Catheter-directed thrombolysis guided by pulmonary artery pressure registration in pulmonary embolism: a case report.

Background: Duration and dosage of thrombolysis for ultrasound-assisted catheter-directed thrombolysis (UACDT) in patients with intermediate high-risk pulmonary embolism remain controversial and treatment protocols vary. Case summary: A 58-year-old female patient suffered from a right-sided urolithiasis. The clinical course was complicated by an intermediate high-risk pulmonary embolism [pulmonary embolism severity index (PESI) score 108 points and simplified PESI ≥1] with bilateral proximal thrombus and significant right heart dysfunction. The pulmonary embolism response team (PERT) made a decision towards UACDT. The standard duration of UACDT ranges between 6 and 15 h depending on clinical parameters. In this particular case, the clinical parameters such as heart rate (no tachycardia) or oxygen saturation (chronic obstructive pulmonary disease) might lead to premature termination of UACDT. Therefore, PERT decided to additionally monitor pulmonary artery pressure (PAP) continuously during the UACDT via a separate pigtail catheter in the pulmonary artery. Ultrasound-assisted catheter-directed thrombolysis was performed using 1 mg/h recombinant tissue plasminogen activator (rtPA) per catheter, while PAP was registered continuously. Heart rate and oxygen saturation remained unchanged during UACDT. However, after 6 h of UACDT, systolic PAP decreased slightly from 62 to 55 mmHg and therapy was prolonged to 15 h. Pulmonary artery pressure dropped to 46 mmHg after 15 h. The patient was discharged from hospital at Day 7, and echocardiography revealed no signs of right heart dysfunction. Discussion: Dosage of the thrombolysis agent and duration of UACDT are still a matter of debate. Besides clinical parameters and transthoracic echocardiography, invasive real-time PAP monitoring during UACDT could facilitate important information for therapy guidance in selected cases.

Intraprocedural Residual Mitral Regurgitation and Survival After Transcatheter Edge-to-Edge Repair: Prospective German Multicenter Registry (MITRA-PRO).

BACKGROUND: Residual mitral regurgitation (MR) is thought to be an important predictor of long-term survival following transcatheter edge-to-edge repair (TEER). Intraprocedural MR assessment using transesophageal echocardiography could be limited by image quality, hemodynamics, and patient sedation. The MitraScore is a validated multimodal approach for intraprocedural MR assessment during TEER. OBJECTIVES: This study aimed to assess the impact of residual MR using the MitraScore on 1-year mortality. METHODS: Patients undergoing mitral TEER were eligible for inclusion in the prospective, multicenter MITRA-PRO registry (A Prospective Registry Study on 1-Year Mortality and the Prognostic Significance of MitraScore After MitraClip Implantation in Patients With Mitral Regurgitation). Patients with a MitraScore ≤3 were defined as patients with mild residual MR after mitral TEER, whereas a MitraScore ≥4 was considered as relevant residual MR. Mortality, rehospitalization, and major adverse events were assessed 1 year after TEER. RESULTS: A MitraScore ≤3 was found in 1,059 patients (71.0%), whereas 432 patients revealed a MitraScore ≥4 (29.0%). One-year mortality was significantly lower in patients with nonrelevant residual MR (MitraScore ≤3 14.6% vs MitraScore≥4 22.1%). An almost linear relationship between intraprocedural MitraScore after TEER and mortality was observed. The combined clinical endpoint of mortality and rehospitalization within the 1-year follow-up was also significantly lower in the MitraScore ≤3 group (31.5%) than in the MitraScore ≥4 group (40.8%). A subgroup analysis confirmed the predictive value of the MitraScore in patients with primary, secondary, or mixed MR etiologies. CONCLUSIONS: Residual MR assessed by intraprocedural MitraScore after TEER predicts 1-year mortality and rehospitalization. Therefore, the multimodal MitraScore improves MR assessment during mitral TEER and might improve patient survival.(A Prospective Registry Study on 1-Year Mortality and the Prognostic Significance of MitraScore After MitraClip Implantation in Patients With Mitral Regurgitation [MITRA-PRO]; DRKS00012288).

Anatomy and Topography of Coronary Sinus and Mitral Valve Annulus in Functional Mitral Regurgitation.

Background: We aimed to investigate the anatomical relationship of the coronary sinus (CS) and the mitral valve annulus (MVA) in patients with or without functional mitral regurgitation (FMR) using a multislice CT (MSCT) software to determine (a) the distance and angle of both CS and MVA plane and (b) the mitral annulus geometry. Methods: A total of 215 patients with MSCT and CS to MVA topography evaluation were enrolled in this retrospective study. Results: This patient cohort included 145 patients without FMR (67.4%, FMR ≤ 1+) and 70 patients (32.6%) with clinically relevant FMR (FMR ≥ 2+). Distance and angulation of CS to MVA planes were highly variable. In all groups, no significant correlation was documented between the distance or angle of CS to MVA planes and left ventricular ejection fraction, left ventricular end-diastolic diameter, or left atrial volume. A significant increase in total CS length could be found in patients with FMR ≥ 2+ compared to the FMR ≤ 1+ group. MVA diameter, area, and perimeter were significantly increased in FMR ≥ 2+ compared to FMR ≤ 1+. In the FMR ≥ 2+ cohort 61% showed a distance of CS to MVA plane <7.8 mm and 58% revealed an angle of CS to MVA plane <14.2°. Conclusion: Distance and angulation of CS to MVA topography using an MSCT approach are similar between patients with or without FMR, while CS length, MVA area, MVA perimeter, anterior-posterior diameter, and intercommissural diameter are significantly increased in all FMR subgroups. However, ~60% of FMR ≥ 2+ patients showed favorable CS to MVA topography for indirect mitral annuloplasty.

Mitral valve edge-to-edge repair versus indirect mitral valve annuloplasty in atrial functional mitral regurgitation.

OBJECTIVES: We aimed to compare indirect mitral annuloplasty using the Carillon Mitral Contour System and edge-to-edge repair via MitraClip in atrial functional mitral regurgitation (aFMR). BACKGROUND: In patients with left ventricular dilation, both edge-to-edge repair and indirect mitral annuloplasty are effective in reducing mitral regurgitation, while no clinical trial has compared both interventional methods in aFMR. METHODS: In a retrospective single-center analysis, 41 patients with aFMR underwent either edge-to-edge mitral valve repair (MitraClip group, n = 20) or indirect annuloplasty (Carillon group, n = 21). RESULTS: Both treatment groups showed high procedural success (100%) and low complication rates. Both treatment groups showed a comparable reduction of New York Heart Association (NYHA) classification postimplantation, after 3- and 12-months follow-up. Quantitative reduction in echocardiographic FMR parameters was significantly pronounced in the MitraClip group (reduction in vena contracta MitraClip vs. Carillon: postimplantation -74.6 ± 25.8 vs. -29.1 ± 17.8%, 3-months follow-up -65.8 ± 31.2 vs. -33.9 ± 17.5%, 12-months follow-up -50.8 ± 27.9 vs. -23.9 ± 17.0%, p < 0.05). Qualitative mitral valve assessment showed improved FMR class postimplantation, at 3-and 12-months follow-up in both treatment groups. Edge-to-edge repair revealed better results with lower average FMR classification compared to indirect coronary sinus-based annuloplasty. After 12-months left atrial (LA) volume was significantly reduced in the Carillon group, while in the MitraClip group no LA remodeling was found (reduction in LA volume MitraClip vs. Carillon at 12 months: +9.6 ± 25.1% vs. -12.3 ± 12.7%, p < 0.05). CONCLUSIONS: Both indirect mitral valve annuloplasty and edge-to-edge repair are feasible and safe in patients with aFMR, while the reduction in FMR was pronounced in the edge-to-edge repair group.

Continuous atrial pressure monitoring via steerable guide catheter in transcatheter mitral and tricuspid edge-to-edge repair.

Transcatheter edge-to-edge repair (TEER) has emerged to address severe mitral and tricuspid valve regurgitation in patients who are at high perioperative risk for open-heart surgery. No clinical data is available for continuous left and right atrial pressure monitoring using the steerable guiding catheter (SGC) during TEER. In a prospective single-center study, 40 patients with severe mitral (n = 20) or tricuspid (n = 20) regurgitation underwent TEER with the registration of atrial pressure via the SGC. All patients had successful TEER using the PASCAL Ace repair system, while atrial pressure was monitored continuously via the SGC. Simultaneous right or left atrial pressure monitoring via the SGC and a pigtail catheter during mitral and tricuspid TEER showed excellent reliability for SGC pressure registration. While for mitral TEER the beneficial effects of continuous atrial pressure monitoring are well known, we further evaluated the outcome of patients with tricuspid TEER. Echocardiographic and clinical results after tricuspid TEER showed a reduction of quantitative echocardiographic tricuspid regurgitation parameters and improved New York Heart Association classification after 3-month follow-up. Also, qualitative tricuspid valve assessment showed improved tricuspid regurgitation classification postimplantation and at 3-month follow-up. Furthermore, right atrial pressure was reduced by 37.6% and mean right atrial pressure by 30.6% after successful tricuspid TEER using the PASCAL Ace device. Continuous atrial pressure monitoring using the SGC of the PASCAL Ace repair system is reliable during mitral and tricuspid TEER. Furthermore, successful tricuspid TEER leads to reduced right atrial pressure.

Percutaneous Coronary Sinus-Based Mitral Valve Repair Differentially Modulates Coronary Sinus to Mitral Valve Annulus Geometry and Topography.

Objectives: Coronary sinus (CS) based mitral annuloplasty using the Carillon device is a therapeutic option for the treatment of functional mitral valve regurgitation (FMR). Background: Little is known about the change of CS and mitral valve annulus (MVA) planes following Carillon implantation and how they are modulated by the tension applied on the device. Methods: In a retrospective single-center analysis, 10 patients underwent Carillon device implantation and received CT-angiography (CTA) prior and post CS based percutaneous mitral valve repair. Patients were assigned to responders or non-responders according to the 3-month transthoracic echocardiographic follow-up. A prototype software was used to assess distance and angulation of both CS (pre) or Carillon-device (post) and mitral annulus planes. Results: Comparison of the distance and angulation of the CS plane or Carillon device plane and the MVA plane prior and post intervention showed significant reduction of distance and unchanged angulation in responders while angulation was increased and distance reduced in non-responders without statistical significance. Furthermore, in FMR responders MVA perimeter, anterior-posterior diameter, intercommisural diameter and MVA area were decreased following successful indirect mitral valve annuloplasty, while in FMR non-responders Carillon device implantation had no effect on MVA geometry. Conclusions: Insufficient reduction of FMR following indirect mitral valve annuloplasty is associated with device malposition in relation to the mitral valve annulus. Patient selection using CTA-derived distance and angulation of CS to MVA planes is one option to increase effectiveness of indirect mitral valve annuloplasty.

Procedural planning of CS-based indirect mitral annuloplasty using CT-angiography.

OBJECTIVES: Coronary sinus (CS) based mitral annuloplasty using the Carillon device could be limited by compromise of the left circumflex artery (Cx). BACKGROUND: Computed tomography (CT) might be a feasible tool for preprocedural planning of indirect mitral valve annuloplasty. METHODS: In a retrospective analysis, 25 patients underwent Carillon device implantation and received CT-angiography (CTA) analysis prior to CS based percutaneous mitral valve repair. We used a retrospective approach with preprocedural CTA and intraprocedural coronary sinus angiography (CSA) measurements to determine the CS to Cx distance at the occlusion or compression point or in the distal landing zone in absence of Cx compromise. RESULTS: According to left coronary artery angiography, we identified 7 patients with Cx occlusion, 7 with Cx compression and 11 without Cx compromise. No difference in minimal CS to Cx distance between the three groups could be obtained. Also, neither distal CS diameter nor distal Carillon anchor size were related to Cx impingement. However, ROC analysis identified a CS to Cx distance of <8.6 mm specifically in the distal device landing zone to predict Cx compromise. Furthermore, CTA was accurate in assessing device length in comparison to CSA, but failed predicting Carillon device anchor size. CONCLUSIONS: CTA derived CS to Cx distance in the device landing zone might be helpful to predict Cx occlusion during Carillon device implantation. Furthermore, CTA predicted CS length but not anchor size correctly. Therefore, CT-angiographic procedural planning might help improving the results of percutaneous CS-based mitral valve repair.

Diagnostic role of coronary CT angiography in paroxysmal or first diagnosed atrial fibrillation.

OBJECTIVES: The presence of coronary artery disease (CAD) in patients hospitalised with paroxysmal or first diagnosed atrial fibrillation (AF) has major implications for antithrombotic therapy and cardiovascular event rate. Coronary CT angiography (CCTA) is a feasible tool to identify patients with concealed CAD. We aimed to evaluate the diagnostic role of early CCTA in patients hospitalised with paroxysmal or first diagnosed AF. METHODS: In a 5-year single-centre retrospective analysis, 566 patients with paroxysmal or first diagnosed AF who underwent CCTA were enrolled to investigate the presence of CAD. RESULTS: In patients with paroxysmal or first diagnosed AF, CCTA revealed CAD (coronary artery stenosis ≥50%) in 39.2%. Cardiac catheterisation was performed in 31.6%, confirming CAD in 13.1% of all patients. In 8.0% percutaneous coronary intervention and in 0.5% coronary artery bypass grafting was performed. In patients with paroxysmal or first diagnosed AF: (1) angina pectoris per se does not predict CAD; (2) multivariable regression analysis revealed age, male sex and diabetes as risk factors for CAD in AF; (3) Framingham Risk Score for coronary heart disease and CHA2DS2-VASc-Score were relevant risk scores of CAD and (4) the classification of Coronary Artery Calcium score reference values according to the Multi-Ethnic Study of Atherosclerosis was a predictor of CAD. CONCLUSION: Patients with paroxysmal or first diagnosed AF are at risk for CAD, while CCTA is a feasible diagnostic tool for CAD. We recommend to integrate CT calcium scoring and CCTA into the diagnostic workup of patients with new-onset or paroxysmal AF.

Case Report: Living on the Edge-Transcatheter Mitral Valve Repair Related Infective Endocarditis.

Background: Infective endocarditis (IE) following mitral valve edge-to-edge repair is a rare complication with high mortality. Case summary: A 91-year-old male patient was admitted to intensive care unit with sepsis due to urinary tract infection after insertion of a urinary catheter by the outpatient urologist. Two weeks ago, the patient was discharged from hospital after successful transcatheter edge-to-edge mitral valve repair (TEER) using a PASCAL Ace device. The initially withdrawn blood revealed repeatedly Proteus mirabilis bacteremia as causal for the sepsis due to urinary tract infection. An antibiotic regime with Ampicillin/Sulbactam was initiated and discontinued after 7 days. During the clinical course the patient again developed fever and blood cultures again revealed P. mirabilis. In transesophageal echocardiography (TOE), IE of the PASCAL Ace device was confirmed by a vegetation accompanied by a mild to moderate mitral regurgitation. While the patient was stable at this time and deemed not suitable for cardiac surgery, the endocarditis team made a decision toward a prolonged 6-week antibiotic regime with an antibiotic combination of Ampicillin 2 g qds and Ciprofloxacin 750 mg td. Due to posterior leaflet perforation severe mitral regurgitation developed while PASCAL Ace vegetations were significantly reduced by the antibiotic therapy. Therefore, the patient underwent successful endoscopic mitral valve replacement. Another 4 weeks of antibiotic treatment with Ampicillin 2 g qds followed before the patient was discharged. Discussion: P. mirabilis is able to form biofilms, resulting in a high risk for endocarditis following transcatheter mitral valve repair especially when device endothelization is incomplete. Endoscopic mitral valve replacement could serve as a bailout strategy in refractory Clip-endocarditis.

CT-Angiography to predict outcome after indirect mitral annuloplasty in patients with functional mitral regurgitation.

OBJECTIVES: Coronary sinus (CS) based mitral annuloplasty using the Carillon device is effective in reducing functional mitral valve regurgitation (FMR). However, this positive effect might be dependent on the relation between CS and the mitral annulus. BACKGROUND: Computed tomography (CT) assessment prior to mitral valve interventions is an emerging technique to optimize patient selection. METHODS: In a retrospective analysis 30 patients underwent Carillon device implantation and received CT-angiography prior to CS based percutaneous mitral valve repair. Patients were assigned to responders or non-responders according to the 3-month transthoracic echocardiographic follow-up including quantitative mitral valve regurgitation assessment. A prototype software for CS reconstruction was used to assess distance and angle of both CS and mitral annulus planes. RESULTS: Comparison of the distance and angle of the CS plane and the mitral valve annulus plane showed a significant shorter distance and lower angle in the responder group implicating an impact on procedure success. Our results suggest a CS plane and MV annulus plane with a favorably distance of <7.8 mm and an optimal angle of <14.2° could be considered favorably for mitral annuloplasty using a Carillon device. CONCLUSIONS: Distance and angle of mitral annulus and CS planes determined by three-dimensional reconstructions of CT-angiography might predict a reduction in echocardiographic FMR using Carillon Mitral Contour System.

[Systemic hantavirus-infection in a comatose HIV patient]. / Systemische Hantavirus-Infektion bei einem komatösen HIV Patienten.

SYMPTOMS: A 40 year old, disoriented, HIV- and Hepatitis B positive male patient was admitted with 40.3 °C. Clinically he presented a sinustachycardia (160/min) and hypotension (70/60 mmHg). INVESTIGATIONS/DIAGNOSIS: Laboratory analyses showed elevated infection parameters, azotemia, proteinuria and thrombopenia. CD(4+)T-helper cells: 320/µl (32 %), HIV RNA: <40 copies/ml, Hepatitis B DNA: 20800 copies/ml. Hantavirus serology (immunofluorescence antibody assay): 1:2048; serotype Puumala. TREATMENT/COURSE: An early-goal-directed therapy and antibiotic treatment with Piperacillin and Tazobactam was initiated. The patient developed a bipulmonal infiltrate and an acute respiratory distress syndrome (ARDS ) requiring tracheal intubation, as well as a triad of fever, renal failure and profound hemorrhagic symptoms. This led to the diagnosis of the Puumala infection. Due to the parallel HIV- and Hepatits B infection an antiretroviral therapy was initiated. CONCLUSION: In summary the Puumala infection bears the potential for a severe multi-organ failure, which is not typical for this usually benign infection.

Spironolactone prevents aldosterone induced increased duration of atrial fibrillation in rat.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. The Renin-Angiotensin-Aldosterone-System plays a major role for the atrial structural and electrical remodelling. Recently elevated aldosterone levels have been suggested to increase the risk for the development of AF. METHODS: Rats were treated with aldosterone by means of an osmotic minipump (0.5µg/h) over a period of 4 weeks. AF was induced by transesophageal burst pacing. Action potentials (AP) were recorded from left atrial preparations with microelectrodes. Atrial collagen was quantified by histological studies. RESULTS: Aldosterone treatment resulted in hypertrophy as indicated by an increased ratio of heart weight/tibia length and doubled the time until the AF converted spontaneously into sinus rhythm (85.8±13.4 s vs. 38.3±6.9 s, p<0.01). This was associated with a significant shortening of the AP (APD90 26.2±1.1 vs. 31.2±1.9, p<0.05) and an increased protein expression of Kir2.1 and Kv1.5. Atrial collagen deposition was significantly greater in aldosterone-treated rats. The alterations could be prevented by additional application spironolactone. CONCLUSIONS: The results of the present study suggest that in addition to the structural remodelling aldosterone also promotes AF by altering repolarising potassium currents leading to action potential shortening.

Increased expression of the auxiliary beta(2)-subunit of ventricular L-type Ca(2)+ channels leads to single-channel activity characteristic of heart failure.

BACKGROUND: Increased activity of single ventricular L-type Ca(2+)-channels (L-VDCC) is a hallmark in human heart failure. Recent findings suggest differential modulation by several auxiliary beta-subunits as a possible explanation. METHODS AND RESULTS: By molecular and functional analyses of human and murine ventricles, we find that enhanced L-VDCC activity is accompanied by altered expression pattern of auxiliary L-VDCC beta-subunit gene products. In HEK293-cells we show differential modulation of single L-VDCC activity by coexpression of several human cardiac beta-subunits: Unlike beta(1) or beta(3) isoforms, beta(2a) and beta(2b) induce a high-activity channel behavior typical of failing myocytes. In accordance, beta(2)-subunit mRNA and protein are up-regulated in failing human myocardium. In a model of heart failure we find that mice overexpressing the human cardiac Ca(V)1.2 also reveal increased single-channel activity and sarcolemmal beta(2) expression when entering into the maladaptive stage of heart failure. Interestingly, these animals, when still young and non-failing ("Adaptive Phase"), reveal the opposite phenotype, viz: reduced single-channel activity accompanied by lowered beta(2) expression. Additional evidence for the cause-effect relationship between beta(2)-subunit expression and single L-VDCC activity is provided by newly engineered, double-transgenic mice bearing both constitutive Ca(V)1.2 and inducible beta(2) cardiac overexpression. Here in non-failing hearts induction of beta(2)-subunit overexpression mimicked the increase of single L-VDCC activity observed in murine and human chronic heart failure. CONCLUSIONS: Our study presents evidence of the pathobiochemical relevance of beta(2)-subunits for the electrophysiological phenotype of cardiac L-VDCC and thus provides an explanation for the single L-VDCC gating observed in human and murine heart failure.