Accuracy of intracoronary ECG parameters for myocardial ischemia detection.

INTRODUCTION: The electrocardiogram (ECG) is a valuable diagnostic tool for the diagnosis of myocardial ischemia during acute coronary syndrome. Aside from the commonly used ST-segment shift indicative of ischemia, several other ECG parameters are pathophysiologically reasonable. Thus, the goal of this study was to assess the accuracy of different ischemia parameters as obtained by the highly susceptible intracoronary ECG (icECG). METHOD: This was a retrospective observational study in 100 patients with chronic coronary syndrome. From each patient, a non-ischemic as well as ischemic icECG at the end of a one-minute proximal coronary balloon occlusion was available, and analysed twice by three different physicians, as well as once together for consensual results. The evaluated parameters were icECG ST-segment shift (mV), ST-integral (mV*sec), T-wave-integral (mV*sec), T-peak (mV), T-peak-to-end time (TPE; msec) and QTc-time (msec). RESULTS: All six icECG parameters showed significant differences between the non-ischemic and the ischemic recording. Using the icECG recording during coronary patency or occlusion as criterion for absent or present myocardial ischemia, ROC-analysis of icECG ST-segment shift showed an area under the curve (AUC) of 0.963 ± 0.029 (p < 0.0001). AUC for ST-integral was 0.899 ± 0.044 (p < 0.0001), for T-wave integral 0.791 ± 0.059 (p < 0.0001), for T-peak 0.811 ± 0.057 (p < 0.0001), for TPE 0.667 ± 0.068 (p < 0.0001), and for QTc-time 0.770 ± 0.061 (p < 0.0001). The best cut-off point for the detection of ischemia by icECG ST-segment shift was 0.365 mV (sensitivity 90%, specificity 95%). CONCLUSION: When tested in a setting with artificially induced absolute myocardial ischemia, icECG ST-segment shift at a threshold of 0.365 mV most accurately distinguishes between absent and present ischemia.

The Human Coronary Collateral Circulation, Its Extracardiac Anastomoses and Their Therapeutic Promotion.

Cardiovascular disease remains the leading global cause of death, and the number of patients with coronary artery disease (CAD) and exhausted therapeutic options (i.e., percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical treatment) is on the rise. Therefore, the evaluation of new therapeutic approaches to offer an alternative treatment strategy for these patients is necessary. A promising research field is the promotion of the coronary collateral circulation, an arterio-arterial network able to prevent or reduce myocardial ischemia in CAD. This review summarizes the basic principles of the human coronary collateral circulation, its extracardiac anastomoses as well as the different therapeutic approaches, especially that of stimulating the extracardiac collateral circulation via permanent occlusion of the internal mammary arteries.

Deep learning-based classification of the capillary ultrastructure in human skeletal muscles.

Background: Capillary ultrastructure in human skeletal muscles is dynamic and prone to alterations in response to many stimuli, e.g., systemic pathologies such as diabetes mellitus and arterial hypertension. Using transmission electron microscopy (TEM) images, several studies have been conducted to quantify the capillary ultrastructure by means of morphometry. Deep learning techniques like convolutional neural networks (CNNs) are utilized to extract data-driven characteristics and to recognize patterns. Hence, the aim of this study was to train a CNN to identify morphometric patterns that differ between capillaries in muscle biopsies of healthy participants and patients with systemic pathologies for the purpose of hypothesis generation. Methods: In this retrospective study we used 1810 electron micrographs from human skeletal muscle capillaries derived from 70 study participants which were classified as "healthy" controls or "patients" in dependence of the absence or presence of a documented history of diabetes mellitus, arterial hypertension or peripheral arterial disease. Using these micrographs, a pre-trained open-access CNN (ResNet101) was trained to discriminate between micrographs of capillaries of the two groups. The CNN with the highest diagnostic accuracies during training were subsequently compared with manual quantitative analysis of the capillary ultrastructure to distinguish between "healthy" controls and patients. Results: Using classification into controls or patients as allocation reference, receiver-operating-characteristics (ROC)-analysis of manually obtained BM thickness showed the best diagnostic accuracy of all morphometric indicators (area under the ROC-curve (AUC): 0.657 ± 0.050). The best performing CNN demonstrated a diagnostic accuracy of 79% (sensitivity 93%, specificity 92%). DeLong-Test of the ROC-curves showed a significant difference (p < 0.001) between the AUC of the best performing CNN and the BM thickness. The underlying morphology responsible for the network prediction focuses mainly on debridement of pericytes. Conclusion: The hypothesis-generating approach using pretrained CNN distinguishes between capillaries depicted on electron micrographs of "healthy" controls and participants with a systemic pathology more accurately than by commonly used morphometric analysis.

Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Chronic Coronary Syndrome: A Double-Blind, Randomized, Sham-Controlled Trial.

The Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Chronic Coronary Syndrome (CLIMACCS) trial, a randomized, sham-controlled trial, tested the clinical efficacy of permanent internal mammary artery (IMA) device occlusion on symptoms in patients with chronic coronary syndrome (CCS), coronary artery occlusive blood supply, and myocardial ischemia. This was a prospective trial in 101 patients with CCS randomly allocated (1:1) to IMA device occlusion (verum group) or to IMA sham intervention (placebo group). The primary study end point was the change in treadmill exercise time (ET) (ΔET in seconds) at 6 weeks after trial intervention. Secondary study end points were the changes in collateral flow index (CFI) and angina pectoris during a simultaneous 1-minute proximal balloon occlusion of a coronary artery. CFI is the ratio between simultaneous mean coronary occlusive, divided by mean aortic pressure, both subtracted by central venous pressure. In the verum and placebo groups, the ET changed from 398 ± 176 seconds to 421 ± 198s in the verum group (p = 0.1745) and from 426 ± 162 seconds to 430 ± 166 seconds in the placebo group (p = 0.55); ΔET amounted to +23 ± 116s and +4 ± 120 seconds, respectively (p = 0.44). CFI change during follow-up equaled +0.022 ± 0.061 in the verum and -0.039 ± 0.072 in the placebo group (p <0.0001). Angina pectoris at follow-up during the coronary balloon occlusion for CFI measurement had decreased or disappeared in 20 of 48 patients in the verum group and in 9 of 47 patients in the placebo group (p = 0.0242). In conclusion, permanent IMA device occlusion tends to augment treadmill ET in response to increased coronary artery occlusive blood supply, which is reflected by mitigated symptoms and signs of myocardial ischemia.

Algorithm for real-time analysis of intracoronary electrocardiogram.

Introduction: Since its first implementation in 1985, intracoronary (ic) electrocardiogram (ECG) has shown ample evidence for its diagnostic value given the higher sensitivity for myocardial ischemia detection in comparison to surface ECG. However, a lack of online systems to quantitatively analyze icECG in real-time prevents its routine use. The present study aimed to develop and validate an autonomous icECG analyzing algorithm. Materials and methods: This is a retrospective observational study in 100 patients with chronic coronary syndrome. From each patient, a non-ischemic as well as ischemic icECG at the end of a 1-min proximal coronary balloon occlusion was available. An ECG expert as well as the newly developed algorithm for autonomous icECG analysis measured the icECG ST-segment shift in mV for each icECG tracing. Results: Intraclass correlation coefficient (ICC) demonstrated low variability between the two methods (ICC = 0.968). Using the time point of icECG recording as allocation reference for absent or present myocardial ischemia, ROC-analysis for ischemia detection by the manually determined icECG ST-segment shift showed an area under the curve (AUC) of 0.968 ± 0.021 (p < 0.0001). AUC for the algorithm analysis was 0.967 ± 0.023 (p < 0.0001; p = 0.925 for the difference between the ROC curve AUCs). Time to complete analysis was below 1,000 ms for the autonomous icECG analysis and above 5 min for manual analysis. Conclusion: A newly developed autonomous icECG analysing algorithm detects myocardial ischemia with equal accuracy as manual ST-segment shift assessment. The algorithm provides the technical fundament for an analysing system to quantitatively obtain icECG in real-time.

Therapeutic Management of Anomalous Coronary Arteries Originating From the Opposite Sinus of Valsalva: Current Evidence, Proposed Approach, and the Unknowing.

Anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS) are a challenge because of their various anatomic and clinical presentation. Although the prevalence is low, the absolute numbers of detected ACAOS are increasing because of the growing use of noninvasive anatomical imaging for ruling out coronary artery disease. As evidence-based guidelines are lacking, treating physicians are left in uncertainty for the optimal management of such patients. The sole presence of ACAOS does not justify surgical correction, and therefore a thorough anatomic and hemodynamic assessment is warranted. Invasive and noninvasive multimodality imaging provides information to the clinical question whether the presence of ACAOS is an innocent coincidental finding, is responsible for the patient's symptoms, or even might be a risk for sudden cardiac death. Based on recent clinical data, focusing on the pathophysiology of patients with ACAOS, myocardial ischemia is dependent on both the extent of fixed and dynamic components, represented by anatomic high-risk features. These varying combinations should be considered individually in the decision making for the different therapeutic options. This state-of-the-art review focuses on the advantages and limitations of the common contemporary surgical, interventional, and medical therapy with regard to the anatomy and pathophysiology of ACAOS. Further, we propose a therapeutic management algorithm based on current evidence on multimodality invasive and noninvasive imaging findings and highlight remaining gaps of knowledge.

Detection of myocardial ischemia by intracoronary ECG using convolutional neural networks.

INTRODUCTION: The electrocardiogram (ECG) is a valuable tool for the diagnosis of myocardial ischemia as it presents distinctive ischemic patterns. Deep learning methods such as convolutional neural networks (CNN) are employed to extract data-derived features and to recognize natural patterns. Hence, CNN enable an unbiased view on well-known clinical phenomenon, e.g., myocardial ischemia. This study tested a novel, hypothesis-generating approach using pre-trained CNN to determine the optimal ischemic parameter as obtained from the highly susceptible intracoronary ECG (icECG). METHOD: This was a retrospective observational study in 228 patients with chronic coronary syndrome. Each patient had participated in clinical trials with icECG recording and ST-segment shift measurement at the beginning (i.e., non-ischemic) and the end (i.e., ischemic) of a one-minute proximal coronary artery balloon occlusion establishing the reference. Using these data (893 icECGs in total), two pre-trained, open-access CNN (GoogLeNet/ResNet101) were trained to recognize ischemia. The best performing CNN during training were compared with the icECG ST-segment shift for diagnostic accuracy in the detection of artificially induced myocardial ischemia. RESULTS: Using coronary patency or occlusion as reference for absent or present myocardial ischemia, receiver-operating-characteristics (ROC)-analysis of manually obtained icECG ST-segment shift (mV) showed an area under the ROC-curve (AUC) of 0.903±0.043 (p<0.0001, sensitivity 80%, specificity 92% at a cut-off of 0.279mV). The best performing CNN showed an AUC of 0.924 (sensitivity 93%, specificity 92%). DeLong-Test of the ROC-curves showed no significant difference between the AUCs. The underlying morphology responsible for the network prediction differed between the trained networks but was focused on the ST-segment and the T-wave for myocardial ischemia detection. CONCLUSIONS: When tested in an experimental setting with artificially induced coronary artery occlusion, quantitative icECG ST-segment shift and CNN using pathophysiologic prediction criteria detect myocardial ischemia with similarly high accuracy.

A case report of a symptomatic right anomalous coronary artery with concomitant atherosclerotic disease: the benefit of a sequential comprehensive non-invasive and invasive diagnostic approach.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital disease associated with an increased risk of myocardial ischaemia, ventricular arrhythmias, and heart failure. CASE SUMMARY: A 75-year-old Caucasian man was referred for invasive coronary angiography (ICA) due to atypical chest pain. Invasive coronary angiography demonstrated non-significant atherosclerotic disease of the left coronary artery and an anomalous origin of the right coronary artery (RCA); without selective intubation. Coronary computed tomography angiography (CCTA) revealed a right-AAOCA with interarterial and intramural course, and a soft plaque in the distal RCA. Subsequent physical-stress single-photon emissions computed tomography (SPECT) showed exercise-induced inferoapical myocardial ischaemia, giving a Class IC level of evidence for surgical correction of the AAOCA. Repeated ICA with selective R-AAOCA intubation confirmed an 80% distal atherosclerotic stenosis, which was treated with direct stenting. Subsequent invasive physiologic evaluation under maximal dobutamine-volume challenge (gradually increasing dose of dobutamine max. 40 µg/kg per body weight/min, 3000 mL ringer lactate and 1 mg atropine was given until the patient reached a maximum of 145 b.p.m.), revealed a haemodynamically non-relevant anomalous segment with a fractional flow reserve (FFR) of 0.91. A follow-up SPECT was normal, and the patient was completely symptom-free at 1 month. DISCUSSION: We present the sequential diagnostic approach in a symptomatic patient with a right anomalous coronary artery and concomitant atherosclerotic disease. Using this approach, the patient could be deferred from guideline recommended open-heart surgery of the AAOCA, as direct invasive dobutamine/volume FFR revealed haemodynamic non-relevance of the anomalous segment after stenting the concomitant atherosclerotic stenosis in the distal segment within the same coronary artery.

Extracardiac coronary steal induced by upper limb hyperemia: a feature of internal mammary artery arteriogenesis.

Function of naturally existing internal mammary artery (IMA)-to-coronary artery anastomoses has been shown by augmented blood supply to the coronary collateral circulation in response to IMA occlusion. Theoretically, this beneficial functional connection is invertible and can be linked to coronary steal, the verification of whose hypothesis would provide alternate proof to the mentioned functional evidence. This was an observational study including 40 patients with chronic coronary syndrome, distal IMA occlusion, and upper limb hyperemia (verum group), and 40 propensity score matched controls (placebo group) without IMA occlusion or hyperemia. Primary study end point was the intergroup difference and temporal development in coronary collateral function (i.e., collateral flow index; CFI) as obtained at 30, 45, and 60 s following a proximal coronary artery balloon occlusion. CFI is the ratio between simultaneous mean coronary occlusive pressure divided by mean aortic pressure both subtracted by central venous pressure. To provoke a steal phenomenon, upper limb hyperemia was induced by upper arm blood pressure cuff deflation following a 5-min suprasystolic inflation ipsilateral to the sensor-wired coronary artery with release immediately after the first CFI measurement. Between the first and the second CFI measurement, CFI change (i.e., CFI@45s - CFI@30s) was absent in the verum group whereas there was CFI recruitment in the placebo group: 0.000 ± 0.023 and +0.009 ± 0.013, respectively; P = 0.032. Among patients with artificial distal IMA occlusion, induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal as expressed by temporarily absent collateral recruitment as it normally takes place without upper limb hyperemia.NEW & NOTEWORTHY Induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal among patients with artificial distal internal mammary artery occlusion. Coronary steal via the occluded internal mammary arteries serves as alternate proof of concept of the already existing evidence of their functional extracoronary collateral supply.

Functional assessment of myocardial ischaemia by intracoronary ECG.

INTRODUCTION: In patients with chronic coronary syndrome, percutaneous coronary intervention targets haemodynamically significant stenoses, that is, those thought to cause ischaemia. Intracoronary ECG (icECG) detects ischaemia directly where it occurs. Thus, the goal of this study was to test the accuracy of icECG during pharmacological inotropic stress to determine functional coronary lesion severity in comparison to the structural parameter of quantitative angiographic per cent diameter stenosis (%S), as well as to the haemodynamic indices of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). METHOD: The primary study endpoint of this prospective trial was the maximal change in icECG ST-segment shift during pharmacological inotropic stress induced by dobutamine plus atropine obtained within 1 min after reaching maximal heart rate(=220 - age). IcECG was acquired by attaching an alligator clamp to the angioplasty guidewire positioned downstream of the stenosis. For the pressure-derived stenosis severity ratios, coronary perfusion pressure and simultaneous aortic pressure were continuously recorded. RESULTS: There was a direct linear relation between icECG ST-segment shift and %S: icECG=-0.8+0.03*%S (r2=0.164; p<0.0001). There were inverse linear correlations between FFR and %S: FFR=1.1-6.1*10-3*%S (r2=0.494; p<0.0001), and between iFR and %S: iFR=1.27-8.6*10-3*%S (r2=0.461; p<0.0001). Using a %S-threshold of ≥50% as the reference for structural stenosis relevance, receiver operating characteristics-analysis of absolute icECG ST-segment shift during hyperemia showed an area under the curve (AUC) of 0.678±0.054 (p=0.002; sensitivity=85%, specificity=50% at 0.34 mV). AUC for FFR was 0.854±0.037 (p<0.0001; sensitivity=64%, specificity=96% at 0.78), and for iFR it was 0.816±0.043 (p<0.0001;sensitivity=62%, specificity=96% at 0.83). CONCLUSIONS: Hyperaemic icECG ST-segment shift detects structurally relevant coronary stenotic lesions with high sensitivity, while they are identified highly specific by FFR and iFR.

Pulmonary Artery Pressure Ventricularization in a Patient With Carcinoid Heart Disease.

Ventricularization of the pulmonary artery pressure curve is shown, characterized by a steep diastolic pressure fall with mid-diastolic pressure equalization with the right ventricle, which was caused by severe pulmonary valvular regurgitation in a patient with carcinoid heart syndrome. (Level of Difficulty: Beginner.).

Hemodynamic Relevance of Anomalous Coronary Arteries Originating From the Opposite Sinus of Valsalva-In Search of the Evidence.

Coronary artery anomalies (CAA) represent a heterogeneous group of congenital disorders of the arterial coronary circulation, defined by an anomalous origin of the coronary ostium and/or vessel course. Of particular interest are anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS). The interarterial variants (with the anomalous vessel situated between the great arteries) are historically called "malignant," based on an anticipated higher risk for myocardial ischemia and sudden cardiac death (SCD), especially affecting young patients during strenuous physical activity. However, the interarterial course itself may not be the predominant cause of ischemia, but rather represents a surrogate for other ischemia-associated anatomical high-risk features. As the exact pathophysiology of ACAOS is not well-understood, there is a lack of evidence-based guidelines addressing optimal diagnostic work-up, downstream testing, sports counseling, and therapeutic options in patients with ACAOS. Therefore, treating physicians are often left with uncertainty regarding the clinical management of affected patients. This review focuses on the pathophysiologic consequences of ACAOS on myocardial ischemia and discusses the concept of the interplay between fixed and dynamic coronary stenosis. Further, we discuss the advantages and limitations of the different diagnostic modalities and give an outlook by highlighting the gaps of knowledge in the assessment of such anomalies.

Invasive Assessment of the Human Arterial Palmar Arch and Forearm Collateral Function During Transradial Access.

BACKGROUND: The present study aimed to quantitatively measure the pressure-derived function of the palmar arch and forearm arterial collateral circulation during transradial access. METHODS AND RESULTS: Palmar arch and forearm collateral function was determined using radial artery pressure signals in the nonobstructed vessel and during brief manual occlusions of the more proximal radial artery and of the radial plus ulnar arteries. Collateral flow index (CFI), the ratio of mean occlusive divided by mean nonocclusive arterial blood pressure, both subtracted by central venous pressure, was determined for CFI during radial artery occlusion (CFIrad) and CFI during radial plus ulnar artery occlusion. Before invasive CFI measurements, arterial palmar arch and forearm function was tested noninvasively by the modified Allen test (MAT). Two hundred fifty patients undergoing transradial access coronary angiography were included in the study. CFIrad was equal to 0.802±0.150 (95% CI, 0.783-0.820). CFI during radial plus ulnar artery occlusion was equal to 0.424±0.188 (95% CI, 0.400-0.447). There was an inverse linear relation between CFIrad and MAT in seconds (s): MAT=64-63×CFIrad ( r2=0.229; P<0.0001). Two hundred eleven patients had a normal and 39 patients an abnormal (>15 seconds) MAT. The group with normal MAT had a CFIrad of 0.830±0.111, and patients with abnormal MAT had a CFIrad of 0.648±0.224 ( P<0.0001). CONCLUSIONS: Direct invasive hemodynamic assessment of the palmar arch and forearm arterial function reveals collateral supply to the briefly occluded in comparison to the patent radial artery of 0.802. During external occlusion of both radial and ulnar artery, CFI amounts to an unexpectedly high value of 0.424.