Parameters predicting COVID-19-induced myocardial injury and mortality.

Clinical manifestations of COVID-19 affect many organs, including the heart. Cardiovascular disease is a dominant comorbidity and prognostic factors predicting risk for critical courses are highly needed. Moreover, immunomechanisms underlying COVID-induced myocardial damage are poorly understood. OBJECTIVE: To elucidate prognostic markers to identify patients at risk. RESULTS: Only patients with pericardial effusion (PE) developed a severe disease course, and those who died could be identified by a high CD8/Treg/monocyte ratio. Ten out of 19 COVID-19 patients presented with PE, 7 (78%) of these had elevated APACHE-II mortality risk-score, requiring mechanical ventilation. At admission, PE patients showed signs of systemic and cardiac inflammation in NMR and impaired cardiac function as detected by transthoracic echocardiography (TTE), whereas parameters of myocardial injury e.g. high sensitive troponin-t (hs-TnT) were not yet increased. During the course of disease, hs-TnT rose in 8 of the PE-patients above 16 ng/l, 7 had to undergo ventilatory therapy and 4 of them died. FACS at admission showed in PE patients elevated frequencies of CD3+CD8+ T cells among all CD3+ T-cells, and lower frequencies of Tregs and CD14+HLA-DR+-monocytes. A high CD8/Treg/monocyte ratio predicted a severe disease course in PE patients, and was associated with high serum levels of antiviral cytokines. By contrast, patients without PE and PE patients with a low CD8/Treg/monocyte ratio neither had to be intubated, nor died. CONCLUSIONS: PE predicts cardiac injury in COVID-19 patients. Therefore, TTE should be performed at admission. Immunological parameters for dysfunctional antiviral immunity, such as the CD8/Treg/monocyte ratio used here, supports risk assessment by predicting poor prognosis.

DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice.

OBJECTIVE: Myocardial ischemia and reperfusion (I/R) injury is associated with oxidative stress and inflammation, leading to scar development and malfunction. The marine omega-3 fatty acids (ω-3 FA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are mediating cardioprotection and improving clinical outcomes in patients with heart disease. Therefore, we tested the hypothesis that docosahexaenoic acid (DHA) supplementation prior to LAD occlusion-induced myocardial injury (MI) confers cardioprotection in mice. METHODS: C57BL/6N mice were placed on DHA or control diets (CD) beginning 7 d prior to 60 min LAD occlusion-induced MI or sham surgery. The expression of inflammatory mediators was measured via RT-qPCR. Besides FACS analysis for macrophage quantification and subtype evaluation, macrophage accumulation as well as collagen deposition was quantified in histological sections. Cardiac function was assessed using a pressure-volume catheter for up to 14 d. RESULTS: DHA supplementation significantly attenuated the induction of peroxisome proliferator-activated receptor-α (PPAR-α) (2.3 ± 0.4 CD vs. 1.4 ± 0.3 DHA) after LAD occlusion. Furthermore, TNF-α (4.0 ± 0.6 CD vs. 1.5 ± 0.2 DHA), IL-1ß (60.7 ± 7.0 CD vs. 11.6 ± 1.9 DHA), and IL-10 (223.8 ± 62.1 CD vs. 135.5 ± 38.5 DHA) mRNA expression increase was diminished in DHA-supplemented mice after 72 h reperfusion. These changes were accompanied by a less prominent switch in α/ß myosin heavy chain isoforms. Chemokine mRNA expression was stronger initiated (CCL2 6 h: 32.8 ± 11.5 CD vs. 78.8 ± 13.6 DHA) but terminated earlier (CCL2 72 h: 39.5 ± 7.8 CD vs. 8.2 ± 1.9 DHA; CCL3 72 h: 794.3 ± 270.9 CD vs. 258.2 ± 57.8 DHA) in DHA supplementation compared to CD mice after LAD occlusion. Correspondingly, DHA supplementation was associated with a stronger increase of predominantly alternatively activated Ly6C-positive macrophage phenotype, being associated with less collagen deposition and better LV function (EF 14 d: 17.6 ± 2.6 CD vs. 31.4 ± 1.5 DHA). CONCLUSION: Our data indicate that DHA supplementation mediates cardioprotection from MI via modulation of the inflammatory response with timely and attenuated remodeling. DHA seems to attenuate MI-induced cardiomyocyte injury partly by transient PPAR-α downregulation, diminishing the need for antioxidant mechanisms including mitochondrial function, or α- to ß-MHC isoform switch.

Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI) : Joint Consensus Document of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V. (ALKK) and cooperating Cardiac Surgery Departments.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4-8%) as well as in low-risk patients (STS-Score < 4%). However, risk scores exhibit limitations and, as a single criterion, are unable to establish an appropriate indication of TF-TAVI vs transapical TAVI vs SAVR (surgical aortic valve replacement). The ESC (European Society of Cardiology)/EACTS (European Association for Cardio-Thoracic Surgery) guidelines 2017 and the German DGK (Deutsche Gesellschaft für Kardiologie)/DGTHG (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie) commentary 2018 offer a framework for the selection of the best therapeutic method, but the individual decision is left to the discretion of the heart teams. An interdisciplinary TAVI consensus group of interventional cardiologists of the ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V.) and cardiac surgeons has developed a detailed consensus on the indications for TF-TAVI to provide an up-to-date, evidence-based, comprehensive decision matrix for daily practice. The matrix of indication criteria includes age, risk scores, contraindications against SAVR (e.g., porcelain aorta), cardiovascular criteria pro TAVI, additional criteria pro TAVI (e.g., frailty, comorbidities, organ dysfunction), contraindications against TAVI (e.g., endocarditis) and cardiovascular criteria pro SAVR (e.g., bicuspid valve anatomy). This interdisciplinary consensus may provide orientation to heart teams for individual TAVI-indication decisions. Future adaptations according to evolving medical evidence are to be expected. Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI).

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.

Safety and efficacy of the percutaneous transaxillary access for transcatheter aortic valve implantation using various transcatheter heart valves in 100 consecutive patients.

OBJECTIVES: Transcatheter Aortic Valve Implantation (TAVI) can be performed via the transaxillary approach, but data about complications and procedural outcome is limited. INTRODUCTION: TAVI is an established treatment option for patients at high risk for conventional aortic valve replacement. Nowadays, the transfemoral approach is the most commonly used access for TAVI. Nevertheless, the transfemoral access is not suitable in many patients necessitating alternative approaches. METHODS: We analyzed the outcome of 100 consecutive cases receiving percutaneous transaxillary TAVI at two different hospitals. Data were retrospectively analyzed by means of procedural, hemodynamic and clinical outcome. In addition, 1st versus 2nd generation devices were analyzed. RESULTS: Mean age was 78.2±2.1years and the logEuroSCORE I was 24.6±13.9%. Transaxillary TAVI was performed in 85% via the left and in 15% via the right axillary artery. Device success was achieved in 95%. In general, there was a clear learning curve with this approach. No patient experienced a major and 11% a minor access site complication. There was one procedural death (annular rupture) and one peri-procedural TIA. 23% of the patients received a new pacemaker. At discharge, effective orifice area was 1.94±0.16cm2 and the mean aortic gradient was 6.8±2.1mmHg. Moderate aortic regurgitation/paravalvular leakage was documented in two patients. Mortality rates at 30days and one year were 6% and 14.8%. Last but not least, 2nd generation devices showed improved procedural outcomes. CONCLUSIONS: The percutaneous transaxillary access for TAVI is technically feasible and safe thereby yielding excellent clinical results. CONDENSED ABSTRACT: We investigated In 100 consecutive patients undergoing percutaneous transaxillary transcatheter aortic valve implantation thereby demonstrating that this approach is technically feasible and safe with acceptable numbers of minor vascular complications.

Symetis ACURATE TAVI: review of the technology, developments and current data with this self-expanding transcatheter heart valve.

The Symetis ACURATE TA and ACURATE neo technology is a novel transcatheter heart valve for treatment of aortic valvular stenosis. This review illustrates the implantation steps, which are designed for an easy and intuitive transapical and transfemoral TAVI procedure. The most important difference to other self-expanding platforms is the top-down deployment with minimal protrusion of the stent towards the left ventricular outflow tract. In addition, the supra-annularly placed porcine leaflets provide very low gradients and the pericardial skirt acts very effectively to seal against paravalvular leaks. This review reports about the hemodynamic features, low rates of paravalvular leaks and very low rates of pacemaker implantation, which have been observed in various registries. Meanwhile more than 3000 patients have been treated worldwide and additional registries are currently under investigation.

Transcatheter aortic valve implantation: alternative access options.

Calcific aortic valve stenosis represents the most common acquired valvular heart disease in adults. Transcatheter aortic valve implantation (TAVI) has been established as a widely accepted therapeutic option in elderly and multimorbid patients with severe aortic stenosis not amenable to conventional surgery. Retrograde transfemoral and antegrade transapical approaches are commonly used for implantation. However, there are a certain number of patients who are not candidates for either approach due to poor vascular access, severe pulmonary dysfunction or other prohibitive chest pathologies. Recently, different alternative access route options have been proposed and described. These alternative access routes include approaches via the subclavian/axillary artery, the ascending aorta, the carotid artery, and the brachiocephalic artery.

Mid-term prognostic value of coronary artery disease in patients undergoing transcatheter aortic valve implantation: a meta-analysis of adjusted observational results.

AIMS: Coronary artery disease (CAD) negatively affects prognosis in patients undergoing surgical aortic valve replacement, being currently evaluated in the most common used risk score. Our meta-analysis aims to clarify the prognostic role of CAD on mid-term survival in patients undergoing TAVI. METHODS AND RESULTS: Studies reporting multivariate predictors of adverse outcomes in patients undergoing TAVI were systematically searched for and pooled, when appropriate, using a random-effect method. 960 citations were first screened and finally 7 studies (2472 patients) were included. Diagnosis of CAD was reported in 52%(42-65) of patients and 1169 Edwards SAPIEN and 1303 CoreValve prostheses were implanted. After a median follow up of 452 days (357-585) 24% of patients (19-33) died, and 23 (14-32) for cardiovascular death. At pooled analysis of multivariate approach, diagnosis of coronary artery disease did not increase risk of death (OR 1.0, 95% CI, confidence interval, 0.67-1.50 I(2) 0%). CONCLUSION: CAD does not affect mid-term TAVI outcome: this finding should be weighted to accurately evaluate risk and strategies for patients with severe aortic stenosis.

What's new in transapical aortic valve implantation: clinical experience with second generation devices.

Within 10 years after transcatheter aortic valve implantation (TAVI) was first accomplished for treatment of calcified aortic stenosis, this new technology has rapidly evolved to become clinical routine. Today it may be considered standard treatment for inoperable patients with superior outcomes compared to best medical therapy. Furthermore, it represents an alternative therapeutic option compared to surgical aortic valve replacement in high-risk patients. According to current international guidelines and expert consensus statements, TAVI should be performed as a joint effort by an interdisciplinary heart team to ensure input from multiple skill sets for optimal patient outcome. Major safety concerns include neurologic complications, acute kidney injury, access site complications, procedure-related conduction disturbances, paravalvular leakage valve durability. At present, only one device for transapical TAVI is in widespread clinical use: the Edwards Sapien transcatheter valve (Edwards Lifesciences, Irvine, CA, USA). Recently, however, a number of second generation devices for transapical TAVI have been developed in order to address some of the limitations of first generation valves. In this paper, current data on second generation devices for transapical TAVI will be reviewed and ongoing trials discussed.

Simultaneous transcatheter aortic and mitral valve-in-valve implantation in a patient with degenerated bioprostheses and high surgical risk.

Transcatheter valve-in-valve implantation is evolving as a promising alternative to reoperative valve replacement in selected high-risk patients, considering the increasing need for redo surgery due to bioprosthetic degeneration in the future. Reoperative double valve replacements are particularly associated with an elevated surgical risk. The transapical access provides the opportunity to approach the aortic and mitral valves during one intervention. We report the case of a successful transcatheter valve-in-valve implantation in the aortic and mitral position within a single procedure.

[Treating mitral regurgitation: a surgical and interventional update]. / Therapie der Mitralklappeninsuffizienz: Chirurgische und interventionelle Neuerungen.

Surgical mitral valve repair has constantly evolved to become the standard of care for severe mitral regurgitation (MR) with superior acute and long-term results compared to valve replacement. Minimally-invasive surgical techniques have been successful in reducing operative trauma while yielding equivalent or even superior results compared to the conventional sternotomy approach. However, due to elevated operative risk a growing proportion of patients are not referred for surgery, especially elderly patients with reduced ventricular function and functional MR who often present with relevant comorbidities. It is for these patients that transcatheter-based therapies may represent an attractive option. While most interventional techniques are still in experimental or early clinical stages of development, relevant clinical experience has been gained with the MitraClip® device. For successful implementation of a patient-centered mitral valve program, integration of surgical and interventional treatment modalities within a heart center is of paramount importance. This is best accomplished by an interdisciplinary dedicated heart team consisting of cardiologists and cardiac surgeons.

[Diagnosis and options for reconstructive heart valve surgery in the Marfan syndrome].

Marfan syndrome is a disorder of the connective tissue that is inherited in an autosomal-dominant fashion and that is caused by mutations in the gene coding for fibrillin-1, FBN1. Although complications of the syndrome may involve the eye, the lung and the skeleton, the high mortality of untreated cases results almost exclusively from cardiovascular complications, including aortic dissection, rupture and mitral valve regurgitation. The multiorgan involvement of many of these syndromes requires multidisciplinary expert centers that can increase the average life expectancy of affected patients from only 32 years to over 60 years. The present article both reviews classical standards of managing cardiovascular manifestations and highlights the surgical approach for aortic and mitral valve surgery in Marfan patients.

Minimally invasive resection of a right atrial mass in a cardiac transplant recipient: a case report.

Intracardiac thrombus formation usually occurs in the left-sided cavities of the heart, most frequently in the presence of atrial fibrillation or cardiomyopathy. We report the case of an initially unclear mass developing in the right atrium (RA) of a heart transplant recipient, which was subsequently resected via a minimally invasive surgical approach. Access via right anterior minithoracotomy using videoscopic assistance allowed for uncomplicated RA thrombectomy in the presented case, avoiding reentry sternotomy with the potential risk of cardiac injury and without aortic cross-clamping or cardioplegic arrest. The patient is doing fine with excellent graft function at the latest follow-up 4 months after minimally invasive thrombectomy and 30 months after cardiac transplantation. To the best of our knowledge, this is the first report describing minimally invasive resection of a right atrial thrombus in a heart transplant recipient.

Transcatheter aortic valve implantation in a heart transplant recipient: a case report.

Transcatheter aortic valve implantation (TAVI) has evolved into a feasible therapeutic option for the management of selected patients with severe aortic stenosis and high or prohibitive risk for standard surgery. Symptomatic severe aortic stenosis occasionally occurs in the allograft long after heart transplantation. Because of specific characteristics and comorbidities of heart transplant recipients, these patients may be considered candidates for this less invasive approach. We report a first case of successful transapical TAVI in a heart transplant recipient with symptomatic severe calcific aortic valvular disease and relevant comorbidities long after heart transplantation.

Aortic aneurysms after correction of aortic coarctation: a systematic review.

Despite advanced techniques for surgical or percutaneous therapy coarctation of the aorta continues to carry a high risk of aneurysmal formation. Mortality of these aneurysms ranges between <1 and >90%, reflecting remarkable differences in surgical strategies and the follow-up management of coarctation. We review the frequency, anatomical types, risk factors and mechanisms of aortic aneurysm forming late after surgical or percutaneous therapy of aortic coarctation. We emphasize that aneurysms do not form exclusively at the site of previous intervention, but also at remote locations such as the ascending aorta. Moreover, aneurysm formation may only in part be attributed to a specific technique of coarctation therapy, and we emphasize the role of a bicuspid aortic valve and inherent weakness of the aortic wall as significant risk factors for aneurysm after aortic coarctation. We report the presenting symptoms, follow-up protocols, and imaging criteria for local and proximal aneurysms. Finally, we discuss criteria for prophylactic intervention at the site of such aneurysms, and present therapeutic options for different types of aneurysms. With this systematic review, we wish to provide data for establishing more uniform strategies for preventing, diagnosing and treating aneurysms associated with aortic coarctation.

Marfan syndrome and the evolving spectrum of heritable thoracic aortic disease: do we need genetics for clinical decisions?

Marfan syndrome (MFS) is a disorder of the connective tissue that is inherited in an autosomal dominant fashion and that is classically caused by mutations in the gene coding for fibrillin-1, FBN1. The high mortality of untreated MFS results almost exclusively from aortic complications such as aortic dissection and rupture. However, more than half of patients with Marfan-like features do not have MFS, but have other diseases including inherited aortic aneurysms and dissections (TAAD). We elucidate the increasing spectrum of syndromes associated with Marfan-like features and discuss the clinical implications of these diseases. We performed a systematic review to tabulate all known inherited diseases and syndromes carrying a risk for thoracic aortic disease. We discuss evidence that different syndromes with different causative genes and mutations have different prognoses and profiles of cardiovascular manifestations. We conclude that future decisions for optimized management of patients with inherited TAAD require a comprehensive clinical and genetic work-up.

Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols.

BACKGROUND: The need for better immunosuppressive protocols after lung transplantation led us to investigate tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and steroids or cyclosporine (CsA) in combination with MMF and steroids in a prospective, open, randomized trial after lung transplantation. METHODS: Between September 1997 and April 1999, 50 lung transplant recipients were randomized to receive either Tac (n = 26) or CsA (n = 24) in combination with MMF and steroids. All patients underwent induction therapy with rabbit antithymocyte globulin (ATG) for 3 days. Freedom from acute rejection (AR), patient survival, infection episodes, and side effects were monitored. RESULTS: There was no difference in patient demographics between the two groups. Six-month and 1-year survival was similar (84.6% and 73.1% in the Tac group vs 83.3% and 79.2% in the CsA group). Freedom from AR at 6 months and 1 year after lung transplantation was slightly higher in the Tac group (57.7% and 50% vs 45.8% and 33.3%, p = not significant [n.s.]), whereas the number of treated rejection episodes per 100 patient days in the Tac group was significantly lower (0.225 vs 0.426, p < .05). Four patients in the CsA group had to be switched to Tac. Two patients in the CsA group had to be retransplanted. Incidence of infections was similar in both groups with a trend toward more fungal infections in the Tac group (n = 7 vs n = 1, p = n.s.). CONCLUSIONS: The combination of Tac and MMF seems to have slightly higher immunosuppressive potential compared with CsA and MMF. The effectiveness of Tac as a rescue agent is not paralleled with undue signs of overimmunosuppression.