Search

The transfemoral and the transradial approach are the standard access routes for coronary angiography and percutaneous coronary interventions. A transapical left ventricular access is sometimes used for diagnostic purposes and has been described for structural cardiac interventions, but not for coronary artery interventions.1–4 A significant number of patients who undergo catheter-based aortic valve implantation also require coronary intervention. In selected cases, it may be desirable to perform coronary revascularization via the transapical access, for example if aortic disease makes a transfemoral or transradial approach impossible or may lead to complications. We report a case of successful transapical coronary intervention in a patient undergoing transapical catheter-based aortic valve implantation. #### Case A 92-year-old male patient with severe symptomatic aortic stenosis (valve area, 0.4 cm2; peak pressure gradient, 87 mm Hg; mean pressure gradient, 47 mm Hg), diabetes, renal failure (epidermal growth factor receptor, 28 mL/min per 1.73 m2), obstructive pulmonary disease, and EURO …

The term hibernating myocardium applies to regional left ventricular dysfunction caused by chronic ischemia. It has been postulated that this phenomenon represents a functional adaptation to the chronic lack of oxygen but our own morphological-clinical studies are in contrast to this hypothesis. Recently, we described in human hibernating myocardium a self-perpetuating continuous vicious circle of cellular degeneration, which leads to progressive tissue damage. Here, we put forward the assumption that this vicious circle of structural deterioration is initiated by a disturbed steady state between myocardial oxygen supply and demand followed by intracellular degenerative processes and extracellular repair mechanisms. Structural alterations of cardiomyocytes characterized by a reduced rate of protein synthesis and predominating degradation induce sequestration of cellular particles into the interstitial space accompanied by atrophy of cardiomyocytes. Consecutively, repair mechanisms in the extracellular matrix are initiated. During the inflammatory and fibrogenic phases of this reaction, replacement fibrosis is synthesized leading to a reduction of cell-cell-contacts and of intra- and extracellular coupling followed by derangement of mechanical and signal transduction. Due to the increasing degree of replacement fibrosis, microvascular density is reduced while the oxygen diffusion distance is increased until the oxygen supply to the cardiomyocytes becomes critical resulting in a further progression of intracellular degeneration. For this reason, we propose that this vicious circle is a self-perpetuating process of tissue injury leading to further reduction of regional left ventricular function. This circle can only be interrupted by restoration of an adequate myocardial perfusion.

The role of apoptosis in cardiac ischemia is not clarified yet. Own data show that suicidal cell death is apparently not important in global ischemia where it only affects a small number of myocytes (8 %) while the majority of cells, i.e. 92 % die by oncosis. In acute regional ischemia it is most probably not a decisive factor. However, more solid data are needed to justify this statement. Human hibernating myocardium shows an activation of the apoptotic cascade, i.e., apoptosis might contribute to cell loss in this pathophysiological situation of multiple ischemic episodes. Manifold unresolved issues contribute to problems in determining the role of apoptosis in ischemia. These include 1) Uncertainty of the duration of the apoptotic cascade from activation of death receptors at the cellular membrane until DNA fragmentation occurs, 2) The role of the mitochondrial pathway, 3) The mode of removal of myocytes after cell death has occurred, 4) Technical problems such as specificity of the TUNEL method, detection of low abundance proteins such as activated caspases or cytochrome C, statistical considerations. These issues and many others should be clarified before any definite conclusion as to the role of apoptosis in ischemia may be drawn.

The presence of an aberrant origin of left main coronary artery from the right sinus of valsalva passing between the aorta ascendens and pulmonary trunk is one of the anomalies most frequently associated with malignant clinical events, and surgical treatment is recommended. We report of a 64-year-old patient with a highly increased risk for surgery due to severe chronic obstructive pulmonary disease. This case demonstrates that the use of a drug-eluting stent offers a suitable and valuable alternative.

The aim of this study was to evaluate the usefulness of dobutamine echocardiography and quantitative thallium-201 single photon emission computed tomography myocardial scintigraphy with reinjection in the detection of viable myocardium in patients with coronary artery disease and reduced left ventricular function, which will improve after aortocoronary bypass surgery. Forty-eight patients (47 men, aged 61 +/- 6 years) with angiographically documented reduced left ventricular function (ejection fraction 35 +/- 14, 63% with chronic transmural myocardial infarction) were examined by dobutamine two-dimensional echocardiography (before and during low dosage), 201Tl, and gated radionuclide ventriculography before and 3 +/- 2 months after aortocoronary bypass surgery. Four of 55 areas classified viable before operation were revascularized inadequately and discarded. Global left ventricular ejection fraction at rest rose from 35% +/- 14% before operation to 40% +/- 13% (p0.05) after operation. Stress-induced perfusion defects involved 40% +/- 19% of the left ventricle circumference after stress and showed a significant reduction of size to 23% +/- 14% (p0.01) at rest, 4 hours later, and after reinjection. This value fell to 16% +/- 12% (p0.05) 3 months after aortocoronary bypass surgery. We conclude that both dobutamine echocardiography (sensitivity 95%, specificity 80%, positive predictive value 87%, negative predictive value 88%) and 201Tl studies (sensitivity 87%, specificity 98%, positive predictive value 97%, negative predictive value 93%) are suitable and comparable accurate methods for predicting improvement in systolic function 3 months after revascularization in a selected population with a high prevalence of viable but hypokinetic or akinetic myocardium.

Recently, we described chronic intracellular degeneration accompanied by fibrosis as typical structural features of hibernating myocardium and we concluded that cellular degeneration as a sign of the incomplete adaptation to the reduced blood flow is characteristic of hibernation. This study has been extended by analyzing the composition of the extracellular matrix proteins of the diseased myocardium. Areas of hibernating myocardium were identified in 38 patients by angiography, multigated radionuclide ventriculography, thallium scintigraphy with reinjection and low-dose dobutamine echocardiography. These areas were biopsied at cardiac surgery and were studied by electron microscopic and immunofluorescence techniques. Electron microscopy showed an enlarged extracellular space containing numerous particles of cellular debris, macrophages, fibroblasts, homogeneous matrix material and collagen fibrils. The basement membrane of the cardiomyocytes was thickened by an augmentation of laminin, fibronectin and collagen VI, but these proteins also were present in the matrix itself. Collagen fibrils were numerous and macrophages (CD68) and fibroblasts (vimentin) were increased. In situ hybridization showed an increase in mRNA for laminin, fibronectin and collagen. This observation is consistent with the conclusion that fibrotic scar formation was occurring continuously. It is postulated that fibrosis is the consequence of myocyte loss due to chronic underperfusion in the hibernating tissue. This will further injure myocytes so that a vicious cycle is established that leads to progressive loss of structural integrity and functional capacity. Since these changes are progressive, revascularization should be performed at the earliest time point possible in patients with areas of hibernating myocardium. (Mol Cell Biochem 186:147–158, 1998)

Background We tested the hypothesis that hibernating myocardium represents an incomplete adaptation to a reduced myocardial oxygen supply. Methods and Results In 38 patients, areas of hibernating myocardium were identified by angiography, multigated radionuclide ventriculography, thallium scintigraphy with reinjection, and low-dose dobutamine echocardiography. Biopsies removed at cardiac surgery showed structural degeneration characterized by a reduced protein and mRNA expression and disorganization of the contractile and cytoskeletal proteins myosin, actin, desmin, titin, α-actinin, and vinculin by electron microscopy, immunohistochemistry, and in situ hybridization. Additionally, an increased amount of extracellular matrix proteins resulting in a significant degree of reparative fibrosis was present. Dedifferentiation, ie, expression of fetal proteins, was absent. Apoptosis indicating suicidal cell death was found by the terminal deoxynucleotidyl transferase end-labeling method and electron microscopy. Radionuclide ventriculography showed improvement of regional function at 3 months postoperatively compared with preoperative values (mean values, 23.5% and 48%, respectively), and the echocardiographic wall-motion score index decreased from 3.4 to 1.8. The degree of severity of the morphological changes (three stages) correlated well with the extent of postoperative functional recovery: more advanced clinical improvement was observed in patients with slight and moderate morphological degeneration (stages 1 and 2), but recovery was only partial in severe degeneration (stage 3). Conclusions Cellular degeneration rather than adaptation is present in hibernating myocardium. The consequence is progressive diminution of the chance for complete structural and functional recovery after restoration of blood flow. The practical consequence from this study should be early revascularization in patients showing areas of hibernating myocardium.

The definition of hibernating myocardium (HM) implies that due to chronic underperfusion, the function of the myocardial area afflicted is reduced. It is claimed that the tissue survives at a new level of reduced oxygen supply and demand. After restoration of adequate perfusion, cardiac function will recover (Rahimtoola S. H.: The hibernating myocardium, Am Heart J. 117, 211–220, 1989).

With the introduction of drug eluting stents (DES) in this decade, treatment of patients with STEMI with these devices has emerged as a rational PCI alternative. In spite of the unquestionable benefits of DES in terms of reduction of restenosis and TVR, specific concerns have arisen with regard to

Background Electrocardiogram (ECG) assessment plays a crucial role in patients presenting with chest pain and suspected acute coronary syndrome (ACS). In a pilot study, we previously evaluated a capacitive ECG system (cECG) as a novel ECG technique for a fast and simple ECG assessment in patients with ST-elevation myocardial infarction (STEMI). In a next step, the sensitivity and specificity of this novel ECG technique have to be assessed in patients with ACS. Hypothesis The Fast Infarction Diagnosis ECG Trial (FIDET) is a prospective, bi-center, observer-blinded noninferiority study to evaluate the cECG compared to the conventional ECG (kECG) in the clinical practice for ECG assessment in consecutive patients presenting with suspected ACS. Methods In 250 patients who were admitted to the hospital, because of an ACS [including STEMI and non-ST-elevation acute coronary syndrome (NSTE-ACS)], both a kECG and a cECG recording were performed within a time lag of less than 10 min. End points The primary end point will be sensitivity and specificity of the cECG compared to the kECG in diagnosing a STEMI with a margin of noninferiority of 7.5 %. Secondary end points include sensitivity and specificity of the cECG compared to the kECG in diagnosing an NSTE-ACS, safety of the cECG system (adverse event, serious adverse event and suspected unexpected serious adverse reaction), parameters of the ECG measurement (PQ-interval, QT-interval, ST-amplitude and heart rate) and measurement duration of the two methods. Conclusion FIDET is designed as a noninferiority study to show that a novel cECG system is suitable for the diagnosis of myocardial infarction in the clinical context and might even have benefits, for example by offering a faster and easier ECG assessment.

ObjectivesThe aim of the present study was to objectify the loss of myocytes and the mechanism by which myocytes die in human hibernating myocardium (HHM).BackgroundIntracellular degeneration, reduced cellular protein synthesis, and the replacement fibrosis contribute to structural disintegration of HHM.MethodsIn 14 patients, HHM was diagnosed by dobutamine echocardiography, radionuclide ventriculography, and thallium-201 scintigraphy. Functional recovery was documented by repeating the preoperative clinical investigations three months after successful coronary artery bypass graft surgery (CABG). During CABG, transmural biopsies were taken from the center of HHM regions and studied by electron microscopy, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) method, reverse transcription-polymerase chain reaction, and Western blotting. Control samples were taken from nondiseased human myocardium.ResultsAll patients showed significant improvement or normalization of the regional function of HHM. Ubiquitin-related autophagic cell death was evident ultrastructurally by the occurrence of autophagic vacuoles, cellular degeneration, and nuclear disassembly. Ubiquitin-protein complexes were found in 0.03 ± 0.008% (control: 0%, p < 0.005) of all myocytes. The proteasome 20S subunit/total myocytes were reduced from 63.3 ± 9.6% in control myocardium to 36.9 ± 8.4% in HHM. Complement-9, indicating oncosis, was found in only one of 14 biopsies. TUNEL-positive myocytes were 0.002 ± 0.0003%. Electron microscopy showed apoptotic cells in 3 of 14 samples. However, the bcl-2/baxratio was significantly reduced. Moreover, caspase-3 messenger ribonucleic acid was 8.5 times upregulated, and caspase-3 was activated. Cell death was absent in controls.ConclusionsIn HHM, ubiquitin-related autophagic cell death and apoptosis cause a loss of myocytes. This plays an important role in progressive tissue damage and causes a reduction of the extent of functional recovery of HHM.

ObjectivesWe tested the hypothesis that severe alterations in myocardial energy metabolism play an important role in the pathophysiology of human hibernating myocardium (HHM).BackgroundIt is well established that a disturbed myocardial energy metabolism results in impairments of contractile performance, structure and viability. All of these are important characteristics of HHM.MethodsIn 16 patients with documented coronary artery disease and impaired left ventricular function, HHM was preoperatively detected by thallium-201 scintigraphy, radionuclide ventriculography and low-dose dobutamine echocardiography. These regions were validated as HHM by their recovery of contractile function three months following revascularization. During open-heart surgery, transmural biopsies were removed from the hibernating areas and analyzed both biochemically and morphologically. These findings were compared to normal human myocardium. All metabolite contents given were normalized for the degree of fibrosis (control: 9.8 ± 0.5%; HHM: 28.1 ± 3.0%; p < 0.05), providing myocellular contents.ResultsIn HHM, decreased contents (μmol/g wet weight) in adenosine triphosphate (ATP) (control: 4.17 ± 0.26; HHM: 1.72 ± 0.25; p < 0.001), creatine phosphate (5.67 ± 0.70 vs. 0.84 ± 0.13; p < 0.001) and creatine (27.6 ± 3.19 vs. 11.2 ± 1.56; p < 0.0001) were found, but contents in lactate (2.22 ± 0.26 vs. 25.38 ± 3.53; p < 0.001), purine bases (0.58 ± 0.09 vs. 1.26 ± 0.13; p < 0.001) and protons (pH units: 7.199 ± 0.01 vs. 6.59 ± 0.07; p < 0.001) were increased. Levels in adenosine diphosphate, adenosine monophosphate and inorganic phosphate remained unchanged. Energy depletion in HHM was reflected by decreases in the free energy of ATP hydrolysis and in energy charge.ConclusionsThese data confirm our hypothesis that HHM is energy-depleted myocardium, exhibiting signs of chronic reduction in resting blood flow and a downregulation of energy turnover. The alterations in energy metabolism observed may become operative in triggering and maintaining contractile dysfunction, continuous tissue degeneration and cardiomyocyte loss.

To the Editor: Renal sympathetic denervation (RSD) is an interventional treatment option for resistant arterial hypertension (HT) ([1][1]). Previous investigations of RSD excluded patients with progressive chronic kidney disease because of potential RSD-related kidney damage ([1,2][1]). Diagnosis

In 40 patients with stable coronary artery disease, we prospectively tried to predict the recovery of left ventricular regional wall motion abnormalities. Echocardiographic examination was done before and 3 months after coronary artery bypass surgery (CABG), 16 distinct regions were judged as normal, mildly hypokinetic, severely hypokinetic or akinetic without knowing the results of CABG. Before CABG, dobutamine echocardiography (5 to 10 μ /kg bw/min iv) was done. Regions with improvement of wall motion during dobutamine infusion (Dob+) were expected to recover after CABG. Results Of 412 regions with wall motion abnormalities and angiographically proven successful revascularisation 315 were Dob+, 263 showed improved wall motion after CABG, 52 do not. Out of 97 regions without improvement after dobutamine, only 6 showed improved wall motion after CABG. Sensitivity of Dob+ is 97.8%, specificity 63.6%, positive predictive value 83.5%, negative predictive value 93.8%. Conclusion Dobutamine Echocardiography is useful to predict improvement of wall motion after CABG in hypokinetic or akinetic regions and differentiates viable (hibernating) myocardium from scar tissue areas.