Theo De By

Increasingly, health care providers must demonstrate that they are able to meet the justified expectation that they can actually deliver results of care according to the definition: “quality of care is the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge”.

Measuring the outcomes of health services as such doesn’t provide adequate information about the quality of services of an individual provider. It’s when we compare the outcomes of that provider with those of other providers, offering similar services, that the results can be analysed in perspective. In this way best practises can be defined and the relative outcomes of an individual provider of (health) services can be determined. This process is called benchmarking. (Chapter 1)

In this thesis different benchmarking studies in the field of cardio-thoracic surgery are presented.

The instruments and platforms, used in these studies, in order to objectively assess outcomes are databases and registries. In addition professional societies and peer-organisations play a key role in organising focus-meetings and workshops indicating the possible causes, and directions to solve the negative differences.

A systematic literature review (Chapter 2) of benchmarking studies showed that the causal relationship between the use of registries and increased quality could be proven. Benchmarking provided tangible evidence of measurable qualitative improvement of outcomes. All studies provided additional instruments to come to best practises.

Heart failure is an important cause of morbidity and mortality. Ultimately, heart transplantation was -and perhaps is- the therapy of choice for heart failure patients. Since more than 2 decades, a technological innovation in the form of Mechanical Circulatory Support (MCS) in the form of blood-pumps has made it possible to support the heart, and therewith the blood circulation of these patients. Several studies about the use of MCS are presented in this thesis (Chapters 3-8). Since the common denominator of this thesis is the benchmarking of methods and outcomes, these studies provide benchmarks based on registry data, specifically of the European EUROMACS registry.

Two studies (Chapters 3 and 4) provide reports on the application of MCS respectively in adult and in paediatric patients. The reports show the applied practises in the field of MCS by the accumulation of base-line data. Follow-up analyses analyse the factors contributing to short- and long-term outcomes.

Such data have been made available on a global level too. One chapter (Chapter 5) of this thesis is a study of the International Society for Heart and Lung Transplantation Registry for Mechanical Circulatory Support (IMACS Report), in which, besides data from EUROMACS, contributions of similar data from other parts of the world are brought together. The source of these data is mostly from the United States, while data from countries such as Canada, Japan, Singapore and Australia are integrated as well. The IMACS report offers multiple benchmarks with respect to device strategies, risk factors, adverse events and predictors for mortality.

A difference between female and male patients in terms of selection for as well as outcomes of MCS therapy was demonstrated as part of this thesis (Chapter 6). While heart failure is more frequent in women, only 15.6% of the patients in the EUROMACS database was female, and short- as well as long-term mortality appeared to be higher. One of the causes may be the limited availability of smaller devices (only 1 manufacturer offered smaller devices at the time of the study). The results of the study have provided a benchmark for future analysis of the differences in outcomes in female patients.

Another benchmark has been set in the paper (Chapter 7) about patients whose MCS device has been explanted after adequate recovery of the heart muscle, showing that weaning from an MCS device shows excellent results, and that only a minority of the patients suffer from a relapse or significant heart failure.

The EUROMACS registry enabled us to compare different strategies when it comes to patients with leakage of the tricuspid valve. While some studies underlined the necessity to repair the tricuspid valve during valve implantation. The study in this thesis (Chapter 8) demonstrates that such an intervention doesn’t necessarily lead to better results, and that an improved patient selection may possibly give better results.

The transplantation of human tissues (allografts), focused on cardio-vascular allografts, comprises several chapters of this thesis (Chapters 9 and 10). First, a wide-range study, carried out for the European Commission, looks into the clinical use. Qualified as “replacement tissues” cardiovascular allografts are implanted in those patients with illnesses or malfunction of the heart-valves or arteries. The causes can be congenital or acquired, such as by infections or sepsis.

To make replacement tissues available for transplantation they must be donated by a deceased donor. Contrary to organ donation, in which the short time between donation and transplantation is a qualitative factor, tissues can be stored for a longer period of time. This enables tissue establishments to evaluate the quality of the tissue in different ways.

The presented studies give an insight in the different methods that are applied. Rates of donations and transplantations are quantified for countries in the EU, while cross-border activities have been chartered. A breakdown of factors influencing the availability of sufficient grafts learns that in countries with an opting-in system, the additional efforts to obtain permission for donation is threshold to overcome to get sufficient grafts to cover the clinical need.

These studies also provide an economic evaluation into the costs, generated because of the necessary quality and safety requirements. Although donated for altruistic reasons, the processing and investment costs require compensation of the hospital, or the patient’s insurance once the graft is transplanted.

Our conclusion is that there is a decreasing trend in the use of cardiovascular donor tissues, but that there will always be a - albeit lower - demand. For the long term, we expect better long-term results due to the application of new techniques such as decellularized heart valves before implantation.

Four chapters (Chapters 11-14) of this thesis consist of studies focusing on different methods used by tissue establishments and their outcomes.

Contamination of the implanted tissue graft can lead to severe complications in the vulnerable recipient. In order to determine that no micro-organisms are transferred to the recipient, tests are carried out. In a first study (Chapter 12) we observed great differences in methods and results of the different tissue establishments in Europe and in third countries. And concluded that there was a need for an international standard.

A second study (Chapter 12) made a quantitative inventory of numbers of donations and transplantations as well of methods used in the processes from donation, excision, decontamination and storage. The observed differences triggered us to execute a “quality round” in which the tissue establishments were asked to determine which micro-organisms could be found in samples that were purposely contaminated. From the 20 participating establishments, 13 appeared to use methods that were insufficiently effective to perform adequate decontamination. Moreover, some methods could save a substantial level of costs if they would re-design their processes in a more logical way.

The conclusion was that, in order to come to best practises, harmonisation of methods was, and is an necessity to enable exchange of grafts on a European level. Moreover, surgeons -in the interest of their patients- must be able to rely on the methods used.

In an additional study (Chapter 13) we focused on mapping the factors that lead to the rejection donation of heart or tissues of hearts from donors. This time, great differences were found in e.g. donor management, age limits and the acceptance of non-organ donors, thus limiting of the availability of tissues for transplant. The decontamination methods and the temperatures were again found to be different and correlation with rejection rates of potential donors was observed.

The last study (Chapter 14) reports the results of a 2nd quality round in tissue establishment in which from 21 European and 4 third countries participated. The instruction was to identify micro-organisms in each of 3 samples. Repeatedly, some establishments provided incorrect results. What became clear though is that low temperatures of 4° C to 22 C° are inadequate to decontaminate, thus setting a standard and a benchmark for applied methodologies in cardiovascular tissue establishment.

In a future perspective (Chapter 16) we stated that the necessity to come to national and international European registries that provide adequate data for benchmarking is increasing. In order to demonstrate that health care providers can deliver the health outcomes that are desired by society, they must prove, by benchmarking and transparent publication of their outcomes, that their results and outcomes are consistent with current professional knowledge. As for patients who need MCS several factors will determine future results. One is the early selection of eligible patients, and another is that devices will become smaller, which will benefit women and children. A third is the development of peripherals such as apps that enable monitoring patients at a distance, on-line, that enable clinicians to detect adverse events in an early stage.

The tissue establishments that collaborate in the international benchmarking project are looking to eliminate factors that negatively influence quality by setting up an affiliation with NEQAS (National External Quality Assessment Service) an independent, now international, consortium that focuses on improving test results in laboratories. Eventually the observed differences in outcomes will disappear and the certainty that the quality of the tests is reliable will increase.

The use of human heart valve tissue will generally decrease, for specific indications decellularized tissues will be preferred, although due to the high processing costs, no total substitution of traditionally processed heart valves can be expected.

Finally, it is hoped that this thesis contributes to the work of cardiac surgeons and cardiologists who are responsible for the clinical care of patients.