Author + information
- aMedical Clinic I, and Campus Kerckhoff, University of Giessen, Giessen, Germany
- bDepartment of Cardiac Surgery, University of Leipzig, Leipzig, Germany
- cInstitute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, Essen, Germany
- ↵∗Address for correspondence:
Professor Gerd Heusch, MD, Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, Hufelandstrasse 55, Essen, Germany 45122.
Aortic stenosis is the most prevalent valve disease in the elderly. Surgical aortic valve replacement was until recently the treatment of choice and has excellent outcomes in patients amenable to surgery. Transcatheter aortic valve replacement (TAVR) has evolved over the last 10 years as an alternative, less-invasive therapeutic option. Germany was one of the first countries to introduce TAVR routinely in some selected centers by 2006. In the following years, TAVR grew rapidly, and by 2013 it surpassed conventional surgical aortic valve replacements (SAVR). For many years, Germany had the highest number of TAVR procedures worldwide and was able to introduce new devices at an early stage. Accordingly, the development of the technique was to a great degree driven by German investigators (1).
Initially, TAVR was reserved for inoperable patients. Due to favorable results from randomized controlled trials (RCTs) and improved technology, however, the indication was rapidly extended to most elderly and high-risk patients for whom conventional surgery was previously the only option. This resulted in a paradigm change, as cardiac surgeons and cardiologists together as a heart team decided about the best patient management on an individual basis.
Today, around 18,000 TAVR per year are performed in Germany in 97 centers using about 7 different valve types. For reimbursement, it is mandatory to provide data from the in-hospital outcome, but not from long-term follow-up. To evaluate the results of the RCTs under real-world conditions, 2 scientific societies—the German Cardiac Society (DGK) and the German Society for Thoracic and Cardiovascular Surgery (DGTHG)—joined forces in a special endeavor and founded the GARY (German Aortic Valve Registry) in 2010. The aim was to collect data from all patients undergoing aortic valve interventions in Germany and to analyze early and particularly late outcomes (2).
All sites that perform surgical or catheter-based aortic valve replacements in Germany committed themselves to providing prospective in-hospital data to an independent institution (BQS, Institut für Qualität und Patientensicherheit, Düsseldorf, Germany) that analyzes the data and performs the follow-up by telephone calls or questionnaires over at least 5 years. Financial support for GARY was provided by the DGK and DGTHG, the health care industry, the German Heart Foundation, the Deutsches Zentrum für Herz-Kreislaufforschung, private donations, and more recently, minor contributions from official government sources.
Over the years, 97 participating sites have prospectively enrolled >150,000 patients who gave consent to be followed (Figure 1). Thus, GARY constitutes the largest dataset of aortic valve interventions worldwide, and it is the only registry that represents the complete spectrum of aortic disease and interventions. About 63% are surgical procedures, and the remainder catheter-based. Because participation in GARY is not yet mandatory and is not reimbursed, only about two-thirds of all patients undergoing interventions are being captured. However, follow-up of registered patients, which is 98%, ranks at a very high level and illustrates the quality of this registry.
The use of this large GARY database has allowed an appreciable number of interesting analyses to be presented at major international meetings and published in leading journals. We have learned a number of lessons from GARY:
1. Role of the heart team and good outcome of TAVR: Heart team decisions seemed to be very appropriate and to reflect best management. This can be concluded from the assessment of acute in-hospital outcome in GARY based on 13,860 patients registered in 2011 (3). The in-hospital mortality was 2.1% for SAVR alone and 4.5% for SAVR combined with bypass grafting. Compared with the surgical cohort, TAVR patients were around 10 years older and had substantially higher risk profiles. Nevertheless, in-hospital mortality of patients treated with TAVR was relatively low (transfemoral TAVR: 5.1%; transapical TAVR: 7.7%). Therefore, SAVR was concluded to be associated with very good early outcome, whereas TAVR in high-risk and elderly patients achieved results comparable to RCTs.
2. Improvements of TAVR results over time: TAVR results improve over time and have an impact on the spectrum of SAVR patients, based on perioperative results and complications of 15,964 TAVR procedures from 2011 to 2014 (4). In-hospital mortality was only 5.2%, even though the TAVR population had a mean age of 81 years, was 54% female, and had a mean Society of Thoracic Surgeons (STS) score of 5.0%. Severe vital complications (defined as death on the day of TAVR, conversion to sternotomy, low cardiac output that required mechanical support, annular rupture, and aortic dissection) occurred in 5.0%, and technical complications of the procedures occurred in 4.7% of the registry population. A significant decrease in the rate of technical complications was recognized in the 4-year observational period. In parallel, based on 42,776 patients undergoing SAVR between 2011 and 2015, there was a decline in median age by 1 year (from 73 to 72 years), and a lower risk profile was documented (5). Obviously, this was the effect of a shift of patients to TAVR.
3. Improvement in quality of life with TAVR: Valve replacement leads to improvements in health-related quality-of-life outcomes, especially in terms of mobility and daily activities (6). This was based on 3,875 TAVR patients assessed 1 year after the intervention. The magnitude of improvements was higher in the TAVR-transvascular group than in the TAVR-transapical group. However, there was a sizable group of patients who did not derive any quality-of-life benefits. Several independent pre- and post-operative factors (age, female sex, body mass index, New York Heart Association functional class III or IV, neurological dysfunction, renal replacement therapy, peripheral arterial vascular disease, mitral insufficiency ≥2°, and post-operative transient ischemic attack or stroke) were identified as predictive of some less pronounced benefits.
4. Sex differences in TAVR results: TAVR in women is associated with a lower 1-year mortality (adjusted hazard ratio: 0.88) (7). Depressed left ventricular function plays a prominent role in adverse outcomes in male patients, but less so in female patients. In a further study in patients with low-gradient aortic stenosis, the prognostic role of impaired left ventricular function, as opposed to preserved function, was demonstrated during 1-year follow-up (8).
5. Superiority of conscious sedation over general anesthesia in TAVR: Conscious sedation should become the routine mode of patient management during the procedure. A recent study (9) addressed different modes of anesthesia for TAVR, which was never investigated in a RCT. Local anesthesia or conscious sedation was used in 49% of 16,543 patients undergoing transfemoral TAVR. Compared with general anesthesia, this approach was associated with lower rates of low-output syndrome, respiratory failure, delirium, cardiopulmonary resuscitation, and early mortality.
Because GARY focuses primarily on longer follow-up periods (3 to 5 years), the most important data are expected to become available over the next few years. In addition, analyses of specific subgroups of patients (those with diabetes, renal failure, and so on), different valves and prosthetic technologies, intermediate-risk patients, asymptomatic presentations, and bicuspid valves are underway and will be presented soon.
Whereas many procedural and technical challenges of TAVR have been overcome, the important issue of valve durability remains open. Although data on the biological SAVR valves are also rather scarce, the question of durability becomes critical when TAVR is offered to younger age groups. Thus far, transvalvular gradients and aortic valve areas seem to be rather favorable, and at this stage, there is no valid evidence that TAVR valves are less durable than SAVR valves; however, this issue needs to be settled in the coming years. Thus, since January 2018, the focus of GARY has been to collect data on long-term durability of SAVR and TAVR valves. Accordingly, only younger patients (age 70 to 79 years) are now being recruited who will undergo standardized follow-up echocardiography over at least 10 years.
Today, registries such as GARY play an essential role in determining whether the results of RCTs hold true after market introduction. The size of an all-comers registry like this allows various aspects of the disease and the optimal treatment to be addressed in a real-world scenario. Therefore, this type of science becomes a cornerstone of decision making, particularly when new technologies are introduced into clinical practice. Many questions that cannot be answered by RCTs can be answered only by using data from large registries. Accordingly, government authorities also pay more attention to this kind of data collection and have started to provide support for this type of research.
Drs. Hamm and Mohr have cochaired the executive board of GARY (German Aortic Valve Registry). Dr. Heusch has promoted the foundation of GARY as president of the German Cardiac Society and served on its executive board.
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