Progression Of Myocardial Ischemia Research Articles

Involvement of HIF1α/Reg protein in the regulation of HMGB3 in myocardial infarction

AimsMyocardial ischemia and infarction are the number one cause of cardiovascular disease associated mortality. Cardiomyocyte death during ischemia leads to the loss of cardiac tissue and initiates a signaling cascade between the infarct zone and the area at risk of the myocardium. Here, we sought to determine the involvement of one of the damage-associated molecular patterns HMGB3 in myocardial ischemia and infarction. Methods and resultsWe used the left anterior descending coronary artery ligation model to study the involvement of HMGB3 in myocardial ischemia and infarction. Our results indicated the presence of HMGB3 at a low level under normal conditions, while myocardial injury caused a robust increase in HMGB3 levels in the heart. Further, intra-cardiac injection of mabHMGB3 had improved cardiac function at day 3 by downregulating HMGB3 levels. In contrast, injection of recombinant rat HMGB3 for 7 days during the adaptation phase of myocardial ischemia improved cardiac functional parameters by increasing regenerative protein family expression. Further, to mimic the disease condition, neonatal rat ventricle cardiomyocytes and fibroblasts were exposed to hypoxia; we observed a significant upregulation in the HMGB3, HIF1α, and Reg1α levels. Endothelial cells exposed to recombinant HMGB3 increased the tubule length. Further, the mitochondrial oxygen consumption rate was reduced with the acute induction of recombinant HMGB3 on cardiomyocytes and fibroblasts. ConclusionHMGB3 plays a dual role during the progression of myocardial ischemia and infarction. Clinically, post-myocardial infarction HMGB3-induced sterile inflammation needs to be tightly controlled, as it plays both a pro-inflammatory role and improves cardiac function during the cardiac remodeling phase.

Forensic Significance of Messenger RNA and Protein Expression of Genes Downstream of Hypoxia Inducible Factor 2 in Myocardial Tissue for Death Discrimination

AbstractBackgroundAs a heterodimeric transcription factor, hypoxia-inducible factor 2 alpha subunit (HIF2A), is an important member of the HIF family. It plays a significant role in the hypoxia adaptation process by regulating the different types of downstream transcription factors and auxiliary regulatory factors. HIF2A-related factors are believed to participate in the progression of myocardial injury or myocardial ischemia, support the protection of ischemic myocardium, and provide guiding significance for the diagnosis and discrimination of sudden cardiac death in forensic pathology.Aim and ObjectivesThis study aimed to explore the discriminability and applicability of HIF2A-related factors in myocardial infarction cases compared with other causes of death, provide further insights for the forensic diagnosis of heart failure (HF) cases with myocardial infarction, and support the clinical treatment of patients with HF after myocardial infarction.Materials and MethodsThe relative expression levels of HIF2A, amphiregulin (AREG), potassium large conductance calcium-activated channel subfamily M β1 (KCNMB1), peroxisome proliferator-activated receptor α (PPARA), vascular endothelial growth factor (VEGF), and VEGFR2 messenger RNAs (mRNAs) in myocardial tissue samples were performed using quantitative reverse transcriptase-polymerase chain reaction. A partial least squares-discriminant analysis model was constructed to select the indicators with better identification effects for myocardial infarction cases. The protein levels of HIF2A, AREG, KCNMB1, and PPARA were further detected by immunohistochemistry. The forensic autopsy cases (27 cases in total, postmortem interval <72 h) included seven cases of acute myocardial infarction and ten cases of myocardial ischemia. There were ten cases in the control group, including four cases of traffic injury, one case of injury by fall from height, and five cases of blunt force injury.ResultsCharacteristic results were observed in the myocardial ischemia/infarction samples. Compared with the control group, the relative mRNA expression levels of AREG, KCNMB1, and PPARA were significantly increased during the progression of myocardial ischemia, but this was not observed for HIF2A, VEGF, or VEGFR2 mRNA. Immunohistochemistry assays further verified the expression levels of the related factors at the protein level, and H and E staining showed signs of angiogenesis and inflammation in the ischemia/infarction group.ConclusionsBy controlling the expression of downstream target genes (AREG, KCNMB1, and PPARA) during myocardial cell hypoxia adaptation, HIF2A has a potential significance in the diagnosis of myocardial infarction in forensic medicine. We believe that HIF2A, AREG, KCNMB1, and PPARA can be used as molecular pathological biomarkers for the discrimination of causes of death in myocardial infarction cases.

Meta-analysis reveals inhibition of the inflammatory cytokine IL-6 affords limited protection post-myocardial ischemia/infarction

BackgroundProinflammatory cytokine cascades play crucial roles in the onset and progression of myocardial ischemia and infarction. Clinically, elevated serum levels of pro-inflammatory cytokine interleukin-6 is a poor prognostic indicator for future cardiac events and cardiac morbidity. Despite several reports, there is no clear evidence of cardiac benefits of inhibiting IL-6 in pre-clinical and clinical settings. ObjectiveTo analyze the available data systematically and perform a meta-analysis to show the evidence of effects of IL-6 inhibition on cardiac remodeling and mortality in ischemic animal models. MethodsWe used PICO framework and the quality of the studies was assessed using SYRCLE's risk of bias tool. Studies with interventions i.e., genetic deletion or pharmacological inhibition of IL-6/IL-6R were included for the meta-analysis. Systematic review was synthesized by including pre-clinical as well as randomized clinical trials involving myocardial infarction patients treated with IL-6 inhibitors. The effect size of the pooled data was determined using standard mean difference and 95% confidence intervals. ResultsA total of 12 pre-clinical studies were included in the review for analysis. Most of the studies showed an unclear risk of bias as the selection and reporting criteria were poorly described. We observed high heterogeneity in the included studies due to the varying duration of myocardial infarction and the dosage of IL-6 antibodies used in the studies. Overall inhibition of IL-6 significantly increased area at risk [p = 0.001, SMD = 0.49 (95% CI: -0.36, 1.35)] and significantly reduced ejection fraction [p = 0.001, SMD = -0.19 (95% CI: -1.39, 1.01)] and end-diastolic diameter [p = 0.02, SMD = -0.25 (95% CI: -0.87, 0.36)] of left ventricle post-MI, but no effects on infarct size [p < 0.01, SMD = 0.00; 95% CI: -1.34, 0.58). In randomized clinical trials, the overall effect on C-reactive protein remains significantly unchanged on CRP levels (SMD = -0.38; 95% CI: -1.94, 0.55) post-treatment with IL-6R inhibitor tocilizumab. The meta-regression demonstrates a significant positive correlation (p = 0.058) between the increase in ischemic area and duration of ischemia post-surgery in the absence of IL-6. This meta-analysis indicates mixed effect of IL-6 inhibition on cardiac remodeling post-MI, particularly in protecting the myocardium viability from damaging acute inflammation but not significant on cardiac function of ischemic animal models. ConclusionDespite the well-established pro-inflammatory nature of IL-6 in myocardial ischemia, our meta-analysis reports a limited contribution of IL-6 in the cardiac remodeling of hearts in animal models of myocardial ischemia. Moreover, genetically deleted IL-6 murine models produced contrasting results. Additional pre-clinical studies exploring the pharmacological inhibition of IL-6R are required to determine the beneficial effects of IL-6 inhibitors in regulating cardiac remodeling. The findings from IL-6R inhibition have better clinical relevance compared to genetically inhibited IL-6.

Mechanisms of ventricular arrhythmias elicited by coexistence of multiple electrophysiological remodeling in ischemia: A simulation study.

Myocardial ischemia, injury and infarction (MI) are the three stages of acute coronary syndrome (ACS). In the past two decades, a great number of studies focused on myocardial ischemia and MI individually, and showed that the occurrence of reentrant arrhythmias is often associated with myocardial ischemia or MI. However, arrhythmogenic mechanisms in the tissue with various degrees of remodeling in the ischemic heart have not been fully understood. In this study, biophysical detailed single-cell models of ischemia 1a, 1b, and MI were developed to mimic the electrophysiological remodeling at different stages of ACS. 2D tissue models with different distributions of ischemia and MI areas were constructed to investigate the mechanisms of the initiation of reentrant waves during the progression of ischemia. Simulation results in 2D tissues showed that the vulnerable windows (VWs) in simultaneous presence of multiple ischemic conditions were associated with the dynamics of wave propagation in the tissues with each single pathological condition. In the tissue with multiple pathological conditions, reentrant waves were mainly induced by two different mechanisms: one is the heterogeneity along the excitation wavefront, especially the abrupt variation in conduction velocity (CV) across the border of ischemia 1b and MI, and the other is the decreased safe factor (SF) for conduction at the edge of the tissue in MI region which is attributed to the increased excitation threshold of MI region. Finally, the reentrant wave was observed in a 3D model with a scar reconstructed from MRI images of a MI patient. These comprehensive findings provide novel insights for understanding the arrhythmic risk during the progression of myocardial ischemia and highlight the importance of the multiple pathological stages in designing medical therapies for arrhythmias in ischemia.

180Myocardial perfusion imaging detected progressive myocardial ischemia in a chronic kidney disease patient with normal coronary angiography

180Myocardial perfusion imaging detected progressive myocardial ischemia in a chronic kidney disease patient with normal coronary angiography

Detection of Post-systolic Shortening by Tissue Doppler Imaging for the Risk Stratification for Chest Pain in Emergency Department Settings

A progression of myocardial ischemia (MI) may result a fatal ventricular arrhythmia and heart failure. Risk stratification for chest pain in emergency department (ED) settings is an important issue in cardiology practice. Post-systolic shortening (PSS) is a sensitive maker of myocardial ischemia.

In vivo study of myocardial elastography under graded ischemia conditions

The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction. Good agreement (0.22% strain bias, 95% limits of agreement) using Bland–Altman analysis and good correlation (r = 0.84) were found between the ME and SM measurements. These findings demonstrate for the first time that ME could map angle-independent strains to non-invasively detect, localize and characterize the early onset of myocardial ischemia, i.e. at 40%, and possibly as low as 20%, LAD flow reduction, which could be further associated with the severity of coronary stenosis.

Cardioprotective effect of percutanous intramyocardial stem cell injection in hibernating myocardium

Aims: Intramyocardial and intracoronary stem cell injection has been shown to improve myocardial function in preclinical and clinical studies. These effects have been desribed in acute myocardial infarction so far, although the mechanism is still unclear. We investigated the effects of bone marrow derived stem cells in a porcine model of chronic progressive myocardial ischemia.

Vascular Endothelial Growth Factor C–induced Collateral Formation in a Model of Myocardial Ischemia

Besides being a known lymphangiogenic activator, vascular endothelial growth factor (VEGF)-C may express angiogenic potential by proteolytic cleavage and activation of endothelial cells. We assessed myocardial collateral formation and functional changes after adenovirus-mediated VEGF-C gene transfer in an ischemic porcine model. Fifteen Landrace piglets underwent Ameroid-induced gradual occlusion of the left circumflex artery (LCx) and consequent progressive myocardial ischemia. Three weeks after Ameroid placement, the animals underwent gated 99mTc SPECT during rest and stress, in vivo angiography and 18FDG PET. Pigs were randomized to intramyocardial injections of adenoviruses encoding vascular endothelial growth factor (VEGF-C; n = 7) or control beta-galactosidase (LacZ; n = 5). Four weeks later, the examinations were repeated and histology was analyzed. Angiography showed significant progression of LCx stenosis in both groups during the treatment period. Left ventricular wall thickening (LVWT) at the LCx area in gated 99mTc SPECT remained unchanged in the VEGF-C group, indicating that VEGF-C prevented progression of myocardial ischemia, whereas LVWT deteriorated in the LacZ group (p = 0.042). Semi-quantitative assessment of 18FDG PET suggests more reduction in ischemia in the adVEGF-C group than in controls (p = 0.052). Angiography showed significant clustering of collaterals in the adVEGF-C gene transfer area compared that in LacZ (p = 0.004). von Willebrand factor staining revealed a significantly (p = 0.03) greater number of microvessels in the adVEGF-C-treated myocardium. This appears to be the first large-animal study in which, during progressive ischemia, functional and metabolic benefits of intramyocardial VEGF-C gene transfer were apparent. VEGF-C-induced collateral formation occurred at the site of gene transfer. The angiogenic potency of VEGF-C deserves further study as a therapeutic option.

Increased Plasma Group II Phospholipase A2 Concentrations in Patients with Acute Myocardial Infarction: Correlation with Tumor Necrosis Factor-Alpha

Aims: Group II phospholipase A₂ (PLA₂) is thought to play an important role in inflammation and tissue injury. It has been suggested that the inflammatory process is important in the setting and progression of myocardial ischemia or reperfusion. We measured plasma PLA₂ as well as inflammatory cytokines in patients in the acute stage of myocardial infarction. Methods and Results: In 48 patients with acute myocardial infarction, blood samples were taken to measure plasma PLA₂, tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) 36–48 h after onset. Serial changes in plasma PLA₂ were also examined in 15 consecutive patients in this group. Plasma PLA₂ levels were significantly higher in complicated patients (Killip’s class ≧ II) than in uncomplicated patients (Killip’s class = I) (35.9 ± 11.9 vs. 5.3 ± 1.1 ng/ml, p < 0.01). Plasma PLA₂ concentrations increased gradually over time during the first 3 days and at 36–48 h after onset were correlated with left-ventricular ejection fraction on admission (r = –0.42, p < 0.01), and with plasma TNF-α (r = 0.39, p < 0.01), but not with IL-1β. Conclusion: Plasma PLA₂ concentrations rose during the acute stage of myocardial infarction, especially in severe cases mainly with heart failure. TNF-α may be associated with PLA₂activity as a potent stimulator in vivo.

Perfusion-assisted direct coronary artery bypass: selective graft perfusion in off-pump cases

Background. Hemodynamic instability during multivessel off-pump coronary artery bypass grafting can lead to hypotension, progressive myocardial ischemia, further hypotension, and the need for urgent cardiopulmonary bypass.Methods. In 10 patients undergoing off-pump coronary artery bypass grafting, a novel technique of pressure-controlled blood delivery has been used that allows the immediate restoration of arterial blood to distal coronary beds after distal coronary anastomosis. This technique utilizes a servo-controlled pump to allow delivery of blood at systemic or suprasystemic pressures, and provides the option for infusion of supplemental additives for myocardial resuscitation, myocardial vasodilation, and enhancement of myocardial performance.Results. Myocardial perfusion was successfully enhanced via one or two grafts in all 10 patients with an average graft flow of 98 ± 8 mL/min. In 3 patients, a 27% increase in perfusion pressure led to a 59% increase in perfusate flow. All patients were hemodynamically stable after initiation of selective graft perfusion.Conclusions. Based on this preliminary patient series, the selective perfusion of grafted vessels seems to facilitate multivessel off-pump coronary artery bypass grafting by promoting rapid recovery of grafted segments, by enhanced hemodynamic stability during subsequent anastomoses, and by providing increased flexibility in the sequence of grafting.

Images in cardiovascular medicine. Noninvasive imaging of anomalous origin of the left coronary artery from the pulmonary artery.

Electron beam computerized tomography (EBCT) during intravenous administration of contrast medium showed an anomalous origin of the left coronary artery from the pulmonary artery, sometimes known as the Bland-White-Garland syndrome. This 28-year-old woman presented with chest pain caused by progressive myocardial ischemia. In this case, a right coronary arteriogram confirmed …

Effects of progressive myocardial ischaemia on systolic function, diastolic dysfunction, and load dependent relaxation

The aims were to determine (1) the relationship between changes in contractile function (systolic shortening) and the appearance of diastolic dysfunction (postsystolic shortening) during progressive regional left ventricular ischaemia; (2) the effects of increased afterload (acute constriction of the descending thoracic aorta) on ischaemic contractile dysfunction; and (3) the effects of loading during ischaemia on load dependent relaxation. Regional myocardial function, using sonomicrometry, was measured in the short and long axes of the apex of the left ventricle of eight open chest anaesthetised dogs (16-20 kg). Progressive apical ischaemia was induced by graded reductions in left anterior descending coronary artery flow (critical constriction, ischaemia 1, ischaemia 2, total coronary occlusion, and postocclusive maximum reactive hyperaemia). Acute afterloading was induced by a snare placed around the descending aorta. Consistent decreases in systolic shortening and increases in postsystolic shortening relative to the total segmental shortening in the short axis of the apical region were seen with worsening ischaemia. Aortic constriction increased the magnitude of apical postsystolic shortening and decreased apical systolic shortening in the short axis during critical constriction, ischaemia 1, and ischaemia 2. Long axis function changed in a qualitatively similar but quantitatively different manner. There was a significant decrease in the load dependency of relaxation with total coronary occlusion. (1) Changes in systolic and diastolic function occurred concomitantly as mild regional myocardial ischaemia developed and intensified; (2) afterloading significantly worsened regional systolic and diastolic dysfunction during mild ischaemia; and (3) progression of regional ischaemia resulted in loss of load dependent relaxation.

Platelet-leukocyte-endothelial interactions in coronary artery disease

It is generally recognized that formation of a platelet-fibrin-rich thrombus in an atherosclerotic coronary artery is the baste of unstable angina and acute myocardial infarction. Platelet hyperactivity has been identified in coronary risk factors such as hyperlipidemia and diabetes mellitus. Persistent activation of these cells results in release of growth factors that may contribute to the progression of atherosclerosis. Several recent studies show that endothelium, by generating or metabolizing a host of vasoactive substances, plays a critical rote in the modulation of vascular tone. Important among these substances are prostacyclin (PGI 2) and endotheliumderived relaxing factor (EDRF). The endotheliumdependent modulation of coronary artery tone correlates with the severity of atherosclerosis and the number of coronary risk factors. Procedures such as angioplasty and coronary bypass surgery injure the endothelium. The loss of endothelial smooth muscle relaxant function may contribute to the vasoconstriction and thrombosis often observed soon after these procedures. Thrombolysis (and subsequent reperfusion of the coronary artery) is also associated with severe endothelial dysfunction, with a resulting vasoconstrictor influence on the coronary vascular bed. Activation of leukocytes and their presence in the reperfused myocardium contribute to progression of myocardial injury by release of oxygen free radicals and proteolytic enzymes. Thus, it seems that a perturbation in this delicate equilibrium in cellular interactions relates to genesis and progression of myocardial ischemia.

Modulation of coronary circulation and the cardiac matrix by the renin-angiotensin system

There are short-term and long-term modulations of cardiac function and cardiac composition by the endocrine and paracrine renin-angiotensin system. First, there is an enhancement of coronary vasoconstrictor tone in severe congestive heart failure due to stimulation of this system. Therapeutic interventions that block the RA-system are able to reduce the increased resistance to coronary flow. Second, there is a relationship between the occurrence of arrhythmias and the degree of sympathetic stimulation in congestive heart failure. The renin-angiotensin system may be involved in arrhythmogenesis because of presynaptic modulation of sympathetic neurotransmitter release. However, in the isolated perfused rat heart no class-specific antiarrhythmic properties could be found for ACE inhibitors during progressive myocardial ischaemia. Third, proliferation of the neointima following injury of a coronary artery is at least in part mediated by angiotensin II. Although ACE inhibition was an effective tool in animal experiments to prevent excessive proliferation of the neointima following ballooning, it was less effective in preventing restenosis in man following a repeat coronary angioplasty. Fourth, preferential proliferation of the cardiac interstitium in experimental hypertension has been associated with activation of the renin-angiotensin system. In patients with essential hypertension ACE inhibitors were not only capable of controlling blood pressure but also of normalizing the previously pathological pattern of diastolic left ventricular filling. In summary, by therapeutic intervention that cause a blockade of this system, cardioprotective and cardioreparative processes can be supported.

Neural control of sympathetic nerve response to cardiogenic hypotension in anesthetized cat.

The present study was designed to determine effect of the preganglionic splanchnic nerve activity (SNA) on the brief hypotension accompanied with the occlusion of left circumflex coronary artery (CxCAO) in chloralose anesthetized cats. Following CxCAO in animals with neuraxis intact, no significant alterations of SNA occurred despite the significant fall in mean blood pressure (MBP). A significant fall in MBP also occurred in vagotomized animals with arterial baroreceptors intact, but SNA was significantly augmented from 12.9 +/- 2.7 impulses/sec before CxCAO to 24.4 +/- 4.3 impulses/sec 60 sec after the occlusion. In vagotomized animals, in which their carotid sinuses were isolated and perfused with the constant pressure at a level equal to systemic blood pressure (112 +/- 6 mmHg) and with higher pressure (167 +/- 7 mmHg), SNA was not altered significantly during the hypotension due to CxCAO. When the carotid sinuses were perfused with lower pressure (53 +/- 8 mmHg), a significant increase in SNA occurred simultaneously with the decrease in MBP after CxCAO. The peak decreases in blood pressure during the coronary occlusion were significantly greater in the vagotomized group (-46 +/- 5 mmHg) and in the Low-CSP group (-50 +/- 5 mmHg) than in other groups. Onset of this excitatory efferent sympathetic response to the hypotension due to the coronary occlusion in the vagotomized and Low-CSP groups was delayed significantly despite a significant fall in arterial blood pressure. These results show that vagal afferents from the heart may play a role of inhibiting the sympathetic augmentation mediated by arterial baroreceptors during cardiogenic hypotension. An excessive activation of cardiac receptors with sympathetic afferents may be induced by the profound fall in blood pressure, resulting in further impairment of cardiac function due to progressive myocardial ischemia under the condition of high sympathetic tone activated by baroreceptor reflex.

Cardiac sequelae of acute head injury.

An intensive 72 hour study of the cardiovascular effects of severe diffuse brain injury was made in seven patients. No other major injury was present. Patients received optimal care very rapidly after injury and intracranial pressure, which was continuously monitored, was maintained at or just above normal by elective positive pressure ventilation techniques. Three patients showed evidence of progressive myocardial ischaemia on continuous electrocardiographic monitoring. Two of these patients died. Ventricular arrhythmias were uncommon but one of the patients with ischaemia developed ventricular tachycardia. Heart rate patterns were very abnormal but did not predict complications. Blood pressure did not vary greatly and cardiac outputs were usually normal. Pronounced excesses of urinary catecholamines and serum creatine kinase 2 isoenzyme (CK MB) as well as total creatine kinase were found. Histological evidence of myocardial damage could be shown at necropsy in the one case whose heart was available for study. This study shows that the cardiac effects of isolated diffuse cerebral injury may be harmful and even fatal despite correction of secondary factors such as anoxia and raised intracranial pressure. The findings suggest that evaluation of the potential benefits of sympathetic blockade is warranted. Cardiac complications of cerebral damage deserve wider recognition by intensive care personnel, neurologists, and neurosurgeons.

Progression of myocardial ischemia from endocardium to epicardium after coronary occlusion assessed by NADH fluorescence photography: Y. Taira, H. Kanaide, M. Nakamura. Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University Medical School, Fukuoka, Japan

Progression of myocardial ischemia from endocardium to epicardium after coronary occlusion assessed by NADH fluorescence photography: Y. Taira, H. Kanaide, M. Nakamura. Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University Medical School, Fukuoka, Japan

SINGLE CORONARY ARTERY

Abstract. Three cases of single coronary artery are reported. All had bicuspid aortic valves and one case also a ventricular septal defect. A 24‐year‐old woman had suffered from angina pectoris from the age of 16. Over the last years electrocardiographic signs of progressive myocardial ischemia and an additional right bundle branch block have developed. Angiography has shown the presence of a single left coronary artery and bicuspid aortic valves. A 65‐year‐old woman with aortic stenosis and insufficiency has a single right coronary artery and bicuspid aortic valves. The ECG reveals the presence of a left bundle branch block. A man aged 34 years with a single left coronary artery, bicuspid aortic valves and a ventricular septal defect had a subacute bacterial endocarditis with rapid development of aortic insufficiency. He died from intractable heart failure. Emphasis is laid upon the recognition of single coronary artery as the potential cause of severe heart disease such as subacute bacterial endocarditis, aortic valvular disease and premature myocardial ischemia.