Recommendations from the Consensus Conference on Hypertension in the Elderly.

Since 1978 there have been dramatic advances in the understanding of the pathophysiologic features of unstable angina pectoris and in the availability of new therapies of proven efficacy. Coronary artery spasm has been shown to be an important mechanism of acute myocardial ischemia in patients with unstable angina, and coronary thrombosis has been established as an early event in the development of acute myocardial infarction and, possibly, sudden death. Intravenous nitrates and oral calcium antagonists have been made available and are now widely used. Acetylsalicylic acid has been shown to be of benefit. Improved techniques of myocardial preservation and the introduction of percutaneous transluminal coronary angioplasty have modified the surgical management of coronary artery disease.     

Association between coronary lesion severity and distal microvascular resistance in patients with coronary artery disease

Homogeneity of microvascular resistance in different perfusion areas of the same heart is generally assumed. We investigated the effect of the severity of an epicardial stenosis on microvascular resistance in 27 patients with coronary artery disease and stable angina. All patients had an angiographically normal coronary artery, an artery with an intermediate lesion, and an artery with a severe lesion; the latter was treated with angioplasty. In each patient, distal blood flow velocity and pressure were measured during baseline and maximal hyperemia (induced by intracoronary adenosine) using a Doppler and pressure guide wire, respectively. The ratio of mean distal pressure to average peak blood flow velocity was used as an index for the microvascular resistance (MRv). Within patients, the hyperemic MRv was higher in arteries with more severe stenosis (P = 0.021). After percutaneous transluminal coronary angioplasty (PTCA), the hyperemic MRv decreased (pre-PTCA, 2.6 vs. post-PTCA, 1.9 mmHg.cm(-1)s(-1), P < 0.01) toward the value of the reference artery (1.7 mmHg.cm(-1)s(-1); P = 0.67). We conclude that there is a positive association between coronary lesion severity and variability of distal microvascular resistance that normalizes after angioplasty. This study challenges the concept of uniform distribution of hyperemic MRv that is relevant for the interpretation of both noninvasive and invasive diagnostic tests.     

Long-term assessment of clinical parameters in patients with coronary heart disease after balloon angioplasty and stenting balloon angioplasty

The aim of this study was to assess clinical parameters in patients with coronary heart disease (CHD) in the late period after balloon coronary angioplasty (BCA) and intracoronary stenting (ICS). The study included 104 patients who underwent repeated coronary angiography (CA) 2-10 months after successful coronary angioplasty. Clinical parameters were analyzed in 2 groups comparable at the moment of its performance in terms of major clinical characteristics. Group 1 comprised 51 patients following BCA and group 2 included 53 patients after ICS. Six months after the first procedure, repeated coronary angioplasty was performed in 19 (37.2%) and 6 (9.4%) patients after BCA and ICS, respectively (p < 0.05). Recurrent angina pectoris was observed in 42 patients from group 1 and in 25 ones from group 2, which was 82.3 and 47.2%, respectively (p < 0.05). Control CA revealed restenosis of the dilated artery in 22 (43.1%) of the 51 patients of group 1 and in 12 (22.6%) of the 53 patients of group 2. There were no differences between the groups in late postoperative bicycle ergometric and 24-hour ECG monitoring findings. The findings have led to the conclusion that implantation of a stent into the coronary artery greatly prolongs the antiischemic effect of coronary angioplasty and reduces a need for repeated endovascular intervention, which appears as lower incidence rates of restenosis and recurrent angina as compared to routine balloon angioplasty.     

Provisional stenting in small vessels

Based on the currently available data, the strategy of routine stent placement in unselected lesions located in small coronary arteries provides good immediate results but is still associated with a high incidence of in-stent restenosis. Randomized trials comparing elective stenting with balloon angioplasty have not provided the demonstration that routine stenting is the best strategy for percutaneous intervention in coronary arteries with a reference diameter smaller than 2.75-3.0 mm. This paper describes the rationale for provisional stenting in this clinical setting and reviews the role of quantitative coronary angiography, intracoronary ultrasound and intracoronary Doppler measurements in the identification of lesions that would benefit from adjunctive stent placement after balloon angioplasty and in guiding stent implantation.     

Brachytherapy with gamma radiation of a coronary artery for in-stent restenosis may induce the regression of in-stent restenosis of an adjacent coronary artery without angioplasty. First case report and review of the literature

Here, we present a case of a 63-year-old male who presented with in-stent restenosis of two coronary arteries simultaneously (mid circumflex and proximal ramus). After the brachytherapy of the circumflex artery for in-stent restenosis, the patient refused the staged procedure for the ramus in-stent restenosis. After approximately 2 years, the patient underwent coronary angiography for recurrent chest pain. Surprisingly, the proximal ramus stent showed marked regression of in-stent restenosis. We hypothesized that the gamma brachytherapy of the circumflex artery could have induced the regression of in-stent restenosis of the adjacent ramus artery due to the deep tissue penetration of gamma radiation. Based on our observation, we believe that in the treatment of in-stent restenosis of a coronary artery, the initial balloon angioplasty may not be as important as the radiation itself. This observation warrants further study to evaluate the effect of external or internal radiation on in-stent restenosis without balloon angioplasty. If our hypothesis is confirmed, the treatment of in-stent restenosis with external radiation could substantially simplify the treatment of this disease. This case report follows a brief review of the literature.     

A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general. However, the precise mechanism(s) by which coronary spasm occurs remains to be elucidated. Coronary spasm may arise from interactions between environmental and genetic factors. Endothelial derived nitric oxide (NO) has been implicated in the control of vascular tone. We have recently shown that both basal and acetylcholine (ACh)-induced NO activities are impaired in the coronary arteries of patients with coronary spasm. The purpose of this study has been to elucidate the possible variants that occur in the coding region of the endothelial nitric oxide synthase (eNOS) gene and that may be associated with coronary spasm. After initial screening in the entire 26 coding regions of the eNOS gene, we found a missense Glu298Asp variant in exon 7 in patients with coronary spasm. We subsequently performed a larger scale study involving 113 patients with coronary spasm and 100 control subjects, who were all diagnosed by intracoronary injection of ACh. The analysis revealed a significant difference in the distribution of the variant between the coronary spasm group (21.2%) and control group (9.0%; P=0.014 for dominant effect). Thus, we have found the missense Glu298Asp variant in the eNOS gene by the analysis of its entire 26 coding regions. The variant is significantly associated with coronary spasm. Received: 2 February 1998 / Accepted: 9 April 1998     

Modulation of protein expression and activity by radiation: relevance to intracoronary radiation for the prevention of restenosis

Restenosis is a common complication of percutaneous transluminal coronary angioplasty. Recent studies have demonstrated a striking reduction in the neointimal hyperplasia characteristic of restenosis following intracoronary radiation (IR), but the mechanisms by which radiation reduces neointima formation following balloon overstretch injury are not elucidated fully. In addition to direct antimitotic effects mediated via oxygen free radicals, ionizing radiation can induce the expression of numerous genes and thereby mediate indirect effects. Additionally, IR prevents restenosis at the cost of decreased healing and increased thrombosis, and we suggest that these adverse reactions can be modulated by adjunct pharmacology or gene-based strategies. This review discusses several genes and proteins modulated by radiation in the context of arterial injury, and their possible therapeutic relevance.     

Verapamil Reverses Myocardial No-Reflow After Primary Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction

The present study evaluated the efficacy of intracoronary administration of verapamil to attenuate the no-reflow phenomenon following the primary percutaneous coronary intervention (PCI) in patients with the ST-segment elevation acute myocardial infarction (STEMI). A total of 201 patients with STEMI who underwent primary PCI within 12 h from the beginning of the heart attack were included. The no-reflow phenomenon was defined as substantial coronary anterograde flow of TIMI ≤2. Verapamil (100–200 μg) was injected into coronary artery immediately after no-reflow; the coronary arteriography was repeated later. Hundred and ninety-eight patients with STEMI successfully underwent primary PCI, and 246 stents were implanted with the average of 1.2 stents per patient. No-reflow occurred in 25 out of 198 patients (12.6 %). Twenty-one (84 %) patients developed the flow of TIMI ≥3 after intracoronary administration of verapamil, as revealed by repeated coronary angiography. Two patients developed transient hypotension which normalized without treatment within 3–5 min. Three patients showed sinus bradycardia, in one patient there was transient II sinoatrial block, and one patient developed type 1 atrioventricular block. All adverse effects were alleviated after intravenous injection of atropine (0.5–1 mg). In conclusion, the no-reflow phenomenon following primary PCI in patients with STEMI is significantly improved by intracoronary administration of verapamil which is useful to reduce cardiovascular events during operation.     

C型利钠利尿肽对犬冠脉循环的作用

Ｃ型利钠利尿肽（ＣＮＰ）是新近发现的一种由内皮细胞分泌的利钠利尿肽,本研究采用冠脉内给药方法对比观察了ＣＮＰ、心房利钠尿肽（ＡＮＰ）对犬正常及心肌缺血后冠脉循环的作用,并应用常规离体血管灌流的方法测定了离体冠脉对ＣＮＰ、ＡＮＰ的舒张反应。结果显示：（１）对正常犬,ＣＮＰ、ＡＮＰ均可降低平均动脉压（ＭＡＰ）、远端小冠脉压和大、小冠脉阻力,增加冠脉流量,而不影响心率;（２）心肌缺血后,ＣＮＰ的上述作用依然存在,但ＡＮＰ降低ＭＡＰ的作用基本消失。（３）离体心外膜冠状动脉对ＣＮＰ、ＡＮＰ均呈剂量依赖性舒张反应。结果提示ＣＮＰ、ＡＮＰ均可舒张冠状动脉而改善冠脉循环,并可能对急性心肌缺血的治疗有益     

Intracoronary C5a induces myocardial ischemia by mechanisms independent of the neutrophil: leukocyte filters desensitize the myocardium to C5a.

Activation of the complement cascade with the generation of anaphylatoxins accompanies the inflammatory response elicited by acute myocardial ischemia and reperfusion. Although complement is activated in the interstitium during acute myocardial ischemia, we have studied mechanisms whereby complement might exacerbate ischemia by using a model employing intracoronary injection of C5a in nonischemic hearts. Intracoronary injection of complement component C5a induces transient myocardial ischemia, mediated through the production of the coronary vasoconstrictors thromboxane A2 and peptidoleukotrienes (LTC4, LTD4), and causes sequestration of polymorphonuclear leukocytes (PMN) in the coronary vascular bed. To further investigate the role of the PMN in the C5a-induced vasoconstriction, the left anterior descending coronary artery (LAD) in pigs was perfused at constant pressure and measurements of coronary blood flow, myocardial contractile function (sonomicrometry), arterial/coronary venous blood PMN count, and thromboxane B2 (TxB2) levels were performed. The myocardial response to intracoronary C5a (500 ng) was determined before, during, and after perfusion with blood depleted of PMNs using leukocyte filters (Sepacell R-500, Pall PL-100). In additional animals, the myocardial response to the PMN chemotactic agent, LTB4, and the effects of intracoronary C5a during constant flow perfusion were measured. Control intracoronary injection of C5a decreased flow (41% of baseline) and contractile function (39% of baseline), PMNs were trapped (5.1 x 10(3) cells/microliters), and TxB2 concentration increased in coronary venous blood. The response to C5a during coronary perfusion with arterial blood depleted of PMNs with Sepacell or Pall filters (less than 0.1 x 10(3) cells/microliters) was greatly blunted, with flow and contractile function falling by less than 14 and 8%, respectively, from baseline, and release of TxB2 was greatly attenuated. However, the myocardial ischemia and TxB2 release remained depressed in response to C5a after removal of the filters and perfusion with either arterial blood containing normal levels of PMNs or stored arterial blood never exposed to filters. In contrast, the repeat C5a challenge resulted in equivalent myocardial extraction of PMNs, thus indicating a dissociation of PMN sequestration from the acute ischemic response and release of TxB2. In separate experiments, the intracoronary injection of LTB4 also resulted in a pronounced myocardial extraction of PMNs (8.6 x 10(3) cells/microliters) greater than during C5a, but did not depress coronary flow or function. Perfusion at constant flow greatly diminished the ischemic response to C5a, indicating that vasoconstriction and resultant ischemia is the main cause of the contractile dysfunction. These data indicate that leukocyte filters inhibit the myocardial ischemia and release of TxB2 induced by C5a via mechanisms not related to PMN depletion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography

Progress in understanding, diagnosis, and treatment of coronary artery disease (CAD) has been hindered by our inability to observe cells and extracellular components associated with human coronary atherosclerosis in situ. The current standards for microstructural investigation, histology and electron microscopy are destructive and prone to artifacts. The highest-resolution intracoronary imaging modality, optical coherence tomography (OCT), has a resolution of ~10 μm, which is too coarse for visualizing most cells. Here we report a new form of OCT, termed micro-optical coherence tomography (μOCT), whose resolution is improved by an order of magnitude. We show that μOCT images of cadaver coronary arteries provide clear pictures of cellular and subcellular features associated with atherogenesis, thrombosis and responses to interventional therapy. These results suggest that μOCT can complement existing diagnostic techniques for investigating atherosclerotic specimens, and that μOCT may eventually become a useful tool for cellular and subcellular characterization of the human coronary wall in vivo.     

Primary percutaneous coronary angioplasty in patients with acute coronary syndrome and concomitant cancer

The paper gives the results of X-ray surgical treatment in patients with acute coronary syndrome who have been ascertained to have concomitant cancer during their examination. Cancer was found in 11 patients in their medical history and diagnosed in 2 patients during examination after surgical treatment and 1 patient one year after his hospital discharge. The results of combination treatment showed the high efficiency of X-ray surgical treatment for acute coronary syndrome. Recovery of TIMI-III blood flow through the infarct-related coronary artery was achieved in 100% of cases; immediate clinical efficiency was 97.4%. In the concomitant cancer group, the therapeutic efficacy was 100%; there were no complications during X-ray surgery. All the patients from this group were discharged from hospital in a satisfactory state to be followed up by a cardiologist and oncologist for further treatment. The study performed suggests that concomitant cancer is not a contraindication to primary coronary angioplasty in patients with acute coronary syndrome. Primary coronary angioplasty with stenting is a safe effective treatment for acute coronary syndrome in this category of patients.     

Echocardiographically documented acute aortic insufficiency induced by Amplatz left guide catheter

This paper examines a case of sudden systolic pressure fall, tachycardia, low pulse pressure, and high pulmonary artery wedge pressure due to acute aortic insufficiency which was induced by an Amplatz left (AL-1) guide catheter used for better guide support during percutaneous transluminal coronary angioplasty of the right coronary artery. AL guide catheters can cause acute aortic insufficiency, of which practitioners should be aware when sudden hemodynamic collapse occurs.     

Coronary spasm reflects inputs from adjacent esophageal system

Mechanisms underlying coronary spasm are still poorly understood. The aim of the study was to assess the hypothesis that fluctuations in the development of coronary spasm might reflect inputs from the adjacent esophageal system. We enrolled patients admitted to the coronary care unit for episodes of nocturnal angina. Seven patients with variant angina and five with coronary artery disease (CAD) had concurrent ECG and esophageal manometric monitoring. ECG monitoring documented 28 episodes of ST elevation in variant angina patients and 16 episodes of ST depression in CAD patients. Manometric analysis showed that esophageal spasms resulted remarkably more frequently in variant angina patients (143 total spasms; individual range 9-31) than in CAD patients (20 total spasms; individual range 0-9; P < 0.01). Time series analysis was used to assess fluctuations in the occurrence of abnormal esophageal waves and its relationship with spontaneous episodes of ST shift. Episodes of esophageal spasm in CAD were sporadic (<1 in 30 min) and not related to ECG-recorded ischemia. In the variant angina group, esophageal spasms were time related to ischemia (>1 into 5 min before ECG-recorded ischemia) (P < 0.05). A bidirectional analysis of causal effects showed that the influence processes between esophageal and coronary spasms were mutual and reciprocal (transfer function model, P < 0.05) in variant angina. We concluded that in variant angina patients, episodes of esophageal spasms and myocardial ischemia influenced each other. Mechanisms that cause esophageal spasm can feed back to produce coronary spasm. Coronary spasm may feed forward to produce additional episodes of esophageal spasm.     

Intravascular brachytherapy to prevent restenosis: dosimetric considerations.

Acute myocardial infarction is often the result of occlusion of one or more coronary arteries. Occlusion and restenosis (re-closing of the vessel) are principal reasons that percutaneous transluminal coronary angioplasty (PTCA) may fail to provide long-term benefit. PTCA has been a popular treatment, which is less invasive than surgeries involving revascularization of the myocardium, promising a better quality of life for patients. Unfortunately, the rate of restenosis after balloon angioplasty is high (approximately 30-50% in the first year after treatment). Recent data suggest that intraluminal irradiation of coronary arteries in conjunction with balloon angioplasty and/or stent implantation reduces the proliferation of smooth muscle cells and neointima formation, thereby inhibiting restenosis. In order to study radiation dosimetry in the patient and for this therapy, dose distributions for electrons and photons, with discrete energies, were simulated for blood vessels of diameter 1.5, 3 and 4.5 mm irradiated with balloon and wire sources. Electron and photon transport was performed in a simple model representing the system used for irradiation using the MCNP 4B code (Monte Carlo N-Particles). Specific calculations for balloon and wire sources were also carried out for a few radionuclides. In this work, strengths and drawbacks conceming the use of each radionuclide simulated, as well as source geometries are discussed. The dosimetry performed in this study will improve understanding of the benefit-to-risk ratio in intracoronary brachytherapy.     

Oxidative stress in myocardial ischaemia reperfusion injury: a renewed focus on a long-standing area of heart research

Advances in the treatment of coronary artery disease have seen a significant drop in mortality and morbidity particularly amongst patients with acute myocardial infarction (MI). In particular, percutaneous trans-luminal balloon angioplasty (PTCA) with stenting to re-open atherosclerotic coronary arteries has yielded marked improvement in clinical outcome for patients with acute MI. Furthermore, with the advent of drug-eluting stents occurrence rates for coronary artery restenosis, one common clinical problem associated with angioplasty and stent deployment, have declined markedly. However, coronary restenosis in diabetic patients remains an on-going problem. The success of drug-eluting stents has seen a renewed focus on myocardial ischaemia reperfusion (IR) injury as this represents one area of research where many questions remain unanswered. In particular, the relationship between myocardial IR injury and decreased myocardial micro-vasculature re-flow post PTCA (that ultimately leads to poor clinical outcome and myocardial damage/dysfunction) is one area of research with the potential to decrease current complication rates further in patients suffering myocardial IR injury sustained during MI. This review discusses the role for oxidative stress, oxidant source(s) and both gene regulation and stem-cell therapy as potential strategic targets in the ischaemic myocardium, with the ultimate aim of providing significant cardioprotection in the setting of acute MI.     

Focus: Sex and Gender Health: Women and Chest Pain: Recognizing the Different Faces of Angina in the Emergency Department

Emergency departments (ED) in the United States see over eight million cases of chest pain annually. While a cardinal symptom of acute coronary syndrome (ACS), multiple emergent and non-emergent causes can attribute to chest pain. This case-based perspective describes the different sex-specific causes of angina seen in ED patients. Once coronary artery disease (CAD) is ruled out with standard protocols, microvascular dysfunction is perhaps the most prevalent but under-diagnosed cause of non-CAD related angina in ED patients. Additional causes include coronary artery spasm, coronary artery dissection, coronary artery endothelial dysfunction and myocardial bridging. Non-CAD related angina is associated with persistent chest pain causing poor function, quality of life, and recidivism. Clinicians should consider additional diagnostics to routinely screen for non-CAD related causes of angina in patients with recurrent chest pain. Future work is needed to better define the epidemiological, clinical, biological, and genetic correlates of microvascular dysfunction in these patients.     

Myocardial blood volume and coronary resistance during and after coronary angioplasty

Animal experiments have shown that the coronary circulation is pressure distensible, i.e., myocardial blood volume (MBV) increases with perfusion pressure. In humans, however, corresponding measurements are lacking so far. We sought to quantify parameters reflecting coronary distensibility such as MBV and coronary resistance (CR) during and after coronary angioplasty. Thirty patients with stable coronary artery disease underwent simultaneous coronary perfusion pressure assessment and myocardial contrast echocardiography (MCE) of 37 coronary arteries and their territories during and after angioplasty. MCE yielded MBV and myocardial blood flow (MBF; in ml · min(-1) · g(-1)). Complete data sets were obtained in 32 coronary arteries and their territories from 26 patients. During angioplasty, perfusion pressure, i.e., coronary occlusive pressure, and MBV varied between 9 and 57 mmHg (26.9 ± 11.9 mmHg) and between 1.2 and 14.5 ml/100 g (6.7 ± 3.7 ml/100 g), respectively. After successful angioplasty, perfusion pressure and MBV increased significantly (P < 0.001 for both) and varied between 64 and 118 mmHg (93.5 ± 12.8 mmHg) and between 3.7 and 17.3 ml/100 g (9.8 ± 3.4 ml/100 g), respectively. Mean MBF increased from 31 ± 20 ml · min(-1) · g(-1) during coronary occlusion, reflecting collateral flow, to 121 ± 33 ml · min(-1) · g(-1) (P < 0.01), whereas mean CR, i.e., the ratio of perfusion pressure and MBF, decreased by 20% (P < 0.001). In conclusion, the human coronary circulation is pressure distensible. MCE allows for the quantification of CR and MBV in humans.     

Inhibition of calmodulin prevents spasms in autologous arterial bypass grafts during coronary disease surgery

The tonic lability of isolated segments of the human radial artery was studied isometrically. The mechanical shock to this artery produced by its separation prior to its subsequent use as an autologous arterial bypass graft for coronary arteries provokes a persistent spasm of its smooth muscle that lasts for at least 5 h. Its tonic lability could be preserved by incubation in the presence of 0.5 mM Verapamil, which blocks Ca²⁺ channels in the membranes of smooth muscle cells. A 5-h perfusion recovered more than 20% of the initial tone. Lability of the tone could also be preserved by a 1 μM solution of Aminazine, a well-known inhibitor of calmodulin, an intracellular Ca²⁺-binding protein. In this case, a 3-h perfusion caused a 40% decrease in the tone. Hence, during the pretreatment of the radial artery for its subsequent coronary bypass grafting, the inhibition of calmodulin can be efficacious in preventing intra-and postoperative complications that can be produced by the spasm of arterial grafts.