Thomas Konorza

Cerebral Embolization During Transcatheter Aortic Valve Implantation A Transcranial Doppler Study

Background— Transcatheter aortic valve implantation (TAVI) is associated with a higher risk of neurological events for both the transfemoral and transapical approach than surgical valve replacement. Cerebral magnetic resonance imaging has revealed more new, albeit clinically silent lesions from procedural embolization, yet the main source and predominant procedural step of emboli remain unclear. Methods and Results— Eighty-three patients underwent transfemoral (Medtronic CoreValve [MCVTF], n=32; Edwards Sapien [ESTF], n=26) and transapical (ESTA: n=25) TAVI. Serial transcranial Doppler examinations before, during, and 3 months after TAVI were used to identify high-intensity transient signals (HITS) as a surrogate for microembolization. Procedural HITS were detected in all patients, predominantly during manipulation of the calcified aortic valve while stent valves were being positioned and implanted. The balloon-expandable ES prosthesis caused significantly more HITS (mean [95% CI]) during positioning (ESTF, 259.9 [184.8–334.9]; ESTA, 206.1[162.5–249.7]; MCVTF, 78.5 [25.3–131.6]; P<0.001) and the self-expandable MCV prosthesis during implantation (MCVTF, 397.1 [302.1–492.2]; ESTF, 88.2 [70.2–106.3]; ESTA, 110.7 [82.0–139.3]; P<0.001). Overall, there were no significant differences between transfemoral and transapical TAVI or between the MCV and ES prostheses. No HITS were detected at baseline or 3-month follow-up. There was 1 major procedural stroke that resulted in death and 1 minor procedural stroke with full recovery at 3-month follow-up in the MCV group. Conclusions— Procedural HITS were detected by transcranial Doppler in all patients. Although no difference was observed between the transfemoral and the transapical approach with the balloon-expandable ES stent valve, transfemoral TAVI with the self-expandable MCV prosthesis resulted in the greatest number of HITS, predominantly during implantation.

MitraClip therapy in daily clinical practice: initial results from the German transcatheter mitral valve interventions (TRAMI) registry

A substantial percentage of patients with mitral regurgitation (MR) in need of mitral valve repair are currently considered not suitable for conventional surgery. In Germany, the largest cohort of patients studied to date has been treated using a percutaneous, catheter‐based approach. We report the acute outcomes of patients enrolled in the investigator‐initiated German transcatheter mitral valve interventions (TRAMI) registry.

Supported High-Risk Percutaneous Coronary Intervention With the Impella 2.5 Device: The Europella Registry

OBJECTIVES This retrospective multicenter registry evaluated the safety and feasibility of left ventricular (LV) support with the Impella 2.5 (Abiomed Europe GmbH, Aachen, Germany) during high-risk percutaneous coronary intervention (PCI). BACKGROUND Patients with complex or high-risk coronary lesions, such as last remaining vessel or left main lesions, are increasingly being treated with PCI. Because periprocedural hemodynamic compromise and complications might occur rapidly, many of these high-risk procedures are being performed with mechanical cardiac assistance, particularly in patients with poor LV function. The Impella 2.5, a percutaneous implantable LV assist device, might be a superior alternative to the traditionally used intra-aortic balloon pump. METHODS The Europella registry included 144 consecutive patients who underwent a high-risk PCI. Safety and feasibility end points included incidence of 30-day adverse events and successful device function. RESULTS Patients were older (62% >70 years of age), 54% had an LV ejection fraction < or = 30%, and the prevalence of comorbid conditions was high. Mean European System for Cardiac Operative Risk Evaluation score was 8.2 (SD 3.4), and 43% of the patients were refused for coronary artery bypass grafting. A PCI was considered high-risk due to left main disease, last remaining vessel disease, multivessel coronary artery disease, and low LV function in 53%, 17%, 81%, and 35% of the cases, respectively. Mortality at 30 days was 5.5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively. CONCLUSIONS This large multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI.

Intracardiac Echocardiography Is Superior to Conventional Monitoring for Guiding Device Closure of Interatrial Communications

Background—This study sought to test whether intracardiac echocardiography (ICE) is superior to conventional monitoring in guiding device closure of interatrial communications (atrial septal defect [ASD] and patent foramen ovale [PFO]). Methods and Results—Forty-four patients undergoing device closure of ASD (n=6) or PFO (n=38) were randomized to have the procedure guided by either ICE (group 1; n=22) or by transesophageal echocardiography (TEE) (group 2; n=22). All interventions were completed successfully. In 1 patient from group 2, atrial fibrillation occurred 1 day after device implantation; the patient was successfully cardioverted on the next day. There were no other complications. Fluoroscopy time (FT) (6.0±1.7 minutes versus 9.5±1.6 minutes;P <0.0001) as well as procedure time (PT) (33.4±4.7 minutes versus 37.8±5.6 minutes;P <0.01) were shorter in group 1 than in group 2. Group 2 patients required general anesthesia without (n=19) or with endotracheal intubation (n=3). In contrast, ICE allowed continuous monitoring of the whole procedure, including balloon sizing before device closure, without sedation. Conclusions—ICE is a safe tool to guide device closure of PFO and ASD. Supine patients tolerate ICE better than TEE. ICE reduces FT and PT. ICE seems to be advantageous, especially when long continuous or repeated echocardiographic viewing is required.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a review and update

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a predominantly genetically determined and heritable form of cardiomyopathy that is characterized pathologically by the replacement of myocytes by adipose and fibrous tissue and leads to right ventricular failure, arrhythmias, and sudden cardiac death. The estimated prevalence of ARVC/D in the general population ranges from 1 in 2,000 to 1 in 5,000, men are more frequently affected than women, with an approximate ratio of 3:1. ARVC/D can be inherited as an autosomal dominant disease with reduced penetrance and variable expression, autosomal recessive inheritance is also described. There have been 12 genes identified which are linked to ARVC/D, encoding several components of the cardiac desmosome. Dysfunctional desmosomes resulting in defective cell adhesion proteins, such as plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP-2), and desmoglein-2 (DSG-2) consequently cause loss of electrical coupling between cardiac myocytes, leading to myocyte cell death, fibrofatty replacement and arrhythmias. Diagnosis is based on the finding a combination of characteristic abnormalities in family history, electrocardiography, cardiac imaging as well as endomyocardial biopsy (original task force criteria). Therapeutic options remain limited because of the progressive nature of ARVC/D. Competitive athletics should be avoided. Patients with ARVC/D with a history of having been resuscitated from sudden cardiac death, patients with syncope, very young patients, and those who have marked right ventricular involvement are at the highest risk for arrhythmic death and also, the presence of left ventricular involvement is a risk factor. Several authors concluded that patients who meet the Task Force criteria for ARVC/D are at high risk for sudden cardiac death and should undergo ICD placement for primary and secondary prevention, regardless of electrophysiologic testing results. The role of electrophysiologic study and VT catheter ablation in ARVC/D remains poorly defined, and is frequently used as a palliative measure for patients with refractory VT. The progressive nature of ARVC/D suggests that catheter ablation would not be a long-term curative procedure. Sotalol proved to be highly effective in patients with ARVC/D and inducible as well as non-inducible ventricular tachycardia; if it is ineffective in inducible ventricular tachycardia response to other antiarrhythmic drugs is unlikely and therefore non-pharmacological therapy without further drug testing should be considered. Orthotopic heart transplantation is considered in patients with progressive heart failure and intractable recurrent ventricular arrhythmias

Prognostic implication of cardiac troponin T increase following stent implantation

Objective: To identify the incidence and clinical significance of myocardial injury following elective stent implantation. Design: Prospective clinical study with 278 consecutive patients undergoing stenting of de novo coronary or saphenous vein graft lesions. Incidence of periprocedural myocardial injury was assessed by analysis of 12 lead ECG, creatine kinase (CK; upper limit of normal (ULN) 70 IU/l for women, 80 IU/l for men), and cardiac troponin T (cTnT; point of care test; threshold 0.1 ng/ml) before and 6, 12, and 24 hours after the intervention. Major adverse cardiac events (MACE: acute myocardial infarction, bypass surgery, and cardiac death) were recorded during clinical follow up (mean (SD) 7.8 (5.3) months). Results: Following elective stenting, the rate of a positive cTnT status was 17.3%, the rate of CK increase of 1–3× ULN 14.7%, the rate of CK increase of > 3× ULN 1.4%, and the rate of Q wave myocardial infarction 0.4%. Cardiac mortality during follow up was higher in patients with postprocedurally increased CK (7.1% v 1.3%, p = 0.01, log rank) and cTnT (9.1% v 0.9%, p < 0.001, log rank). In addition, postprocedurally increased cTnT was associated with a higher overall incidence of MACE (13.1% v 4.0%, p < 0.01, log rank) and was identified as an independent factor for MACE during follow up (hazard ratio 3.27, 95% confidence interval 1.14 to 9.41, p = 0.028). Conclusions: Following elective stent implantation, a positive cTnT status identified patients at risk of a worse long term outcome. Treatment strategies have to be developed that lead to prognostic improvement by reducing periprocedural myocardial injury.

Vasoconstrictor Potential of Coronary Aspirate From Patients Undergoing Stenting of Saphenous Vein Aortocoronary Bypass Grafts and Its Pharmacological Attenuation

Rationale: Stent implantation into atherosclerotic plaques releases, apart from particulate debris, soluble substances that contribute to impaired microvascular perfusion. Objective: To quantify the release of vasoconstrictors and to determine the efficacy of coronary dilators to attenuate their action. Methods and Results: Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stenting in 22 patients with severe saphenous vein aorto-coronary bypass stenoses. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor (TNF)&agr; was measured. The response of rat mesenteric arteries with intact (+E) and denuded (−E) endothelium to aspirate plasma was normalized to that by KCl. Responses to selective receptor blockade, adenosine, nitroprusside, and verapamil against the aspirate-induced constriction were determined. The coronary arterial plasma withdrawn before stenting induced 21±5% and the aspirate plasma after stenting induced 95±8% of maximum KCl-induced vasoconstriction. Serotonin, thromboxane B2, and TNF&agr; release into aspirate plasma increased by 1.9±0.2 &mgr;mol/L, 25.6±3.1 pg/mL, and 19.7±6.1 pg/mL, respectively, during stenting. The aspirate-induced vasoconstriction was largely antagonized by selective serotonin receptor blockade, with little further antagonism by additional thromboxane receptor blockade. TNF&agr; did not induce constriction per se but potentiated the constriction with serotonin and the thromboxane-analog U-46619 in arteries +E. The concentrations to induce half-maximal vasodilation were comparable for nitroprusside (+E, 3.3×10−8; −E, 1.9×10−8 mol/L) and verapamil (+E, 8.3×10−8; −E, 7.8×10−8 mol/L), and the vasoconstriction was eventually eliminated. The vasodilator response to adenosine was dependent on functional endothelium and weaker. Conclusion: Serotonin is the main coronary vasoconstrictor after stenting, and thromboxane and TNF&agr; somewhat potentiate the serotonin response. Nitroprusside and verapamil are more potent than adenosine to attenuate the aspirate plasma-induced vasoconstriction, and they are not dependent on functional endothelium.

Hybrid operating room concept for combined diagnostics, intervention and surgery in acute type A dissection †

OBJECTIVES In acute type A dissection (AAAD), it is commonly decided to carry out immediate surgical repair without invasive diagnostics. The hybrid operating room (Hybrid OR) concept encompasses simultaneous haemodynamic control, non-invasive and invasive diagnostics and immediate surgical and/or interventional treatment. Results over a seven-year period are presented here. METHODS From March 2004 to March 2011, 1883 cardiological and surgical patients were treated in a Hybrid OR. Of these, 124 patients (age 60 ± 13, 64% male) diagnosed with AAAD were operated upon. External computed tomography (CT) was available for 87% (108/124) of cases and angiography in 15% (19/124). Preoperative transoesophageal echocardiography (TEE) was done in all patients and angiography in 57% (71/124). Surgery was performed without angiography in 27% (34/124), of which 14% (17/124) was due to shock. Postoperative control angiography followed in 18% (22/124) due to suspected ongoing malperfusion. RESULTS Preoperative angiography was performed in 71 patients, and no angiography related complications were observed during the procedure. A total of 32% (23/71) of these underwent coronary artery bypass graft (CABG)--for newly-diagnosed coronary artery disease in 21% of cases and for coronary malperfusion in 11%. Visceral/peripheral malperfusion syndromes, necessitating primary endovascular intervention, were detected in 23% (16/71). Ascending aorta replacement was performed in 100% (124/124) of patients, arch replacement in 88% (109/124) and descending aorta repair in 35% (44/124). Five postoperative endovascular interventions became necessary due to persistent malperfusion. In-hospital mortality was 13% (12/90) in patients who had undergone preoperative invasive diagnostics and 24% (8/34) in patients who had not. CONCLUSIONS The Hybrid OR concept enables the exact diagnosis of coronary status and downstream malperfusion sites and influences the design of surgical and/or endovascular treatment, without time delay and at negligible risk to the patient.

Systematic analysis of functional and structural changes after coronary microembolization: a cardiac magnetic resonance imaging study.

OBJECTIVES Our study aimed to detect the morphological und functional effects of coronary microembolization (ME) in vivo by cardiac magnetic resonance (CMR) imaging in an established experimental animal model. BACKGROUND Post-mortem morphological alterations of coronary ME include perifocal inflammatory edema and focal microinfarcts. Clinically, the detection of ME after successful coronary interventions identifies a population with a worse long-term prognosis. METHODS In 18 minipigs, ME was performed by intracoronary infusion of microspheres followed by repetitive in vivo imaging on a 1.5-T MR system from 30 min to 8 h after ME. Additionally, corresponding ex vivo CMR imaging and histomorphology were performed. RESULTS Cine CMR imaging demonstrated a time-dependent increase of wall motion abnormalities from 9 of 18 animals after 30 min to all animals after 8 h (0.5 h, 50%; 2 h, 78%; 4 h, 75%; 8 h, 100%). Whereas T2 images were negative 30 min after ME, 4 of 18 animals showed myocardial edema at follow-up (0.5 h, 0%; 2 h, 6%; 4 h, 25%; 8 h, 17%). In vivo late gadolinium enhancement (LGE) was observed in none of the animals after 30 min, but in 33%, 50%, and 83% of animals at 2 h, 4 h, and 8 h, respectively, after ME. Ex vivo CMR imaging showed patchy areas of LGE in all but 1 animal (2 h, 83%; 4 h, 100%; 8 h, 100%). A significant correlation was seen between the maximum troponin I level and LGE in vivo (r = 0.63) and the spatial extent of ex vivo LGE (r = 0.76). CONCLUSIONS Our results show that in vivo contrast-enhanced CMR imaging allows us to detect functional and structural myocardial changes after ME with a high sensitivity. Ex vivo, the pattern of LGE of high-resolution, contrast-enhanced CMR imaging is different from the well-known pattern of LGE in compact myocardial damage. Thus, improvements in spatial resolution are thought to be necessary to improve its ability to visualize ME-induced structural alterations even in vivo.

How Much Myocardial Damage Is Necessary to Enable Detection of Focal Late Gadolinium Enhancement at Cardiac MR Imaging

PURPOSE To assess the visibility of small myocardial lesions at magnetic resonance (MR) imaging and to estimate how much myocardial damage is necessary to enable detection of late gadolinium enhancement (LGE) in vivo. MATERIALS AND METHODS The study was approved by the local bioethics committee. Coronary microembolization was performed by injecting 300,000 microspheres into the distal portion of the left anterior descending artery in 18 anesthetized minipigs to create multifocal areas of myocardial damage. In vivo MR imaging was performed a mean of 6 hours after microembolization by using an inversion-recovery spoiled gradient-echo sequence (repetition time msec/echo time msec, 8/4; inversion time, 240-320 msec; flip angle, 20 degrees; spatial resolution, 1.3 x 1.7 x 5.0 mm(3)) after injection of 0.2 mmol gadopentetate dimeglumine per kilogram of body weight. High-spatial-resolution imaging of the explanted heart was performed by using the same sequence with a higher spatial resolution (0.5 x 0.5 x 2.0 mm(3)). Imaging results were verified with histologic examination. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of in vivo and ex vivo images were calculated, and a t test was used to analyze observed differences. RESULTS Multifocal myocardial damage was successfully induced in all animals. Areas of LGE with low SNR (mean, 36.3 +/- 29.4 [standard deviation]) and CNR (23.7 +/- 19.8) were observed in vivo in 12 (67%) of 18 animals, whereas ex vivo imaging revealed spotted to streaky areas of LGE with higher SNR (91.4 +/- 27.8, P < .0001) and CNR (72.1 +/- 25.4, P < .0001) among normal-appearing myocardium in all cases (100%). Focal myocardial lesions exceeding 5% of myocardium per slice at histologic examination were detected in vivo with a sensitivity of 83%. CONCLUSION Focal myocardial damage exceeding 5% of myocardium within the region of interest seems to be necessary for detection of LGE in vivo in an experimental model of coronary microembolization.