Established interventions for mitral valve regurgitation. Current evidence.

Severe mitral regurgitation (MR) is a growing medical challenge in today's aging population, leading to increased health expenditure due to the resultant morbidity and mortality. Surgery, either replacement or repair, has been the mainstay of therapy for primary MR. In high-risk or inoperable patients, treatment was limited to medical therapy until 2008. Since then, alternative percutaneous therapies have been introduced and have proven to be safe and effective in patients with secondary MR. Edge-to-edge repair with the MitraClip system is applied worldwide for primary and secondary MR. Randomized data do not support its application in low-risk patients with primary MR. Results from ongoing and future randomized trials will clarify its impact on important clinical endpoints in high-risk and inoperable patients. The Carillon device is a percutaneous indirect annuloplasty technique introduced in 2009 for secondary MR. Clinical data for the novel Cardioband system, using a different intra-atrial annuloplasty technique, have been gathered from more than 40 patients and the system recently received CE mark approval. Other percutaneous repair devices and implantable valves are under development and may be introduced into clinical practice soon. The percutaneous interventional therapy of MR is a highly dynamic field of cardiovascular medicine and has the potential to improve quality of life as well as morbidity and mortality in selected patients.

[Interventional Mitral valve repair with the MitraClip® procedure. Patient selection criteria]. / Interventionelle Mitralklappenrekonstruktion mit dem MitraClip®-Verfahren. Patientenauswahlkriterien.

In current practice the MitraClip® procedure is increasingly being used for patients unsuitable or at high risk for cardiac surgery. This article initially describes the patient groups that are suitable for percutaneous edge-to-edge repair. For this purpose the echocardiographic criteria for severe mitral regurgitation are first characterized and treatment algorithms for patients with primary as well as secondary mitral regurgitation according to current guidelines are illustrated. Basic anatomical requirements for the successful implantation of a MitraClip® are described and a distinction is made between various valve morphologies ranging from optimal to unsuitable anatomical conditions. Finally, three patient groups eligible for percutaneous edge-to-edge repair considering clinical and anatomical criteria are defined: (1) optimal for MitraClip®, (2) MitraClip® could be considered and (3) MitraClip® only in exceptional cases.

[Rational CT imaging in cardiology]. / Rationale CT-Bildgebung in der Kardiologie.

Due to continuous technical developments computed tomography (CT) is increasingly being used for cardiac diagnostics, especially for diagnosis of coronary artery disease (CAD) or less commonly for evaluation of coronary artery anomalies, cardiac valves or cardiac function. Because CT exposes patients to ionizing radiation it should only be performed in patients with a clear indication. Calcium scoring for example may improve risk stratification in asymptomatic patients with an intermediate risk profile or coronary CT angiography may be used to exclude or confirm obstructive CAD in symptomatic patients at intermediate cardiovascular risk. However, other patients, such as symptomatic patients with high cardiovascular risk should not be examined using CT. Therefore, a reasonable use of CT in cardiology requires a differentiated selection of patients.

Coronary plaque volume and predictors for fast plaque progression assessed by serial coronary CT angiography-A single-center observational study.

PURPOSE: The rationale of this study was to identify patients with fast progression of coronary plaque volume PV and characterize changes in PV and plaque components over time. METHOD: Total PV (TPV) was measured in 350 patients undergoing serial coronary computed tomography angiography (median scan interval 3.6 years) using semi-automated software. Plaque morphology was assessed based on attenuation values and stratified into calcified, fibrous, fibrous-fatty and low-attenuation PV for volumetric measurements. Every plaque was additionally classified as either calcified, partially calcified or non-calcified. RESULTS: In total, 812 and 955 plaques were detected in the first and second scan. Mean TPV increase was 20 % on a per-patient base (51.3 mm³ [interquartile range (IQR): 14.4, 126.7] vs. 61.6 mm³ [IQR: 16.7, 170.0]). TPV increase was driven by calcified PV (first scan: 7.6 mm³ [IQR: 0.2, 33.6] vs. second scan: 16.6 mm³ [IQR: 1.8, 62.1], p < 0.01). Forty-two patients showed fast progression of TPV, defined as >1.3 mm3 increase of TPV per month. Male sex (odds ratio 3.1, p = 0.02) and typical angina (odds ratio 3.95, p = 0.03) were identified as risk factors for fast TPV progression, while high-density lipoprotein cholesterol had a protective effect (odds ratio per 10 mg/dl increase of HDL cholesterol: 0.72, p < 0.01). Progression to >50 % stenosis at follow-up was observed in 34 of 327 (10.4 %) calcified plaques, in 13 of 401 (3.2 %) partially calcified plaques and 2 of 221 (0.9 %) non-calcified plaques (p < 0.01). CONCLUSION: Fast plaque progression was observed in male patients and patients with typical angina. High HDL cholesterol showed a protective effect.

Quantification of coronary low-attenuation plaque volume for long-term prediction of cardiac events and reclassification of patients.

BACKGROUND: To investigate the incremental prognostic value of low-attenuation plaque volume (LAPV) from coronary CT angiography datasets. METHODS: Quantification of LAPV was performed using dedicated software equipped with an adaptive plaque tissue algorithm in 1577 patients with suspected CAD. A combination of death and acute coronary syndrome was defined as primary endpoint. To assess the incremental prognostic value of LAPV, parameters were added to a baseline model including clinical risk and obstructive coronary artery disease (CAD), a baseline model including clinical risk and calcium scoring (CACS) and a baseline model including clinical risk and segment involvement score (SIS). RESULTS: Patients were followed for 5.5 years either by telephone contact, mail or clinical visits. The primary endpoint occurred in 30 patients. Quantified LAPV provided incremental prognostic information beyond clinical risk and obstructive CAD (c-index 0.701 vs. 0.767, p < .001), clinical risk and CACS (c-index 0.722 vs. 0.771, p < .01) and clinical risk and SIS (c-index 0.735 vs. 0.771, p < .01. A combined approach using quantified LAPV and clinical risk significantly improved the stratification of patients into different risk categories compared to clinical risk alone (categorical net reclassification index 0.69 with 95% CI 0.27 and 0.96, p < .001). The combined approach classified 846 (53.6%) patients as low risk (annual event rate 0.04%), 439 (27.8%) patients as intermediate risk (annual event rate 0.5%) and 292 (18.5%) patients as high risk (annual event rate 0.99%). CONCLUSION: Quantification of LAPV provides incremental prognostic information beyond established CT risk patterns and permits improved stratification of patients into different risk categories.

Local organ dose conversion coefficients for angiographic examinations of coronary arteries.

New organ dose conversion coefficients for coronary angiographic interventions are presented, as well as dose distributions and resulting maximal local dose conversion coefficients in the relevant organs. For the Monte Carlo based simulations, voxel models of the human anatomy were employed which represent the average Caucasian adult man and woman as defined by the International Commission on Radiological Protection. In the 21 investigated projections, the mean organ dose conversion coefficients vary from a few 0.01 to 2 mGy(Gy cm(2))(-1), depending on the projections. However, especially in portions of the lungs and the active bone marrow, the conversion coefficients can locally amount up to 10 mGy(Gy cm(2))(-1), which is half the average conversion coefficient of the skin at the field entrance. In addition to the dose conversion coefficients, the dependence of the patient dose on the projection has been estimated. It could be shown that the patient doses are highest for left anterior oblique views with strong caudal or cranial orientation. Nevertheless, for a large range of image-intensifier positions no significant dose differences could be found.

Retrospective analysis of circulatory support with the Impella CP® device in patients with therapy refractory cardiogenic shock.

BACKGROUND: In cardiogenic shock (CS) the Impella CP® device provides a fast available left ventricular circulatory support of up to 4.0L/min. However, the use of the Impella CP® device was not systematically analysed yet. METHODS: We performed a retrospective analysis of 28 consecutive patients suffering from severe therapy refractory CS treated with Impella CP®. Mortality was estimated using the SAPS II-Score. Primary outcome was 30-day survival. We compared the different aetiologies of CS and the effect of additional extracorporeal life support (ECLS). RESULTS: Aetiology of CS was acute coronary syndrome (ACS) in 15 patients, 9 patients received additional therapy with ECLS. SAPS II was 73±14, representing an estimated mortality of 87.1%. 18 patients deceased representing a 30-day survival of 36%. Comparing the different aetiologies, ACS-CS patients show a trend towards better survival. Additional therapy with ECLS did not change 30-day survival. In 3 cases, vascular complication needing surgical treatment occurred. All other patients showed no relevant complications except for the commonly seen haemolysis with consecutive need of transfusion. CONCLUSION: Our data could demonstrate that the Impella CP® application in these severely diseased patients is feasible and safe. Compared to the estimated mortality, the 30-day survival seems to be improved.

Effects of beta(-)-emitting (188)Re balloon in stented porcine coronary arteries: an angiographic, intravascular ultrasound, and histomorphometric study.

BACKGROUND: Restenosis within stents may be prevented by ionizing radiation from an intravascular source. METHODS AND RESULTS: A liquid beta(-) radiation ((188)Re) balloon was evaluated in a randomized and blinded porcine coronary model of stent restenosis. Group A pigs (n=17) received 0,16, 22, or 29 Gy at 0.5-mm depth, followed by stenting. Restenosis was quantified by angiography, ultrasound, and histomorphometry at 30 days. Group B (n=7) was stented first and then treated with 0 or 29 Gy with follow-up at 60 days. There was a measurable effect at 16 Gy, which improved with increasing doses. At 29 Gy, the histological stenotic area was reduced by 67% (22% versus 66% in controls, P<0.001). Radiation after stenting was equally effective; the stenotic area was reduced (21% versus 65%, P<0.001). At 16 Gy, the vessel just distal to the stent was significantly smaller than control vessels because of intimal thickening (P=0.003). Radiated vessels had distinctive histology consisting of neointimal fibrin and reduced smooth muscle cells and matrix (P<0.0001). CONCLUSIONS: (188)Re balloon brachytherapy in porcine coronary arteries results in dose-dependent and injury-independent inhibition of stent restenosis for up to 60 days. Restenosis at the borders of the irradiated zone is a potential limitation and may be related to underdosing. Brachytherapy with the (188)Re balloon appears to be safe and feasible for clinical studies.

Recovery of myocardial perfusion in acute myocardial infarction after successful balloon angioplasty and stent placement in the infarct-related coronary artery.

OBJECTIVES: This study sought to investigate changes in myocardial perfusion after direct percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (MI). BACKGROUND: After initially successful recanalization of the infarct-related artery, coronary perfusion may deteriorate as a result of reocclusion, distal embolization of platelet aggregates formed at the dilated plaque or microvascular reperfusion injury. This change could offset the benefit from early intervention. METHODS: The study included 19 patients in whom the infarct-related artery was successfully recanalized by PTCA with Palmaz-Schatz stent placement within 24 h after the onset of pain. Basal and papaverine-induced coronary blood flow were assessed by Doppler flow velocity measurements and quantitative coronary angiography. In addition, basal and adenosine-induced myocardial blood flow were measured by nitrogen-13 ammonia positron emission tomography (PET). RESULTS: Immediately after completion of the intervention, the average coronary flow reserve (CR) in the recanalized vessel was 1.56 +/- 0.51; it increased to 2.04 +/- 0.65 at 1 h (p = 0.013) and to 2.66 +/- 0.72 at 2 weeks after reperfusion (p = 0.008, n = 16). PET studies in 12 patients revealed that perfusion defect size and CR in the infarct region (2.19 +/- 0.89 vs. 2.33 +/- 0.86) did not change significantly between day 2 after recanalization and 2 weeks. However, we found significant (p < 0.03) increases in basal (by 26%) and adenosine-induced (by 40%) blood flow in the infarct region. CONCLUSIONS: Despite the persistence of a perfusion defect after successful recanalization of the occluded artery in acute MI, CR of the infarct region improves in most patients within 1 h and further improves within 2 weeks.

Coronary stent placement in patients with acute myocardial infarction: comparison of clinical and angiographic outcome after randomization to antiplatelet or anticoagulant therapy.

OBJECTIVES: The Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial is a randomized comparison of combined antiplatelet with anticoagulant therapy after coronary Palmaz-Schatz stent placement. The objective of this study was to compare early and late clinical and angiographic outcome in a subgroup of patients with stent placement for acute myocardial infarction. BACKGROUND: Stenting has become a treatment option for acute myocardial infarction, but it is not known which antithrombotic regimen is more adequate after stent implantation. METHODS: One hundred twenty-three patients with successful stenting after acute myocardial infarction were randomized to receive aspirin plus ticlopidine (n = 61) or intense anticoagulant therapy (n = 62). Six-month repeat angiography was performed in 101 (86.3%) eligible patients. RESULTS: During the first 30 days after stenting, patients with antiplatelet therapy had a significantly lower clinical event rate (3.3% vs. 21.0%, p = 0.005) and stent vessel occlusion rate (0% vs. 9.7%, p = 0.03) and a trend to fewer cardiac events (1.6% vs. 9.7%, p = 0.12). After 6 months, the survival rate free of recurrent myocardial infarction was higher in patients with antiplatelet therapy (100% vs. 90.3%, p = 0.03), and the rate of stent vessel occlusion was lower (1.6% vs. 14.5%, p = 0.02). Both groups had comparable restenosis rates (26.5% vs. 26.9%, p = 0.87). CONCLUSIONS: This study demonstrates that combined antiplatelet therapy after stent placement in patients with acute myocardial infarction is associated with an overall better clinical and angiographic outcome than anticoagulant therapy.

Predictive factors of restenosis after coronary stent placement.

OBJECTIVES: The objective of this study was to identify clinical, lesional and procedural factors that can predict restenosis after coronary stent placement. BACKGROUND: Coronary stent placement reduces the restenosis rate compared with that after percutaneous transluminal coronary angioplasty (PTCA). However, restenosis remains an unresolved issue, and identification of its predictive factors may allow further insight into the underlying process. METHODS: All patients with successful coronary stent placement were eligible for this study unless they had had a major adverse cardiac event during the 1st 30 days after the procedure. Of the 1,349 eligible patients (1,753 lesions), follow-up angiography at 6 months was performed in 80.4% (1,084 patients, 1,399 lesions). Demographic, clinical, lesional and procedural data were prospectively recorded and analyzed for any predictive power for the occurrence of late restenosis after stenting. Restenosis was evaluated by using three outcomes at follow-up: binary restenosis as a diameter stenosis > or =50%, late lumen loss as lumen diameter reduction and target lesion revascularization (TLR) as any repeat PTCA or coronary artery bypass surgery involving the stented lesion. RESULTS: Multivariate analysis demonstrated that diabetes mellitus, placement of multiple stents and minimal lumen diameter (MLD) immediately after stenting were the strongest predictors of restenosis. Diabetes increased the risk of binary restenosis with an odds ratio (OR) [95% confidence interval] of 1.86 [1.56 to 2.16] and the risk of TLR with an OR of 1.45 [1.11 to 1.80]. Multiple stents increased the risk of binary restenosis with an OR of 1.81 [1.55 to 2.06] and that of TLR with an OR of 1.94 [1.66 to 2.22]. An MLD <3 mm at the end of the procedure augmented the risk of binary restenosis with an OR of 1.81 [1.55 to 2.06] and that of TLR with an OR of 2.05 [1.77 to 2.34]. Classification and regression tree analysis demonstrated that the incidence of restenosis may be as low as 16% for a lesion without any of these risk factors and as high as 59% for a lesion with a combination of these risk factors. CONCLUSIONS: Diabetes, multiple stents and smaller final MLD are strong predictors of restenosis after coronary stent placement. Achieving an optimal result with a minimal number of stents during the procedure may significantly reduce this risk even in patients with adverse clinical characteristics such as diabetes.

Usefulness of intracoronary brachytherapy for in-stent restenosis with a 188Re liquid-filled balloon.

The objective of this randomized pilot trial with 21 patients was to evaluate the effectiveness of a rhenium-188 liquid-filled balloon system to prevent recurrent restenosis after percutaneous transluminal coronary angioplasty for in-stent restenosis. A significant benefit from brachytherapy was seen at 6-month repeat angiography, as well as during the clinical follow-up of 12 months.

Observer performance for JPEG vs. Wavelet image compression of x-ray coronary angiograms.

Development of "filmless" cardiac catheterization laboratories is eminent. The problems of implementing a digital catheterization laboratory involve archiving large amounts of data per procedure and high transfer rates to retrieve previous procedures. Lossy compression can ccommodate these changes, but at the cost of possibly impairing detection of clinically important angiographic features. Our study involves the observer detection and classification of features in clinical images and the effects that JPEG and wavelet compression have on the detectability of these features. We found no significant degradation in human observer performance with 7:1 and 15:1 JPEG compressed images in 6 clinically relevant visual tasks. Human observer performance for wavelet compression degraded significantly for 2 out of 6 tasks at 7:1 compression and 4 out of 6 tasks at 19:1 compression.

Comparative in-vitro validation of eight first- and second-generation quantitative coronary angiography systems.

BACKGROUND: It is known that first-generation quantitative coronary angiography (QCA) systems overestimate small vessel sizes owing to the point-spread function of the respective X-ray imaging chain. With second-generation systems new algorithms were introduced to correct for this source of error. OBJECTIVE: To evaluate the efficiency of the modified contour detection algorithms. METHODS: Six second-generation QCA systems (CMS, QANSAD, AWOS, CAAS II, Cardio 500, and Angioimage) were validated and compared with first-generation systems (CAAS and ARTREK). By using an arterial phantom consisting of stenotic and nonstenotic glass tubes (of diameters 0.5-5.0 mm) the accuracy and precision of each analysis system, as well as their additional accuracy and precision values for phantom diameters < or = 1.0 mm were determined. RESULTS: All systems had high accuracy and precision values, but first-generation systems overestimated small vessel diameters. With second-generation systems a significantly improved accuracy in the submillimeter range (an accuracy within +/-0.028 mm) was obtained. This improvement was accompanied by a moderate reduction in precision in the submillimeter range. CONCLUSION: The new algorithms of the second-generation QCA systems allow accurate and reliable measurements of small coronary dimensions and, therefore, precise analysis of coronary stenoses of moderate-to-high grade seems feasible with the improved accuracy of the new systems.

A comparative cohort study on personalised antiplatelet therapy in PCI-treated patients with high on-clopidogrel platelet reactivity. Results of the ISAR-HPR registry.

In clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI), high platelet reactivity (HPR) is associated with a higher risk for thrombotic events including stent thrombosis (ST). A personalised therapy with selective intensification of treatment may improve HPR patients´ outcome in this setting although recent randomised trials are against this hypothesis. The aim of the ISAR-HPR registry was to assess whether clopidogrel-treated HPR patients benefit from selective intensification of P2Y12 receptor inhibition. For the registry, outcomes were compared between two cohorts. We identified 428 clopidogrel treated HPR patients (AU x min ≥468 on the Multiplate analyser) between 2007-2008 (historical control cohort) without a change of treatment based on platelet function (PF) testing results. Between 2009-2011, we identified 571 HPR patients (guided therapy cohort) and used this information for guidance and selective intensification of P2Y12 receptor directed treatment (reloading with clopidogrel, switch to prasugrel, re-testing) in a setting of routine PF testing. The primary outcome was the composite of death from any cause or ST after 30 days. Major bleeding according to TIMI criteria was also monitored. The incidence of the primary outcome was significantly lower in the guided vs the control cohort (7 [1.2%] vs 16 [3.7%] events; HR 0.32, 95% CI 0.13-0.79; p=0.009). The incidence of major bleeding was numerically but not statistically higher in the guided vs the control cohort (1.9 vs 0.7%; p=0.10). In conclusion, present findings are in support for a PF testing guided antiplatelet therapy with selective intensification of P2Y12 receptor inhibition. The issue of personalised antiplatelet treatment warrants further investigation in randomized and well-controlled clinical trials.

Percutaneous interventional mitral regurgitation treatment using the Mitra-Clip system.

The interventional treatment of mitral valve regurgitation by the MitraClip procedure has grown rapidly in Germany and Europe during the past years. The MitraClip procedure has the potential to treat high-risk patients with secondary mitral valve regurgitation and poor left ventricular function. Furthermore, patients with primary mitral valve regurgitation may be treated successfully by the MitraClip procedure in case of high surgical risk or in very old patients. At the same time it has been emphasised that the MitraClip interventional treatment is still at an early stage of clinical development. The largest clinical experience with the MitraClip procedure so far is probably present in some German cardiovascular centers, which here summarise their recommendations on the current indications and procedural steps of the MitraClip treatment. These recommendations of the AGIK and ALKK may present a basis for future development.

Prasugrel vs clopidogrel in cardiogenic shock patients undergoing primary PCI for acute myocardial infarction. Results of the ISAR-SHOCK registry.

There is limited clinical data comparing different P2Y12-receptor inhibitors in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock. The aim of the ISAR-SHOCK registry was to compare the clinical outcome of patients treated with clopidogrel vs prasugrel in this setting. Patients (n=145) with AMI complicated by cardiogenic shock and undergoing primary PCI in two centres (Deutsches Herzzentrum München and Klinikum rechts der Isar, Technical University Munich) between January 2009 and May 2012 were included in this registry. The use of prasugrel for patients within this registry reflected co-morbidities and platelet function testing results during the acute AMI phase. Early outcome at 30-days was reported with regard to all-cause mortality, myocardial infarction (MI), stent thrombosis (ST) and bleeding events. With regard to antiplatelet treatment in the 145 cardiogenic shock patients, 50 patients were initially treated or immediately switched to prasugrel while 95 patients were treated with clopidogrel. All-cause mortality was lower in prasugrel- vs clopidogrel-treated patients (30 % vs 50.5%, HR: 0.51, 95% CI [0.29-0.92], p=0.025). No significant differences in prasugrel- vs clopidogrel-treated patients were observed for the occurrence of MI (p=0.233), ST (p=0.306) or TIMI major bleedings (p=0.571). Results of the ISAR-SHOCK registry suggest that the use of prasugrel in AMI patients complicated by cardiogenic shock might be associated with a lower mortality risk as compared to clopidogrel therapy without increasing the risk of bleeding. These findings, however, need confirmation from specifically designed randomised studies in this high-risk cohort of patients.