Reversibility of coronary endothelial vasomotor dysfunction in idiopathic dilated cardiomyopathy: acute effects of vitamin C.

In patients with idiopathic dilated cardiomyopathy, endothelium vasomotor function is disturbed. Increased oxidative stress and the consecutive formation of oxygen free radicals have been implicated as one possibility for this observation, suggesting that nitric oxide (NO) is inactivated by oxygen free radicals. We tested the hypothesis that the antioxidant, vitamin C, may improve endothelial function in idiopathic dilated cardiomyopathy. In 11 patients, the endothelium-dependent vasomotor response of the left anterior descending coronary artery to intracoronary acetylcholine (ACh) infusion (1/2 x 10(-6) mol/L, 1/4 x 10(-5) mol/L; respectively) was determined before and immediately after intravenous infusion of 3 g of vitamin C. Coronary cross-sectional diameter was obtained by quantitative coronary angiography, average peak velocity was measured by an intracoronary Doppler flow wire, and coronary blood flow (CBF) was calculated. Maximum cross-sectional diameter was determined after administration of nitroglycerin. Dose-dependent ACh showed a decrease in cross-sectional diameter (-5% to -7%, p <0.05) and an increase in average peak velocity (+16% to +25%, p <0.05); the CBF was unchanged (+1% to -2%, p = NS). After vitamin C infusion, the cross-sectional diameter increased in a dose-dependent manner from +11% to +15%, the average peak velocity increased from +20% to + 41% (p <0.05), and the CBF increased from +38% to + 82% (p <0.01, p <0.001, respectively). Thus, patients with idiopathic dilated cardiomyopathy had endothelial dysfunction, and administration of vitamin C reversed endothelium-dependent dysfunction.     

Extensive intramural hematoma as the cause of failed coronary angioplasty: Diagnosis by intravascular ultrasound and treatment by stent implantation

Dissections after coronary angioplasty are the major cause of ischemic events following percutaneous transluminal coronary angioplasty (PTCA) and may require additional measures such as intravascular stent deployment to relieve or prevent acute vessel closure. We describe a rare type of dissection after PTCA which caused a severe obstruction of the vessel segment proximal to the dilatation site without a visible dissection flap. Intravascular ultrasound was used to elucidate the morphology of the proximal vessel obstruction, which revealed an intramural hematoma extending into the proximal vessel segment as underlying mechanism. A Palmaz-Schatz stent was placed at the entry site of this hematoma, which led to the relief of the proximal vessel obstruction. After 3 months of anticoagulation therapy the repeat coronary angiography showed no significant restenosis. This demonstrates the unique insight into the underlying morphology of failed PTCA by intravascular ultrasound, which can help to manage even rare and unusual complications. © 1995 Wiley-Liss, Inc.     

Structure and function of contractile proteins in human dilated cardiomyopathy

The pathogenesis of reduced systolic left ventricular function in dilated cardiomyopathy is yet unclear. To analyze a possible involvement of contractile protein, function and structure of left ventricular myofibrils were examined in hearts of patients with advanced cardiomyopathy undergoing heart transplantation and in normal control hearts (from renal transplant donors). Myosin and actin content of the left ventricular myocardium was slightly reduced in cardiomyopathic hearts. Myofibrillar polypeptide composition was determined using two-dimensional electrophoresis and immunoblotting. No differences in constituting polypeptides were apparent, including Z-line proteins and proteins of the endosarcomeric lattice. M-line-bound creatine kinase was identical in both groups. Further, basal and maximal myofibrillar adenosine triphosphatase (ATPase) activities were unaltered in dilated cardiomyopathy. The structure of purified myosin was identical in both groups by the following criteria: electrophoretic mobility of native myosin, identical pattern of light chains after isoelectric focusing, identical cleavage peptides of myosin's heavy chain, and identical patterns after immunoblotting of heavy chain cleavage peptides using polyclonal antibodies generated against myosin from normal and cardiomyopathic ventricles. Ca2+-activated, K+-EDTA-activated and actin-activated myosin ATPase activities were identical in control and cardiomyopathic hearts. A structural alteration or functional defect of myofibrils does not seem to be primarily involved in the pathogenesis of reduced myocardial contractility in dilated cardiomyopathy.     

Evaluation of an active coronary perfusion balloon device using Doppler flow wire during PTCA

The aim of this study was to assess whether active coronary perfusion catheters (APC) can provide a sufficient coronary flow in large caliber vessels during balloon inflation. To prevent myocardial ischemia during PTCA, these APC may be employed. However, it is as yet unknown whether the active flow rate of these devices approaches the flow rate prior to PTCA during balloon inflation. Therefore, we measured the efficacy of the APC during balloon inflation in vessels supplying a large amount of myocardium. In 12 patients (1 female, 11 males, 53 ± 12.6 yr) with stenosed vessels (average diameter 3.4 ± 0.26 mm), the coronary flow velocity was measured using a 0.014“ Doppler guidewire, which was placed distally bypassing the balloon of the APC. The active perfusion balloon catheter was advanced through a 7F guiding catheter along a 0.014” guidewire. After removal of the guidewire, arterial blood being withdrawn from the side port of the femoral angioplasty sheath was pumped through the catheter to the distal coronary vessel. The perfusion volumes of the pump were set to different levels between 30 to 60 ml/min. Intracoronary flow rate was calculated by the angiographically assessed vessel luminal area × average peak velocity × 0.5. The mean coronary flow rate prior to PTCA was 43 ± 17.7 ml/min. Maximum flow during PTCA was 55 ± 19.6 ml/min. We found a good correlation between the preset external pump rate and the coronary flow in situ (r=0.92). Pre-PTCA flow rates were achieved in 11 of 12 patients (92%) during balloon inflation. No relevant decrease in the arterial pressure occurred during dilation times of 4.6 ± 1.63 min. Only two patients showed significant ECG changes during these balloon inflations. After an average follow-up period of 13 ± 6.3 mo, only one patient (8%) had a significant re-stenosis requiring the implantation of a stent. The combination of intravascular Doppler velocity measurements with quantitative coronary angiography offers the opportunity of exact online flow registration during angioplasty. Using APC, it is possible to maintain a sufficient coronary flow in the distal vessel during balloon inflation even in large vessels. Therefore, as compared with mechanical circulatory assist devices, coronary assist by APC is a little invasive, but according to our measurements it might be a sufficient tool for performing PTCA also in high-risk patients. Cathet. Cardiovasc. Diagn. 42:84-89, 1997. © 1997 Wiley-Liss, Inc.     

The German Aortic Valve Registry (GARY): A Nationwide Registry for Patients Undergoing Invasive Therapy for Severe Aortic Valve Stenosis

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent.     

Intravascular ultrasound-guided optimized stent deployment: Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study)

Objectives A study was set up to validate the safety and feasibilityof intravascular ultrasound-guided stenting without subsequentanticoagulation, and its impact on the 6 months restenosis rate. Methods The study was designed to be multicentred, prospective,and observational. Results One hundred and sixty-one patients with stable anginaand a de novo coronary artery lesion were enrolled. In fourpatients, the implantation of a Palmaz–Schatz (with spiralbridge) stent had failed. One of these four patients died 3days following bypass surgery. In two other patients, intravascularultrasound assessment was not performed. One hundred and twenty-fiveof the remaining 155 patients (81%) were treated with aspirin(100mg.day^–1), because all three criteria for optimizedstent expansion were met. Twenty-two of the remaining 38 patients(25%), in whom at least one criterion was not met were treatedwith aspirin and acenocoumarol (3 months, INR 2·5–3·5),while 16 patients only received aspirin. Stent thrombosis wasdocumented in two patients (1·3%) for which repeat angioplastywas performed. During the hospital stay, there were no deathsor Q-wave myocardial infarctions. Five patients (3·2%)sustained a non-Q-wave myocardial infarction. During the follow-upperiod (198±38 days, complete for all patients, exceptone), one patient (0·6%) sustained a Q-wave myocardialinfarction, one (0·6%) underwent bypass surgery, andrepeat angioplasty was performed in nine patients (5·7%).In two of the nine patients, repeat angioplasty involved anotherlesion. Therefore, the target lesion revascularization rateduring follow-up was 4·5% (seven patients).At quantitativecoronary angiography, the minimal lumen diameter (mean±SD)increased from 1·12± 0·34mm before to 2·89±0·35mmafter stenting. Repeat angiography at 6 months was performedin 144 patients (92%). The minimal lumen diameter at follow-upwas 2·12±0·67mm. Restenosis (diameter stenosisof 50% or more) was documented in 12 patients or 8·3%.When the two patients with documented stent thrombosis are included,the restenosis rate amounts to 9·7%. Conclusions These data confirm that, in selected patients, stentscan safely be implanted without the use of systemic anticoagulation,provided optimal stent expansion is achieved. The exact roleof intravascular ultrasound in the achievement of these resultsneeds to be established by appropriately designed studies. Inthe meantime, intra-vascular ultrasound coupled with the Palmaz–Schatzstent incorporating a spiral bridge, may have contributed considerablyto the immediate angiographic outcome, which in turn may explainthe favourable clinical and angiographic outcome at 6 months.     

Mechanical left ventricular unloading during high risk coronary angioplasty: First use of a new percutaneous transvalvular left ventricular assist device

A new catheter mounted, transvalvular left ventricular assist device has been designed for percutaneous transfemoral access. The device, the Hemopump? [14 French (Fr.) outer diameter], is based on a mixed flow rotary pump and is capable of flow rates of 1.5–2.2 1/min. The pump is inserted using a specialized 16 Fr. femoral introducer sheath. The first application of the percutaneous Hemopump? in man was performed in two patients with hemodynamic compromise during high risk coronary angioplasty. In these patients, Hemopump? support resulted in hemodynamic stabilization (increase in aortic pressure from 60/42 to 87/61 and from 80/60 to 100/70 mm Hg, respectively) and marked left ventricular unloading (decrease in pulmonary capillary wedge pressure from 25 to 10 and from 14 to 10 mm Hg) during balloon inflation. In both patients, percutaneous transluminal coronary angioplasty (PTCA) could be accomplished successfully. Using the system for periods of about 2 hr in each patient, we observed no vascular, hemorrhagic, or embolic complications. In both patients, only a minor increase in both plasma free hemoglobin and lactate dehydrogenase levels was noted. Our preliminary experiences suggest that the percutaneous Hemopump? is safe and effective and may be a powerful alternative to other devices used for supported angioplasty.     

Enterovirus-induced myocarditis: Hemodynamic deterioration with immunosuppressive therapy and successful application of interferon-α

In 1985Myocarditis was diagnosed by endomyocardial biopsy in a 53-year-old woman who was free of symptoms of heart insufficiency. Immunosuppressive therapy with azathioprine and prednisolone was prescribed as the patient had deteriorated to NYHA II heart insufficiency in March 1986. When application of immunosuppressive agents was terminated in 1987, serial endomyocardial biopsies revealed no signs of myocarditis, thus indicating effectiveness of immuno uppression. Nevertheless, the patient had worsened clinically and hemodynamically. At follow-up in 1991, the patient had progressed to dilated cardiomyopathy resulting in NYHA III heart insufficiency. Enterovirus infection of the heart was detected by in situ nucleic acid hybridization. In addition, retrospective serology indicated a significant increase of coxsackievirus B2 antibodies between 1985 and 1991. Investigational antiviral therapy with recombinant interferon a-2a was tolerated well and a favorable clinical, hemodynamic, and virologic response was observed. Thus, progression of biopsy-proven myocarditis to dilated cardiomyopathy may have been facilitated by immunosuppressive therapy in enterovirus infection. Antiviral therapy might be advantageous in patients with enterovirus myocarditis and dilated cardiomyopathy.     

Oral treatment with probucol in a pharmacological dose has no beneficial effects on mortality in chronic ischemic heart failure after large myocardial infarction in rats

Cardiac remodeling after myocardial infarction is in part triggered and maintained by reactive oxygen species. Antioxidants such as probucol have shown positive short-term effects on these cardiac interstitial changes in different experimental models after intraperitoneal administration or after per-oral administration with a long pre-treatment period or in high doses. In this study, the long-term effects on mortality and cardiac remodeling were examined after induction of a large myocardial infarction in a clinical daily-life-like setting. Male Lewis rats were randomized to the study groups. Large anterolateral myocardial infarctions were induced or sham operations performed. The oral treatment was started after 48 h either with probucol or placebo after myocardial infarction and with placebo after sham operation. Induction of large myocardial infarctions led to changes of the left ventricular stiffness constants, a dilatation of the left ventricle and an increased interstitial fibrosis in the remote non-infarcted part. These changes were in tendency, but not significantly, reversed after treatment with probucol. The 6-month survival rates were 53.1% in the group probucol-myocardial infarction, 43.2% in the group placebo-myocardial infarction and 100% in the group after sham operation. There were no significant differences at Kaplan-Meier analysis between the groups after myocardial infarctions. Oral treatment with the antioxidant probucol started after myocardial infarction in a pharmacological dose does not have favourable effects on the long-term mortality in the chronic ischemic heart failure model in the rat.     

Positionspapier zur kathetergeführten Aortenklappenintervention

?

Due to the increasing number of percutaneous aortic valve replacements carried out, particularly in Germany, the position adopted by the German Cardiac Society (DGK) and the German Society of Thorax, Heart and Vessel Surgery (DGTHG) is set out below:

Indication

In a joint meeting between cardiologists and heart surgeons, the indications for a percutaneous aortic valve replacement (PAVR) should be reviewed. At present, PAVR seems to be indicated in patients who cannot be operated on (due to malformation of the thorax, porcelain aorta, etc.) or in patients older than 75 years in combination with an STS (Society of Thoracic Surgeons) score of more than 10 but no more than 20, or a logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) of more than 20 but no more than 40. PAVR is not recommended or is contraindicated (recommendation level II b, III) in patients with a higher STS score or EuroSCORE, patients with a life expectancy of less than 1 year, patients with more than second-degree aortic regurgitation, or patients with a valve diameter of <18 or >27 mm. At present, the average 30-day mortality rate following PAVR is approximately 10%.

Procedure

The procedure should be performed by cardiologists together with heart surgeons in either a hybrid operation theater or in a cardiac cath lab after an intense training program. The latter management of complications requires the experience of both disciplines. All procedures, including aortic balloon valvuloplasty, are only performed as palliative procedures should be registered in the aortic valve registry (http://www.herzinfarktforschung.de/Projekte/RegisterN/Aortenklappenregister.html).