Excellence in Cardiovascular Medicine and Research€¦ · of Cardiovascular and Thoracic Surgery and Pediatric Cardiology, we are certiﬁed as a specialist EMAH center for adult

Excellence in CardiovascularMedicine and ResearchDepartment of CardiologyUniversity Medical Center Mainz, GermanyJohannes Gutenberg University

Introductionto theInstitution

(HVU) in Europe, thuscontributing towards dealingwith the drastic increase inincidence of heart valvedisorders in Germany.

Together with the Departmentof Cardiovascular and ThoracicSurgery and PediatricCardiology, we are certified asa specialist EMAH center foradult congenital heart diseasein 2017.

Our Chest Pain Unit deals withmore than 6,000 patientsannually; 2,500-3,000 of theseare hospitalized for furthertreatment. In this issue, we will beconsidering how this new patientcare structure in Germany hasevolved and whether allexpectations were fulfilled.

In our Angiology Departmentwe offer all necessary

accordance with the latesttreatment standards.

We have 135 beds including anintensive and coronary careunit, a chest pain and atrialfibrillation unit, a heart valveunit and 6 heart catheterizationlaboratories. Per year we see 11,500 inpatients and20,000 outpatients.

The Center for CardiovascularMedicine performs more than650 heart valve procedures ayear, 1,000 atrial fibrillationablation procedures andimplants around 700 devices(defibrillators and pacemakers).We perform 4,200 coronarydiagnostic caths and almost3,000 percutaneous coronaryand peripheral interventions.

In spring 2018, we opened thevery first Heart Valve Unit

www.unimedizin-mainz.de/kardiologie-1/2

Department of Cardiology

The Center forCardiovascularMedicine at the

University MedicalCenter in Mainz hasan internationally

recognizedleadership in the

area of cardiac andvascular medicine.

The center has currentlyapproximately 400 staffmembers employed asphysicians, nurses, techniciansand administrators, who ensurethat patients receive the highestquality of safe, professional andalso highly innovative care in

http://www.unimedizin-mainz.de/kardiologie-1/

diagnostic procedures withspecial focus on peripheralartery disease. We alsoperform around 500peripheral interventions.

In the Preventive Medicine weoffer comprehensive, state-of-the-art check-up investigationsfor national and internationalpatients in primary, secondaryand tertiary prevention. Theindividually designedexamination program over 2 (tomax. 3) days coversinterdisciplinary diagnostics.After completion, a detailedreport and personal treatmentrecommendations areexplained to the patient.

With respect to research weinitiated the Gutenberg HealthStudy in 2007, one of the worldlargest population-based,interdisciplinary cohort studies

and we are member of theGerman Center forCardiovascular Research.

We are continuing to placeemphasis on research in thesector of environment andhealth. A major achievementhere was the identification ofthe molecular mechanisms by which aircraft noise can cause deterioration ofvascular function.

Our department has beenresponsible for more than 100specialist publications on thesubjects of vascular biology,blood coagulation and onsubjects relating to theGutenberg Health Study,demonstrating our dedicationto research.

The Mainz Heart Foundation,which also celebrated its 10th

anniversary in 2017, issupporting the clinic withfundraising of about €500,000per year. The Foundation Heartof Mainz has extended itsannual courses in prevention aspart of the ‘Children’s AcademyHealth’ project to a totalcapacity of 55 school classes (>1,300 pupils). The purpose ofthese is to encourage schoolpupils and young people not tosmoke and to eat healthy foodand to teach them how toresuscitate people with asudden cardiac death.

In this center of excellencereport we want to focus on thearea of minimally invasive,percutaneous heart valvetherapy, on Chest Pain Unit andon our preclinical and clinicalresearch activities and on thefoundation Heart of Mainz.

3www.unimedizin-mainz.de/kardiologie-1/




The following paragraph provides abrief introduction into the physiology ofthe heart. The human heart consists offour chambers: The right and leftventricles, and the right and left atria.These chambers are separated fromeach other by four heart valves. Theirtask is to ensure that blood is pumpedin the correct direction through theheart chambers each time the heartbeats. In the right heart, the tricuspidvalve and the pulmonary valve ensurethat the blood can only flow in onedirection of the lungs. In the heart`s leftside, the mitral valve and the aorticvalve control the direction of blood flow.

Fig. 1 Broad spectrum of interventional heart valve therapy in Mainz.

Interventional, minimallyinvasive heart valve therapy

When it comes to catheter-basedminimally invasive treatments of disordersof the left heart valves - particularly inolder patients or patients with relevantrisk profiles – a Transcatheter AorticValve Implantation or TAVI isprincipally used and there are up to19,000 procedures of this kind annuallyin Germany alone, while a cure of mitralvalve regurgitation via implantation of aMitraClip® is undertaken in more than5,600 cases a year.

Importantly, over a period of just tenyears, catheter-based therapy of heartvalves has developed from a niche

4 www.unimedizin-mainz.de/kardiologie-1/

The increase in the incidence ofheart valve disorders such asstenosis or regurgitation

(incompetence) of the valves involvingthe left, but also the right side of theheart is currently reaching epidemicproportions. The main reason for thisdevelopment is the progressive ageingof the population being associated withan increase in the incidence of aorticvalve stenosis. In addition, we see amajor increase in diseases of theatrioventricular valves (the mitral andtricuspid valve), mainly as theconsequence of an increased incidenceof heart failure.



treatment used in otherwise inoperablepatients to a significant and safe generaltherapeutic option. These procedures arenow considered routine in this country -the safety of catheter-based interventionis very good and the survival rate isgreater than 98%. Importantly, Mainz isone of the few centers worldwide offeringthe complete spectrum of minimallyinvasive heart valve repair.

However, as in the case of all heartvalve procedures, these minimallyinvasive interventions do guaranteeindefinite durability because of thenatural heart valve tissue (BioValve)being involved. Depending on theunderlying disorder, follow-upintervention may be required afterseveral - up to ten - years.

In addition to the TAVI and Mitraclip®procedure, other minimally invasivevalve interventions include annuloplastyprocedures for the mitral and tricuspidvalve such as CARILLON® and theNEOCHORD® approach (Fig. 1).

This year, the Cardiology Departmentwill do for the first time more than 200MitraClips® and more than 300interventions with respect toatrioventricular valves (Fig. 2).

TAVI has become a routine hospitalprocedure. Transcatheter aortic valveimplantation (TAVI) is a procedure thatrepresents one of the major innovationsin cardiac medicine and its use hasspread remarkably rapidly. Asmentioned already, in Germany, patientswith aortic valve stenosis are beingtreated more frequently with TAVI thanwith open-heart surgery. Prof. EberhardSchulz, Director of the InterventionalHeart Valve Therapy Unit at MainzUniversity Medical Center, values thisform of ‘keyhole surgery’ becausesubsequent recovery times are shorter.He and his team have performed morethan 1,500 TAVI procedures – while thenumber of patients that require this typeof intervention is still increasing. In theyear 2018 we will implant more than400 TAVIs (Fig. 3)

Fig. 2 Growth rates of interventions concerning the mitral and tricuspid valves

Fig. 3 Number of TAVI implantations since 2011. TA: transapical, TF: transfemoral



Fig. 4 Contemporary TAVI prostheses: Edwards Sapien 3 (Left; © Edwards Lifesciences) andMedtronic Evolut Pro (Right; © Medtronic)

Fig. 5 Reconstructionof multislice CT Scanfor proceduralplanning. Upperpanel: anatomy ofthe aortic valve, leftventricle and aorta.Lower panel: annularplane of the aorticvalve, ostium of theleft coronary artery,3D reconstruction ofthe iliac-femoralarteries

Fig. 6 Fusionimaging(CT/fluoroscopy)during a TAVIprocedure (valve-invalve) With thishigh degree ofinnovation andincreasing demandfor catheter-basedvalve procedures,the Mainz UniversityMedical Center isamong the 10largest centers forinterventional heartvalve therapy inGermany.

In the beginning, only patients who werenot suitable for conventional surgerywere offered a TAVI procedure, in themeantime TAVI has emerged as thestandard approach for all patients withincreased risk for open heart surgery.The preferred access route istransfemoral, since latest study datashow the lowest complication rates andrapid recovery. Modern, third generationTAVI prostheses (Fig. 4) have nearlyeliminated early problems in thebeginning of the TAVI era such asrelevant paravalvular leakage, frequentneed for a permanent pacemaker,access site bleeding, annular rupture ordevice malpositioning.

With a multidisciplinary team of highlyspecialized interventional cardiologists,heart surgeons, cardiacanesthesiologists, valve nurses andtechnicians, TAVI procedures in Mainzare performed in a hybrid OR. Besidesthe interventional expertise, a detailedplanning of the procedure is key forsuccess. Every patient receives amultisclice CT before the procedure inorder to determine access route,prothesis type and size (Fig. 5)

In contrast to open heart surgery, directvisualization of cardiac structures is notpossible with catheter-based treatmentoptions and therefore high-qualityimaging is important and in complexprocedures mandatory. Thanks to alongstanding expertise inechocardiography and other imagingmodalities, the team has co-operationswith the developing units of the echoindustry and early access to innovateimaging techniques such as 3D virtualreality echocardiography or fusionimaging (CT/fluoroscopy;echo/fluoroscopy) (Fig. 6).

Minimally invasive rightheart valve proceduresinvolving the tricuspid valve The Department of Cardiology ofMainz University Medical Center isalso very successful in the treatmentof right-sided heart valve disease.Only a few hospitals are able to offercatheter-based treatments of thetricuspid valve. In fact, only just over




300 such procedures have beenperformed for therapeutic reasons oras part of clinical trials in recentyears. Thus, our department is one ofthe few centers able to offer this kindof treatment.

In a patient with tricuspid valveregurgitation, one of the undesirableside effects is accumulation of fluids inthe legs and abdomen and inparticular the quality of life of thoseaffected deteriorates significantly. Thesurgical methods used to date havenot resulted in significantimprovements overall and there is stilla high mortality rate especially in theweeks following surgery.

The team under Dr. Ralph Stephan vonBardeleben and Prof. Eberhard Schulznow employs two new techniques for thetreatment of tricuspid valve

Fig. 7 The Valve Team during a case conference and in the hybrid operating theater

Fig. 8 A tricuspid valve procedure

regurgitation, the cardioband® or atricuclip® (Fig. 7 and 8). Thesetechniques have already been used inmore than 60 patients to date, puttingMainz University Medical Center at thetop of the national and internationalleagues in this sector.

The Department of Cardiology ofMainz University Medical Center alsooffers a diverse range of informationand training events in this area both forreferring physicians, nurses and patients.The aim is to increase the awareness ofthe risk of problematic and life-threatening heart valve disease, offerbasic insights into the situation andensure that effective therapy is providedover the long term. At the same time,medical staff and the patients in theircare now have access to an innovative,less invasive catheter-based technique.




substantial reduction of the in-hospitalstay period by almost 20% during thefirst few months.

To our knowledge, the unit is the first ofits kind and we are convinced that it willbe a role model for Germany and therest of the world since it provides anoptimal answer to the rapidly growingchallenges due to an increased need fortranscatheter heart valve procedures.This model will go national andinternational soon, as happened whenwe installed the Chest Pain UnitNetwork in Germany years ago.5

References:1 Schulz E, Beiras-Fernandez A, Rohsbach U,

von Bardeleben RS, Sotiriou E, Tamm A, VahlCF, Münzel T. Successful transcatheter aorticvalve-in-valve implantation in a patient havinga chronic type A aortic dissection. Eur Heart J2017;38:3391-3392.

2 von Bardeleben RS, Kasper-Konig W, SotiriouE, Beiras-Fernandez A, Friedrich Vahl C,Münzel T, Schulz E. Transcatheter transapicalleft ventricle remodelling in ischaemiccardiomyopathy with apical aneurysm using3rd generation 3D cardiac computedtomography fusion imaging. Eur Heart J2017;38:2378.

3 von Bardeleben RS, Tamm A, Emrich T,Münzel T, Schulz E. Percutaneous transvenousdirect annuloplasty of a human tricuspid valveusing the Valtech Cardioband. Eur Heart J2017;38:690.

4 von Bardeleben RS, Colli A, Schulz E, Ruf T,Wrobel K, Vahl CF, Gerosa G, Werner C,Münzel T, Beiras-Fernandez A. First in humantranscatheter COMBO mitral valve repairwith direct ring annuloplasty and neochordleaflet implantation to treat degenerativemitral regurgitation: feasibility of thesimultaneous toolbox concept guided by 3Decho and computed tomography fusionimaging. Eur Heart J 2018;39:1314-1315.

5 Münzel T, Post F. The development of chestpain units in Germany. Eur Heart J2011;32:657-658.

The first European HeartValve Unit (HVU) Due to increasing life expectancy, moreand more people worldwide are sufferingfrom valvular heart diseases. Theseinclude aortic stenosis due to calcifiedaortic valve cusps or a regurgitation ofthe mitral or tricuspid valves. The annualgrowth rates of heart valve implantationsby minimal invasive transcatheterprocedures averages 10- 15% nationallyand internationally, while TAVI andMitraclip implantations have numericallyoutperformed open-heart valve surgeryduring the last few years in Germany.Importantly, the growth perspective to2025 is about 10-20% per year asrecently predicted in the Heart ValveDevices/Medtech 360/ Market Analysis/Europe/2017 Report by the decisionresearch group (https://decisionresourcesgroup.com/report/14453-medtech-heart-valve-devicesmedtech-360-market/).Patients with these heart valve diseasescan nowadays benefit tremendously froma minimally invasive heart valveintervention. The Mainz UniversityMedical Center is one of the leadingcenters in Germany and worldwide1-4 formitral and tricuspid valve interventions(including MitraClip NT/NTr/XTr,TricuClip and Cardioband Mitral /Tricuspid). It is expecting to treatapproximately 700 heart valves in 2018.

The increasing need for suchinterventions, the advanced age as wellas complex and serious comorbidities ofthese patients, the rapid developmentand establishment of innovative heartvalve procedures and almost a dailychange in the recommendations formedical treatment includingrecommendations for anticoagulation,have prompted the Department ofCardiology at the University MedicalCenter in Mainz to start with a newpatient care structure for patients withHeart Valve Disease, The Heart ValveUnit (Fig. 9 and 10).

Currently, patients are admitted to anormal ward for preparation of theheart valve procedure. After theprocedure they are transferred to theICU and thereafter to an additionalward with monitoring facilities fromwhich they are discharged.

What are the benefits of thenew HVU to patients? The new unit will combine all patientcare in a single unit. The advantage ofthis new patient care structure is that allrelevant steps of patient care during thehospital stay for heart valveimplantation are conducted in oneplace including: patient admission and

eventually recompensation;

complete planning of the procedure (including imagingmodalities such as TTE, TEE, CTscans, coronary angiogram);

monitoring on the intermediate care(IMC) part of the HVU directly afterheart valve implantation;

transfer within the HVU from IMC tomonitor beds for heart rhythmdocumentation and initiation ofoptimal and in particular consistentmedical therapy; and

complete case management anddischarge of patients is leading tofaster and better patient information,optimal patient diagnostic andtreatment algorithms in order toimprove the safety of theperiprocedural setting and finally toimprove patient satisfaction.

All measures now take place on oneward, thus avoiding frequent transfersof the patients to different wards. Theheart valve unit in Mainz consists of 25beds, including 8 IMC beds and 17normal beds equipped with monitors.Six doctors and 15 nurses working inshifts are taking care of the heart valvepatients. The establishment of the HeartValve Unit (HVU) has led to a



https://decisionresourcesgroup.com/report/14453-medtech-heart-valve-devicesmedtech-360-market/




Fig. 9 The new heart valve unit provides specialized, fast and efficient care for patients under highest quality standards

Fig. 10 Intermediate care room as part of our new heart valve unit




Fig. 11 Interventional therapy of a main stem bifurcation lesion with the reverse TAP technique

Coronary diagnostics,interventions and research

Intravascular Ultrasound (IVUS)Similar concepts apply to the use ofimaging techniques such asopticalcoherence tomography andintravascular ultrasound. Intravascularultrasound (IVUS) uses ultrasoundproduced by a small probe that isinserted over a guidewire into thecoronaries. The frequency of theultrasounds emitted by this probereaches 60MHz, which allows visualizingthe vessels´ walls with a ~30 micrometerresolution. Post-hoc processing of thefrequency shift also allowscharacterization of the composition ofthe wall, identifying calcific, fatty andfibrotic lesions (Fig.12).

Optical coherencetomography (OCT)Optical coherence tomography is atechnology that is based on infrared lightto achieve a resolution that is in the range

procedures and interventionaltechniques for our patients withcoronary artery disease andpulmonary embolism.

Coronary Intervention Special types of coronaryinterventions represent particularchallenges: for instance the treatmentof bifurcation lesions, i.e. lesions thatare placed in segments where twoblood vessels part from each other.These lesions may be complex to treatbecause both branches of the bloodvessels need to be treated and keptopen. To overcome this specificchallenge, our team developed a newmethod to treat this type of disease,which we are now testing in a study.The method is called reverse TAP (Tand protrusion), and is surely fasterand technically less challenging thantraditional methods (Fig.11).



More than 4,200 patientsundergo coronaryangiography every year in

our catheterization laboratory and2,200 receive a stent. Among thosemore than 700 patients with an acutecoronary syndrome are treated. Thisnumbers make us one of the largestcenters in Germany. The rapidity andefficacy of these coronary interventionsreally change people´s life: 50% of thepatients who die of heart attack do sobefore they reach the hospital. Ourstaff is trained to react 24 hours a day,each day of the year, within 30minutes of the first call. Our door-to-balloon time (an index of quality, thattell how much time it takes betweenpatient arrival inthe hospital andopening of the blood vessel), is below30 minutes and therefore clearlybetter than the average in Germany.With the next paragraphs we willintroduce some examples of diagnostic


Fig. 12 Intravascular ultrasound (IVUS) and(bottom) virtual histology, green: fibrous tissue,red: necrotic core, white: calcium

Fig. 13 Examples of OCT imaging in thecatherization laboratory

of 10micrometers (Fig. 13). Post-hoccomputer three- dimensionalreconstructions allow imaging the vessel‘from within’, using so-called fly-throughviews. These modern technologies allowdetection of coronary artery abnormalitieswith an unprecedented level of accuracy.For instance, stent fractures, a conditionin which the metal of the stent is broken,potentially causing inflammation of thevessel wall, can only be diagnosed usingthese methods. Other examples includethe presence of micro vessels in the bloodvessel wall, which predispose the bloodvessel to rupture or occlude, causing amyocardial infarction. Or the diagnosis ofcoronary wall dissections, i.e. a rupture ofthe vessel wall which causes the lumen(inner cavity of the blood vessel toocclude). These types of diagnoses areextremely important in cases in whichtraditional angiography is not sufficient toallow accurate diagnosis. In ourexperience, this accounts to up to 50% ofthe patients. These data show how the useof modern technologies, in a center thathas adequate experience, is important forthe prognosis of the patients.

Coronary Flow Reserve The assessment of the hemodynamicrelevance of a stenosis and of thefunction of the coronary microcirculationhas prognostic implications for thepatient and can be performed usingtechniques called coronary flow reserveand fractional flow reserve (Fig. 14).

Fig. 14 The left panel shows a typical stenosis of the right coronary artery. In the right panel, the hemodynamic relevance of the stenosis wasassessed using FFR. The two pressure curves (red for the aortic pressure and green for the pressure distal to the stenosis) diverge when the FFRpressure sensor is pushed into the vessel

Our laboratory has a large clinical andresearch experience in this field. Whilethese procedures are well established,our ambition is to continue to improvetheir quality, safety and efficacy. Webelieve that education has a centralimportance for this purpose. Ourcardiac catheterization team regularlyholds conferences during which complexcases are discussed and participates ina number of national and internationalcongresses each year.

As well, we have now achieved a nationaland international lead in the use ofmodern technologies that allow theassessment and treatment of blood vesselfunction: for instance, in 2017, wepublished an atlas on the techniques usedfor the hemodynamic assessment ofcoronary artery disease. These techniquesallow the investigation of the severity ofcoronary artery stenoses, i.e. they allowdetecting which blood vessel tighteningcauses a decrease in the blood supply tothe heart. Such information can only bederived with a significantly larger marginof error from a traditional cardiaccatheterization. These methods have aresolution that is as low as one millimeter,and therefore are of critical importancefor decisions on which patients and bloodvessels need to be treated.

While these procedures are wellestablished, our ambition is to continue toimprove their quality, safety and efficacy.We believe that education has a central




importance for this purpose. Our cardiaccatheterization team regularly holdsconferences during which complex casesare discussed and participates in anumber of national and internationalcongresses each year. As well, we havenow achieved a national andinternational lead in the use of moderntechnologies that allow the assessmentand treatment of blood vessel function:for instance, in 2017, we published anatlas on the techniques used for thehemodynamic assessment of coronaryartery disease. These techniques allow theinvestigation of the severity of coronaryartery stenoses, i.e. they allow detectingwhich blood vessel tightening causes adecrease in the blood supply to the heart.Such information can only be derivedwith a significantly larger margin of errorfrom a traditional cardiac catheterization.These methods have a resolution that isas low as one millimeter, and thereforeare of critical importance for decisions onwhich patients and blood vessels need tobe treated.

The Pulmonary EmbolismRapid Response Team (PERT)Beyond treatment of heart bloodvessels, our catheterization laboratoryperforms a number of other procedures.As one of the few centers in Germany,we have a so-called PERT, a group ofphysicians specialized in the treatmentof acute lung embolism, one of the mostfrequent causes of death. Pulmonaryembolism is an extremely dangerousdisorder that in many cases proves fatal.Employing an innovative technique, wecan now extract the blood clots usingcatheters, thus helping those patients atextreme risk. The picture below showsone of these cases (Fig. 15).

Finally, we regularly perform complexprocedures such as alcohol septumablation for patients with hypertrophiccardiomyopathy, or chronic totalocclusions (using these techniques we arenow able to open blood vessels that havebeen occluded for more than ten years).In all these fields, our laboratory is wellintegrated and visible in national andinternational working groups. Finally, and

most importantly, we take the safety ofour patients at heart. In comparison withother types of exams, cardiaccatheterization is surely more invasive,which means it that it also involves risks.It is therefore important that patientsunderstand what the indication and thepossible consequences of a heartcatheterization are, since the safety ofpatients is the priority when performingthis type of procedures. Information istherefore one of the major focuses of ourgroup: we organize trainings forphysicians, and provide patients withinformation material that prepares themfor this type of procedure.

Research in interventional cardiology Beyond patient care, our mission is alsothe investigation of mechanisms ofcoronary artery disease, as well as theeffects and efficacy of drugs and deviceslike stents. In the last years, our researchhas focused particularly on three fields:the first is the use of the intravascularimaging techniques such as OCT in thediagnosis of complex diseases of thecoronary arteries. Our group contributedto the classification and standardizationof the diagnosis of particular imagescalled ‘peri-strut low intensity areas’(PSLIA – Fig. 16) evaginations.

We are also conducting a study toclassify stent fractures and investigatetheir impact on the outcome afterimplantation of stents. Our Core Labsalso provides support for externalcooperation partners who ask us toanalyze their data in a standardized,certified way. Based on this experience,we recently founded the GermanCenter for Cardiovascular Research(DZHK), a network of centers inGermany participating in commonprojects in this field of research.

The second area of research includesoutcome and mechanistic research inthe field of coronary bioresorbablescaffolds, a novel technology which oneday might substitute traditional metallicstents. In this area we recently identifiedthe mechanisms that lead to scaffoldthrombosis, a potentially very

Fig. 16 Example ofcoronaryevaginations in apatient treated witha bioresorbablescaffold, particularimages called “peri-strut low intensityareas” evaginations

Fig. 15 Top is a CT angiogram before thrombusaspiration, in the middle the thrombus, andbottom the same CT after aspiration




© Peter Pulkowski

dangerous complication (with amortality of up to 45%) that wasobserved with this type of devices.

Finally, our center focuses on the studyof coronary and peripheral endothelialfunction, an important parameter thatdetermines the function of blood vesselsand the prognosis of patients. Althoughbasic, this research is important as itmight one day lead to the developmentof novel therapies and improves ourunderstanding of the effects of drugs onthe heart´s blood vessel system.

References1 Gori T, Polimeni A, Indolfi C, Adriaenssen T,

Räber L, Münzel T. Update on the mechanisms

of stent and scaffold thrombosis. Naturereviews in Cardiology, in press.

2 Gori T, Weissner M, Gönner S, Wendling F,Ullrich H, Ellis S, Anadol R, Polimeni A, MünzelT. Characteristics, Predictors, and Mechanismsof Thrombosis in Coronary BioresorbableScaffolds: Differences Between Early and LateEvents.JACC Cardiovasc Interv. 2017 Dec11;10(23):2363-2371.

3 Polimeni A, Weissner M, Schochlow K, UllrichH, Indolfi C, Dijkstra J, Anadol R, Münzel T,Gori T. Incidence, Clinical Presentation, andPredictors of Clinical Restenosis in CoronaryBioresorbable Scaffolds. JACC CardiovascInterv. 2017 Sep 25;10(18):1819-1827.

4 Gori T, Münzel T. First Evidence of CompleteResorption 4 Years After Bioresorbable ScaffoldImplantation in the Setting of ST Segment

Elevation Myocardial Infarction. JACCCardiovasc Interv. 2017 Jan 23;10(2):200-202.

5 Puricel S, Cuculi F, Weissner M, SchmermundA, Jamshidi P, Nyffenegger T,Binder H,Eggebrecht H, Münzel T, Cook S, Gori T.Bioresorbable Coronary Scaffold Thrombosis:Multicenter Comprehensive Analysis ofClinical Presentation, Mechanisms, andPredictors. J Am Coll Cardiol. 2016 Mar1;67(8):921-31.

6 Gori T, Jansen T, Weissner M, Foin N, WenzelP, Schulz E, Cook S, Münzel T.Coronaryevaginations and peri-scaffold aneurysmsfollowing implantation of bioresorbablescaffolds: incidence, outcome, and opticalcoherence tomography analysis of possiblemechanisms. Eur Heart J. 2016 Jul7;37(26):2040-9.




Fig. 17 CPU of Mainz certified by the German Society of Cardiology

Fig. 18 Medical round on the CPU

Now that our Chest Pain Unit(CPU) is 13 years old, it seemstimely to provide a summary

of our experience to date with thisrelatively new form of patient carefacility. The university hospital in Mainzwas one of the first in Germany (2005)to put in place this unit for patients withchest pain.

An article on the German CPU Networkby Prof. Thomas Münzel and Prof.Gerd Heusch was recently published intheJournal of the American College ofCardiology 2017.1

The authors point out that there havebeen significant improvements in thequality of diagnosis and treatment ofpatients with chest pain following thecreation of the CPU Network inGermany. Associated with this areprognoses for patients with acutecoronary syndrome that are better than

those of patients treated in standardemergency departments. This is becausethe time from onset of symptoms toinitiation of targeted measures is muchshorter in a CPU than in a normalemergency department. In addition, it ispossible to undertake effectiveintervention in a directly associatedcardiac catheterization lab. It isessential that a chest pain unit hasimmediate access to a cardiaccatheterization lab.

“I am of course proud that I am able tosteer the development of a CPU networkin Germany from here in Mainz,”explains Prof. Münzel. “We set up one ofthe first university hospital-based CPUshere in 2005 and the German CPUNetwork that we have helped build is –together with the network in the US -quite unparalleled elsewhere.”

It is the intention of the GermanCardiac Society (DGK) to disseminatethis CPU concept throughout Europe.Accredited CPUs have already beenestablished in other German-speakingcountries – Switzerland (Zurich andLucerne) and Austria (Vienna). Therequirements for the certification ofCPUs have been translated into English,making it possible for CPUs in othercountries to apply for accreditation

(http://cpu-international.dgk.org).Motivated by the implementation of theCPU network in Germany and thepublication of certification criteria, theEuropean Acute Cardiovascular CareAssociation has produced its ownguidelines for the realization of thisconcept throughout Europe.

Every minute counts. Time isheart muscle

Reference1 Münzel T, Heusch G. Chest Pain Unit Network

in Germany: Its Effect on Patients With AcuteCoronary Syndromes. J Am Coll Cardiol2017;69:2459-2460.

The German Chest Pain Unit (CPU) Networkof the German Cardiac Society (DGK) attractsinternational attention



http://cpu-international.dgk.org


understand the variability of diseasein humans; and

improve patient care.

The hypothesis is that bioprofiles ofindividuals including variousinformation levels from the molecularprofile to the subclinical and clinicaldisease, environment, lifestyle andpersonality will help to understand thedevelopment and course of diseases. Avaluable resource is a centralizedrepository of biomaterials with approx.seven million biospecimens of varioussources and qualities.

Fig. 20 Medical data are recorded in acentralized electronic file, which allows formonitoring health development oversequential visits over years. The findings areexplained by specialists and summarized in acomprehensive concluding review with aprevention specialist. A comprehensive checkupis usually performed within two to a maximumof three days, as there are no long distancesbetween specialists and waiting times arereduced to a minimum.

Fig. 19 Our expertise for your health

© Peter Pulkowski

© Peter Pulkowski

Ophthalmology

Otolaryngology (ENT)

Psychosomatic Medicine andPsychotherapy Radiology

The use of this check-up examinationis predominantly used byinternational patients with a highpercentage of country representativesand leading personalities.

University Center forPreventive Medicine Mainz

Epidemiological research at the Center forCardiovascular Medicine

The interdisciplinary teamwork ofvarious clinics and institutions ofthe University Medical Center

Mainz results in the opportunity tocreate a comprehensive health checkcovering all medical fields. Theexamination program has an age- andsex-dependent design and is adaptedaccording to the individual needs and requests.

A full investigation is conducted in thefollowing departments:

General Medicine andCardiovascular Medicine

Interventional Cardiology

Urology

Gynecology

Gastroenterology

Endocrinology

Dermatology

The research program in theDepartment of Cardiology has aspecial focus on translational

research and splits up into basic science,epidemiological science and clinicaltrials. A focus is put on the developmentof large-scale databases with theobservation of diseased patients, butalso the population over long-termperiods. These large databases help to: translate new findings from basic

science into the clinical setting;

return clinically observed associationsback to the laboratory bench (reversetranslation) for further investigations;





BYthe time the fourthround of follow-upexaminations was

started in 2017, it had been ten yearssince the First Patient First Visit (FPFV)for the Gutenberg Health Study (GHS).The GHS is a flagship project in theresearch landscape of the UniversityMedical Center Mainz. The GHS aimsto improve the prediction of theindividual risk for the development andprogression of various common diseases.Its findings will hopefully contribute toimproving medical prevention, diagnosisand treatment. The interdisciplinarydesign of GHS makes it ideally suitedfor this purpose.

The GHS is a population-based cohortstudy conducted by University MedicalCenter Mainz (UMCM), in which apopulation sample of over 15,000 menand women from the City of Mainz andthe District of Mainz-Bingen undergoregular and highly standardized healthexaminations at fixed intervals.

As an interdisciplinary researchconsortium, the GHS is financially,scientifically and structurally supportedby various central and partnerinstitutions of UMCM and externalpartner organizations. The GHS is partof a broad national and internationalresearch network. The second

examination in the study center afterfive-years was completed in April 2017.Over 90% of the 15,000 subjectsinitially included remained in theGutenberg Health Study.

The second phase of the GutenbergHealth Study was kicked off in 2017.Although the successful concept of thefirst phase (2007-2017) was retained,the examination program underwentsignificant expansion and developmentin light of the multicausality of commondiseases, and now takes between fiveand six hours to complete. In addition,a broader age range and datacollection on an even wider range ofbiomaterials enable the generation ofnew data levels, which will ultimatelyenhance the unique features of theGutenberg Health Study in translationalresearch. This makes the GHS an all themore unique translational researchplatform and a distinguishing attributeof UMCM. Over 100 employees workon data recording, processing andanalysis at the study site, in laboratoriesand affiliated departments.

The high participation reflects thestrong willingness of the localpopulation to actively contribute to theadvancement of medical research.

Several cohorts of diseased individualshave been established to enable clinicalresearch on clinically overtcardiovascular disease and the dailyapplied clinical care (Fig. 21). Thecohorts include institutionalized samplesfrom the University Medical CenterMainz (UMCM) and the establishednetworks of hospitals, but also patientsfrom ambulatory health care. Theycomprise 16 cohorts in the fields of acutecoronary syndrome, myocardial infarctionat younger age, heart failure, venousthromboembolism, cardiovascularsequelae in childhood cancer survivors orpsoriasis, interventional valveimplantations (mitral, tricuspid andaortic position), and drug interventions

The Gutenberg Health Study:Population-based science witha large-scale, state-of-the-artcohort study with amultidimensional biodataBASE




Disease Cohorts

Population-based

Fig. 21 Cohorts with comprehensive biobanking are available for research in various indications in the field of cardiovascular medicine

Pulmonary EmbolismDeep Vein Thrombosis Heart Failure

Pilot Study in Population

Acute Coronary Syndrome Interventional Cardiology

Acticoagulation Therapy Diabetes

Retinal Vein Occlusion

Hypertension

Atrioventricular Valve Repair

Myocardial Infarction

Sequelae of Pulmonary Embolism

Cardiomyopathy Psoriasis

Atrial Fibrillation

Cardiac & VascularSequelae in Survivors of

Childhood Cancer

Endothelial Dysfunction

Transcatheter Aortic Valve Implantation

(arterial hypertension, diabetes mellitus, dyslipidemia).

Data from diseased individuals can becompared to the population by makinguse of the GHS, as cohorts have beenharmonized with regard to dataassessment and biobanking.

The German Center for CardiovascularResearch (DZHK) is one of six healthresearch centers funded by the GermanFederal Ministry of Education andResearch (BMBF). The goals of thecenter are to improve the prevention,

diagnosis and treatment ofcardiovascular diseases. UMCMbelongs to the Rhein-Main site of theDZHK (together with Johann WolfgangGoethe University Hospital Frankfurt,Max Planck Institute Bad Nauheim andKerckhoff Hospital Bad Nauheim).

As part of this national network ofexcellence, UMCM focuses on patientcentered research in heart failure,coronary heart disease, acute coronarysyndrome and myocardial infarction.The Mainz site of the DZHK supports

national cooperation projects in thenetwork through the exchange ofscientific expertise and methods (Fig.22). Various cooperative projects werelaunched within the framework of thefunding scheme and six scientificplatforms for research partnerships innational and international networks areoffered. In addition, the careers of juniorscientists are fostered by a dedicatedprogram and long-term support withinthe framework of the DZHK.



Fig. 23 Complex cartoon about the mechanisms of how noise can causevascular damage because of a review published in the Journal of theAmerican College of Cardiology, TIME was making a brilliant moviesummarizing our review(https://www.youtube.com/watch?v=fkraKdJXJsY).

One of the main focuses in the area of vascularbiology is the impact of environmental stressors suchas transportation noise on vascular function. We

believe that noise represents a novel and importantcardiovascular risk factor.

It has been known for many years that noise can causecardiovascular disease but the mechanisms underlying noiseinduced vascular dysfunction remained obscure. In 2013 wedemonstrated for the first time that nighttime aircraft noisecauses endothelial dysfunction in healthy volunteers.1Importantly, endothelial dysfunction was markedly improvedby the oral administration antioxidant vitamin C indicatingthat most of endothelial dysfunction was secondary toincreased production of reactive oxygen species.

We also established increased stress hormone levels ofadrenaline in noise-exposed subjects. Over a couple of years,we extended this observation by demonstrating that insubjects with coronary artery disease, nighttime noise causedan increase in blood pressure, an even stronger degree ofendothelial dysfunction that was interestingly not explainedby the noise annoyance reaction. The underlying molecularmechanisms of these phenomena remained unclear. Using anewly developed animal model, our research team was ableto establish vascular dysfunction and increased oxidativestress within the vasculature. As superoxide sources aNicotinamide adenine dinucleotide phosphate (NADPH)oxidase (phagocytic Nox2) and an uncoupled nitric oxidesynthase were identified.2 More recent studies demonstratethat night time aircraft noise is responsible for vessel andbrain damage and that a Nox2 knockout completely preventsaircraft induced adverse effects.3

In addition, we have demonstrated that the disturbance ofsleep and of the circadian rhythm causes vascular and braindamage,3 suggesting that stress due to too short sleep and/orfragmentation of sleep is responsible for this phenomenon.These findings have provided, for the first time, a molecularinsight into noise-induced vascular and brain damage. Allresults that were published in the European Heart Journal,the world’s most prestigious cardiovascular journal, mayrepresent indeed a breakthrough in (aircraft) noise researchhelping to develop mitigation and treatment strategies inorder to avoid these noise-induced side effects. Based on thefindings in our recent translational patient and animal studieswe developed a scheme with a pathophysiological concepthow noise causes vascular damage (Fig. 23).

References1 Schmidt FP, Basner M, Kroger G, Weck S, Schnorbus B, Muttray A,

Sariyar M, Binder H, Gori T, Warnholtz A, Münzel T. Effect of nighttimeaircraft noise exposure on endothelial function and stress hormone releasein healthy adults. Eur Heart J 2013;34:3508-3514a.

2 Münzel T, Daiber A, Steven S, Tran LP, Ullmann E, Kossmann S, SchmidtFP, Oelze M, Xia N, Li H, Pinto A, Wild P, Pies K, Schmidt ER, Rapp S,Kroller-Schon S. Effects of noise on vascular function, oxidative stress, andinflammation: mechanistic insight from studies in mice. Eur Heart J2017;38:2838-2849.

3 Kroller-Schon S, Daiber A, Steven S, Oelze M, Frenis K, Kalinovic S,Heimann A, Schmidt FP, Pinto A, Kvandova M, Vujacic-Mirski K, FilippouK, Dudek M, Bosmann M, Klein M, Bopp T, Hahad O, Wild PS,Frauenknecht K, Methner A, Schmidt ER, Rapp S, Mollnau H, Münzel T.Crucial role for Nox2 and sleep deprivation in aircraft noise-inducedvascular and cerebral oxidative stress, inflammation, and gene regulation.Eur Heart J 2018.

Fig. 22 A protein profiling platform based on the PEA-technology(OLINK, Uppsala, Sweden) is available for high-throughput investigations

Research on theimpact ofenvironmentalstressors oncardiovascular health



https://www.youtube.com/watch?v=fkraKdJXJsY



Fig. 24 Children in our walk-in heart leaninghow the heart functions and how to listen toheart sounds

Fig. 25 Children during resuscitation training

Fig. 26 10th Anniversary of the Mainz Castle Heart Gala, November 2017

The Mainz Heart Foundation wasfounded in 2007 with the aim of promoting:

Research and education

Improvement in patient care and

Prevention.

The Mainz Heart Foundation hastherefore set itself the task ofapproaching children and adolescentsearly on with a targeted preventionprogram, the Children’s Academy ofHealth. A total of 4,000 school childrenfrom the Rhineland Palatinum, Hessenand Saarland regions have sinceparticipated in the program. The maintopics of this education program are toteach the children how our heart and ourcirculation works, why not to smokecigarettes, why not to smoke E-cigarettesand Shisha, to inform about healthy foodhabits and why to do exercise (Fig. 24).

The children also learn how toresuscitate patients with a suddencardiac arrest (Fig. 25).

It is exciting that the Prime Minister ofthe Rhineland Palatinum, Mrs MaluDreyer, has always loved being thechair of our academy.

The foundation raises around€500,000 in support of research witha focus on health and the environment.The most important event is the HeartGala held every year since 2007 inMainz Castle (Fig. 26).

FoundationHeart of Mainz



Univ. Prof. Dr. Thomas MünzelDepartment of Cardiology

University Medical Center MainzJohannes Gutenberg University

Langenbeckstrasse 155131 Mainz

Germany

+49 6131 17 7250

tmuenzel@uni‐mainz.de

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