Obstructive Atherosclerotic Coronary Artery Disease Research Articles

Prevalence of premature coronary artery disease (CAD) according to genetic familial hypercholesterolaemia (FH) diagnosis in Lithuania

Background and Aims : FH is known to be a predisposing cause of premature CAD. We aimed to determine the distribution of premature CAD according to genetic diagnosis of FH in Lithuania.Methods: Prospective observational cohort study enrolled patients with clinically diagnosed FH according to Dutch Lipid Clinic Network (DLCN) criteria treated in Vilnius University Hospital Santaros Klinikos during the period of 2016-2021. Premature CAD was defined as occuring in men younger than 55 years and women younger than 60 years. Data of 60 study patients were included in the analysis. Obstructive Atherosclerotic CAD was defined as the presence of stenosis ≥50% in at least one coronary vessel in Coronary Computed Tomography Angiography (CCTA) or coronary angiography, as well as performed percutaneous coronary intervention (PCI) or coronary arteries bypass grafting (CABG). Genetic testing was performed using genomic DNA, which was enzymatically fragmented, and regions of interest were enriched using DNA capture probes. The final indexed libraries were sequenced on an Illumina platform. The prevalence of CAD according to genetic diagnosis of FH was analysed. Statistical analysis was performed using R (v. 4.0.4) program package.Results: Of 60 examined patients 28,3% (n=17) had the genetic diagnosis of FH and 71,7% (n=43) had no FH mutation. Premature CAD was found in 47% (n=8) patients with genetic diagnosis of FH and in 19% (n=8) with no mutations determined (p=0,049).Conclusions: Premature CAD was more prevalent among patients with genetically confirmed FH. Background and Aims : FH is known to be a predisposing cause of premature CAD. We aimed to determine the distribution of premature CAD according to genetic diagnosis of FH in Lithuania. Methods: Prospective observational cohort study enrolled patients with clinically diagnosed FH according to Dutch Lipid Clinic Network (DLCN) criteria treated in Vilnius University Hospital Santaros Klinikos during the period of 2016-2021. Premature CAD was defined as occuring in men younger than 55 years and women younger than 60 years. Data of 60 study patients were included in the analysis. Obstructive Atherosclerotic CAD was defined as the presence of stenosis ≥50% in at least one coronary vessel in Coronary Computed Tomography Angiography (CCTA) or coronary angiography, as well as performed percutaneous coronary intervention (PCI) or coronary arteries bypass grafting (CABG). Genetic testing was performed using genomic DNA, which was enzymatically fragmented, and regions of interest were enriched using DNA capture probes. The final indexed libraries were sequenced on an Illumina platform. The prevalence of CAD according to genetic diagnosis of FH was analysed. Statistical analysis was performed using R (v. 4.0.4) program package. Results: Of 60 examined patients 28,3% (n=17) had the genetic diagnosis of FH and 71,7% (n=43) had no FH mutation. Premature CAD was found in 47% (n=8) patients with genetic diagnosis of FH and in 19% (n=8) with no mutations determined (p=0,049). Conclusions: Premature CAD was more prevalent among patients with genetically confirmed FH.

Prevalence of premature coronary artery disease (CAD) according to clinical familial hypercholesterolaemia (FH) diagnosis in Lithuania

Background and Aims : We aimed to determine the prevalence of CAD according to clinical diagnosis of Familial Hypercholesterolemia(FH) in Lithuania.Methods: Prospective observational cohort study enrolled patients with clinically diagnosed FH treated in Vilnius University Hospital Santaros Klinikos during the period of 2016-2021. According to Dutch Lipid Clinic Network (DLCN) diagnostic criteria for FH, definite FH was diagnosed when a total point score was>8, probable–6-8, possible-3-5,unlikely<3 points. Premature CAD was defined as occuring in men <55 years and women <60 years. Obstructive Atherosclerotic CAD was defined as the presence of stenosis ≥50% in at least one coronary vessel in Coronary Computed Tomography Angiography(CCTA) or coronary angiography, as well as performed percutaneous coronary intervention(PCI) or coronary arteries bypass grafting(CABG). Data of 119 study patients were included in the analysis. The prevalence of premature CAD was compared in different groups according to FH diagnosis. Statistical analysis was performed using R(v. 4.0.4) program package.Results: Of 119 examined patients 52,1%(n=62) were women and47,9%(n=57) were men.In the study population, premature CAD was diagnosed for 26%(n=31) patients. 21,8%(n=26) of study patients had definite FH diagnosis, 37,8%(n=45) had probable FH, 28,6%(n=34) - possible FH and11,8% (n=14) had unlikely FH diagnosis. Premature CAD was diagnosed to 38,5%(n=10) patients with definite FH, 33,3%(n=15) with probable FH, 14,7%(n=5) with possible FH and 7,1%(n=1) among people with unlikely FH.Conclusions: Our findings indicate that among individuals with premature CAD there is an opportunity to detect an index case for initiation of cascade FH screening, especially in definite and probable FH cases. Background and Aims : We aimed to determine the prevalence of CAD according to clinical diagnosis of Familial Hypercholesterolemia(FH) in Lithuania. Methods: Prospective observational cohort study enrolled patients with clinically diagnosed FH treated in Vilnius University Hospital Santaros Klinikos during the period of 2016-2021. According to Dutch Lipid Clinic Network (DLCN) diagnostic criteria for FH, definite FH was diagnosed when a total point score was>8, probable–6-8, possible-3-5,unlikely<3 points. Premature CAD was defined as occuring in men <55 years and women <60 years. Obstructive Atherosclerotic CAD was defined as the presence of stenosis ≥50% in at least one coronary vessel in Coronary Computed Tomography Angiography(CCTA) or coronary angiography, as well as performed percutaneous coronary intervention(PCI) or coronary arteries bypass grafting(CABG). Data of 119 study patients were included in the analysis. The prevalence of premature CAD was compared in different groups according to FH diagnosis. Statistical analysis was performed using R(v. 4.0.4) program package. Results: Of 119 examined patients 52,1%(n=62) were women and47,9%(n=57) were men.In the study population, premature CAD was diagnosed for 26%(n=31) patients. 21,8%(n=26) of study patients had definite FH diagnosis, 37,8%(n=45) had probable FH, 28,6%(n=34) - possible FH and11,8% (n=14) had unlikely FH diagnosis. Premature CAD was diagnosed to 38,5%(n=10) patients with definite FH, 33,3%(n=15) with probable FH, 14,7%(n=5) with possible FH and 7,1%(n=1) among people with unlikely FH. Conclusions: Our findings indicate that among individuals with premature CAD there is an opportunity to detect an index case for initiation of cascade FH screening, especially in definite and probable FH cases.

Clinical features, sex differences and outcomes of myocardial infarction with nonobstructive coronary arteries: a registry analysis.

Clinical characteristics and outcomes of patients diagnosed with myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) remain largely unknown. Furthermore, we do not yet understand if women with MINOCA have worse outcomes similar to what has historically been observed with MI. The aims of the current study were to evaluate the (1) incidence of MINOCA in patients presenting with MI, (2) compare in-hospital outcomes of MINOCA and obstructive atherosclerotic coronary artery disease MI (OACD-MI), and (3) comparison of in-hospital clinical outcomes of patients with MINOCA stratified by sex. In this observational study, we combined data from two large university hospitals from Canada and Australia. Clinical characteristics and in-hospital outcomes of MINOCA and OACD-MI were analyzed by matching these patients in a 1:1 ratio after selecting patients with OACD-MI by systematic random sampling. Clinical characteristics associated with MINOCA were identified through multivariate logistic regression. Primary outcome of interest was net adverse cardiovascular events (NACE) defined as death, heart failure, stroke, and major bleeding. The incidence rate of MINOCA was 9.5%. Women, absence of traditional cardiac risk factors, and absence of ST-deviations on ECG were associated with diagnosis of MINOCA on angiography. NACE (P = 0.0001), death (P = 0.019), stroke (P = 0.002), and heart failure (P = 0.001) were significantly lower in patients with MINOCA. Subgroup analysis of women and men diagnosed with MINOCA revealed similar in-hospital outcomes. The incidence of MINOCA was 9.5%. Compared to OACD-MI, patients with MINOCA have less cardiac risk factors. In-hospital outcomes of patients diagnosed with MINOCA were better than OACD-MI.

Coronary artery disease among young drivers (&lt;40 years): Occupational hazard or air pollution driving it?

Aims: To study clinico-social, biochemical and angiographic profile of patients presenting with premature coronary artery disease (PCAD) who are drivers by profession. To highlight the impact of occupational hazard and air pollution in them. Subjects and Methods: Of 3450 patients registered in the PCAD registry till date, 755 (21.88%) were found to satisfy the inclusion criteria. The data was analyzed by statistical software R version 3.5.0. Further analysis of smokers versus nonsmokers was done. Results: The average age of the group was 33.10 years. Almost all 754 (99.8%) were males, of which 323 (42.78%) smoked. The group had 83 (10.95%) diabetics and 71 (9.4%) hypertensives. Around 99 (13.11%) had a family history of coronary artery disease (CAD). Majority of them, 440 (58.27%), were urban drivers with average driving of 10 h/day. In the group, 482 (63.8%) had abnormal body mass index (BMI) and 539 (71.41%) had abdominal obesity. Low HDL was seen in 508 (67%) patients. ST-elevation myocardial infarction was the most common presentation in 415 (54.96%). Obstructive atherosclerotic CAD was seen in 217 (34.22%). Further analysis of smokers versus nonsmokers showed that hypertension, diabetes, and abnormal BMI were less common among nonsmokers, indicating the probable role of air pollution in them. Conclusions: Occupational hazard due to the stress related to prolonged driving hours, obesity, smoking and the possible role of air pollution are the important cardiovascular (CV) risks which come to light in this group of patients. Furthermore, the majority of them presented with predominant thrombotic lesions, however, smokers, who also had other CV risk factors, presented more often with obstructive atherosclerotic CAD.

TRENDS IN MYOCARDIAL INFARCTION WITHOUT OBSTRUCTIVE ATHEROSCLEROTIC CORONARY ARTERY DISEASE: SINGLE CENTER ANALYSIS FROM NORTHERN NEW ENGLAND

Registry data suggests that up to 20% of patient presenting with myocardial infarction (MI) have no evidence of obstructive atherosclerotic coronary artery disease (aCAD). Whether this diagnosis is increasing in prevalence in contemporary practice remains unknown. We evaluated 16960 patients

Postoperative left ventricular apical ballooning: Transient Takotsubo cardiomyopathy following orthotopic liver transplantation

Patient: Female, 51Final Diagnosis: Takotsubo cardiomyopathySymptoms: —Medication: —Clinical Procedure: —Specialty: Cardiology • TransplantologyObjective:Rare diseaseBackground:Left ventricular apical ballooning syndrome (LVAB), also known as Takotsubo cardiomyopathy, is a cardiac syndrome characterized by transient left ventricular dysfunction in the absence of obstructive atherosclerotic coronary artery disease. An episode of emotional stress, typically in female patients, is believed to precede and trigger the development of this syndrome.Case Report:We report a case of Takotsubo cardiomyopathy that developed after orthotopic liver transplantation in a 51-year-old woman. On D2 (day 2) the patient had severe hemodynamic compromise. Echocardiography showed systolic dysfunction of the left ventricle (LV), with ejection fraction (EF) of 20% and anteroapical akinesis and ballooning of the apical 2/3 of the LV. Troponin T was elevated but other markers of myocardial necrosis were negative, as was coronary angiography. From D7 onward, there was an improvement in the hemodynamics in conjunction with a gradual increase of LV EF. The patient was dismissed from the hospital on D30 with signs of normal cardiac function and LV motion and EF of 50%. Liver function was also excellent.Conclusions:Every major operation, including liver transplantation, is associated with emotional stress for the patient. Therefore, it is necessary to consider Takotsubo cardiomyopathy in the differential diagnosis of heart failure developing early after LT, and clinicians should subsequently use adequate diagnostic and therapeutic measures.

Understanding the Utility of Zero Coronary Calcium as a Prognostic Test

Coronary artery calcium (CAC) is nearly pathognomonic for the presence of coronary atherosclerosis, although not all coronary plaque is calcified.1,2 As such, cardiac CT scans for CAC are highly specific but less sensitive for the presence of some coronary atherosclerosis. In contrast, these tests are highly sensitive but less specific for detecting obstructive atherosclerotic coronary artery disease (CAD). A Bayesian approach is critical for discerning the value of new tests. When used in the intended population, a test with high sensitivity is excellent for ruling out disease (ie, highly sensitive tests produce a high negative predictive value [NPV] when negative). For this reason, there is interest in using “zero” CAC scores to predict excellent prognosis—and potentially conserve medical resources—in the large population of patients at intermediate midterm risk of developing clinical cardiovascular disease. The efficiency of any test relies on the frequency of disease in the population tested (the prior probability distribution). For example, take the d-dimer test for deep venous thrombosis and pulmonary embolism. If a d-dimer is checked in all outpatients, a low positive predictive value (PPV) will result given the low frequency of thrombosis in this scenario. If a d-dimer is tested exclusively in patients with acute dyspnea and a swollen lower extremity, there will be a low NPV given the high incidence of pulmonary embolism in such patients. Stated in mathematical terms, the likelihood of thrombosis (A) given a positive d-dimer (B) depends not only on the conditional probability of B given the presence or absence of A (the test characteristics), but also on the marginal probability of A independent of B (the prior probability distribution). This principle is summarized in probability theory by Bayes theorem (Figure 1). Knowingly or unknowingly, Bayes theorem underlies essentially all clinical decision making. …

From Systemic Shotgun to Site-Specific Nanoparticle-Targeted Delivery

HomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 28, No. 11From Systemic Shotgun to Site-Specific Nanoparticle-Targeted Delivery Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBFrom Systemic Shotgun to Site-Specific Nanoparticle-Targeted DeliveryA New Paradigm for Drug Delivery Ian J. Sarembock Ian J. SarembockIan J. Sarembock From the Ohio Heart & Vascular Center, The Lindner Clinical Research Center and The Heart & Vascular Center, The Christ Hospital, Cincinnati. Search for more papers by this author Originally published1 Nov 2008https://doi.org/10.1161/ATVBAHA.108.175190Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1879–1881Since the introduction of percutaneous techniques for the relief of symptomatic obstructive atherosclerotic coronary artery disease in the late 1970s, the major Achilles heel was restenosis. After nearly 3 decades of study, the cellular and molecular biology of this complex response to injury is now far better understood and includes the role of thrombosis, cellular proliferation, inflammation, matrix production, and elastic recoil.1,2 Some 15 years ago there was enthusiastic interest in the concept of “site specific” or “direct delivery” of antiproliferative or anticoagulant therapies.3–6 Edelman et al reported on the inhibition of SMC proliferation after vascular injury by surgical placement of heparin-impregnated polymer matrix in the periadventitial tissue of rat carotid arteries.3 At that time a catheter-based porous balloon catheter became available for “site specific” delivery7 but failed to be effective in limiting restenosis in an atherosclerotic rabbit femoral artery injury model.4 Although labeled heparin could be demonstrated to be present in the injured vessel wall, retention time of the drug and potential additional injury created by a jet effect of the porous balloon catheter were cited as potential explanations for the lack of efficacy. Subsequently, the concept of local delivery remained dormant and a multitude of clinical trials using systemically administered pharmacological agents to reduce or prevent restenosis demonstrated no benefit.8See accompanying article on page 1960In the late 1980s and early 1990s, coronary stents, providing the necessary scaffolding to prevent elastic recoil become the new standard for the percutaneous treatment of obstructive coronary disease.9 Nevertheless, in-stent restenosis remained the major limitation of coronary stenting, with the predominant mechanism being intimal hyperplasia.10 Despite an improved understanding and identification of patient-specific, lesion-specific, and procedure-specific factors, in-stent restenosis remained a challenge despite newer therapies including intravascular brachytherapy.11 Subsequently the concept of local drug delivery using the surface area of the stent was proposed and investigated, allowing for drug application at the specific injury site with minimal systemic release or toxicity of drug.12 Since the introduction of drug-eluting stents (DES) into clinical practice in 2002, this approach has transformed the practice of interventional cardiology by dramatically reducing in-stent restenosis and the need for repeat revascularization.13,14 Although animal models have in general predicted the response to DES in humans with a near absence or minimal intimal hyperplasia, what is characteristically different is the temporal response to healing which is substantially delayed in humans.15 This has been painfully borne out by reports of late stent thrombosis, again highlighting the need for verification of proof of efficacy (“to help”) with the risk-benefit relationship (“do no harm”) for specific new technologies and therapies.16 Although there remains an incomplete understanding of the etiology of late stent thrombosis, discontinuation of dual antiplatelet therapy, in particular clopidogrel use, appears to be the most important risk factor.17 These unanticipated and potentially catastrophic adverse outcomes continue to remind us of the need to pursue improved and safer alternatives to the presently available therapies. Newer stent platforms, biocompatible and bioabsorbable polymer alternatives, and new drugs and drug combinations are being developed as we strive toward safer DES.18In this issue of Arteriosclerosis, Thrombosis and Vascular Biology, Joner et al report that site specific targeting of nanoparticle prednisolone reduced in-stent restensosis in a rabbit model of established atheroma. Using the rationale that the present generation of DES are hampered by local drug toxicity and polymer-induced inflammation with resultant delayed healing, the investigators use a novel strategy of prednisolone phosphate encapsulated in pegylated 3,5-dipentadecyclobenzamidine hydrochloride (TRX-20) liposomes which specifically bind to chondroitin sulfate proteoglycans (CPSGs) which are differentially expressed in the subendothelial matrix and exposed after vascular injury. CPSGs are not expressed in vascular endothelial cells.19 This strategy has previously been shown to have high affinity for injury sites and can be delivered at doses far lower than systemic delivery of free prednisolone phosphate, thereby minimizing the risk of systemic side effects.20 Once localized to sites of vascular injury, the cationic lipid component of TRX-20 is endocytosed by cellular mechanisms resulting in direct intracellular drug release. Using a well accepted rabbit model of experimental atherosclerosis and exemplary experimental design and techniques, the authors performed a proof of concept study to demonstrate that nanoparticle-laiden drug can be site-directed to areas of vascular injury and showed that therapeutic concentrations of prednisolone phosphate were achieved at approximately 100-fold higher concentration in stented compared to nonstented arteries after a single injection at 1 mg/kg. This resulted in a significant 24% to 27% reduction in intimal area within the stent with a 40% reduction in neointimal macrophages and an approximately 60% reduction in inflammatory score. Importantly, reendothelialization was not retarded and was not different between the experimental groups, with no signs of systemic toxicity. Of note, empty liposomes did induce an inflammatory response despite attempts to minimize opsonization by modification of the nanoparticles with polyethylene glycol (PEG). The ability to minimize this phenomenon will need further refinement.21 Macrophages were localized to the adventitia, suggesting that opsonin-tagged empty liposomes accumulated via transport through the vasa vasorum rather than transmural trafficking from the luminal surface. In contrast, steroid-loaded liposomes were deposited in the neointima. The explanation for this observation and its potential implications require further investigation.Although this study used glucocorticoids as a primary antiinflammatory strategy with a secondary suppression of neointimal growth, advances in the cellular and molecular biology of atherosclerosis and vascular injury responses, provide promising new therapeutic opportunity for more specific, potent, and efficacious molecular targeting. The rapid growth of nanotechnology and the potential dual use of nanoparticles for both molecular imaging and site-directed delivery of therapeutic agents offers great promise for individualizing therapeutics for vascular disease.22 Previous reports in a rabbit model of atherosclerosis and vascular injury demonstrate that intravenous fumagillin-loaded nanoparticles targeted to αvβ3-integrin epitopes on the vasa-vasorum of arteries resulted in marked inhibition of plaque angiogenesis in cholesterol-fed atherosclerotic rabbits.23 Using a novel cremophor-free albumin-stabilized nanoparticle formulation of paclitaxel, Kolodgie et al reported sustained suppression of neointimal thickening with nearly complete reendothelialization after only 2 doses of systemically administered drug in a rabbit iliac stent model.24 With this relatively wide therapeutic index, and repeat dosing as necessary, optomization of neointimal suppression with a normal healing response appears attainable. This new paradigm for drug delivery thus represents a unique opportunity to improve efficacy and minimize adverse effects as first described by the father of medicine, Hippocrates, “As to diseases, make a habit of two things—to help, or at least do no harm.”Taken together, it is fair to conclude that the future is bright and the journey has begun, so let us continue to strive for safer and more effective therapies for the control of vascular disease in our patients. Download figureDownload PowerPointFigure. Cartoon illustrating “striped” nanoparticles capable of entering a cell without rupturing it. In the background are cells that have taken up nanoparticles carrying fluorescent imaging agents. Nanoscale objects are typically internalized by cells into membrane-bound endosomes and fail to access the cytosolic cell machinery. Studies aimed at generating cell-penetrating nanomaterials have focused on the effect of size, shape, and composition. Here, two nanoparticle “isomers” with similar composition (same hydrophobic content), one coated with sub-nanometer striations of alternating anionic and hydrophobic groups, and the other coated with the same moieties but in a random distribution, demonstrate that the former particles penetrate the plasma membrane without bilayer disruption, whereas the latter are mostly trapped in endosomes.25 (Image courtesy: Francesco Stellacci, Darrell Irvine and colleagues, MIT).DisclosuresNone.FootnotesCorrespondence to Ian J. Sarembock, MB, ChB, MD, Ohio Heart & Vascular Center & The Lindner Clinical Research Center, 2123 Auburn Avenue, Suite 136, Cincinnati, Ohio 45219. E-mail [email protected] References 1 Liu MW, Roubin GS, King SB III. Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia. Circulation. 1989; 79: 1374–1387.CrossrefMedlineGoogle Scholar2 Harker LA. Role of platelets and thrombosis in mechanisms of acute occlusion and restenosis after angioplasty. Am J Cardiol. 1987; 60: 20B–28B.CrossrefMedlineGoogle Scholar3 Edelman ER, Adams DH, Karnovsky MJ. Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury. Proc Natl Acad Sci U S A. 1990; 87: 3773–3777.CrossrefMedlineGoogle Scholar4 Gimple LW, Gertz SD, Haber HL, Ragosta M, Powers ER, Roberts WC, Sarembock IJ. Effect of chronic subcutaneous or intramural administration of heparin on femoral artery restenosis after balloon angioplasty in hypercholesterolemic rabbits. A quantitative angiographic and histopathological study. Circulation. 1992; 86: 1536–1546.CrossrefMedlineGoogle Scholar5 Riessen R, Isner JM. Prospects for site-specific delivery of pharmacologic and molecular therapies. J Am Coll Cardiol. 1994; 23: 1234–1244.CrossrefMedlineGoogle Scholar6 Ettenson DS, Edelman ER. Local drug delivery: an emerging approach in the treatment of restenosis. Vasc Med. 2000; 5: 97–102.CrossrefMedlineGoogle Scholar7 Wolinsky H, Thung SN. Use of a perforated balloon catheter to deliver concentrated heparin into the wall of the normal canine artery. J Am Coll Cardiol. 1990; 15: 475–481.CrossrefMedlineGoogle Scholar8 Rosanio S, Tocchi M, Patterson C, Runge MS. Prevention of restenosis after percutaneous coronary interventions: the medical approach. Thromb Haemost. 1999; 82 Suppl 1: 164–170.CrossrefMedlineGoogle Scholar9 Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med. 1987; 316: 701–706.CrossrefMedlineGoogle Scholar10 Schiele TM. Current understanding of coronary in-stent restenosis. Pathophysiology, clinical presentation, diagnostic work-up, and management. Z Kardiol. 2005; 94: 772–790.CrossrefMedlineGoogle Scholar11 Gruberg L, Waksman R. Intravascular radiation for the prevention of recurrence of restenosis in coronary arteries. Expert Opin Investig Drugs. 2001; 10: 891–907.CrossrefMedlineGoogle Scholar12 Regar E, Sianos G, Serruys PW. Stent development and local drug delivery. Br Med Bull. 2001; 59: 227–248.CrossrefMedlineGoogle Scholar13 Daemen J, Serruys PW. Drug-eluting stent update 2007: part I. A survey of current and future generation drug-eluting stents: meaningful advances or more of the same? Circulation. 2007; 116: 316–328.LinkGoogle Scholar14 Daemen J, Serruys PW. Drug-eluting stent update 2007: part II: Unsettled issues. Circulation. 2007; 116: 961–968.LinkGoogle Scholar15 Virmani R, Kolodgie FD, Farb A, Lafont A. Drug eluting stents: are human and animal studies comparable? Heart. 2003; 89: 133–138.CrossrefMedlineGoogle Scholar16 Kereiakes DJ. Hippocrates revisited: the evidence for drug-eluting stents. Circulation. 2003; 107: 3012–3014.LinkGoogle Scholar17 Garg P, Mauri L. The conundrum of late and very late stent thrombosis following drug-eluting stent implantation. Curr Opin Cardiol. 2007; 22: 565–571.CrossrefMedlineGoogle Scholar18 Kukreja N, Onuma Y, Daemen J, Serruys PW. The future of drug-eluting stents. Pharmacol Res. 2008; 57: 171–180.CrossrefMedlineGoogle Scholar19 Harigai T, Kondo M, Isozaki M, Kasukawa H, Hagiwara H, Uchiyama H, Kimura J. Preferential binding of polyethylene glycol-coated liposomes containing a novel cationic lipid, TRX-20, to human subendthelial cells via chondroitin sulfate. Pharm Res. 2001; 18: 1284–1290.CrossrefMedlineGoogle Scholar20 Morimoto K, Kondo M, Kawahara K, Ushijima H, Tomino Y, Miyajima M, Kimura J. Advances in targeting drug delivery to glomerular mesangial cells by long circulating cationic liposomes for the treatment of glomerulonephritis. Pharm Res. 2007; 24: 946–954.CrossrefMedlineGoogle Scholar21 Owens DE III, Peppas NA. Opsonization, biodistribution, and pharmaco-kinetics of polymeric nanoparticles. Int J Pharm. 2006; 307: 93–102.CrossrefMedlineGoogle Scholar22 Wickline SA, Neubauer AM, Winter P, Caruthers S, Lanza G. Applications of nanotechnology to atherosclerosis, thrombosis, and vascular biology. Arterioscler Thromb Vasc Biol. 2006; 26: 435–441.LinkGoogle Scholar23 Winter PM, Neubauer AM, Caruthers SD, Harris TD, Robertson JD, Williams TA, Schmieder AH, Hu G, Allen JS, Lacy EK, Zhang H, Wickline SA, Lanza GM. Endothelial alpha(v)beta3 integrin-targeted fumagillin nanoparticles inhibit angio-genesis in atherosclerosis. Arterioscler Thromb Vasc Biol. 2006; 26: 2103–2109.LinkGoogle Scholar24 Kolodgie FD, John M, Khurana C, Farb A, Wilson PS, Acampado E, Desai N, Soon-Shiong P, Virmani R. Sustained reduction of in-stent neointimal growth with the use of a novel systemic nanoparticle paclitaxel. Circulation. 2002; 106: 1195–1198.LinkGoogle Scholar25 Verma A, Uzun O, Hu Y, Hu Y, Han HS, Watson N, Chen S, Irvine DJ, Stellacci F. Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. Nat Mater. 2008; 7: 588–595.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Maksimenko A and Turashev A (2014) Endothelial glycocalyx of blood circulation system. II. Biological functions, state under normal and pathological conditions, and bioengineering applications, Russian Journal of Bioorganic Chemistry, 10.1134/S106816201403008X, 40:3, (237-251), Online publication date: 1-May-2014. Maksimenko A and Turashev A (2012) No-Reflow Phenomenon and Endothelial Glycocalyx of Microcirculation, Biochemistry Research International, 10.1155/2012/859231, 2012, (1-10), . Yallapu M, Jaggi M and Chauhan S (2011) Design and engineering of nanogels for cancer treatment, Drug Discovery Today, 10.1016/j.drudis.2011.03.004, 16:9-10, (457-463), Online publication date: 1-May-2011. November 2008Vol 28, Issue 11 Advertisement Article InformationMetrics https://doi.org/10.1161/ATVBAHA.108.175190PMID: 18946050 Originally publishedNovember 1, 2008 PDF download Advertisement

Transient Apical Ballooning

Takotsubo cardiomyopathy is a unique acute cardiac syndrome characterized by typical ischemic chest symptoms, an elevated ST segment on the electrocardiogram, and elevated cardiac disease markers. It is often misdiagnosed as acute myocardial infarction. Coronary angiography usually shows no evidence of obstructive atherosclerotic coronary artery disease. Left ventriculography and echocardiography reveal a peculiar regional systolic dysfunction with akinesis of the midventricle and apex and compensatory hyperkinesis of the basal ventricular segments. This syndrome has been shown to have a distinct temporal relationship with intense emotional stressors, and is characterized by an excellent clinical recovery when appropriate conservative measures are taken during the acute phase of the illness. In this review, we highlight the proposed pathophysiology and clinical manifestations of this recognized reversible form of myocardial failure.

Sudden Death Associated With Anomalous Coronary Origin and Obstructive Coronary Disease in the Young

Sudden cardiac death in a young patient is a catastrophic occurrence. Anomalous coronary origin (ACO) is a significant cause of sudden cardiac death among individuals under the age of 35 years. We sought to define the premortem clinical and postmortem histopathologic findings in victims of sudden cardiac death resulting from either ACO or obstructive atherosclerotic coronary artery disease (CAD) among U.S. military recruits (ages 17-35 years). The autopsy records of all sudden cardiac deaths occurring among recruits during their basic military training period from 1977 through 2001 were reviewed. Twenty-one deaths were associated with ACO and 10 with CAD. Recruits with ACO were more likely to have prodromal symptoms of exertional syncope and/or chest pain (48% vs. 0%, P = 0.011). All sudden cardiac deaths resulting from ACO involved a left main coronary artery takeoff from the right coronary sinus with a course between the aorta and the right ventricular outflow tract and an otherwise normal distribution of the major epicardial coronary arteries. Myocardial fibrosis was seen equally in those with both CAD and ACO (30% vs. 20%, P = 0.66), but the finding of necrosis tended to be more common among recruits with CAD (50% vs. 15%, P = 0.08). In conclusion, review of autopsy data of sudden cardiac deaths among U.S. military recruits reveals myocardial fibrosis or necrosis occurred in 70% of cases with CAD and 35% of cases with ACO. Sudden cardiac deaths resulting from ACO were more likely to be associated with premortem exertional chest discomfort and/or syncope compared with deaths resulting from CAD.

Unstable angina during pregnancy in two patients with premature coronary atherosclerosis and aortic stenosis in association with familial hypercholesterolemia

Obstructive atherosclerotic coronary artery disease is uncommon in women during childbearing age, and the occurrence of myocardial ischemia during pregnancy has therefore been anecdotal. Two young patients with premature coronary arterary disease in association with familial hypercholestrolemia had unstable angina in the second trimester of pregnancy. Workup revealed coronary artery disease and aortic stenosis. One patient opted for abortion at the twentieth week of gestation, and the other decided to continue pregnancy and was delivered by cesarean at 28 weeks’ gestation. Coronary artery bypass grafting was performed after pregnancy in both patients. In addition, one of the patients underwent aortic valve replacement, and other had replacement of the narrowed ascending aorta with uneventful recovery. Our report describes an uncommon presentation of unstable angina during pregnancy in 2 young women with premature coronary artery disease and aortic valvular and supravalvular stenosis as a result of familial hypercholesterolemia. The management of these conditions during pregnancy is influenced by the effects of available therapeutic modalities on both maternal and fetal outcome. (Am J Obstet Gynecol 2000;182:1152-5.)

Sudden death in the young. Is acute coronary thrombosis the major precipitating factor?

Atherosclerotic coronary artery disease, complicated by acute thrombosis, is the usual cause of sudden death in adults. This study addresses the pathology of coronary arteries in sudden death in the young (< or = 35 years old). Among 200 consecutive cases of sudden death in youth in the Veneto region of Italy, 37 (33 men and 4 women, age 18 to 35 years; mean, 29.4 years) showed obstructive atherosclerotic coronary artery disease in the absence of other cardiac pathological conditions and causes of death. No patient had previous angina pectoris or myocardial infarction. Cardiac arrest occurred at rest in 30 subjects and was related to effort in 7. A histological study was carried out on the obstructive coronary plaques. Degree of lumen stenosis and extension of lipid core and intimal fibrocellular hyperplasia facing the lumen were calculated morphometrically. Immunohistochemistry and electron microscopy were used to further characterize the plaque cell population. Single-vessel disease was found in 33 patients and triple-vessel disease in 4, with an overall total of 45 obstructive plaques, 34 of which were located in the proximal left anterior descending coronary artery. At histological study, only 10 plaques from 10 patients showed acute thrombosis (occlusive in 5 and subocclusive in 5); the remaining 35 were uncomplicated. Thirty-one plaques were fibrous in nature, while the other 14 were atheromatous. Compared with the atheromatous lesions, the fibrous plaques were rarely complicated by thrombosis (3% versus 64%; P < .001) and distinctly exhibited a fairly well-preserved tunica media (81% versus 21%; P < .001) as well as a stratum of neointimal fibrocellular hyperplasia (68% versus 7%; P < .001), which on immunohistochemistry and electron microscopy appeared to be proliferating smooth muscle cells. In our study population, sudden death was precipitated by acute coronary thrombosis in only 27% of patients with obstructive coronary atherosclerotic plaque. Most of the young victims of sudden death with obstructive coronary atherosclerosis showed single-vessel disease that affected the left anterior descending coronary artery and was due to fibrous plaques with neointimal smooth muscle cell hyperplasia and a preserved tunica media in the absence of acute thrombosis.

Intravascular ultrasound evaluation of the effect of rotational atherectomy in obstructive atherosclerotic coronary artery disease.

High-speed rotational atherectomy uses a diamond-coated, elliptical burr to abrade occlusive atherosclerosis, especially noncompliant calcified plaque. Intravascular ultrasound (IVUS) was used to analyze 28 patients after atherectomy. Arteries treated and imaged were left main (three), left anterior descending (12), left circumflex (five), right coronary (seven), and saphenous vein graft (one). Twenty patients had adjunct balloon angioplasty. Twenty-two (79%) target lesions were calcified; the intimal arc of calcium was 160 +/- 126 degrees (range, 0-360 degrees). After atherectomy, the intima-lumen interface was unusually distinct and circular. The lumen was larger than the largest burr used for both stand-alone (1.19 +/- 0.19-fold the largest burr size) and adjunct balloon procedures (1.30 +/- 0.15-fold the largest burr). Three-dimensional reconstruction of the ultrasound images showed a smooth lumen, especially in calcified plaque. Deviations from cylindrical geometry occurred only in areas of soft plaque or superficial tissue disruption of calcified plaque. Five patients were studied before and after rotational atherectomy. IVUS showed an increase in lumen size, a decrease in plaque-plus-media area and in arc of target lesion calcification, and no change in target lesion external elastic membrane cross-sectional area. Rotational atherectomy causes atheroablation with only moderate evidence of barotrauma in heavily calcified arteries, even after adjunct balloon angioplasty. The lumen is cylindrical, especially in areas of calcified plaque, and somewhat larger than the largest burr tip used.