abnormal aortic stiffness, which has a negative impact on left ventricular (LV) diastolic function. The study aim was to investigate the relationship between LV diastolic function, as measured with two-dimensional speckle tracking echocardiography (2D-STE), and arterial stiffness. METHODS: A total of 38 patients with isolated BAV, and 18 age- and gender-matched healthy controls were enrolled prospectively. Patients with aortic valve velocity > 1.7 m/s, more than mild aortic regurgitation (AR) and ascending aorta diameter > 3.6 cm (indexed diameter > 2.1 cm/m2) were excluded. BAV was classified as either anterior-posterior (AP) orientation or right-left (RL) orientation. The LV diastolic function (E/A and E/Em ratio), left atrial (LA) volume index (LAVI), LA systolic strain and strain rate (SR) was assessed using echocardiography. Strain measurements were reported as longitudinal LA strain during ventricular systole (LA-Res), strain during late diastole (LA-Pump), and also as SR during ventricular contraction (LA-SR(s)), during passive ventricular filling (LA-SR(E)), and during active atrial contraction (LA-SR(A)) from four-chamber views. Arterial stiffness was evaluated by measuring the aortic pulse wave velocity (PWV), wave reflection was assessed by measuring the central systolic blood pressure (cSBP), central pulse pressure (cPP) and augmentation index (AIx) with applanation tonometry. RESULTS: The aortic diameter at the proximal ascending aorta was larger in patients with BAV than in controls. Compared to controls, the E/Em ratio and LAVI were significantly higher in BAV patients. Although PWV was higher in BAV patients than in controls, no differences were found between the groups in terms of cSBP, cPP and AIx. The BAV group was observed to have significant lower LA-Res and LA-Pump strain values compared to controls. Significant correlations were identified between the PWV and echocardiographic parameters of LV diastolic function determinants, such as LA-Res and LA-Pump. However, there were no significant differences between BAV subgroups in terms of LV diastolic parameters and PWV. CONCLUSION: Patients with isolated BAV have early features of subclinical LV diastolic dysfunction, as measured with 2D-STE. In addition, aortic stiffness assessed by PWV was impaired. The LV diastolic parameters were related to aortic stiffness.

Learning electrocardiogram on YouTube: how useful is it?

BACKGROUND: YouTube has become a useful resource for knowledge and is widely used by medical students as an e-learning source. The purpose of this study was to assess the videos relating electrocardiogram (ECG) on YouTube. METHODS: YouTube was searched on May 28, 2013 for the search terms "AF ecg" for atrial fibrillation, "AVNRT" for atrioventricular nodal reentrant tachycardia, "AVRT" for atrioventricular reentrant tachycardia, "AV block or heart block" for atrioventricular block, "LBBB, RBBB" for bundle branch block, "left anterior fascicular block or left posterior fascicular block" for fascicular blocks, "VT ecg" for ventricular tachycardia, "long QT" and "Brugada ecg". Non-English language, unrelated and non-educational videos were excluded. Remaining videos were assessed for usefulness, source and characteristics. Usefulness was assessed with using a checklist developed by the authors. RESULTS: One hundred nineteen videos were included in the analysis. Sources of the videos were as follows: individuals n=70, 58.8%, universities/hospitals n=10, 8.4% and medical organizations n=3, 2.5%, health ads n=10 8.4%, health websites n=26, 21.8%. Fifty-six (47.1%) videos were classified as very useful and 16 (13.4%) videos were misleading. 90% of the videos uploaded by universities/hospitals were grouped as very useful videos, the same ratio was 45% for the individual uploads. There were statistically significant differences in ECG diagnosis among the groups (for very useful, useful and misleading, p<0.001, 0.02 and 0.008, respectively). The ratio of the misleading information in ventricular tachycardia videos was found to be 42.9%. CONCLUSIONS: YouTube has a substantial amount of videos on ECG with a wide diversity from useful to misleading content. The lack of quality content relating to ECG on YouTube necessitates that videos should be selected with utmost care.

Drospirenone-containing oral contraceptives and risk of adverse outcomes after myocardial infarction.

BACKGROUND: The association between oral contraceptives (OC) and myocardial infarction remains controversial. The new generation contraceptive Yasmin (30 µg ethinyl estradiol and 3 mg drospirenone) has a lower estrogen and newer progestin component. To date, there are no data available for the myocardial infarction risk and outcome for drospirenone. We aimed to investigate the effect of Yasmin use on cardiovascular outcomes in patients with acute ST segment elevation myocardial infarction (STEMI) undergoing primary angioplasty. METHODS: We retrospectively evaluated 1851 patients who underwent primary angioplasty for acute STEMI. Of them, 440 female patients (23.8%) composed the study population and 12 female (2.7%) were taking the oral contraceptive-Yasmin at the time of infarction. Patients were divided into two groups based on their age (≥50 (n = 339) and <50 years old). Patients under 50 years-old (n = 101) were separated into two groups according to use of OC therapy (OC (+) group n = 12; OC (-) group n = 89). RESULTS: Patients who were older than 50-year-old were more likely to have comorbid conditions like diabetes mellitus and hypertension than other groups. Current smoking status was significantly higher in OC (+) group than OC (-) group (P = 0.007). There was a significant difference in favour of OC (+) group when compared with OC (-) group for the increased angiographic thrombus burden according to both TIMI and Yip classification (P = 0.045 and P = 0.029, respectively). The incidence of final TIMI 3 flow and post-procedural complete ST resolution were significantly lower in OC (+) group (P = 0.019, P = 0.002, respectively). In multivariate logistic regression analysis, use of OC was found to be an independent predictor of high grade thrombus burden (OR 5.13, 95% CI 1.07-24.60, P = 0.04). CONCLUSION: This is the first study to evaluate the myocardial infarction risk and its subsequent clinical sequelae in women having a STEMI while taking the OC-Yasmin. Women on the oral contraception Yasmin, who underwent coronary revascularization had a lower post-procedural complete ST resolution and worse left ventricular function. Furthermore, OC use with Yasmin is an independent predictor of a high-grade thrombus burden.

Varenicline-induced coronary thrombosis.

Varenicline (Champix, Chantix) has been available for use in smoking cessation since 2006. This drug has been associated with adverse cardiovascular events. Potential mechanisms for this association include modulation of parasymphathetic output from the brainstem to the heart, release of catecholamines and prothrombotic effect. We report the case of a 30-year-old man with no known cardiac disease, who developed thrombotic occlusion of left anterior descending artery and presented with acute coronary syndrome secondary to treatment with varenicline. The Naranjo probability scale indicates that varenicline was the probable cause of the myocardial infarction.

Left atrial deformation parameters predict left atrial appendage function and thrombus in patients in sinus rhythm with suspected cardioembolic stroke: a speckle tracking and transesophageal echocardiography study.

The aim of this study was to evaluate left atrial deformations using speckle tracking echocardiography for predicting left atrial appendage (LAA) thrombus in patients with suspected cardioembolic stroke who were in normal sinus rhythm. A total of 153 ischemic stroke patients (89 males, 64 females) in sinus rhythm who were suspected of having cardioembolism were included in the study. The patients underwent conventional two-dimensional (2D) echocardiogram and 2D speckle tracking echocardiogram of the left atrium. Left atrial peak strain (LA-4C-RES) and left atrial precontraction strain (LA-4C-PUMP) were measured. Patients were divided into 2 groups according to the presence of thrombus in the LAA in transesophageal echocardiography. Both LA-4C-RES and LA-4C-PUMP values were found to be significantly lower in patients with LAA thrombus (11.8 ± 1.4% vs. 33 ± 12%, P < 0.001 and 5.8 ± 1.3% vs. 14.2 ± 5.3%, P < 0.001, respectively). A good inverse correlation was present between LA-4C-RES values and LAA morphologic parameters (with LAA area: r = -0.70, P < 0.001, with LAA length: r = -0.60, P < 0.001), and a good positive correlation was present with LAA emptying velocity with pulse Doppler (r = 0.74, P < 0.001). The area under the receiver-operating characteristic curve of the LA-4C-RES was 0.94 (0.90-0.98, P < 0.001), for the LA-4C-PUMP, the area was 0.92 (0.87-0.96, P < 0.001) to predict LAA thrombus. Left atrial deformation parameters measured by 2D speckle tracking method was found to predict impaired LAA functions and the presence of LAA thrombus in ischemic stroke patients with suspected cardioembolism, but who are in sinus rhythm.

Patient Adherence to Secondary Prevention Therapies After an Acute Coronary Syndrome: A Scoping Review.

PURPOSE: Adherence to guideline-recommended, long-term secondary preventative therapies among patients with acute coronary syndrome (ACS) is fundamental to improving long-term outcomes. The purpose of this scoping review was to provide a broad synopsis of pertinent studies in a structured and comprehensive way regarding factors that influence patient adherence to medical therapy after ACS. METHODS: Relevant articles focusing on adherence to medical therapy after ACS were retrieved from the EMBASE and MEDLINE databases (search date, September 7, 2021). Studies were independently screened, and relevant information was extracted. FINDINGS: A total of 58 studies were identified by using the EMBASE and MEDLINE databases. Adherence to secondary prevention was moderate to low and steadily decreased over time. Nearly 30% of patients discontinued one or more medications within 90 days of their primary ACS, and adherence decreased to 50% to 60% at 1 year postdischarge. There were no major differences in adherence between drug classes. Factors influencing patient adherence can be broadly divided into 3 categories: patient related, health care system related, and disease related. Patients managed with percutaneous coronary interventions were more adherent to follow-up treatment than medically managed patients. Depression was reported as a major psychological factor that negatively affected adherence. Improved adherence was observed when higher levels of patient education and provider engagement were delivered during postdischarge follow-up, particularly when scheduled early. Notably, the incidence of major adverse cardiovascular events was lower in hospitals with high 90-day medication adherence than those with moderate or low adherence. IMPLICATIONS: Patient nonadherence to guideline-recommended long-term pharmacologic secondary preventative therapies after ACS is multifactorial. A comprehensive multifaceted approach should be implemented to improve adherence and clinical outcomes. This approach should include key interventions such as early follow-up visits, high medication adherence at 90 days, patient engagement and education, and development of novel interventions that support the 3 broad categories influencing patient adherence as discussed in this review.

Biological basis and proposed mechanism of action of CSL112 (apolipoprotein A-I [human]) for prevention of major adverse cardiovascular events in patients with myocardial infarction.

Despite current standard of care treatment, the period shortly after acute myocardial infarction (AMI) is associated with high residual cardiovascular (CV) risk, with high rates of recurrent AMI and CV death in the first 90 days following the index event. This represents an area of high unmet need that may be potentially addressed by novel therapeutic agents that optimize high-density lipoprotein cholesterol (HDL-C) function rather than increase HDL-C concentrations. Apolipoprotein A-I (apoA-I) is the major constituent of HDL and a key mediator of cholesterol efflux from macrophages within atherosclerotic plaque, a property especially relevant during the high-risk period immediately following an AMI when cholesterol efflux capacity is found to be reduced. CSL112 is a novel formulation of human plasma-derived apolipoprotein A-I (apoA-I), currently being evaluated in a Phase 3 clinical trial (AEGIS-II) for the reduction of major adverse CV events in the 90-day high-risk period post-AMI. In this review, we provide an overview of the biological properties of CSL112 that contribute to its proposed mechanism of action for potential therapeutic benefit. These properties include rapid and robust promotion of cholesterol efflux from cells abundant in atherosclerotic plaque, in addition to anti-inflammatory effects, which together, may have a stabilizing effect on atherosclerotic plaque. We provide a detailed overview of these mechanisms, in addition to information on the composition of CSL112 and how it is manufactured.

Acute inferior myocardial infarction with nephrotic syndrome.

Although thrombotic complications in the venous system are common in patients with nephrotic syndrome, arterial thromboses associated with nephrotic syndrome are much less common. However, coronary thromboses are extremely rarely observed. Whereas venous thromboses predominate in adults, thromboembolic complications of the arterial system are mainly seen in children. We presented a case of acute inferior myocardial infarction secondary to a thrombotic occlusion of the right proximal coronary artery in a 21-year-old man with nephrotic syndrome due to renal amyloidosis. It is interesting that the duration between nephrotic syndrome findings and onset of myocardial infarction was found only 7 days in this case.

An incomplete heart with incomplete lungs.

Congenital hypoplasia or agenesis of mitral valves is a very rare condition. It is sometimes seen together with other congenital anomalies. We present a demonstrative case of posterior mitral leaflet hypoplasia seen together with congenital lungs anomaly.

[Coronary optical coherence tomography in late stent thrombosis: the first application in Turkey]. / Geç stent trombozunda koroner optik koherens tomografi: Ülkemizdeki ilk uygulama.

Stent thrombosis remains an unresolved problem despite advances in coronary revascularization. Incomplete stent apposition (malapposition) and incomplete endothelialization of stent struts, which is more commonly seen with drug-eluting stents, are the primary causes of late or very late stent thrombosis. Optical coherence tomography (OCT) is a novel modality for imaging of these potentially fatal conditions. Coronary angiography performed for non-ST elevation myocardial infarction in a 60-year-old male patient with a three-year history of sirolimus-eluting stent implantation to the left anterior descending coronary artery showed stent thrombosis. In addition to his regular aspirin and clopidogrel therapy, heparin and tirofiban infusions were started. Repeat coronary angiography five days later showed nearly complete disappearance of the thrombus. Further examination with OCT to evaluate stent malapposition and endothelialization revealed separation of stent struts from the vessel wall. Balloon dilatation was performed and complete apposition of the stent struts against the vessel wall was achieved, which was further confirmed by OCT. This represents the first OCT application in our country in a case of very late stent thrombosis.

Early and late recurrent cardiovascular events among high-risk patients with an acute coronary syndrome: Meta-analysis of phase III studies and implications on trial design.

BACKGROUND: Despite low-density lipoprotein cholesterol-lowering therapies and other standard-of-care therapy, there remains a substantial residual atherosclerotic risk among patients with an acute coronary syndrome (ACS). This study aims to estimate the risk of early and late recurrent major adverse cardiovascular events (MACE) and address its implications on trial design. METHODS: A literature search was performed to collect phase III interventional trials on high-risk ACS patients. Pooled event rates at 90 and 360 days were estimated by fitting random-effects models using the DerSimonian-Laird method. Under the assumption of a total sample size of 10,000 and 1:1 allocation at a one-sided alpha of 0.025 using the log-rank test, the relationship between power and relative risk reduction (RRR) or absolute risk reduction (ARR) was explored for early versus late MACE endpoint. RESULTS: Seven trials representing 82,727 recent ACS patients were analyzed. The pooled rates of recurrent MACE were 4.1% and 8.3% at 90 and 360 days. Approximately 49% of events occurred within the first 90 days. Based on the estimated risks at 90 and 360 days, to attain 90% statistical power, a lower magnitude of RRR is required for late MACE than early MACE (22% vs. 30%), whereas a lower magnitude of ARR is required for early MACE than late MACE (1.2% vs. 1.8%). CONCLUSION: The initial 90-day window after ACS represents a vulnerable period for recurrent events. From a trial design perspective, determining a clinically important benefit by RRR versus ARR may influence the decision between early and late MACE as the study endpoint.

Inverse relationship between body mass index and risk of venous thromboembolism among medically ill hospitalized patients: Observations from the APEX trial.

Obesity is associated with cardiovascular complications such as diabetes and hypertension. However, obesity and high body mass index (BMI) can also be linked to improved clinical outcomes in certain patient populations. This counterintuitive observation is called the "obesity paradox." The effect of BMI on the risk of developing venous thromboembolism (VTE) in acutely ill medical patients remains unclear. In the Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial, acutely ill hospitalized medical patients were randomized to receive either extended-duration betrixaban or shorter-duration enoxaparin and followed for 77 days. A total of 7372 patients with evaluable VTE endpoints had BMI measured at baseline. The association between BMI and VTE risk was assessed after adjusting for potential confounders. The multivariable adjusted ORs of VTE risk associated with BMI levels referencing the median BMI value (15, 18.5, 28.3 [reference], 35, 40, 45) were: 2.82 (95% CI, 1.32-6.04, [change from 28.3 to 15]), 1.85 (95% CI, 1.14-2.99, [change from 28.3 to 18.5]), 1.30 (95% CI, 1.04-1.63, [change from 28.3 to 35]), 1.13 (95% CI, 0.84-1.52, [change from 28.3 to 40]), and 0.91 (95% CI, 0.57-1.47, [change from 28.3 to 45]), respectively (p = 0.022). In conclusion, acutely ill hospitalized patients with lower BMI had a higher VTE risk through 77 days, which appears to be a manifestation of the BMI paradox.