Invasive Dental Procedures: Primum non nocere Arnold Seto, MD, MPAAssistant Professor, CardiologyUC-Irvine and Long Beach VA

GoalsMedical risk assessment for dental procedures

New Guidelines on Antibiotic prophylaxis for infective endocarditis

Evidence

Can we provide dental treatment to the patient without endangering their (or our) health and well being? Is the benefit of having dental treatment worth the risk to the patient?

What do you do in the course of providing dental care that can affect the health and well being of a patient?Instill fearInflict painInject local anesthetic solutionsInject potent vasoconstrictorsCause bleedingControl body position

Expose to radiationExpose to dental materialsPrescribe medicationsAlter oral functionCause inflammation

Most Common Medical Emergencies in Dental Practice (4000 dentists over 10 years)Syncope 15,407Mild Allergic Reaction 2,583Angina Pectoris 2,552Postural Hypotension 2,475Seizures 2,195Asthmatic Attack 1,392

Hyperventilation 1,326Epinephrine Reaction 913Insulin Shock 890Cardiac Arrest 331Anaphylaxis 304Myocardial Infarction 289

Many of these events are preventable, or at least the chancesof them occurring can be reduced

Risk of Vascular Events

Risk Factors for the Occurrence of Adverse EventsDependent upon 4 factors:The medical condition of the patient (diagnosis, severity, stability, control)The nature of the dental procedure (invasiveness, length of procedure, blood loss, type of anesthesia, use of vasoconstrictor)The cardiopulmonary reserve which is the ability to respond to physical/emotional challenges (METs; oxygen utilization); can the patient climb a flight of stairs without chest pain or shortness of breath = 4 METsThe emotional stability of the patient (fear, anxiety)

Risk AssessmentMedical Condition? Severity Stability Control

Functional Capacity? METs

Emotional Status? Fear Anxiety

Dental Procedure? Invasiveness Length of procedure Blood Loss Vasoconstrictor use

Decreased RiskIncreased Risk

Risk AssessmentMedical Condition? Recent heart attack Labile Hypertension

Dental Procedure? Full mouth extraction

Functional Capacity? Climbing a flight of stairs causes chest pain and shortness of breath

Emotional Status? Afraid of the dentist

Increased Risk

Risk AssessmentMedical Condition? Stable Angina

Dental Procedure? Exam and x-rays

Functional Capacity? Can climb a flight of stairs

Emotional Status? Doesnt like dentists

Decreased Risk

Risk Assessment?Can we provide routine dental treatment to this patient without endangering their (or our) health and well being?Yes. No problems are anticipated, and treatment can be delivered in the usual manner. (Benefit >> Risk)Yes, but potential problems may be anticipated, and modifications in the delivery of treatment are necessary. (Benefit > Risk)No. Potential problems exist that are serious enough to make it inadvisable to provide elective dental treatment. (Risk > Benefit)

Risk vs BenefitYou may not be able to completely eliminate the risk of an adverse event occurring during dental treatment or as a result of dental treatment, however, our goal is to reduce that risk as much as possibleThe issue then becomes whether the remaining risk is acceptable and that having the dental treatment is of more benefit than not having it

Biggest risk? Delaying needed dental carePeriodontal disease is a chronic gram-negative infection, affecting up to 75% of adultsPeriodontal disease is associated with markers of chronic inflammation like CRPChronic inflammation has been associated with progression of coronary artery disease, which is itself an inflammatory statePeriodontal treatment reduces markers of inflammationCollected studies suggest an 24-35% increased risk of CAD in patients with periodontal disease

CV risk in Periodontal PatientsHumphrey, J. Gen Int Med 23 (12): 2079-86

Effect of periodontal treatmenton vascular endothelium Flow-Mediated Dilatation during the 6-Month Study PeriodTonetti MS et al. N Engl J Med 2007;356:911-920

Circulating Biomarkers in the Two Groups during the 6-Month Study PeriodTonetti MS et al. N Engl J Med 2007;356:911-920Intensive periodontal treatment resulted in acute, short-term systemic inflammation and endothelial dysfunctionHowever, 6 months after therapy, the benefits in oral health were associated with improvement in endothelial function

Periodontal disease and medical riskIn general, most periodontal procedures are low risk and likely have CV benefits.

Only patients at highest risk of medical instability require delay of care and medical evaluationUnstable anginaUncontrolled hypertensionDecompensated congestive heart failure

Management of antiplatelet agents during dental proceduresAspirin should generally be continued for all coronary artery disease patientsClopidogrel (Plavix) should be continued for up to 1 year after myocardial infarction and stenting, to minimize the risk of stent thrombosis

Subacute stent thrombosis

Management of anticoagulantsWarfarin (Coumadin) can usually be stopped for 5-7 days preoperatively, and restartedMost patients Atrial fibrillation, stroke, history of deep venous thrombosisOther patients at higher risk recent DVT/PE, artificial heart valves require close monitoring and possibly bridging therapy with heparin. CONSULT.Dabigatran (Pradaxa) new oral anticoagulant replacing warfarin. Can be stopped just 1 day prior to procedure, and restarted thereafter

Dental management of hypertension

Identify patients with hypertension both diagnosed or undiagnosed.Medical history include diagnosis of it, how it is being treated, identification of antihypertension drugs, compliance of the patient, the presence of the symptoms associated with hypertension and stability of the disease.Blood pressure measurement should be routinely performed for all new patient and recall appointmentsStress and anxiety management which increase BP(relationship among dentists, patient & office staff and longer stressful appointment are best avoided and short morning appointment are recommended) .

Management of antihypertensivesMost should generally be continued to minimize hypertensive reactions to Clonidine is especially prone to withdrawal hypertension and should be continuedAbort the procedure if BP > 180/110

Highest Risk PatientsRecent myocardial infarction (< 3months)Active unstable anginaDecompensated congestive heart failureRecommendations:Avoid elective careIf treatment is necessary , consult with physician and limit treatment to pain relief, treatment of acute infection, or control bleedingConsider including the following:Prophylactic nitroglycerinPlacement of intravenous lineSedationOxygenContinuous electrocardiodiographic monitoringPulse oximeterFrequent monitoring of BPCautious use of epinephrine in local anesthetic.

Other risk reduction measures(Intermediate risk patients)Morning appointmentShort appointmentComfortable chair positionPretreatment vital signsNitroglycerin readily available Stress-reduction measuresGood communicationOral sedation(e.g triazolam 0.125-0.25mg on the night before & 1hr before appointmentIntraoperative N2O/O2 Excellent local anesthesiaLimit use of vasoconstrictor (max.0.038mg epinephrine)Avoidance of epinephrine-impregnated retraction cordAdequate postoperative pain control

Bacterial EndocarditisA microbial infection of the endothelial lining of the heart; most commonly occurring as a vegetation on the valve leaflets

Mortality Rates100% fatal if not treatedWith antibiotic treatment, fatality rate:NVE (native valve)Streptococcus

Endocarditis description

At any rate, at approximately one-quarter to twelve that night, I remember distinctly getting up from my chair and from the table, where my books lay, and taking off my suit coat. No sooner had I removed the left arm of my coat, than there was on the ventral aspect of my left wrist a sight which I shall never forget until I die. There greeted my eyes about fifteen or twenty bright red, slightly raised, hemorrhagic spots about 1 millimeter in diameter which did not fade on pressure and which stood defiant as if they were challenging the very gods of Olympus. ... I took one glance at the pretty little collection of spots and turned to my sister-in-law, who was standing nearby, and calmly said: I shall be dead within six months.

- Alfred Reinhardt, Harvard Medical Student, 1931

Pathogenesis of BEAnatomic/physiologic predisposition (endothelial damage)Non-bacterial thrombotic endocarditis(NBTE)Bacteremia (source??)Bacterial colonization of vegetationAdditional deposition and growth of thrombusEmbolization and bacteremia

PathogenesisMandell

Board Review QuestionWhich organism is the most commonly cause of endocarditis in periodontal disease patients?

A) Strep viridansB) Staph aureusC) Candida albicansD) Coagulase negative staphE) Enterococcus

Diagnosis

Modified Duke Criteria

Modified Duke Criteria

Oslers NodeTender subcutaneous nodulesPulps of digits or thenar eminence

Janeway LesionsNontenderHemorrhagicPalms and solesErythematous

Splinter HemorrhageFinger and toenailsNonspecificLinear and redBrown after 2-3 d

Roth Spots

Valve Surgery

Prophylaxis for IE: First origins1943, Northrup and Crowley postulated that most IE were caused by dental extractions and that Abx would prevent IE.Identified 20% of patients with IE had preceding dental proceduresGave sulfa to separate cohort receiving dental extractions and found that all patients had sterile blood cultures.Concluded that Abx prevent IE and should be given.AHA issued first recommendations in 1955Northrup, Crowley. J Oral Surgery 1943; 1:19-29

Circulation, published online April 19, 2007

GuidelinesAmerican Heart AssociationCommittee on Rheumatic Fever, Endocarditis, and Kawasaki DiseaseCouncil on Cardiovascular disease in the YoungCouncil on Clinical CardiologyCouncil on Cardiovascular Surgery and AnesthesiaQuality of Care and Outcomes Research Working GrpEndorsed by:American Dental AssociationInfectious Diseases Society of AmericaPediatric Infectious Diseases Society

Previous Guidelines1960 emphasized PCN resistance, suggested chloramphenicol for PCN allergic patients1965 First guideline dedicated solely on prophylaxis, recognized enterococci after GI, GU procedures as a risk1972 Joined by ADA, emphasized importance of good oral hygiene1977 introduced high vs. low risk groups1984 simplified antibiotic regimens1990 complete list of procedures and cardiac conditions made, with statement that these serve as a guideline and not as established standard of care1997 high/moderate/low risk groups made, acknowledgement that most cases of IE are not due to a procedure

Previous Guidelines

Durack NEJM 1995; 332(1): 38-44

Estimated risk of IE per procedure1 case of IE per 14 million dental proceduresMVP: 1:1.1 million proceduresCongenital Heart Disease: 1:475,000Rheumatic Heart Disease: 1:142,000Prosthetic Valve: 1:114,000Previous IE: 1:95,000Guidelines

Prophylaxis in 1997Recommended for:High Risk: previous IE, prosthetic heart valve, cyanotic congenital heart diseaseModerate Risk:Hypertrophic cardiomyopathyAcquired valvular diseaseMitral valve prolapse with regurgitationOther congenital anomaliesNot recommended for:Isolated ASD, MVP without regurg, previous CABG, previous pacemaker, surgically repaired ASD/VSD/PDA

Rationale in 19971. IE is an uncommon but life threatening disease, and prevention is preferable to treatment2. Certain underlying cardiac conditions predispose to IE3. Bacteremia with organisms known to cause IE occors commonly in association with invasive dental, GI, GU procedures4. Antimicrobial prophylaxis was proven to be effective for prevention of experimental IE in animals5. Antimicrobial prophylaxis was thought to be effective in prevention of IE in humans

Summary of Changesonly an extremely small number of cases of infective endocarditis might be prevented by antibiotic prophylaxis for dental procedures even if such therapy was 100% effective.

Infective endocarditis prophylaxis for dental procedures should be recommended only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis.

Prophylaxis is not recommended based solely on an increased lifetime risk of acquisition of infective endocarditis.

Change in approachAntibiotic prophylaxis is now recommended only for those patients with the highest risk of adverse outcome from IE, not just those with highest lifetime risk of IEProphylaxis for dental procedures even for these highest risk patients is reasonable but with poor evidence (Class IIb, LOE B)

Treatment

Rationale for Revision

Additional ReasonsOver years, guidelines became complicatedPoor recollection of guidelines by practitionersPoor compliance amongst patients and dentists Ambiguities and inconsistencies were subject to wide interpretations in malpractice casesPrevious guidelines not evidence basedDesire to stimulate research on IE prophylaxis

Nonadherence to prophylaxis70% of 455 Dutch patients recalled being warned to take IE prophylaxis, but only 22% reported actually taking them.Prophylaxis was given to young patients 4x more than older patients.Surgeons are twice as likely to recommend prophylaxis for patients with pacemakers than cardiologists.As summarized in Durack NEJM 1995; 332(1): 38-44

Quiz Question:According to the 1997 AHA Guidelines on endocarditis prophylaxis, which of the following conditions require antibiotic prophylaxis?

Mitral valve prolapse Previous CABG with tricuspid annuloplasty ringPrevious pacemakerSecundum atrial septal defectMild aortic regurgitationMild mitral regurgitationMild aortic stenosisAortic sclerosis without stenosis

Mitral valve prolapse Previous CABG with tricuspid annuloplasty ringPrevious pacemakerSecundum atrial septal defectMild aortic regurgitationMild mitral regurgitationMild aortic stenosisAortic sclerosis

Seto, Am J Med, 2001; 111:657-660

Scope of patientsHow many adults over age 60 would be eligible for IE prophylaxis based on prevalence of cardiac conditions and 1997 guidelines?

A) 2%B) 6% C) 10%D) 24%E) 50%

Croft Am J Card 2004; 94:386-89

Croft Am J Card 2004; 94:386-89

Croft Am J Card 2004; 94:386-89

40% of cases of IE occurs in patients without previously identified risk factors.

Bacteremia and Dental ProceduresLancet 1935

BacteremiaWidely studiedFrequency/intensity related toDensity of floraDegree of inflammationDegree of infectionMagnitude of tissue traumaPeak 10 minutes after tooth extraction, drops off between 10-30 minutesDurack NEJM 1995; 332(1): 38-44

Guntheroth. Am J Card 1984;54:797-801

Chewing?60 normal healthy patientsSupervised brushing for 2 minutesChewing gum for 10 minutesScaling/Root planingNone were culture positive before4/20 with periodontal disease had bacteremia from chewing gum, 1/20 after brushingScaling caused bacteremia in 2/20 healthy patients, 4/20 gingivitis patients, 15/20 periodontal disease patients

Forner. J Clin Periodontology 2006; 33:401-407

Bacteremia in Dental ProceduresRoberts, Pediatric Cardiology 1997; 18:24-27735 pediatric patients with blood cultures drawn 30 seconds after procedure.Cardiac patients received antibiotic prophylaxis.

Cumulative Risk:Total duration of bactermiaGuntheroth. Am J Card 1984;54:797-801Almost 1000x more risk in the month of extraction to daily activities than from extraction.

BacteremiaDental procedures: 104 CFU/mlRoutine daily activities: sameExperimental IE in animal studies: 106-108

Cumulative risk from daily activities:Risk from brushing teeth over 1 year may be 154,000 times greater than single extraction. Risk from all daily activities may be 5.6 million:1

Roberts Pediatric Cardiology 1999. 20: 317-325

Cumulative riskRoberts. Pediatric Cardiology. 1999;20:317-325

BacteremiaIn patients with underlying cardiac conditions, lifelong antibiotic therapy is not recommended to prevent IE that might result from bacteremias associated with routine daily activities.The focus on the frequency of bacteremia have resulted in an overemphasis on antibiotic prophylaxis and an underemphasis on maintanence of good oral hygiene; which is likely more important in reducing the lifetime risk of IE than the administration of antibiotic prophylaxis for a dental procedure.

Do Abx Reduce Bacteremia?Reductions on variety of microbes and duration of positivity demonstrated in some studies, not in othersNot 100% effective in preventing bacteremiaProbably 75% effective at best

Does Prophylaxis Work in Humans?No prospective, randomized, placebo controlled studies in patientsRetrospective and prospective case-cohort trials limited by:1) Low incidence of IE2) Large variety of underlying conditions3) Large variety of dental procedures/states

Dutch Case-control studyNationwide case control study in Netherlands14.5 million patients screened over 2 years.All patients in country with suspected IE reported to author.438 patients with IE over 2 years, 48 included (had surgical/dental procedure within 6 months)Only 18 patients had IE within 30 daysCompared with 200 patients with same cardiac diagnosis, similar procedureVan der Meer. Lancet 1992; 339:135-139

Dutch Case-control studyOnly 1:6 in both groups had IE prophylaxisOnly 12.7% of patients with IE had procedure within 30 days Possible 49% risk reduction with Abx, but not significant (11-229%)At best, full compliance with prophylaxis might prevent:17.1% of 275 patients with an incubation of 180 daysAt most 23 /275 (8.4%) if 30 days.Might prevent 5.3% of all cases with endocarditis.

Van der Meer. Lancet 1992; 339:135-139

Summary: Case Control TrialsPossible benefit for prophylaxis cannot be excludedYale and French studies suggest possible statistically significant benefitSmall numbers, 12 week association, recall bias a problemDutch study had non-significant differenceProphylaxis for IE is inconsistently prescribedInfective endocarditis is not consistently associated with a dental procedure

French study1 year epidemiological study of IE in an area of 16 million peopleEstimates of predisposing cardiac conditions (PCC), # of dental procedures, whether antibiotics were given obtained from survey of 2805 peopleResults extrapolated to country populationPCCs restricted. Highest-risk only in French recommendations 2002 (prosthetic valve, previous endocarditis) Heart 2005 91:715-8

Duval. Clin Infect Dis. 2006;42:e102-e107

French study: ConclusionsEstimated Risk of IE:1:46,000 for unprotected procedures1:10,700 for prosthetic valves1:54,300 for native valves1:150,000 for protected proceduresEven if antibiotics were 66% effective, large number needed to treat, even for high risk patients isolated using French standardsDuval. Clin Infect Dis. 2006;42:e102-e107

Decision AnalysisMarkov multiple states modelTake estimates of benefit, cost, complications, incidence from literature and calculate likelihood of possible options

Agha. Medical Decision Making 2005;25:308

Decision Analysis ResultsIf 10 million patients underwent prophylaxis with amoxicillin19 cases of IE preventedNet loss of 181 lives due to anaphylaxisIf 10 million patients underwent prophylaxis with clarithromycin119 cases of IE prevented, 19 deaths preventedIncremental cost effectiveness of $88,007/QALYValve replacement/previous IE patients had much better CE ratio of $14,000-38,000If true incidence of cases of IE due to dental procedures were less than 17% used in model, cost would increase.Agha. Medical Decision Making 2005;25:308

Future DirectionsDue to the low rate of endocarditis,An adequately powered RCT would require 6,000 60,000 patients over 2 years, and screening of many more patients than this.A prospective cohort study would require 18,000 patients over 10 yearsOnly possible in countries with large organized health systems with centralized records, and including every patient in that system

Cochrane Review 2004

Future DirectionsLarge case-control trial would be more feasibleSelecting appropriate matched controls for cases would be requiredCochrane Review 2004

Medical MalpracticeFour criteria must be metDuty was owed to patientDuty was breached failure to conform to standard of careBreach caused an injury and was proximate cause of the injuryDamages occurred

Recent malpractice casesFailure to diagnose endocarditis:Shea v Dr. F. Mohebban 1999, Minella v. Dr. E AntelisSettled for $1.2 million, $1.95 million after MD failed to order blood CxFailure to prescribe prophylaxis and failure to diagnoseMullen v Zylstra MD, Pederson MD, Maynard DDS 199128 yo man with abnormal bicuspid AVAfter tooth loosened by trauma, DDS attempted to reinsert. No abx given despite history of bicuspid AV.Weeks later, tooth was grossly infected, constitutional symptoms of endocarditis. MD failed to listen to heart or order blood cx, diagnosis delayed, AVR required.$3 million finding against MD. DDS settled for $25,000MoreLaw database

Other CasesFailure to ask?Bacon v Kentopp DDS, 2000, NebraskaPatient required AVR and MVR after dental induced endocarditis. Filed against DDS for failure to ask whether she had heart problems, claimed that Abx would have been prescribed and would have prevented endocarditisDefendant (DDS) won verdict.

Treatment

Dental procedures and IE prophylaxis: RecommendedDental extractionsPeriodontal proceduresDental implants and reimplantation of avulsed teethEndodontic proceuresSubgingival placement of antibiotic fibers and stripsInitial placement of orthodontic bands (not brackets)Intraligamentary local anesthetic injectionsProphylactic cleaning

Dental procedures and IE prophylaxis: Not recommendedRestorative dentistryNon-intraligamentary local anesthetic injectionsTaking oral impressionsFluoride treatmentsOral radiographsOrthodontic appliance adjustmentShedding primary teeth

Discussion?

Criteria for effective prophylaxisIs the disease preventable?Is it worth preventing?Can patients at risk be identified?Is prophylaxis clinically effective?Is prophylaxis safe and well tolerated?Can prophylaxis be delivered consistently and easily?Is prophylaxis cost effective?

Prophylaxis in 1997Dental: Any procedure that might induce bleedingAmoxicillin 2gm PO, 1 hour preprocedureGIERCP, stricture dilatation, varices, surgeryGUCystoscopy, prostate surgery, ureteral stentPulmonaryT&A, rigid bronchoscopyRx: Ampicillin/Gentamicin for non dental procedures.

Unfortunately this table does not match the text of the van de Meer article!

Do Abx Reduce Bacteremia?Animal studies in the 1970s used rabbits, valve damage from catheter, and large inoculum (108 CFU/ml) S. viridans to generate IE.Vancomycin and PCN uniformly effective in preventing IE.Single dose Abx failed when even larger doses of inoculum used.

Do Abx Reduce Bacteremia in Humans?Lockhart. Circulation 2004; 109:2878-2884RCT of 100 children in dental OR given amoxicillin

Do Abx Reduce Bacteremia?Erythromycin 1.5 gm oral before tooth extraction.Randomized double blind trialS. viridans recovered in:6/40 (15%) treated patients18/42 (43%) control patientsShanson. J Antimicrob Chemo 1985; 15:83-90

Do Abx Reduce Bacteremia?39 patients randomized to cefaclor or placebo prior to extractionS. viridans recovered from 79% in treated group50% in placebo group60 patients randomized to PCN, amoxicillin, placebo in another study95%, 90%, 85% positive blood culturesHall. Eur J Clin Microbiol Infectious Dis 1995;15:646-649Hall Clin Infect Dis 1993; 188-94

Do Abx Reduce Bacteremia?Reductions on variety of microbes and duration of positivity demonstrated in some studies, not in othersNot 100% effective in preventing bacteremiaProbably 75% effective at best

Yale-New HavenCase-control trial, 2 hospitals34 patients with IE between 1980-1986 with oral flora and cardiac lesion8/34 (23%) of patients had dental procedure within 12 weeksControls matched for same lesion, same procedure

Imperiale. Am J Med 1990; 88: 131-136

Yale-New HavenImperiale. Am J Med 1990; 88: 131-136

Lacassin studyCase control trial18.5 million population in 1 year, 1990-1Endocarditis, excluding IVDU, Q-fever171 cases, matched to control by age, sex, cardiac conditionQuestionnaire to recollect procedures

Lacassin Eur Heart Journal 1995; 16(12) 1968-74

Lacassin studyLacassin Eur Heart Journal 1995; 16(12) 1968-74

Lacassin studyDental procedures as a whole were not associated with increased risk, although scaling and root canal had trend (P=0.065)In multivariate analysis, only skin wounds and other infections increased overall risk of endocarditis. But when selecting only S. viridans endocarditis, scaling was a significant risk independent of other factors (but data not shown)Tooth extraction was notSkin and other infections were significantly more prevalent in case group (19% vs 5%)

Lacassin Eur Heart Journal 1995; 16(12) 1968-74

Lacassin studyLacassin Eur Heart Journal 1995; 16(12) 1968-74

RejectedBoth these positive studies rejected from an analysis by Cochrane Database as potentially being seriously biased.Prolonged duration (12 weeks) considered too long by Cochrane committeeRecall bias a concernOther limitations:ConfoundersAssociation without causationOliver. Cochrane Database 2004.

Philadelphia ProjectCase-control study: 8 counties around Philadelphia and Delaware, 54 hospitals273 cases with community acquired, non IVDU endocarditisControls were matched only to age, sexNo association found with dental care, frequency of tooth brushing, use of irrigators, denturesVery few patients in either group received Abx prophylaxis (2.2% case, 0.7% controls)Case patients were more likely to have cardiac lesions, be on VA or Medicaid insurance

Strom Ann Int Med 1998; 129(10) 761-769, Circulation 2000; 102:2842-2848

Strom Ann Int Med 1998; 129(10) 761-769, Circulation 2000; 102:2842-2848Case patients with IE no more likely to have received dental procedure (OR 0.8 CI 0.4-1.5)

Philadelphia ProjectStrom Circulation 2000; 102:2842-2848

French EstimateDuval. Clin Infect Dis. 2006;42:e102-e107

French EstimateDuval. Clin Infect Dis. 2006;42:e102-e107

The published AHA guidelines do not specifically define acquired valvular dysfunction, so we applied the following DHHS criteria for significant valvular abnormalities[4]: patients with moderate or greater mitral regurgitation, tricuspid regurgitation, or pulmonary regurgitation qualified for IE prophylaxis. Patients with mild or greater aortic regurgitation qualified. Additionally, mild mitral regurgitation with a thickened or redundant mitral valve as well as mitral valve prolapse with any degree of mitral regurgitation qualified for prophylaxis. [6] Also, any valvular stenosis of mild or greater degree qualified.