Mani Arsalan

The future of transcatheter aortic valve implantation.

Since the introduction of transcatheter aortic valve implantation (TAVI) into clinical practice, the treatment of aortic stenosis has changed dramatically. In the past, medical therapy with or without balloon aortic valvuloplasty was the only option for inoperable patients. More recently, TAVI has become the treatment of choice for these patients and the preferred alternative for high-risk operable patients. Surgical aortic valve replacement (SAVR) currently remains the gold standard for patients at low or intermediate operative risk. As randomized trials have demonstrated comparable results between TAVI and SAVR in the high-risk population, there is now a clear trend towards performing TAVI even in intermediate-risk patients while awaiting the results of randomized trials in that population. Nevertheless, there are still questions regarding TAVI involving paravalvular leak (PVL), stroke, pacemaker requirements, and durability that remain to be more definitively answered before TAVI can routinely be performed in a broader, lower risk population. Improvements in patient selection, imaging, and second and third generation devices have decreased the incidence of PVLs and vascular complications that followed the earliest TAVI procedures, but the rates of perioperative stroke and permanent pacemaker implantation must still be addressed. Furthermore, the long-term durability of TAVI devices and a role for post-procedure antithrombotic management remain unanswered. Until these questions are more clearly answered, it is the Heart Teams task to determine the optimal treatment for each patient based on risk scores, frailty metrics, comorbidities, patient preference, and potential for improvement in quality of life.

Durability of prostheses for transcatheter aortic valve implantation

Transcatheter aortic valve implantation (TAVI) has become the standard of care for inoperable patients, and the preferred treatment option for high-risk patients with severe aortic stenosis. Given that this therapy was intended for elderly patients with limited life expectancy, long-term durability has not been in the focus. Now that TAVI is increasingly being used in patients with intermediate-risk and lower-risk profiles, device durability has gained importance. The available mid-term results for TAVI are promising; however, little is known about the fate of TAVI devices beyond 5 years. The experience with long-term durability of surgical valves shows that ≥10-year follow-up is required to ensure reliable durability data. In this Review, we discuss the existing studies of TAVI durability, highlight differences between surgical and transcatheter treatment of aortic stenosis that might influence durability, and present a clinical solution for failed prostheses. Furthermore, we suggest how device durability might influence the future selection of patients for TAVI.

Should Transcatheter Aortic Valve Replacement Be Performed in Nonagenarians?: Insights From the STS/ACC TVT Registry

BACKGROUND Data demonstrating the outcome of transcatheter aortic valve replacement (TAVR) in the very elderly patients are limited, as they often represent only a small proportion of the trial populations. OBJECTIVES The purpose of this study was to compare the outcomes of nonagenarians to younger patients undergoing TAVR in current practice. METHODS We analyzed data from the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry. Outcomes at 30 days and 1 year were compared between patients ≥90 years versus <90 years of age using cumulative incidence curves. Quality of life was assessed with the 12-item Kansas City Cardiomyopathy Questionnaire. RESULTS Between November 2011 and September 2014, 24,025 patients underwent TAVR in 329 participating hospitals, of which 3,773 (15.7%) were age ≥90 years. The 30-day and 1-year mortality rates were significantly higher among nonagenarians (age ≥90 years vs. <90 years: 30-day: 8.8% vs. 5.9%; p < 0.001; 1 year: 24.8% vs. 22.0%; p < 0.001, absolute risk: 2.8%, relative risk: 12.7%). However, nonagenarians had a higher mean Society of Thoracic Surgeons Predicted Risk of Operative Mortality score (10.9% vs. 8.1%; p < 0.001) and, therefore, had similar ratios of observed to expected rates of 30-day death (age ≥90 years vs. <90 years: 0.81, 95% confidence interval: 0.70 to 0.92 vs. 0.72, 95% confidence interval: 0.67 to 0.78). There were no differences in the rates of stroke, aortic valve reintervention, or myocardial infarction at 30 days or 1 year. Nonagenarians had lower (worse) median Kansas City Cardiomyopathy Questionnaire scores at 30 days; however, there was no significant difference at 1 year. CONCLUSIONS In current U.S. clinical practice, approximately 16% of patients undergoing TAVR are ≥90 years of age. Although 30-day and 1-year mortality rates were statistically higher compared with younger patients undergoing TAVR, the absolute and relative differences were clinically modest. TAVR also improves quality of life to the same degree in nonagenarians as in younger patients. These data support safety and efficacy of TAVR in select very elderly patients.

First-in-man evaluation of the transapical APICA ASC™ access and closure device: the initial 10 patients

OBJECTIVES The aim of this study was to evaluate the initial and short-term results of a new apical access and closure device to facilitate and standardize the transapical (TA) approach to transcatheter aortic valve implantation (TAVI). METHODS The apical access, stabilization and closure (ASC™) device consists of three components: an introducer system, a left ventricular low-profile titanium coil and a closure cap. The ASC™ introducer system is anchored and rotated into the myocardium almost like a corkscrew, using the titanium coil. Following the TA-AVI procedure, the closure cap is introduced and delivered through the system into the titanium coil for final sealing. RESULTS A total of 11 high-risk elderly patients (EuroSCORE I: 27.8 ± 16.7; EuroSCORE II: 6.6 ± 5.0 and The Society of Thoracic Surgeons (STS) score: 5.9 ± 2.7%) were evaluated for TA-AVI by our interdisciplinary Heart Team and subsequently included in the trial after informed consent was obtained. One patient was excluded due to the presence of deep epicardial fat tissue. In all other cases, the titanium coil provided sufficient sealing throughout the procedure without the presence of perisheath bleeding. After delivery of the closure cap, no relevant bleeding was observed in any patient. Pericardial drainages were removed early in all patients. One patient suffered from non-device-related pericardial effusion requiring surgical decompression on postoperative day 6. Two patients suffered from delayed minor strokes, most likely due to arrhythmia. All patients received aspirin, clopidogrel and low molecular heparin after the procedure. Discharge echocardiography revealed no changes in left ventricular function when compared with baseline and no new onset wall motion abnormalities. All 10 patients were alive at 30 days. CONCLUSIONS TA access and closure are both feasible and safe using the APICA ASC™ device. The system facilitates and standardizes TA access and closure by providing a sufficient and secure sealing during and after the TA-AVI procedure.

First experience without pre-ballooning in transapical aortic valve implantation: a propensity score-matched analysis

OBJECTIVES Transapical aortic valve implantation (TA-AVI) using the Edwards SAPIEN™ prosthesis has evolved into a routine procedure for selected high-risk elderly patients. The recently introduced SAPIEN™ delivery system (Ascendra II+™) with an added nose cone seems to facilitate direct valve implantation without prior balloon valvuloplasty (BAV). Here, we report our initial experience with this device. METHODS A total of 128 patients were enrolled in the study in 2012 and 2013 and were designated Cohort I. For a subset of 79 patients, exact cardio- computed tomography-based measurements were available; these patients were assigned to Cohort II. All patients received SAPIEN XT™ valves using the TA approach. TA-AVI without pre-ballooning was performed in 31.2% (Cohort I) and 31.6% (Cohort II) of patients. To adjust for baseline variables, propensity score (PS)-based pair matching was used. RESULTS All valves were implanted successfully. The use of PS matching resulted in bias reduction for both cohorts. For Cohort I, there were no significant differences in the primary end points, which were aortic valve incompetence≥2+, Pmean postimplantation, major stroke, transient ischaemic attack (TIA), requirement for post-dilatation and necessity for new pacemaker implantation. As expected, fluoroscopy time was significantly lower in no-BAV patients. In Cohort II, the 30-day TIA rate was lower in the no-BAV group. CONCLUSIONS Direct TA implantation of the SAPIEN valve without pre-ballooning is feasible, safe, does not seem to compromise functional outcomes and may be associated with fewer neurological events.

Bone marrow-derived stem cells attenuate impaired contractility and enhance capillary density in a rabbit model of Doxorubicin-induced failing hearts.

Abstract  Background: There is a regenerative potential of bone marrow‐derived stem cells (BMCs) in ischemic cardiomyopathy, but little is known of their effects in nonischemic cardiomyopathy. This study evaluates the effects of BMC transplantation on contractility and remote capillary density of doxorubicin‐induced failing hearts. Methods: Heart failure was induced in rabbits by doxorubicin (3 mg/kg; 6 weeks), followed by BMC transplantation (BMC group, 1.5–2.0 × 106 cells, n = 15), sham treatment (Medium group, n = 10), or no therapy (Dox group, n = 6). Healthy rabbits were used as controls (n = 10). Cells were transplanted locally into the left ventricle (LV). Four weeks later, contractility was assessed. Cross‐sections of hearts were investigated by H&E, Picrosirius red stain, and immunohistologically (Troponin I, α‐Actinin, Connexin43). Capillary density (CD31‐antigen) was examined in the LV, septum, and right ventricle (RV). Results: Global contractility was significantly higher in the BMC group versus Medium group (ejection fraction: 39.0 ± 1.4% vs. 30.0 ± 1.9%, p = 0.002, and fractional shortening: 22 ± 0.8 vs. 19 ± 0.6, p < 0.01). Hemodynamic measurements by Millar catheter (Millar Instruments, Houston, TX, USA) were also significantly improved. Capillary density increased in cell‐treated hearts (LV: 55 ± 2.2 vs. 42 ± 2.0, p < 0.001, RV: 40 ± 2.1 vs. 35 ± 1.7, p = 0.065, and septum: 46 ± 1.5 vs. 39 ± 1.7, p = 0.005), when compared to the Medium group. The transplanted cells failed to express cardiac markers. The collagen content was reduced in BMC‐treated rabbits. Conclusion: Despite local cell transplantation, autologous BMCs improve global contractility and enhance remote capillary density and collagen content in doxorubicin‐induced cardiomyopathy. However, BMCs failed to transdifferentiate into new cardiomyocytes.

Comparison of two valve systems for transapical aortic valve implantation: a propensity score-matched analysis

OBJECTIVES Several alternative transapical (TA) aortic prostheses for aortic valve implantation (AVI) have recently become available. Data directly comparing the performance of these different TA-AVI valves, however, are sparse. Therefore, we sought to analyse the performance of the better-established balloon-expandable SAPIEN XT™ valve system, and compare it with the recently approved self-expandable ACURATE TA™ system by means of propensity score (PS) analysis. METHODS Samples from a total of 310 consecutive patients treated with transapical transcatheter aortic valve implantation (TAVI) were included (2010-2014). The ACURATE valve was implanted in 40% (n = 131), SAPIEN in 60% (n = 179). To adjust for baseline differences, 1:1 PS matching was used, and resulted in 103 matched pairs. In addition to demographical and clinical variables, potential anatomical confounders (calcification grade: computed tomography (CT) Agatston score; annulus diameter: CT-effective diameter) were included within the PS estimation. RESULTS For ACURATE- versus SAPIEN-treated patients, the mean age was 83.1 ± 5.4 vs 79.8 ± 9.5 (P < 0.001). Mean Society of Thoracic Surgeon scores were 7.7 ± 4.6 vs 8.1 ± 6.0 (P = 0.56). PS matching resulted in bias reduction <0.2, indicating excellent balance and allowing for valid outcome comparison. Device success, 30-day mortality rate and 1-year survival were comparable. Pacemaker and 30-day neurological event rates were not significantly different. The need for post-ballooning was significantly higher in the self-expandable group (40% vs 9%; P < 0.001). Echocardiography upon discharge demonstrated excellent functional outcomes regarding residual paravalvular leaks (ACURATE: 3% vs SAPIEN: 4%, P = 1.0) with slightly higher mean gradients in the ACURATE group (12 ± 5 mmHg vs 10 ± 5 mmHg, P = 0.003). CONCLUSIONS The two transapical TAVI devices demonstrated comparable haemodynamic performance and clinical outcome. The self-expandable valve required more frequent post-ballooning without affecting the safety profile.

Distribution of Cardiac Stem Cells in the Human Heart

Introduction. The existence of human cardiac stem cells (hCSC) and their regenerative capacity are not fully defined. The aim of this study was to identify and analyse the distribution of hCSCs by flow cytometry (FCM). Methods. Tissue samples from the left ventricle (LV) and the appendages of the right atrium (RA) and left atrium (LA) were taken during cardiac surgery. Mononuclear cells (MNCs) were isolated, labelled for the stem-cell-marker c-kit and hematopoietic-lineage markers and analysed by FCM. Results. HCSCs could be isolated from the RA, LA, and LV without significant quantitative difference between both atria (A) (RA 4.80 ± 1.76% versus LA 4.99 ± 1.69% of isolated MNCs, P = 0.922). The number of hCSCs was significantly higher in both atria compared to the left ventricle (A 4.90 ± 1.29% versus LV 0.62 ± 0.14% of isolated MNCs, P = 0.035). Conclusion. The atria contain a higher concentration of hCSC than the left ventricle. HCSCs located in the atria could serve as an endogenous source for heart regeneration.

Transapical access: current status and future directions

With the rapid evolution of transcatheter aortic valve implantation over the past few years, transapical access has evolved to be a routine approach for the implantation of transcatheter aortic valve prostheses. The approach itself has demonstrated feasibility, safety and reproducibility associated with low complication rates. As the access allows for relatively large profile devices and owing to the short anatomical distance to both the mitral and the aortic valve, the apical approach facilitates a wide range of interventions. Thus, minimally invasive transapical access can be considered as a versatile platform for the development of new transcatheter aortic or mitral devices.

Experimental Evaluation of a New Apical Access and Closure Device

PURPOSE Transapical aortic valve implantation (TA-AVI) has evolved as a treatment option for high-risk patients who have severe aortic stenosis. The aim of this study was to evaluate the feasibility of a novel apical closure device to allow for standardized apical access and closure. DESCRIPTION The Apica ASC system consists of three components: an introducer system, a left ventricular low-profile titanium coil, and a closure cap. The ASC introducer system is fixed to the myocardium by anchoring the titanium coil into the epicardium. After the TA-AVI procedure, the closure cap is introduced through the system and delivered onto the titanium coil for final sealing. EVALUATION After sternotomy, fixation of the introducer system was successfully performed in an acute pig model. The apex was safely secured in all attempts, and the titanium coil created an effective seal around the Ascendra sheath. Finally, the closure cap was shown to be secure even when the hearts were pressurized to 200 mm Hg. Postmortem examination showed a uniform depth of the titanium coil through the endocardium into the myocardial wall without penetration into the left ventricular cavity. CONCLUSIONS Apical access and closure is feasible using the sutureless Apica ASC device. The system seems to have the potential to further standardize the TA-AVI procedure, allowing wider applicability and more generalizability.