This third edition of what has now become a well-established textbook in cardiovascular medicine is again edited by Dr Eugene Braunwald with the assistance of 65 other authors who read like a Who's Who of American Cardiology. Since the second edition, 12 new chapters have been added or substituted and others have been significantly revised. The first volume includes Part I on "Examination of the Patient" and Part II on "Normal and Abnormal Circulatory Function." The second volume deals with specific diseases. Part III, "Diseases of the Heart, Pericardium and Vascular System," includes new sections on "Risk Factors for Coronary Artery Disease," "The Pathogenesis of Atherosclerosis," and "Interventional Catheterization Techniques." Part IV, "Broader Perspectives on Heart Disease and Cardiologic Practice," includes new chapters on "Genetics and Cardiovascular Disease," "Aging in Cardiac Disease," and "Cost Effective Strategies in Cardiology." The last 200 pages of the book (Part V) are devoted to

Heart Disease: A Textbook of Cardiovascular Medicine

The authors undertook a meta-analysis of 37 randomized trials (3369 patients) of off-pump coronary artery bypass surgery versus conventional coronary artery bypass surgery. No significant differences were found for 30-day mortality (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.58-1.80), myocardial infarction (OR, 0.77; 95%CI, 0.48-1.26), stroke (OR, 0.68; 95%CI, 0.33-1.40), renal dysfunction, intraaortic balloon pump, wound infection, rethoracotomy, or reintervention. However, off-pump coronary artery bypass surgery significantly decreased atrial fibrillation (OR, 0.58; 95%CI, 0.44-0.77), transfusion (OR, 0.43; 95%CI, 0.29-0.65), inotrope requirements (OR, 0.48; 95%CI, 0.32-0.73), respiratory infections (OR, 0.41; 95%CI, 0.23-0.74), ventilation time (weighted mean difference, -3.4 h; 95%CI, -5.1 to -1.7 h), intensive care unit stay (weighted mean difference, -0.3 days; 95%CI -0.6 to -0.1 days), and hospital stay (weighted mean difference, -1.0 days; 95%CI -1.5 to -0.5 days). Patency and neurocognitive function results were inconclusive. In-hospital and 1-yr direct costs were generally higher for conventional coronary artery bypass surgery versus off-pump coronary artery bypass surgery. Therefore, this meta-analysis demonstrates that mortality, stroke, myocardial infarction, and renal failure were not reduced in off-pump coronary artery bypass surgery surgery; however, selected short-term and mid-term clinical and resource outcomes were improved compared with conventional coronary artery bypass surgery.

Does off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized trials.

The concept of modulating blood vessel growth—stimulation or inhibition—to serve a desired clinical goal has an enormous intellectual appeal. It can be used to relieve ischemia in tissues with compromised arterial blood supply, improve edema in areas of impaired lymphatic drainage, and inhibit the growth of tumors. Other applications involve facilitating reendothelialization and inhibiting neointima formation after vascular injury, preventing the progression of atherosclerotic plaque, and promoting “vascular health” in general. The least-explored application of this concept involves modulating body and organ size by regulating the endothelial cell mass. All of these areas received a significant, albeit varied, amount of attention in past decades but only recently have we begun approaching clinical applications. Indeed, the first antiangiogenic agent has been approved by the US Food and Drug Administration for the treatment of certain types of cancer, and it is hoped that the emergence of therapeutically useful angiogenesis-promoting agents is not far behind. This article examines some of our current understanding of the regulation of blood vessel growth in mature adult tissues and the various therapeutic applications of this knowledge. Obviously, a review of this size cannot cover such a vast field in any amount of detail, and the author regrets not citing primary references for many of the facts and concepts that are mentioned.

Angiogenesis Where Do We Stand Now

Following an arterial occlusion outward remodeling of pre-existent inter-connecting arterioles occurs by proliferation of vascular smooth muscle and endothelial cells. This is initiated by deformation of the endothelial cells through increased pulsatile fluid shear stress (FSS) caused by the steep pressure gradient between the high pre-occlusive and the very low post-occlusive pressure regions that are interconnected by collateral vessels. Shear stress leads to the activation and expression of all NOS isoforms and NO production, followed by endothelial VEGF secretion, which induces MCP-1 synthesis in endothelium and in the smooth muscle of the media. This leads to attraction and activation of monocytes and T-cells into the adventitial space (peripheral collateral vessels) or attachment of these cells to the endothelium (coronary collaterals). Mononuclear cells produce proteases and growth factors to digest the extra-cellular scaffold and allow motility and provide space for the new cells. They also produce NO from iNOS, which is essential for arteriogenesis. The bulk of new tissue production is carried by the smooth muscles of the media, which transform their phenotype from a contractile into a synthetic and proliferative one. Important roles are played by actin binding proteins like ABRA, cofilin, and thymosin beta 4 which determine actin polymerization and maturation. Integrins and connexins are markedly up-regulated. A key role in this concerted action which leads to a 2-to-20 fold increase in vascular diameter, depending on species size (mouse versus human) are the transcription factors AP-1, egr-1, carp, ets, by the Rho pathway and by the Mitogen Activated Kinases ERK-1 and -2. In spite of the enormous increase in tissue mass (up to 50-fold) the degree of functional restoration of blood flow capacity is incomplete and ends at 30% of maximal conductance (coronary) and 40% in the vascular periphery. The process of arteriogenesis can be drastically stimulated by increases in FSS (arterio-venous fistulas) and can be completely blocked by inhibition of NO production, by pharmacological blockade of VEGF-A and by the inhibition of the Rho-pathway. Pharmacological stimulation of arteriogenesis, important for the treatment of arterial occlusive diseases, seems feasible with NO donors.

/pdf/collateral-circulation-past-and-present-2d7zhx3w67.pdf

Collateral circulation: past and present.

Background— The prognostic relevance of the collateral circulation is still controversial. The goal of this study was to assess the impact on survival of quantitatively obtained, recruitable coronary collateral flow in patients with stable coronary artery disease during 10 years of follow-up. Methods and Results— Eight-hundred forty-five individuals (age, 62±11 years), 106 patients without coronary artery disease and 739 patients with chronic stable coronary artery disease, underwent a total of 1053 quantitative, coronary pressure–derived collateral measurements between March 1996 and April 2006. All patients were prospectively included in a collateral flow index (CFI) database containing information on recruitable collateral flow parameters obtained during a 1-minute coronary balloon occlusion. CFI was calculated as follows: equation where Poccl is mean coronary occlusive pressure, Pao is mean aortic pressure, and CVP is central venous pressure. Patients were divided into groups with poorly developed (CF...

Beneficial Effect of Recruitable Collaterals A 10-Year Follow-Up Study in Patients With Stable Coronary Artery Disease Undergoing Quantitative Collateral Measurements

Important risk factors for cardiovascular disease (CVD) have been identified, but they fail to explain why some patients with atherosclerosis become symptomatic and have recurrent symptomatic disease, and others do not. Apart from the extent of coronary atherosclerosis (among other factors), the sensitivity of organs to episodes of ischemia is probably of importance. An organ may be less sensitive to episodes of ischemia if supplied with sufficient blood flow by well-developed collateral vessels. Unfortunately, some organs or even some individuals do not appear to have well-developed collateral vessels, if developed at all. At present, it is not clear why there are differences between individuals in their capability of developing a sufficient collateral circulation. The potential of individuals to develop coronary collateral circulation has so far been largely neglected but may play a major role in determining myocardial vulnerability.

In the present article, we propose why coronary collaterals are important, and why this individual potential to develop collaterals should be considered an additional indicator of cardiac vulnerability. Also, we review determinants that play a role in collateral coronary blood supply.

Coronary collaterals, or “natural bypasses,” are anastomotic connections without an intervening capillary bed between portions of the same coronary artery and between different coronary arteries (Figure 1).1 Collateral circulation potentially offers an important alternative source of blood supply when the original vessel fails to provide sufficient blood.2 Timely enlargement of collaterals may even avoid transmural myocardial infarction (MI) and death in symptomatic patients.3 As early as in 1956, Baroldi et al4 demonstrated the presence at birth of mostly corkscrew-shaped collaterals in normal human hearts, with a lumen diameter of 20 to 350 μm and lengths ranging from 1 or 2 cm to 4 or 5 cm. In hearts with typical findings of coronary disease at autopsy, …

Coronary Collaterals An Important and Underexposed Aspect of Coronary Artery Disease

Coronary revascularisation plays an important role in the management of patients with ischaemic heart disease. Its principle builds on restoring antegrade flow thereby relieving angina. As a result, the need for medication is reduced which, in turn, may improve quality of life and socioeconomic independency. Also the prognosis is beneficially affected. This is not only true for patients with severe coronary atherosclerosis such as patients with left main or three vessel disease, but also for patients with less advanced disease.w1–3

The first milestones in coronary revascularisation were surgical. It all started after the second world war with the implantation of the internal mammary artery indirectly into the cardiac muscle (the Vineberg procedure). A few years later, procedures for direct coronary artery revascularisation were designed, initially including endarterectomy, followed by the construction of an anastomosis between a donor artery or vein and the coronary artery. Interestingly, these first operations were performed on the beating heart without the use of extracorporeal circulation and cardiac arrest.w4 The results of these early initiatives were generally unpredictable, preventing general acceptance and widespread use. It became clear that the safety and efficacy of surgical coronary revascularisation in terms of in-hospital complications and immediate and long term clinical outcome greatly depends, among other factors, on the quality of the anastomosis between the donor graft and recipient coronary artery. To predictably create these delicate and very precise hand sewn anastomoses, the surgeon needs a still and bloodless field with full exposure of the target area, enabling the required complex and coordinated manipulation of the microsurgical instruments.

In this respect, the introduction of cardiopulmonary bypass (CPB) and cardiac arrest by Favaloro in 1967 proved to be a tremendous step forward. Because basic surgical requirements could now be properly addressed, consistent high quality anastomoses could be produced …

https://heart.bmj.com/content/heartjnl/88/3/313.full.pdf

Off-pump coronary artery bypass surgery

Coronary collateral circulation: the effects of smoking and alcohol.

B genetic and environmental factors are involved in the development of coronary artery disease (CAD). The degree of contribution of each individual risk factor on CAD is unknown. The influence of genetics in the development of CAD could be clarified by investigation of twins. A large cohort of twins with CAD had a significantly higher concordance of coronary heart death in monozygotic twins than dizygotic twins. This effect declined with age. These observations underscore the genetic influence in the development of CAD. Little is known about the angiographic expression of CAD in twins. To address this issue, we report findings of 2 monozygotic twin pairs with CAD and a systematic review of previous publications on this topic. • • • A search of systematic literature in the electronic database “Medline” via “Pubmed” was performed. With the search string “coronary disease” [MESH] and twin, 191 publications were retrieved. Further selections were made by applying the inclusion criteria: monozygotic twins with CAD, performance of coronary angiography, and case reports. The exclusion criterion was concomitant major congenital heart disease. By reading abstracts 20 publications were selected. Nine of these 20 publications were excluded by reading entire papers, because of (1) no performance of angiography, (2) no inclusion of monozygotic twins; and (3) concomitant major congenital heart disease. One additional publication was found by cross-reference search. Finally, 12 publications were suitable for the present review. A 1-page standard form was developed to process the selected publications systematically. This form was the basis for Table 1. Demographic, clinical, and angiographic characteristics of the retrieved case reports, together with the present twin pairs, were analyzed according to the following definitions: concordant coronary anatomy was defined as similar dominance or balance of the coronary system (according to Baim and Grossmann) between respective members of twin pairs. The extent of CAD was defined as (1) 1-, 2-, or 3-vessel disease according to significant lesions in 1 to 3 major epicardial coronary arteries; (2) diameter stenosis of the coronary artery 50%; (3) significant stenosis of the left main coronary artery reported separately as left main disease; (4) concordant coronary lesion defined as location of a coronary lesion in the same segment (American College of Cardiology/American Heart Association classification) in respective members of twin pairs; (5) 1 lesion in the same coronary segment, considered as 1 lesion; and (6) main lesion of major coronary arteries also including the origin of side branches, considered as 1 stenosis of only the major artery. A Pearson correlation coefficient was applied to correlate continuous data among twin members, and a chi-square test was performed for dichotomous data. Twin 1.1: A 58-year-old women with Canadian Cardiovascular Society classification 3 angina was referred to our hospital for coronary angioplasty. Ischemia was documented during the exercise test. Angioplasty of a type B2 lesion in segment 2 (American College of Cardiology/American Heart Association classification) of the right coronary artery was performed with implantation of a 3.0 20 mm stent (Figure 1). Twin 1.2: Six months later the monozygotic twin sister of twin 1.1 also underwent coronary angioplasty because of class 3 angina and ischemia on exercise testing. Angioplasty of a type B1 lesion of segment 2 of the right coronary artery was performed with implantation of a 3.5 13 mm stent. The left coronary arteries of both twins were normal (Figure 2). Twin 2.1: A 39-year-old patient was admitted to our hospital with class 4 angina. He had 3-vessel disease on the coronary angiogram (type B1 lesion in segment 2, type A lesion in segment 7, type B2 lesion in segment 11, and type B1 lesion in segment 12). Coronary artery bypass surgery was performed (Figure 3). Twin 2.2: A 34-year-old male patient, monozygotic twin brother of twin 2.1, was admitted to our hospital because of an acute inferior wall myocardial infarction and was treated with fibrinolysis. Because of postinfarction angina pectoris, coronary angiography was performed and 2-vessel coronary disease was found (type B1 lesion in segment 2 and type B2 lesion in segment 8, Figure 4). He also underwent a coronary artery bypass surgery. Twelve publications composed of 16 monozygotic twin pairs with angiographic assessment of CAD were found. Together with the 2 twin pairs of the present study, data of 18 twin pairs with documented CAD are listed in Table 1. Most patients were men (13 of 18). The age at which twins experienced their first coronary event was 42 12 years (mean SD), with From the Heart Lung Center Utrecht, Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. Dr. Stella’s address is: Department of Cardiology, University Medical Center Utrecht, Room E01-207, PO Box 85500, 508 GA Utrecht, The Netherlands. E-mail: pstella@hli.azu.nl. Manuscript received September 25, 2001; revised manuscript received and accepted January 4, 2002.

Angiographic findings in monozygotic twins with coronary artery disease.

Postprandial hypertriglyceridemia tested under metabolic ward conditions with unphysiological high fat loads has been reported in CAD patients and their relatives even in the presence of normal fasting lipids. It is unclear whether this also occurs in the daytime situation. Twenty-seven normocholesterolemic, non-obese and nondiabetic patients with premature coronary artery disease (CAD) and 56 first-degree relatives without CAD measured daytime capillary triglyceride profiles (TGc-AUC) as an estimate of postprandial lipemia. Fasting capillary triglycerides (TGc) were not significantly different between CAD index patients and their relatives (1.68 ± 0.63 and 1.54 ± 0.71 mmol/L, respectively). In contrast, daytime triglyceridemia was significantly higher in CAD patients (30.7 ± 13.6 mmol · h/L) compared to their relatives (24.4 ± 9.4 mmol · h/L) and this was also the case after correction for fasting TGc (7.24 ± 7.41 and 2.79 ± 6.89 mmol · h/L; P < .05). The best predictors of TGc-AUC by multiple regression analysis in CAD families were fasting TGc, systolic blood pressure, and high-density lipoprotein cholesterol (HDL-C), which are all components of the metabolic syndrome, explaining 65% of the variation. Since there were no major differences in nutritional intake between index patients and their relatives, this could not explain the differences Daytime triglyceridemia, measured under physiological conditions, is increased in patients with premature atherosclerosis and normal fasting TG levels, when compared to their non-CAD relatives. This study confirms previous observations using standardized oral fat loading tests and underlines the importance of postprandial hyperlipidemia in CAD.

Peter P.Th. de Jaegere

Papers

Coronary Collaterals An Important and Underexposed Aspect of Coronary Artery Disease

Off-pump coronary artery bypass surgery

Coronary collateral circulation: the effects of smoking and alcohol.

Angiographic findings in monozygotic twins with coronary artery disease.

Daytime triglyceridemia in normocholesterolemic patients with premature atherosclerosis and in their first-degree relatives