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Ann Thorac Surg 2007;83:542-548
© 2007 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Early Detection of Mechanical Valve Dysfunction Using a New Home Monitoring Device

Dirk Fritzsche, MD, PhDa,*, Thomas Eitz, MDa, Axel Laczkovics, MDb, Andreas Liebold, MDc, Michael Knaut, MDd, Klaus Matschke, MDd, Alex Sagie, MDe, Uwe Mehlhorn, MDf, Dieter Horstkotte, MDa, Reiner Koerfer, MDa

a Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen
b Clinic for Heart Surgery, University of Bochum, Bochum
c Clinic for Heart Surgery, University of Rostock, Rostock
d Heart Center Dresden Ltd, Dresden, Germany
e Department of Cardiology, Rabin Medical Center, Petah Tiqva, Israel
f Clinic for Heart Surgery, University of Cologne, Cologne, Germany

Accepted for publication July 29, 2006.

* Address correspondence to Dr Fritzsche, Heart and Diabetes Center NRW, Georgstr 11, Bad Oeynhausen D-32545, Germany (Email: dfritzsche{at}hdz-nrw.de).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: After heart valve replacement, patients are at risk of complications that are linked to irregular oral anticoagulation therapy. Depending on the type and position of the valve, the complication rate is 3% to 6% per patient-year. This study presents clinical results of a device enabling early detection of prosthetic dysfunction by frequency measurements.

METHODS: Between November 2003 and March 2006, ThromboCheck devices were handed out to 483 patients after mechanical heart valve replacement from six heart centers. In each case, the devices were calibrated for individual patients early postoperatively. Taking control measurements, the device calculated deviations from calibrated frequency and amplitude ranges using a fast Fourier transform and sent a warning message to the display if any relevant changes occurred. This message was taken as cause to determine morphologic correlations of the disturbance using imaging techniques, for example, echocardiography or fluoroscopy (observation period, 550.7 patient-years; median application period, 15.1 months).

RESULTS: Twenty-five true positive, 1 false positive, and no false negative measurements occurred. Eleven patients (44%) received thrombolytic therapy with streptokinase or recombinant tissue-type plasminogen activator, resulting in normalization of the digital frequency analysis. In 4 patients (16%), international normalized ratio levels were adjusted under temporary heparinization therapy. Normalization of the valve sounds were achieved within 3 to 7 days. Seven patients (28%) required reoperation despite lysis therapy. Sensitivity was 100% during the observation period; specificity was 99.8%.

CONCLUSIONS: Digital frequency analysis represents a reasonable addition to the monitoring of patients after artificial heart valve replacement to detect prosthesis-related complications early on.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 
Despite enormous progress in the surgical treatment of heart valve patients, the complication rate is still 3% to 6% per patient annually [1–4]. With more than 100,000 heart valve operations being performed worldwide every year, the risk of serious complications is significantly frequent, amounting to at least 5,000 events per annum. Thromboembolism and hemorrhage under anticoagulation therapy account for 75% of all complications after mechanical heart valve replacement [5].

It is also known that in the presence of certain risk constellations, the statistic probability of a valvular dysfunction is even higher. These risks include mechanical valve replacement in the right heart (in particular, the tricuspid valve), dilated ventricles, dysrhythmias (especially atrial fibrillation), anomalies of the coagulation system, pregnancy, and so forth. Table 1 illustrates the risk of thromboembolic events after mechanical heart valve replacement using an overview of selected international publications on heart-valve-related complications in the last 10 years.


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  		Table 1. Frequency of Thromboembolic Complications (TE) Per Valve Thromboses After Mechanical Heart Valve Replacement
 
Despite obviously good results regarding the prevention of thromboembolic complications through international normalized ratio (INR) self-measurement [6, 7], the problem of how to avoid thrombotic deposits on artificial valves, or how to detect them early on, remains relevant for everyday hospital and surgery routines. On the one hand, the complex handling of the CoaguChek S System device (Roche Diagnostics, Basal, Switzerland) for INR self-measurement will prevent its use by all patients. In addition, a significant discrepancy between INR self-measurement results and control measurements taken in the laboratory has been observed. On the other hand, a number of events in the life of a mechanical heart valve recipient (total hip replacement, gastrointestinal hemorrhaging, and so forth) require oral anticoagulation therapies to be reduced or even stopped temporarily. The resulting heparinization administered in lieu provokes a strong undulation in the biological efficacy of the active agent, representing an interruption in therapeutic anticoagulation that can often trigger the development of valvular thrombosis. In scenarios such as these, physicians are relatively helpless, not noticing the advent of a complication until the patient displays manifest symptoms.

As a result of these observations and considerations, we decided to participate in the development and clinical testing of a novel early warning system for the detection of heart valve dysfunction. This multicentric and double-blind study shows the clinical results of a device enabling the early detection of prosthetic dysfunction by digital frequency analysis measurements.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Acknowledgments
 References
 
The Ethics Committee of the Ruhr University, Bochum, Germany, approved the study. The need for individual informed consent was waived.

The ThromboCheck device (CardioSignal GmbH, Hamburg, Germany) measures the frequency range of mechanical valve sounds digitally and fully automatically. A valve sound is composed of a number of frequencies with a certain amplitude, and each one is as unmistakably recognizable as a fingerprint, owing to the resonance characteristics of individual patients with particular types of valve. From the beats measured in 1 minute, the measurements outside the 95th percentile are excluded. From the other beats, the frequency spectrum is calculated by fast Fourier transformation. If an initial patient-typical signal is stored by the device, and if all sounds recorded later are compared with it using a highly developed software program, then even the slightest deviations are detected by the device as "suspicious." This test can be performed by patients themselves as often as they wish and takes no longer than 1 minute (Fig 1). Comprehensive experimental work (continuous observation of clot formation or lysis in thrombotic alloprostheses in animals) has shown that the acoustic phenomenon of a mechanical heart valve can be significantly altered even when all other imaging techniques fail to register anything suspicious [8–10]. That means that a prosthetic dysfunction in its initial stages (for example, due to thrombosis) can be detected before it is clinically, echocardiographically, or fluoroscopically recognizable (Fig 2A–C).


Figure 1
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  		Fig 1. (A) Patient controlling the functional integrity of his mechanical heart valve replacement in daily self-tests. (B) ThromboCheck hand-held device for digital high-resolution frequency analysis, Cardiosignal GmbH, Hamburg (see: www.cardiosignal.de for functions, applications, and operation).

 

Figure 2
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  		Fig 2. Frequency analysis of (A) a normal bileaflet valve and (B) immediately after first thrombotic deposits. (a.u. = arbitrary units.) (C) Using a fast Fourier transformation (FFT), the device detects the absorption of certain frequency segments in conjunction with a thrombosed prosthetic valve (dotted line) compared with a normal prosthetic valve (solid line).

 
Our primary endpoint was the frequency of prosthetic dysfunction detected by ThromboCheck. Secondary endpoints were as follows: overall number of ThromboCheck warnings; therapeutic strategy and success in cases of prosthetic dysfunction; valve-related complications (thromboembolic events, hemorrhaging); and psychological effect on patients.

As a result of the closely-knit controls, we expected to gain information regarding the frequency of valve dysfunction, as well as thromboembolic events. The early detection of dysfunction should enable suitable treatment strategies to be deduced. Biometric analysis should enable predictors for dysfunction or thromboembolic events to be recognized and future strategies for postoperative care to be deduced. In addition, acceptance of this method would be put to the test. In all patients, we evaluated an altered frequency range as early detection of a mechanical valve dysfunction and recommended medical clarification. In accordance with state-of-the-art recommendations, the diagnostic and therapeutic algorithm was applied as shown in Figure 3.


Figure 3
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  		Fig 3. Algorithm for prosthetic valve thrombosis (PVT) management (according to Eitz et al [8]). (OAT = oral anticoagulation therapy; TEE = transesophageal echocardiography; TTE = transthoracic echocardiography.)

 
Inclusion Criteria
After mechanical heart valve replacement, patients were included who displayed one of the following inclusion criteria and none of the exclusion criteria: patients with mechanical mitral, pulmonary or tricuspid single valve replacement; patients with mechanical multiple valve replacements; patients with mechanical aortic valve replacement and an existing risk constellation such as atrial fibrillation, congenital or acquired thrombophilia, enlarged left atrial (> 30 mm/m2 body surface) and left ventricular end-diastolic diameter (≥ 70 mm) or severely restricted left ventricular ejection fraction (30% or less), or both; patients desiring functional controls using ThromboCheck and who had given their written consent.

Exclusion criteria were as follows: patients with expected or documented poor compliance; patients known to have a short life expectancy, induced by comorbidity; patients unable to understand or speak German or Hebrew; and patients abusing alcohol or drugs.

Between November 2003 and March 2006, a total of 483 ThromboCheck devices were handed out to patients from six heart centers. The observation period was 550.7 patient-years, with a median application period of 15.1 months (range, 1 to 24). In all, 332 patients with aortic valve replacements, 105 with mitral valve replacements, 41 with aortic valve replacement plus mitral valve replacement, 2 with aortic valve replacement plus pulmonary valve replacements, 2 with pulmonary valve replacement plus tricuspid valve replacements, and 1 patient with a mitral valve replacement plus tricuspid valve replacement were analyzed. These patients were all recipients of mechanical heart valves made by Medtronic, St. Jude, On-X, or Carbomedics. In each case, a device was calibrated for a patient at the early postoperative stage and the individual heart rate pattern stored on computer. Taking control measurements, the device calculated deviations in the frequency and amplitude ranges using a fast Fourier transformation and sent a warning message to the display if any relevant changes occurred. A warning message was taken as cause to determine the morphologic correlation of the disturbance using suitable imaging techniques, such as transthoracic echocardiography, transesophageal echocardiography, or fluoroscopy.

Patients were asked to complete questionnaires after 1, 6, and 12 months to submit precise information about clinical conspicuities that might have remained undetected. At the end of the investigation, a questionnaire was sent out to all patients asking them to evaluate the handling of the ThromboCheck device.

All results were multicentric, prospective, and double blind. ("Double-blind" refers to the following procedure, which was practiced on patients at the Heart and Diabetes Center NRW; 70% of all results were ascertained). Results were not displayed on the ThromboCheck device in the usual manner ["OK," "error—please repeat," "2nd error—please consult physician"], but were encrypted using a 10-figure binary code. The meaning of this code was known neither to the study center nor to the patients. The codes were protocolled by the patients and passed on continually to a person anonymous to both the study center and the patients. At this point the code was deciphered. If there were any deviations from the reference code, the study center was immediately informed and the patient in question contacted.)


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Acknowledgments
 References
 
Suspicious valve sound analyses were returned 26 times from the 483 patients examined. In 25 patients (5.17% of the total population), a valve dysfunction suspected as a result of digital frequency analysis could be confirmed using fluoroscopy (25 true positive). In 1 patient (tricuspid valve replacement at the Israeli center), a suspected dysfunction could not be verified using any of the imaging techniques (1 false positive). In 7 patients, it was impossible to prove abnormal occluder motion or valve-related thrombi using transthoracic echocardiography or transesophageal echocardiography.

Eleven patients (44%) immediately received thrombolytic therapy with streptokinase or recombinant tissue-type plasminogen activator. That led to complete normalization in the digital frequency analysis of the sound pressure phenomenon of the artificial valve. In 4 patients (16%), INR levels were adjusted to within the therapeutic range by increasing oral anticoagulation therapy (and temporary heparinization). In this way, normalization of the valve sounds could be achieved within 3 to 7 days.

Nine patients (36%) required reoperation despite lysis therapy. In each case, the explanted valves displayed marked thrombotic formations on the occluder hinges and along the edges of the valves. In one case, tendinous fibers that had been left too long caused a mitral valve occluder to malfunction; in another case, a paravalvular leak in an artificial mitral valve was responsible for shifting the frequency focus.

One other patient displayed a small paravalvular leak, which could also be detected by digital frequency analysis. There had been no consequences to date, owing to a lack of clinical and paraclinical symptoms.

Table 2 summarizes all documented conspicuities from the digital frequency analysis, as well as the resulting therapeutic consequences. The patient with the suspected dysfunction that could not be verified using any of the imaging techniques (false positive) was very tightly controlled. Within a week, the valve sounds returned to normal spontaneously. No clinical events (thromboembolic, endocarditis, leak, and so forth) undetected by the ThromboCheck device occurred (0 false negative). Sensitivity was 100% during the observation period; specificity was 99.8%. No relevant hemorrhaging complications were reported.


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  		Table 2. Overview of Suspicious Prosthetic Sounds in the Digital Frequency Analysis and Resulting Therapeutic Consequences
 
Regarding acceptance and handling of the device, the questionnaires revealed the following patient evaluations: 59% of patients measured daily, 38% measured 2 or 3 times a week, 3% measured less often. The device was regarded by 98% as easy to use and handle, by 2% as complicated. In using the device, 79% of patients felt more certain, 5% uncertain; 16% failed to comment.


   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Acknowledgments
 References
 
These results confirm what experiments had already shown [10] with regard to the high sensitivity and specificity of digital frequency analysis for sound pressure phenomena in mechanical heart valves. During the early stages of such disturbances, this method is clearly superior to detection by transthoracic echocardiography or transesophageal echocardiography. A dysfunction can be detected long before it clinically manifests itself and can be treated accordingly, using lysis therapy or by adjusting INR levels. In our procedure, indication for interventional therapy was always viewed as a suspicious frequency analysis combined with confirmation stemming from at least one imaging technique. When these options failed, 7 patients who until then had been clinically asymptomatic could undergo reoperation without any complications ensuing. Clinically relevant complications could thus be prevented completely.

Digital frequency analysis (the ThromboCheck method) represents a reasonable addition to the monitoring of patients with artificial heart valve replacements and the early detection of prosthesis-related complications, and should in the future receive particular attention for the discussed risk constellations or in conjunction with the high-risk situations of a large number of heart valve patients.

As the frequency spectrum representing the opening and closing sounds of a valve are measured at a certain time, valves in different positions can be differentiated chronologically in patients after double valve replacements (aortic and mitral valve replacement). In triple valve replacement, differentiation is—at least so far—impossible. Even if a differentiation between valves is not yet possible and interferences in multiple valve replacement occur, changes in the frequency spectrum can be postulated and would suffice, as this device has to be seen as a very sensitive screening method.

These clinical findings and their practical relevance for a patient’s individual situation induced us to create a platform at the Institute for Applied Telemedicine at the Heart and Diabetes Center NRW in Bad Oeynhausen that would facilitate an online analysis of the functional integrity of mechanical valves by medical personnel at any time. This alternative is aimed at the early detection of thrombotic deposits, tissue ingrowth, and now also leakages, whereby the clarification of relevant or suspicious findings using suitable documentation and notification remains the responsibility of the cardiologist or center treating the patient.

There have been some crucial changes in the clinical follow-up of patients with mechanical heart valves. The fact that patients can now closely control their own coagulation and valve function means that the diagnostic window during which complications can arise unnoticed and trigger severe consequences (embolisms, hemorrhaging, reoperation) is effectively reduced to almost nothing. In our opinion, it is of vast importance that the ThromboCheck method is addressed in more detail and applied more broadly in the follow-up of patients with artificial heart valves, especially those with the risk constellations discussed above [11].

Against this background, it is our conviction and declared goal to undertake every effort to deepen the understanding of this method and to have it included in the guidelines of cardiological and cardiosurgical associations for the care of heart valve patients.[12–20


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
References
 
We would like to thank all those who helped to produce the data referred to in this manuscript: Professor Axel Laczkovics, University of Bochum, Professor Andreas Liebold, University of Rostock, Dr Michael Knaut and Dr Klaus Matschke, Heart Center Dresden GmbH, Professor Alex Sagie, Rabin Medical Center Israel, Professor Uwe Mehlhorn, University of Cologne, and Professor Nils Riess, Albertinen Hospital, Hamburg.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Horstkotte D, Piper C, Schulte HD. Thrombosierung prothetischer Herzklappen: Diagnostik und Management Z Kardiol 1998;87(Suppl 4):20-32.
  2. Jamieson WR, Munro AI, Miyagishima RT, et al. Multiple mechanical valve replacement surgery comparison of St. Jude Medical and CarboMedics prostheses Eur J Cardiothorac Surg 1998;13:151-159.[Abstract/Free Full Text]
  3. Munclinger MJ, Patel JJ, Mitha AS. Thrombolysis of thrombosed St. Jude Medical prosthetic valves: rethrombosis—a sign of tissue ingrowth J Thorac Cardiovasc Surg Jan 1998;115:248-249.
  4. Alexiou C, McDonald A, Langley SM, Dalrymple-Hay MJ, Haw MP, Monro JL. Aortic valve replacement in children: are mechanical prostheses a good option? Eur J Cardiothorac Surg 2000;17:125-133.[Abstract/Free Full Text]
  5. Forfar JC. A 7-year analysis of hemorrhage in patients on long-term anticoagulant therapy Br Heart J 1979;42:128-132.[Free Full Text]
  6. Koertke H, Minami K, Boethig D, et al. INR Self-management permits lower anticoagulation levels after mechanical heart valve replacement Circulation 2003;108(Suppl 2):75-78.
  7. Horstkotte D, Piper C, Wiemer M. Optimal frequency of patient monitoring and intensity of oral anticoagulation therapy in valvular heart disease J Thromb Thrombol 1998;5:19-24.[Medline]
  8. Eitz T, Fritzsche D, Grimmig O, et al. Acoustic phenomena and valve dysfunction in cardiac prostheses: data acquisition and collection via the internet J Heart Valve Dis 2003;12;:414-419.[Medline]
  9. Fritzsche D, Grimmig O, Eitz T, Minami K, Koerfer R. Home monitoring of patients after prosthetic valve replacementExperimental background and first clinical attempts. Thorac Cardiovasc Surg 2004;52:1-7.[Medline]
  10. Fritzsche D, Eitz T, Grimmig O, Horstkotte D, Körfer R. Postoperative Betreuung von Patienten nach alloprothetischem HerzklappenersatzNeue Methoden zur Risikosenkung sowie Früherkennung von Prothesendysfunktionen. Z Kardiol 2004;93:664-670.[Medline]
  11. Horstkotte D. Point-of-care devices to improve long-term prognosis after valve replacement J Heart Valve Dis 2005;14:472-475.
  12. Talwar M, Kapoor CK, Velayoudam D, Kumar AS. Anticoagulation protocol and early prosthetic valve thrombosis Indian Heart J 2004;56:225-228.[Medline]
  13. Oran B, Lee-Parritz A, Ansell J. Low molecular weight heparin for the prophylaxis of thromboembolism in women with prosthetic mechanical valves during pregnancy Thromb Haemost 2004;92:747-751.[Medline]
  14. Williams MA, Crause L, Van Riet S. A comparison of mechanical valve performance in a poorly anticoagulated community J Card Surg 2004;19:410-414.[Medline]
  15. Lengyel M. Management of prosthetic valve thrombosis J Heart Valve Dis 2004;13:329-334.[Medline]
  16. Reiss N, Kleikamp G, Körtke H, Blanz U, Minami K, Körfer R. Implantation of mechanical bileaflet prostheses in pulmonary position. 200313th ISCTS World Congress, San Diego, California, November.
  17. Nurozler F, Bradley SM. St. Jude Medical valve in pulmonary position: anticoagulation and thrombosis Asian Cardiovasc Thorac Ann 2002;10:181-183.[Abstract/Free Full Text]
  18. Horstkotte D, Bergemann R, Althaus U, et al. German Experience with Low Intensity Anticoagulation (GELIA): protocol of a multi-center randomized prospective study with the St. Jude Medical valve J Heart Valve Dis 1993;2:411-419.[Medline]
  19. Horstkotte D, Bergemann R, Laas J, Schulte HD, Mohr FW, Zerkowski HR. Thromboembolism and bleeding in patients with St. Jude Medical heart valve prostheses: interim results of the GELIA Study Circulation 1998;98(Suppl 1):–60.[Medline]
  20. Horstkotte D, Piper C, Schulte HD. Thrombosierung prothetischer Herzklappen: Diagnostik und Management. In: Horstkotte D (Hrsg.) Antithrombotische Therapie nach Herzklappenersatz Z Kardiol 1998;87(Suppl 4):20-32.



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Reiner Koerfer
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