Transcatheter Mitral Valve Implantation Systematic Review: Focus on Transseptal Approach and Mitral Annulus Calcification.

INTRODUCTION: This systematic review was performed to evaluate the results of transcatheter mitral valve implantation (TMVI) in the native mitral valve. EVIDENCE ACQUISITION: Medline, EMBASE, and the Cochrane Central register were systematically searched for studies that reported results of TMVI in mitral valve regurgitation and/or stenosis and mitral annular calcification. To improve the sensitivity of the literature search, we performed citation chasing in Google Scholar, Scopus, and Web of Science. EVIDENCE SYNTHESIS: Twelve studies reporting results of TMVI in mitral regurgitation were retrieved and included 347 patients. The transseptal approach represented 28% of cases. Secondary mitral regurgitation was the predominant indication in 63% of cases. Thirty-day mortality was 11% and was lowered with the transseptal approach (7%). Technical success was 92%. Surgical conversion was needed in 5% of patients. Only one patient presented moderate to severe mitral regurgitation. These hemodynamic results were sustainable up to one year of follow-up. Three series focused on results of TMVI in mitral annulus calcification including 167 patients. Only nine patients were treated with TMVI dedicated prosthesis. Eighty-seven patients had their prosthesis delivered through a transseptal approach. Mitral stenosis was present in 63% of cases. Thirty-day mortality was 24%, and none with TMVI prosthesis. Technical success was achieved in 71% of cases and was improved by using TMVI prosthesis (89%). The main complication was left ventricular outflow tract obstruction (20%). Post procedural moderate to severe mitral regurgitation was observed in 4% of cases. CONCLUSION: TMVI seems to be feasible, achieving good technical success and predictable and durable MR reduction.

[Evaluation of mitral regurgitation : How much quantification do we need?] / Diagnostik der Mitralinsuffizienz : Wie viel und welche Quantifizierung brauchen wir?

Severe mitral regurgitation (MR) is associated with increased morbidity and mortality. Thus, the correct evaluation of the underlying etiology, pathomechanism and severity is crucial for optimal treatment. Echocardiography is the predominant diagnostic modality in the clinical routine as it enables grading of mitral regurgitation, which can frequently be achieved by readily available qualitative parameters. Additionally, echocardiography provides several methods to quantify the hemodynamic significance of MR. The effective regurgitation orifice area (EROA) is the quantitative parameter best correlated with clinical events. American and European imaging guidelines both recommend the use of quantitative parameters even though they disagree on the cut-off values for secondary MR. The evaluation of MR should always include an assessment of the adjacent heart chambers in order to be able to assess the impact of volume overload on size and function of the left ventricle and left atrium. The final interpretation of the quantitative parameters requires knowledge of left ventricular volume and ejection fraction. Newer 3D-echocardiographic approaches to quantify MR are less dependent on mathematical assumptions and have shown convincing results in several studies but still lack sufficient clinical validation. As an alternative to echocardiography, for specific indications cardiac magnetic resonance imaging (MRI) has proven to be a systematic and observer-independent method for quantification of MR.

Acute and Long-Term Hemodynamic Effects of MitraClip Implantation on a Preexisting Secondary Right Heart Failure.

Positive results of MitraClip in terms of improvement in clinical and left ventricular parameters have been described in detail. However, long-term effects on secondary pulmonary hypertension were not investigated in a larger patient cohort to date. 70 patients with severe mitral regurgitation, additional pulmonary hypertension, and right heart failure as a result of left heart disease were treated in the heart centers Hamburg and Göttingen. Immediately after successful MitraClip implantation, a reduction of the RVOT diameter from 3.52 cm to 3.44 cm was observed reaching a statistically significant value of 3.39 cm after 12 months. In contrast, there was a significant reduction in the velocity of the tricuspid regurgitation (TR) from 4.17 m/s to 3.11 m/s, the gradient of the TR from 48.5 mmHg to 39.3 mmHg, and the systolic pulmonary artery pressure (PAPsyst) from 58.6 mmHg to 50.0 mmHg. This decline continued in the following months (Vmax TR 3.09 m/s, peak TR 38.6 mmHg, and PAPsyst 47.4 mmHg). The tricuspid annular plane systolic excursion (TAPSE) increased from 16.5 mm to 18.9 mm after 12 months. MitraClip implantation improves pulmonary artery pressure, tricuspid regurgitation, and TAPSE after 12 months. At the same time, there is a decrease in the RVOT diameter without significant changes in other right ventricular and right atrial dimensions.

Implication of pulmonary hypertension in patients undergoing MitraClip therapy: results from the German transcatheter mitral valve interventions (TRAMI) registry.

AIMS: We sought to evaluate the impact of pulmonary hypertension on outcomes following MitraClip therapy. METHODS AND RESULTS: The 643 patients in the TRAnscatheter Mitral valve Interventions (TRAMI) registry were divided into three groups according to echocardiographically graded systolic pulmonary artery pressure (sPAP) (Group 1: patients with sPAP of ≤36 mmHg; Group 2: patients with sPAP of 37-50 mmHg; Group 3: patients with sPAP of >50 mmHg) and followed for 1 year. Recent cardiac decompensation, aortic valve disease and tricuspid valve insufficiency were observed more frequently in patients with higher sPAP. Furthermore, logEuroSCORE, Society of Thoracic Surgeons score and age were higher with rising sPAP values. No differences were observed in mitral regurgitation (MR) severity, co-morbidities or clinical findings (New York Heart Association class, 6-min walking distance). Reduction to MR of grade 1 or lower was achieved more often in patients with lower sPAP levels (P = 0.01). In Groups 2 and 3, sPAP was reduced significantly. Major adverse cardiac or cardiovascular events (MACCEs) occurring in hospital (death, myocardial infarction, stroke; <4% in each group), as well as 30-day rates of MACCEs (6.1% in Group 1, 11.9% in Group 2, 12.4% in Group 3) and rehospitalization (18.9% in Group 1, 24.8% in Group 2, 24.8% in Group 3) did not differ significantly. At 1 year, differences in rates of mortality and MACCEs (20.3% in Group 1, 33.1% in Group 2, 34.7% in Group 3; P < 0.01) were significant. Both Groups 2 [hazard ratio (HR) 1.81, P = 0.0122] and 3 (HR 1.85, P = 0.0092) were independently predictive of death. Rehospitalization rates did not differ during follow-up. CONCLUSIONS: Despite higher mortality in patients with elevated sPAP, these data suggest the safety, feasibility and benefit of MitraClip therapy even in advanced stages of disease. An early approach might prevent the progress of pulmonary hypertension and improve outcomes.

[Recommendations for education in ultrasound in medical intensive care and emergency medicine: position paper of DGIIN, DEGUM and DGK]. / Empfehlungen zur Ultraschallausbildung in der internistischen Intensiv- und Notfallmedizin: Positionspapier der DGIIN, DEGUM und DGK.

Point-of-care ultrasound in acute care medicine is a prerequisite for diagnosis and therapy monitoring of critically ill patients. There is currently no uniform education strategy for medical intensive care and emergency medicine. As part of the basic level, the trainee takes theoretical and clinical training covering abdominal and thoracic ultrasonography and focused cardiovascular ultrasound. In a second step, special knowledge and skills can be acquired at an expert level. This two-stage concept is intended to guarantee quality assurance in ultrasound education in medical intensive care and emergency medicine.

Impact of tricuspid valve regurgitation in surgical high-risk patients undergoing MitraClip implantation: results from the TRAMI registry.

AIMS: We sought to assess the impact of tricuspid regurgitation (TR) severity on patient outcome in a collective with relevant mitral regurgitation undergoing MitraClip implantation.. METHODS AND RESULTS: From August 2010 to July 2013, 766 patients (age 75.3±8.5 years, 61% male, median EuroSCORE 24.3%±18.4) were prospectively enrolled in the TRAMI registry and stratified by echocardiography into no/mild, moderate and severe TR. Overall, the mean number of implanted MitraClips was higher in patients with severe TR but increasing TR severity was not associated with procedural success. In-hospital and one-year mortality as well as MACE and MACCE (death, myocardial infarction±stroke) rates were higher with increasing TR severity. Kaplan-Meier curves indicated a significant difference for mortality (p<0.0001), but not for rehospitalisation for heart failure. After multivariate Cox regression, severe TR proved to be a predictor for one-year mortality (HR 2.01, 95% CI: 1.25-3.26, p=0.004). Higher rates of severe bleeding were more frequent with increasing TR grades. CONCLUSIONS: In patients with MitraClip implantation, increasing TR severity is associated with adverse outcome, higher bleeding rates and decreased survival rates.

Intraprocedural assessment of mitral regurgitation during the mitraclip procedure: Impact of continuous left atrial pressure monitoring.

INTRODUCTION: Intraprocedural assessment of mitral regurgitation (MR) is a challenging issue during the MitraClip procedure, which might influence not only the position but also the number of MitraClips implanted. Though transesophageal echocardiography (TEE) is the predominant tool used during the MitraClip procedure, MR assessment might be facilitated by a multimodality approach including continuous and simultaneous determination of left atrial and left ventricular (LV) pressure. METHODS: 86 consecutive patients (76.5 ± 8 years) who qualified for the MitraClip procedure were included into the study. In all patients, the multimodal assessment of MR (TEE, LV angiogram, TEE bubble evaluation, left atrial (LA) pressure => MitraScore) was performed after introducing the MitraClip guide catheter. In the first 42 patients (group A, no CAP), left atrial (LA) pressure (peak pressure of V-wave) was determined only before and after MitraClip implantation, whereas, in the subsequent 44 patients (group B, with CAP), continuous left atrial pressure monitoring (CAP) was performed. RESULTS: Patients with CAP (group B) had similar total procedural durations and no increase in the complication rate. MitraScore decreased from 10.5 to 3.5 in group A compared to 10.7 to *2.8 in group B (*P = 0.021 vs. group B). Whether the significant improvement of intraprocedural MR in group B translated into superior MR reduction in the conscious patient, was analyzed by transthoracic echocardiography (TTE) in a blinded fashion. Again MR reduction was significantly greater (P = 0.03) in group B (MR grade 2.8 to 0.9) as compared to group A (MR grade 2.8 to 1.3) and 2D vena contracta decreased from 0.54 ± 0.15 cm to 0.17 ± 0.10 in group B compared to group A (0.56 ± 0.19 cm to *0.23 ± 0.12; *P = 0.01 vs. group B). CONCLUSIONS: Multimodality assessment of intraprocedural MR supported by continuous left atrial pressure monitoring was associated with superior intraprocedural results translating into improved MR reduction also at the end of the hospital stay. © 2016 Wiley Periodicals, Inc.

Recurrent cerebral ischaemia in a pregnant woman with patent foramen ovale II° and thrombophilia.

This case report concerns a pregnant multipara (age: 27 years) in the 16th gestational week. She developed a sudden onset of paraesthesia in her left lower arm although injecting dalteparin 5000 IU once daily subcutaneously (s. c.) due to a heterozygous factor V Leiden mutation and a prior miscarriage in the first pregnancy and preeclampsia in her third pregnancy. After the miscarriage she delivered two healthy children under prophylactic anticoagulation with low molecular weight heparin (LMWH). Now via magnetic resonance imaging (MRI) she was diagnosed as having multiple cerebral ischaemic lesions. Further workup revealed the presence of a patent foramen ovale (PFO) II° but no venous thrombosis in her legs. She was then treated with dalteparin 5000 IU twice daily by subcutaneous injections. At 19th gestational week she developed paraesthesia in her left lower arm again. The MRI showed a cortical lesion in the territory of the right median cerebral artery. The anticoagulation dose was increased stepwise under surveillance of the anti-FXa-level 3-4 h after subcutaneous injections aiming to achieve the supratherapeutic range of 1.2-1.5 IU/ml anti-Xa-units. No more neurological symptoms appeared under this antithrombotic therapy. The patient delivered by induction of labor at the 38th gestational week.

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.

[Diagnostics and therapy of ischemia in chronic stable angina pectoris. Role of echocardiography]. / Diagnostik und Therapie der chronischen Myokardischämie. Rolle der Echokardiographie.

Early detection of prognostically significant coronary artery disease (CAD) using ischemic tests, including noninvasive cardiac imaging, are fundamental approaches of optimized patient treatment guidelines to lower morbidity and mortality of these patients. Current international guidelines and the national standard of care guidelines from 2006 and 2011 as well as the third universal definition of myocardial infarction stress the increasing role of echocardiography as a favorable noninvasive imaging test. Echocardiography at rest, ergometric and pharmacologic stress echocardiography are established and readily available diagnostic tools with the potential to evaluate global and regional left ventricular function at rest and during exercise combined with information regarding regional perfusion. Especially new data on perfusion analysis allow further extension of the indications spectrum of reperfusion analysis and sensitivity increases in chest pain unit settings. The noninvasive detection of significant and prognostic stenosis burden in CAD without radiation is possible with high sensitivity and good specificity and encompasses functional cardiovascular parameters as well as extension of the ischemic area.The likelihood of future cardiac events can be assessed with high negative predictive accuracy, giving a high safety aspect in the treatment options of patients. The diagnostic potential of stress echocardiography is best in patients with intermediate and higher pretest probabilities. In patients under concurrent antiischemic medication identification of high risk patients seems feasible. Stress echocardiography has an excellent specificity and prognostic value for either indications for revascularization or survival prediction as well as survival benefits after revascularization in test positive patients.The detection of pathologic findings is not impaired by gender differences. New technical approaches include 2-D and 3-D speckle analysis of the myocardial wall and contrast-enhanced improvements in myocardial border delineation and perfusion. A new European multicenter study published in 2013 could demonstrate comparable to improved sensitivities in intermediate to severe coronary stenosis from 50% to 70% and in highly obstructive proximal stenoses compared to a reference electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT).

[Quality assurance in echocardiography. Three-level system in formation and qualifying and concept of an external quality review]. / Qualitätsleitlinien Echokardiographie Stufenkonzept Ausbildung, Qualifizierung und Externe Qualitätssicherung.

Measures of quality assurance in echocardiography can be categorized according to standard principles into measures of reviewing structure, processing, and results. This document contains 1) the description of a three level system for education and qualifying in echocardiographic examinations (quality of structure) and 2) the draft of an external quality assurance process for reviewing the results of one echocardiographic investigator or of one laboratory of echocardiography (quality of results). The document also contains a draft description of a nationwide independent institution for certification, which is needed for both projects.A level 1 investigator should be able to perform and interpret a basic investigation. A basic investigation allows to exclude most of all cardiac diseases that can be diagnosed by echocardiography, and pathological findings should be filtered out. A level 2 investigator is able to perform an extended examination, and a comprehensive echocardiographic diagnosis can be established after her or his examination. Additional specific training and experience is necessary to be certified for TEE and stress echo examinations. A level 3 echocardiographer has done research work in echocardiography and should have performed certified teaching courses in echocardiography. The external quality assurance process should provide the possibility to certify the results and reports of a single investigator or of an echo laboratory, according to standard principles of reviewing the records. The process of certification is exclusively performed on a voluntary basis. The nationwide institution of certification should be part of the academy of education in cardiology of the German Society of Cardiology.

Second-generation real-time three-dimensional echocardiography. Finally on its way into clinical cardiology?

Three-dimensional (3D) echocardiographic imaging has been introduced as a tool to improve the assessment of both morphologic and functional parameters of the cardiovascular system. In the past, data acquisition was limited due to time-consuming sequential acquisition of multiple triggered 2D image planes from 10-60 heart cycles using transesophageal rotational, transthoracic rotational or transthoracic freehand approaches. Recent improvements in the size of matrix array probes and in computing power of modern ultrasound equipment have significantly increased both spatial and temporal resolution of "second-generation" real-time 3D scanners. Although the superiority of 3D echocardiography in the determination of ventricular volume, ventricular mass or valvular orifice area had already been demonstrated in the late 1990s, widespread use in clinical cardiology was limited on account of difficulties in acquisition and post-processing. Clinical use of modern 3D echocardiography is boosted by the marked reduction in acquisition time and the unique possibility of on-line rendering on the ultrasound system. The ability to visualize a virtual 3D surface in real time-although limited to a sector size of about 30 degrees-offers new insights into cardiac pathomorpholgy even in patients with arrhythmias and may in realtime 3D-contrast flow analysis. Analysis of wide-angle 3D datasets (90 by 90 degree pyramidal shape) is possible by combining the 3D information of several [4-7] consecutive heart cycles. 3D datasets including the complete left ventricle provide comprehensive information on ventricular and mitral valve morphology and function. Qualitative and quantitative analyses of regional wall motion at rest and during stress become possible. Combination with 3D color Doppler data allows additional assessment of valvular function as well as determination of flow in the left ventricular outflow tract and across septal defects. The integration and future quantification of these new parameters together with on-line review allows new insights into cardiac function, morphology and synchrony that offer great potentials in the evaluation of right and left ventricular global and regional function, diagnosis of small areas of ischemia, congenital and valvular heart disease and effects of biventricular pacing in dilated heart asynchrony.

Cardiac function and haemodynamics during transition to high-frequency oscillatory ventilation.

BACKGROUND AND OBJECTIVE: This prospective observational study analyses cardiovascular changes in adult patients with acute respiratory distress syndrome (ARDS) during transition from pressure-controlled ventilation to high-frequency oscillatory ventilation (HFOV), using transoesophageal echocardiography (TOE) and invasive haemodynamic monitoring. METHODS: Nine patients (median age 65 years; range 42-70) with ARDS were studied. HFOV was started and maintained with an adjusted mean airway pressure of 5 cmH2O above the last measured mean airway pressure during pressure-controlled ventilation. Haemodynamic and TOE measurements were performed in end-expiration during baseline pressure-controlled ventilation, and again 5 and 30 min after the start of during uninterrupted HFOV. RESULTS: Right atrial pressure increased immediately (P = 0.004). After 30 min, pulmonary arterial occlusion pressure increased (P = 0.008), cardiac index decreased (P = 0.01), stroke volume index decreased (P = 0.02) and both left ventricular end-diastolic and end-systolic area indices decreased (P = 0.02). Fractional area change, left ventricular end-systolic wall stress, heart rate, mean arterial pressure and mean pulmonary artery pressure remained unchanged. CONCLUSIONS: Transition to HFOV at a mean airway pressure of 5 cmH2O above that during pressure-controlled ventilation induced significant, but clinically minor, haemodynamic effects, which are most probably due to airway pressure-related preload reduction.

Lack of association between carotid artery volume blood flow and cardiac output.

OBJECTIVE: The correlation of cardiac output and cerebral perfusion is unclear. We tested this potential association by correlating cardiac output data obtained by echocardiography and cerebral blood flow data as determined by color M-mode measurements of carotid artery blood flow. METHODS: We studied 43 patients with a broad spectrum of cardiac performance by means of transthoracic echocardiography. In these patients, different cardiac indices such as stroke volume, ejection fraction, and heart minute volume were determined. The data were correlated with volumetric flow measurements (color M-mode duplex system) of the common carotid arteries bilaterally. RESULTS: Heart minute volume ranged from 1.632 to 9.836 mL/min (mean +/- SD, 4.652 +/- 1.621 mL/min); ejection fraction ranged from 18% to 76% (mean, 48% +/- 16%). The relative fraction of carotid volume flow compared with heart minute volume was 15% +/- 6%. There was no correlation between ejection fraction, stroke volume, or heart minute volume and absolute volume flow in the carotid arteries when being adjusted for age. There was a highly significant inverse correlation (r = -0.8; P < .0001) of the relative fraction of the carotid volume flow (carotid volume flow/heart minute volume [percent]) and the heart minute volume. CONCLUSION: Our data support the concept that cerebral blood flow is independent of cardiac output.

Prejunctional muscarinic receptors regulating neurotransmitter release in airways.

Prejunctional pA2 values of five muscarinic antagonists were determined in the guinea-pig trachea under stimulation conditions in which the antagonists alone did not enhance acetylcholine release. The antagonists were partly selective at M1 (pirenzepine), M2 (AQ-RA 741, himbacine) and M3 receptors (hexahydrosiladifenidol, dicyclomine). The profile of the antagonist affinities was different from that obtained at cardiac M2 receptors but resembled the profile reported in the literature for the cloned m4 receptor. This suggests that autoinhibition of acetylcholine release in the trachea is mediated via M4 receptors.

Functional relevance of presynaptic muscarinic autoreceptors.

Pre- and postsynaptic muscarinic receptors have been characterized in the isolated trachea and ileal circular muscle of the guinea pig. The muscarinic autoreceptors mediating inhibition of acetylcholine release in the circular muscle belong to the M1 subtype, whereas those inhibiting acetylcholine release in the trachea are M2 or M4 receptors. In both tissues the postsynaptic muscarinic receptors are M3 receptors. Blockade of the autoreceptors by selective M1 and M2/M4 receptor antagonists leads to facilitation of cholinergic neurotransmission.