Author + information
- Received October 13, 2009
- Revision received December 3, 2009
- Accepted February 1, 2010
- Published online April 20, 2010.
- Shahbudin H. Rahimtoola, MB, FRCP, DSc (Hon)* ()
- ↵*Reprint requests and correspondence:
Dr. Shahbudin H. Rahimtoola, University of Southern California, 1200 North State Street, Old GNH 7131, Los Angeles, California 90033
- aortic stenosis
- mitral regurgitation
- mitral stenosis
- mitral valve repair
- prosthetic heart valves
- transcatheter valve therapy
This review covers the time period July 2008 to June 2009 with 1 exception.
Aortic Valve Stenosis (AS)
Sudden death in young athletes
A total of 1,866 athletes, age 19 ± 6 years, died suddenly or survived cardiac arrest in the U.S. from 1980 to 2006. At autopsy, 690 deaths due to cardiovascular (CV) events were confirmed; AS was the only abnormality found in 19 (2.8%) (1).
This study documents that sudden death occurs in young people with AS. The frequency and incidence of sudden death and of AS cannot be determined from this study.
a) Endothelium was found to play a role in regulating the mechanical properties of aortic valve (AV) cusps, emphasizing valve cellular integrity for optimal valve function (2).
b) Valve cusps show increased thermal heterogeneity in AS versus those in aortic regurgitation (AR), which correlated with inflammatory mononuclear cell infiltration, proinflammatory cytokines, and neoangiogenic factors (3).
c) Oxidative stress is increased in calcified regions of valves in AS (4). Increased oxidative stress is partly due to reduction in expression and activity of antioxidant enzymes and possibly to uncoupled nitric oxide synthases. Mechanisms of oxidative stress are different in AS and atherosclerotic arteries (Fig. 1).
The same group reported that rapid normalization of elevated cholesterol had beneficial effects (5).
d) Rapid normalization of elevated cholesterol levels by inducing expression of Crerecombinase in hypercholesterolemic Reversa mice with early AV disease (AVD) normalizes oxidative stress, reduces pro-osteogenic signaling, and halts the progression of AS (Fig. 2)(5).
e) Senescence of valvular endothelial cells reduces its regenerative capacity and decreased levels of endothelial progenitor cells are partly a pathological link for the destruction of valvular endothelial cells, which results in the progression of calcific AS (6).
f) A strong association was established (7) between AS and aortic atherosclerosis (AA) that was independent of age and sex. The prevalence of severe AA increased across grades of AS; 57% of patients had severe AS and severe AA.
Stroke volume (SV) measurement by real-time 3-dimensional echocardiography (RT3DE) is more accurate than by 2-dimensional echocardiography (2DE)
In 68 patients with AS, age 74 ± 12 years, RT3DE color Doppler imaging and 2DE were performed (8). Correlation between AV area (AVA) by 2DESVand AVA3D-SVwas modest, (r = 0.71, p < 0.001; mean difference 0.11 ± 0.23 cm2) (Fig. 3).In a subgroup of 38 cases, AVA3D-SVhad better agreement with AVA3D-Pl(Pl = planimetry) than AVA2D(mean difference = −0.001 ± 0.15 cm2vs. −0.10 ± 0.26 cm2, p = 0.038). Cardiac output and SV measurements were validated against flow probes in experimental sheep with a distorted left ventricular (LV) outflow tract; 3DE was clearly superior to 2 DE (Fig. 4).
Measurements from LV outflow tract for SV and AVA calculations can be very difficult with 2DE, which is well-known to most clinical echocardiographers/clinicians. Studies in humans that measure a range of SV simultaneously with 3DE and an independent technique are needed. Please see RT3DE in mitral regurgitation, which documents better assessment of severity of mitral regurgitation (MR) compared with 2DE. RT3DE provides a much better assessment of severe aortic and mitral valve disease (MVD).
Contribution of the arterial system to response with exercise
Eighteen patients with AS included in the study were age 60 ± 8 years, LV ejection fraction (LVEF) was >0.55 by angiography and had no significant AR or obstructive coronary artery disease (CAD). Using high-fidelity catheter recordings of ascending aortic pressure and blood flow velocity at rest (9), systemic vascular resistance, arterial elastance, and aortic characteristic impedance were increased in patients with AS compared with 11 controls. In contrast, total arterial compliance was lower compared with controls (0.737 ± 0.19 × 10−3cm5/dyne vs. 1,155 ± 0.27 × 10−3cm5/dyne, p < 0.001). With exercise, total arterial compliance increased in controls but did not change in those with AS. Arterial elastance increased on exercise, and aortic characteristic impedance remained elevated. Stroke flow increased in those with AS and controls but to a much lower extent in those with AS (controls: from 230 ± 37 ml/s to 406 ± 69 ml/s, p < 0.001; AS: from 229 ± 69 ml/s to 256 ± 78 ml/s, p < 0.01). On multivariate regression, the increase in stroke flow was related to decreases in systemic vascular resistance (p = 0.03) and arterial elastance (p = 0.02) but an increase in total arterial compliance (p = 0.03).
This is a sophisticated study. Properties of the arterial system distal to the AV directly influence the hemodynamic response to exercise in AS. One thus has to be careful about interpretations and clinical implications of data obtained from simplistic approaches to exercise tests in AS.
Is exercise stress echocardiography (ESE) of additive value to exercise tests (ETs)?
The added value and clinical utility of ESE to ETs were evaluated in 101 asymptomatic patients, 59 men, age 69 ± 10 years, with severe AS (AVA <1 cm2or mean gradient ≥50 mm Hg) and “normal” LV systolic function (10). The ET was a symptom-limited treadmill test using the modified Bruce protocol in 80%, and Bruce modified or manual protocol was applied in the remaining patients. Total exercise time was 5.24 ± 2.6 min and workload was 6.5 ± 2.4 metabolic equivalents. The ET was abnormal in 69 (68%) patients; symptoms developed in 48 patients. An abnormal blood pressure response was the only abnormality in 24 patients. An abnormal “contractile response” was observed in 12 patients, and in 7 of these patients, this was the only abnormal parameter; 10 of these 12 patients had coronary arteriography and significant coronary stenosis was present in 7.
ESE provided additional information for ETs in 12 of 101 patients. However, the treadmill ET is not optimal for ESE because there is a ≥1- to 2-min delay between the end of the test and the beginning of acquisition of adequate echocardiographic data during which time period, that is, at the end of the ET, there is a very rapid defervescence of the cardiac response. Previously Marechaux et al. (11) described a decline in LVEF by echocardiography in 40% of patients undergoing a supine bicycle test; in the present study, LVEF was not measured and visual estimate of LV function documented the additional value in very few patients. In the age group of this study, ≥50% of patients can be expected to have associated CAD (12). In the absence of knowledge about associated CAD, one does not know whether the abnormal ET/ESE is due to AS and/or CAD.
The much-awaited SEAS trial results: negative for AS
The SEAS (Simvastatin and Ezetimibe Aortic Stenosis) trial is a randomized, double-blind trial in 1,873 asymptomatic patients with mild to moderate AS (13). During a median follow-up of 52.2 months, there was no statistically significant difference in “primary outcome” (a combination of 9 different events) between the simvastatin-ezetimibe group (35.3%) and the placebo group (38.2%) (p = 0.59). There was no significant difference in performance of AVR (p = 0.97); however, there were fewer incidents of ischemic CV events in the treated group (p = 0.02), mainly because fewer patients underwent coronary artery bypass graft (CABG). The incidence of cancer was greater (p = 0.01).
The clinical validity of this last observation has been questioned.
Excellent 30-month outcome after AVR for severe AS in selected subgroups
The 30-day mortality of 6,369 patients in New York State from 2003 to 2005 was 3.97% for isolated AVR (n = 3,327, age 68.9 ± 13.4 years) and 5.69% for AVR + CABG (n = 3,042, age 64.2 ± 8.9 years) (14). Two subgroups had particularly notable results at 30-month follow-up: in patients 75 years of age and older who had AVR + CABG, the risk-adjusted survival rate of 83.3% was not significantly different from the rate of 84.0% of age- and sex-matched patients in the population and 64.3% of patients with isolated AVR (who did not have heart failure [HF], LVEF <0.40, acute myocardial infarction <24 h, or hemodynamic instability) had a risk-adjusted survival rate of 89.9%, which was statistically equivalent to the 90% survival rate of an age- and sex-matched population.
Aortic Regurgitation (AR)
Percutaneous transcatheter closure was deemed successful in 89% of 70 patients with ASD and in 92% of 170 patients with a patent foramen ovale (15). At follow-up of 27 ± 15 months, the “overall major” complication rate was 0.8%. Transesophageal echocardiography (TEE) at 3, 6, and 12 months showed newly developed or worsened AR in 9% of those with ASD and in 10% of those with a patent foramen ovale, which was “independent” of age, sex, or size of defect. The authors speculated that a “potential cause for developing AR may be overgrowth of the device by tissue, leading to changes in the interatrial septal geometry and traction on the root of the non-coronary aortic cusp” (Fig. 5).
This complication is in addition to other complications (16).
Mechanism of functional AR (FAR) in ascending thoracic aortic aneurysm (ATAA) with a normal AV
A total of 89 patients with ATAA, age 59 ± 13 years, with varying degrees of FAR were studied. Surgery was performed for ATAA with an aortic diameter of ≥50 mm and a normal AV (17). There were 2 control groups: 40 age-matched patients with ATAA and no FAR and 20 age- and sex-matched subjects without heart disease. Severity of AR was graded by vena contracta (VC) width on TEE; VC width was 5.59 ± 2.59 mm. Various parameters were analyzed. FAR was caused by diastolic tenting of AV leaflets (Fig. 6).On multivariate analysis, the most strongly associated with FAR was the severity of diastolic leaflet tenting; its coaptation height ≥1.1 cm had 98% sensitivity and 95% specificity. The mismatch of the dimension of sinotubular junction and annulus determined the severity of tenting and of AR; its ratio of >1.66 had 98% sensitivity of and 95% specificity.
Bicuspid AV (BAV)
Outcomes in adults
In 642 patients, age 35 ± 16 years, the 10-year survival was 96 ± 1% (18). Primary cardiac events occurred in 25 ± 2%, which included death in 3 ± 1%, valve or aorta intervention in 22 ± 2%, aortic dissection in 2 ± 1%, and HF in 2 ± 1%. Independent predictors of events were age older than 30 years and moderate or severe AS or AR (Fig. 7).
Aortopathy in patients with BAV
a) Decreased metallothionein in AA aneurysm. Microarray analysis of 50 aortic samples (22,000 probe sets) identified 110 dysregulated genes in BAV compared with tricuspid AV and control donors; 8 were genes of the metallothionein family (19). Metallothionein gene expression and protein expression were significantly lower in aortic tissue and cultured aortic smooth cells from BAV patients compared with control subjects. Matrix metalloproteinase-9 expression was increased in BAV samples. The authors concluded that the dysregulated metallothionein expression may “contribute to an inadequate response to oxidative stress and provoke aneurysm formation.”
b) Increased prevalence in relatives of patients with BAV. This was a study of 48 first-degree relatives (FDRs) of 54 BAV patients and 45 control patients. Aortic root dilation was present in 32% of FDRs, 53% in BAV patients and none in the control group (20). FDRs and BAV patients had significantly lower aortic distensibility (p < 0.001) and a greater aortic stiffness index (p = 0.001) compared with controls. This difference remained significant in subjects without aortic root dilation (p = 0.002) or hypertension (p = 0.004).
I recommend FDRs of patients with BAV to undergo screening transthoracic echocardiography (TTE) for assessment of AA and the AV and, if necessary, additional testing, for example, TEE.
Mitral Stenosis (MS)
American Heart Association scientific statement
For the prevention of rheumatic fever and diagnosis and treatment of acute streptococcal pharyngitis (21), this is an update.
At the time of intervention for MVD, the rate of progression of associated mild AVD is very slow
A total of 200 patients (age 30.3 ± 9.9 years; 146 women, 54 men) had interventional therapy for rheumatic MVD and were followed for 9.3 ± 1.07 years to evaluate the development of AVD or progression of AVD (group I, n = 98). Initially, only AV thickening was present in 16 (group IIA), isolated AR was present in 69 (group IIB), and mixed AS/AR in 17 (group IIC) (22). Two patients progressed to severe AS from mild AS at baseline, necessitating AVR. Of 98 patients, new AVD developed in 10. Mild AR developed in 11 of 16 patients in group IIA, and mild AS/AR developed in 1; mild AS and mild or moderate AR developed in 22 (31.9%) of 60 patients in group IIB; 8 of 16 in group IIC progressed to AS, moderate in 6 and severe in 2. Thus, severe AVD rarely developed in patients with no or mild AVD, and they rarely (1%) required AV surgery over long-term follow-up.
Important data. The authors reviewed theirs and 3 other similar studies in the literature. In the 4 studies (22–25), of 890 patients, severe AVD that needed intervention developed in 19 (0.022%). An editorial accompanying the first of those articles had strongly recommended against prophylactic AVR for mild AS (26).
Statins delay progression of rheumatic AS
A retrospective review of patients, age 61 ± 10 years, whose echocardiographic results were typical for rheumatic AS and MVD and who had at least 2 echocardiograms ≥2 years apart yielded 30 patients who had received statins and 134 who had not received such therapy. The progression rate of AS was judged by changes in peak aortic velocity (27). The progression rate in those treated with statins versus not treated was 0.05 ± 0.07 m/s/year versus 0.12 ± 0.11 m/s/year (p = 0.001). In the investigators' laboratory, the interobserver coefficient of reproducibility for recording and measuring peak aortic velocity was 0.20 m/s.
The excellent accompanying editorial (28) provides a thorough and critical review of the study.
Degree of commissural opening of MS with catheter balloon commissurotomy (CBC) influences long-term outcome
A total of 875 patients, age 48 ± 13 years, 83% female and 75% in New York Heart Association functional class III/IV, had “good” immediate results with CBC (mitral valve area [MVA] ≥1.5 cm2and no MR >2/4) (29). Patients were divided into 3 groups: group 1 (n = 189), both commissures were partially opened or not split; group 2 (n = 489) 1 commissure split; group 3 (n = 227), both commissures completely split. The MVAs after CBC in the 3 groups were 1.77 ± 0.19 cm2, 1.93 ± 0.25 cm2, and 2.10 ± 0.27 cm2, respectively (p < 0.0001). On follow-up to 10 years, patient outcomes were best in group 3 and better in group 2 than in group 1. The authors stated “either the degree of CO (commissural opening) or the MVA was an independent predictor of good late functional results (p < 0.05),” but data on MVA were not presented.
This study shows: a) the mechanism of improvement of MS is the extent of commissural opening; and b) the feasibility of evaluating the extent of commissural opening. This can be vividly seen with use of 3-dimensional echocardiography in the accompanying editorial (30). Data on the additional clinical value/benefit of determining commissural opening over the measurement of MVA is important and would have been valuable.
Over the past 20 years, data collected worldwide including data from these investigators had shown that the larger the MVA was after CBC, the better was the patient outcome. From studies of surgical mitral commissurotomy, it has been known for ≥50 years that the increase in MVA is dependent on the extent of commissural opening; therefore, the procedure should be labeled as commissurotomy and not as a valvuloplasty.
Variability in the assessment of MR
a) Intraobserver variability. Twelve “fully qualified echocardiographers” who “routinely and regularly analyze the severity of MR in a clinical setting” at 3 prominent institutions in London, England, participated in the study (31). One (8%) of the 12 observers gave consistent gradings for the triply presented images. Percentages of reporters demonstrating variability in 1 of 6 cases of one-half of 1 grade (i.e., moderate to moderate-severe) ranged from 25% to 67%, that of 1 full grade ranged from 17% to 50%, and that from severe to not severe or from nonsevere to severe ranged from 8% to 33%. The investigators concluded the “even a skilled observer cannot be relied upon to give an identical grading to an identical sample video clip of MR, when re-presented surreptitiously within a few minutes.”
This study highlights the need to develop improved and better standardized measurements of the severity of MR.
b) Variations in calculations of mitral regurgitant SV (MRSV). In 73 patients with MR of various etiologies, MRSV was calculated from an apical 4-chamber view using 4 hemispheric PISA methods (32). Magnetic resonance imaging was used as the reference method. “Single-point PISA methods yielded greater underestimation of MRSV for PISA—VTI: −13.3 ± 10.2 ml, for simplified PISA: −3.5 ± 10.3 ml particularly in functional MR, compared with time-integral PISA methods accounting for variations of mitral regurgitant flow rate (MRFR) and effective regurgitant orifice area (EROA) over time.” The investigators concluded “Depending on the underlying mechanism of MR, dynamic variations of MRFR and EROA revealed important variations of MRSV calculation using single-point and time-integral PISA methods.”
c) Calculated MR volume versus qualitative grading of MR. In 89 patients with mild MR, MR volume was 21 ± 16 (mean ± 1 SD); in 241 patients with moderate MR, MR volume was 35 ± 15 ml; and in 441 patients with severe MR, volume was 83 ± 45 (33). The investigators concluded that their data demonstrated “the general appropriateness of the original qualitative grading.”
Their conclusion raises questions; for example, how good is “general” appropriate? The range of volumes, which is important information, was not provided for each of 3 grades of severity. Only 1 SD in the severe grade yields MR volumes of 38 to 128 ml; thus, clearly a number of patients (?%) with severe MR had MR volumes in the moderate range (30 to 59 ml) (33). Similarly, there must have been overlap in mild and moderate MR.
In addition to these 3 studies, an earlier study (34) showed that the total test-retest variability of assessment of MR by prominent echocardiographers was 24.6 ± 5.2%, which consisted of a variability of 7.9 ± 10.2% for acquisition of the studies and of 16.7 ± 8.8% for intrareader variability.
The severity of regurgitation is influenced by hemodynamic conditions, especially by blood pressure at the time of the recording (35) and also by the timing of atrial contraction. The American Society of Echocardiography recommends determining quantitative parameters of regurgitation. Quantitation of LV size/volume corrected for body size is also very important for determining the severity of chronic MR and AR.
RT3DE is superior to 2DE for assessing severity of MR
In vitro, 3-dimensional VC had better correlation with known orifice area compared with 2-dimensional VC (r = 0.92, p < 0.001 vs. r = 0.56, respectively; p = 0.01) (36) (Fig. 8).In 61 patients, 3-dimensional VC area correlated better with Doppler imaging-derived effective regurgitant orifice area (EROA) than with 2-dimensional VC (r = 0.85, p < 0.001 vs. r = 0.67, respectively; p < 0.001), especially so with eccentric jets (r = 0.87, p < 0.001 vs. r = 0.6, respectively; p < 0.001) and in moderate to severe or severe MR versus mild or mild to moderate MR (r = 0.80, p < 0.001 vs. r = 0.18, respectively; p = 0.4).
For RT3DE in AS, see the Aortic Valve Stenosis section. RT3DE provides a much better assessment of severe MVD and AVD.
Some good news: increasing performance of MV repair (MVrep)
The Society of Thoracic Surgeons database for MV surgery from 2000 to 2007 at 910 hospitals showed that for isolated MR (n = 47,126), the rate of MVrepincreased from 51% to 69% (p < 0.0001) (37). Among 24,404 patients having MV replacement (MVR), the use of mechanical valves decreased from 68% to 37% (p < 0.0001). The operative mortality rate for MVR versus MVrepwas 3.8% versus 1.4%; patients undergoing MVR were older, were more severely symptomatic, and were more likely to be female and to have a higher incidence of comorbid conditions. For asymptomatic patients, the MVrepoperative mortality rate was 0.6%.
These data must be kept in perspective. a) Besides operative mortality, major complications still occurred, which included reoperation, deep sternal wound infection, permanent stroke, and need for dialysis; b) later patient outcomes and complications, that is, beyond 30 days, are not available in the database; and c) the occurrence of major complications and the lack of patient outcome data including recurrence of MR and of reoperation on long-term follow-up is of considerable importance, especially in the 17% of patients who were asymptomatic before surgery.
“Modest” rate of progression to need for surgery in asymptomatic patients with severe MR
In a study from Seoul, 286 of 447 patients were treated conservatively. Indications for surgery developed at a rate of ∼5% per year (24 ± 3% at 5 years and 33 ± 4% at 7 years) (38).
This rate is similar to that described in the Vienna Study in which it was ∼6% per year (22 ± 4% at 4 years and 35 ± 6% at 6 years) (39).
Early surgery for all asymptomatic patients with severe MR due to MV prolapse and/or flail MV?
The same nonrandomized prospective study from Seoul of 161 patients, age 50 ± 15 years, undergoing early MVrepwere compared with 286 patients, age 51 ± 15 years, not having early surgery (39). Comparison of the outcome data was presented only in the 127 propensity-matched patients in each group. The end point of the study was a composite of operative mortality, cardiac death, repeat MV surgery, and hospitalization for HF but did not include all-cause mortality. There were no operative deaths. The event-free survival rate at 7 years was 99 ± 1% in the operated-on group and 85 ± 4% (p = 0.007) in the conventional group; 4% of patients were lost to follow-up. The actuarial 7-year cardiac mortality was 0% in the operated-on group and 5 ±2% in the conventional group (p = 0.008); 2 patients in the operated-on group required repeat MV surgery.
In the whole early surgery group (i.e., not just propensity matched), there were 7 (4.3%) of 161 noncardiac deaths; the causes of death were not presented. There were 12 (4.2%) of 268 noncardiac deaths in the conventional group; causes of death were malignancy in 6, stroke in 3, infection in 2, and suicide in 1. In the conventional group of 286 patients, 207 did not meet criteria for surgery, and there were 3 sudden deaths (2 due to endocarditis); 66 became symptomatic, but surgery was performed only in 50; 13 asymptomatic patients met criteria for surgery, but surgery was performed only in 3 patients.
The Seoul study must be kept in perspective. a) Coronary arteriography was not performed in the conventional group, and they had major risk factors for CAD. In the conventional group at the end of 7 years, the actuarial cardiac mortality rate was only 5% (i.e., ∼0.7%/year). There were 4 sudden deaths and 6 HF deaths. Were all these deaths due to MR or to other causes such as associated CAD and its complications? b) Surgery was not performed in 16 patients who had become symptomatic and 10 who were asymptomatic but met criteria for surgery.
Surgery for papillary muscle rupture (PMR) causing MR
A total of 54 patients, age 70 ±8 years, were operated on for PMR producing severe MR from 1980 to 2000 (40). The rupture involved the posterior papillary muscle in 90%; 91% presented in cardiogenic shock and/or with pulmonary edema and/or in cardiac arrest. Surgery was performed 6 ± 27 days after the first symptoms, within the first month in 45 (83%) and after the first month in 9 (17%). The incidence of 1, 2, 3, and left main CAD was 31%, 35%, 26%, and 6%, respectively. LVEF was 0.56 ± 0.13. MVrepwas performed in 13 patients. Four of 6 patients who did not undergo CABG died. The 10-year survival rate was 35 ± 7%. Among 44 surgery survivors, the 5- and 10-year survival rates were similar to those of matched patients with myocardial infarction without PMR (Fig. 9);68% of patients were in New York Heart Association functional class I or II and 82% were in Canadian Cardiovascular Society angina class I or II.
This is a valuable study. Patients with anterior PMR usually die very rapidly and are not commonly seen at distant referral centers; in this study, 49 of 54 patients had posterior PMR. How many of the 5 early deaths (2 during surgery, 1 on postoperative day 1, and 2 of myocardial rupture) were associated with the 5 patients with anterior PMR? Of importance, those who survived 30 days had a long-term survival similar to that of myocardial infarction without PMR. This is similar to patients with myocardial infarction and cardiogenic shock; after revascularization, patients who survived to 30 days had a long-term survival similar to that of patients with myocardial infarction without shock (41,42).
Tricuspid Regurgitation (TR)
Beneficial effects of the MAZE procedure in functional TR
The impact of the MAZE operation on the progression of mild functional TR was studied in 251 patients with mild functional TR (grade 2) who had successful mitral valve (MV) procedures for rheumatic disease (43). At follow-up of 62.6 ± 39.8 months, “significant” TR increased from 5.2% to 16.4% (p < 0.01). Multivariate analysis for progression of TR included older age, rheumatic etiology of MVD, and no MAZE operation (adjusted hazard ratio: 7.90; 95% confidence interval: 1.90 to 32.86). Of 73 patients with pre-operative atrial fibrillation who underwent a MAZE procedure, normal sinus rhythm persisted in 87.7% at 47.2 ± 26.8 months of follow-up. Patients who did not undergo a MAZE procedure had a much higher incidence of significant TR (p < 0.01).
Data on tricuspid annular size, which is an important determinant of TR, were not presented.
30-year results of surgery
From 1974 to 2005, 328 patients, age 51.3 ± 13.6 years, 82.6% of whom were women, had surgery for rheumatic tricuspid valve disease (44). Actuarial survival rates at 10, 20, and 30 years were 61.8 ± 2.8%, 38.4 ± 3.1%, and 12.1 ± 4.4%, respectively.
Infective Endocarditis (IE)
2008 focused update of the American College of Cardiology/American Heart Association 2006 guidelines for the management of patients with valvular heart disease (45)
The only change was to incorporate into the 2006 guidelines changes so that the recommendations for antibiotic prophylaxis for the prevention of infective endocarditis are identical to those of the 2007 American Heart Association recommendations.
European Society of Cardiology's Guidelines on the Prevention, Diagnosis, and Treatment of IE (New Version 2009) (46)
Hospital mortality from 2000 to 2005 is still high
In the International Collaboration on Endocarditis Prospective Cohort Study of 3,284 patients, the hospital mortality rate was 17.7% (47). Predictors of mortality are shown in Table 1.There were small differences in the data from different continents.
Transcatheter Valve Therapy (TVT)
Extended application of percutaneous pulmonary valve (PV) implantation
Percutaneous PV implantation was successfully performed in 13 patients, age 14.3 years, who had severe PV regurgitation after repair of tetralogy of Fallot using right ventricular outflow tract patch (48). There were significant (p < 0.05) reductions of right ventricular pressure, right ventricle–pulmonary artery gradient and increase in pulmonary artery diastolic pressure. Follow-up at 4 months showed no deleterious results.
European System for Cardiac Operative Risk Evaluation (EuroSCORE) overestimates risks of AVR
a) A total of 1,177 patients, age 68 ± 14.7 years, underwent AVR from 2000 to 2006 in Rochester, Minnesota. The overall operative mortality rate was 2.5% (49). The additive and logistic EuroSCORE had predicted operative mortality rates of 6.9 ± 3.4% and 10.9 ± 12.7%.
b) A total of 1,545 patients, age 67.1 ± 12.9 years, underwent isolated AVR in Heidelberg, Germany, from 1994 to 2006 (50). The 30-day mortality rate was 2.2%, and the EuroSCORE additive and logistic had predicted operative mortality rates of 8.3% and 14.8%, respectively; 71 patients at very high risk had a zero mortality rate, whereas the EuroSCORE had predicted a risk of 11% to 20%.
Two earlier studies had also documented EuroSCORE overestimates of operative mortality rates in valvular heart disease (51,52).
Outcomes of patients referred for TVT for severe AS
Ninety-two patients, age 81 ± 7 years, were referred for percutaneous TVT for severe AS (AVA 0.6 ± 0.2 cm2not corrected for body surface area); LVEF was 0.46 ± 0.16 (53). Under the REVIVAL (Transcatheter Endovascular Implantation Of Valves) study protocol, patients had TVT if they were not candidates for surgical AVR. Nineteen had surgical AVR with a zero operative mortality rate, and 18 had percutaneous AVR with hospital/30-day mortality rate of 5%; the incidence of post-operative complications was almost identical in both groups. Nine (47%) of 19 who were referred for balloon aortic valvuloplasty died. The most common reasons for no intervention included death while awaiting definitive treatment (n = 10 [28%]).
Major MV injury after TVT for severe AS
An 88-year-old symptomatic man with severe AS had TVT with a 26-mm SAPIEN valve (Edwards Lifesciences LLC, Irvine, California) (54). The final valve position was suboptimal, being “slightly” low, with ventricular aspect of the stent abutting the anterior leaflet of the MV. The patient developed MR and AR, and 11 months later, he presented with IE and had 13 × 8-mm ruptured anterior mitral leaflet, severe MR, and mild to moderate AR. At reoperation, the MV was repaired, the percutaneous valve was removed and showed “coccal bacteria”; AVR was performed. The post-operative course was prolonged and complicated.
Core valve: 30-day outcome European Multicenter Registry
A total of 646 patients, age 81 ± 6.6 years, with severe AS (AVA 0.6 ± 0.2 cm2, EuroSCORE 23.1 ± 13.8%), had a third-generation (18-F) Core Valve ReValving System placed. Thirty days after the procedure, mean AV gradient had decreased from 50.4 ± 16.9 mm Hg to 3.2 ± 5.2 mm Hg. All-cause death was 8%, CV death was 5.9%, procedure-related death was 4.2%, stroke or myocardial infarction was 9.3% (55).
The prosthetic heart valve (PHV) area was not presented.
Magnetic resonance imaging for coronary sinus great cardiac vein (CS-GCV)
In 31 participants (24 volunteers and 7 patients, 15 men; 42 ± 19 years), the CS-GCV was located behind the left atrium at a minimum distance of 8.6 ± 3.9 mm from the MV annulus. In 80% of the participants, the left circumflex coronary artery crossed the CS-GCV inferiorly between the CS-GCV and the MV annulus (56).
Similar data were previously obtained using multislice computed tomography (57,58).
Novel device for percutaneous MVrep
In 8 Yucatan pigs, a device consisting of helical stainless steel screws connected by a biocompatible tether was placed by implanting the helical screws directly into the myocardium at the posteromedial MV annulus. The device was inserted from the internal jugular vein and performed at Advanced Preclinical services (Coon Rapids, Minnesota) (59). This procedure is intended for possible use in ischemic MR. Immediately after percutaneous MVrep, there were reductions of the MV annulus by 19.7 ± 0.1% (p = 0.003) and an 18.8 ± 0.1% reduction of anteroposterior dimension (p = 0.0001). These reductions were maintained at 30 and 90 days, at which time there also was reduction of the commissure dimension (p = 0.01).
Atrial transcatheter approach for MV valve-in–valve implantation
Nine adult sheep underwent MVR with a PHV with a 25-mm bioprosthesis. After weaning from cardiopulmonary bypass, the valve-in-valve implantation was performed off-pump using an antegrade transatrial approach. A transcatheter 23-mm pericardial prosthesis was implanted within the conventional bioprosthesis (60). The mean transvalvular gradient was 4.6 ± 1.0 mm Hg; only 2 sheep had mild or moderate MR.
Transapical MV stent implantation
Ten pigs underwent transapical off-pump MV stent implantation (61), after which hemodynamics were “normal”; TEE showed trace MR in 7 and mild MR in 3; LV angiography showed mild MR in 1.
These 3 studies are initial experimental feasibility studies.
Prosthetic Heart Valves
Which valve type (mechanical vs. bioprosthesis) for AVR in “older” patients? … bioprosthesis
b) Data from 3,934 patients who underwent primary AVR procedures were analyzed using microsimulation technique (63). The microsimulation-calculated techniques for survival from the Netherlands were validated both internally and externally. Life expectancy after AVR in studies from 2 countries were compared with that of the population. From 3 countries, 27% of patients had mechanical valves, their mean age at implantation was 58 years, the mean follow-up was 8.5 years, and 73% had bioprosthetic heart valves with mean age at implantation of 70 years and a mean follow-up of 6.1 years. Life expectancy after AVR is lower than in the general population, especially in the younger age group (Fig. 10).For patients older than 60 years, event-free life expectancy was better with a bioprosthesis. For a 60-year-old man, comparing bioprosthesis and mechanical valves, simulated life expectancy was 11.9 and 12.2 years, event-free life expectancy was 9.8 and 9.3 years, and reoperation-free life expectancy was 10.5 and 11.9 years, lifetime risk of reoperation was 25% and 3%, lifetime risk of bleeding was 12% and 41%, respectively (Fig. 11).
This is another valuable study using microsimulation techniques from van Geldorp et al. (63) The previously described 2 studies demonstrate better survival with a bioprosthesis compared with a mechanical prosthesis.
Most strokes with mechanical PHV are hemorrhagic
Over a 10-year period, 89 consecutive patients (64) were hospitalized for stroke (WHO MONICA criteria for stroke registers) (65) >90 days after mechanical valve replacement (49 AVR; 33 MVR, 7 AVR + MVR). Determination of the cause was based on cranial computed tomography or magnetic resonance imaging. The frequency of each etiologic factor is shown in Table 3.The most frequent cause was hemorrhagic (n = 69; 77.5%); the international normalized ratio ranged from <1.8 to >5. In only 2 patients (2.3%), the cause was related to the prosthesis.
Thought provoking. All such patients should have appropriate imaging techniques for initiation of proper treatment.
Ross principle: systematic review and meta-analysis
A systematic review (66) of 39 reports published from January 2000 to January 2008 on outcomes was presented. For adults, it included data from 17 publications comprising 1,749 patients (Table 4).The authors' conclusions included the following: 1) this procedure is almost exclusively used in children and young adults; 2) “noteworthy is the variability between studies in autograft and RVOT (RV outflow tract) structural and nonstructural valve deterioration rates, causing increasing variability in reported freedom from these events by the end of the first postoperative decade”; and 3) “durability limitations become apparent by the end of the first postoperative decade, in particular in younger patients.”
A useful study from Takkenberg et al. (66).
Very wide range of “normal values” of porcine mitral bioprostheses
A total of 240 patients who were considered to have “normal” Carpentier-Edwards Duraflex porcine bioprosthesis were evaluated (67). Of these, 178 (74%) had TTE Doppler imaging performed within the first week after MVR; complete hemodynamic data were available for 198 patients. For any given PHV size (range 25 to 32, there was a wide range of mean PHV gradient and PHV areas (cm2and cm2/m2) (Fig. 12).
Valuable and important study. Assuming that significant endothelialization and/or tissue in-growth had not occurred within 1 week of implantation, these data show that all PHVs of the same size, as stated by the manufacturer, do not have the same effective orifice area (valve size) when implanted in patients.
Very early structural valve deterioration of the bioprosthesis
Of 122 Medtronic Mosaic porcine valves implanted from 2001 to 2005 for AVR, 4 developed SVD (severe stenosis) necessitating PHV replacement at 3, 14, 19, and 44 months (68). “All 4 patients were aged more than 68 years at time of implant.”
Even in older patients, structural valve deterioration can occur very early after porcine PHV implantation.
Valve Prosthesis-Patient Mismatch (VP-PM)
Increases late mortality? a) After AVR. Yes
The index PHV area was determined in 2,576 patients (69). “After adjustment for other risk factors” at 12 years, severe VP-PM was associated with increased overall morality (p = 0.03) and CV mortality (p = 0.0006) (Fig. 13).Subgroups showed that mortality was increased in those younger than 70 years (p = 0.002) and also those with a body mass index of <30 kg/m2(p = 0.006); moderate VP-PM was associated with increased mortality in patients with LVEF <0.50 (p = 0.01).
Although the mortality in patients 70 years of age and older and with a body mass index ≥30 kg/m2was not significantly higher with severe VP-PM, the number of patients at risk were very few: 19 and 16, respectively, at the start of the study and 1 and 2 patients, respectively, at 12 years of follow-up.
b) After MVR. No, but possibly yes
A total of 2,440 patients had MVR between 1982 and 2002. PHV areas were divided into 3 subgroups of VP-PM. No subgroup was predictive of overall mortality, late mortality, or early mortality (70). However, pulmonary hypertension influenced mortality by severity of VP-PM (p = 0.03), and there was “an interaction between pulmonary hypertension and mild to moderate (p = 0.023) and severe (p = 0.03)” VP-PM.
Mitral VP-PM can cause pulmonary hypertension. Missing data (on LV end-diastolic and mean left atrial pressures, and pulmonary vascular resistance) both pre- and post-MVR would have allowed for a proper understanding of the role of LV diastolic dysfunction, VP-PM, and pulmonary vascular disease in pulmonary hypertension, which was a predictor of mortality.
Dr. Rahimtoola has received honoraria for educational lectures from American College of Cardiology Foundation, American College of Physicians, University of California Los Angeles, University of California Irvine, Cornell University, Creighton University, Thomas Jefferson University, Cedars-Sinai Medical Center, Harvard Medical School, University of Wisconsin, University of Hawaii, Cardiologists Association of Hong Kong, China, ATS, St. Jude Medical, Carbomedics, Merck, Pfizer, and Edwards LifeSciences.
- Received October 13, 2009.
- Revision received December 3, 2009.
- Accepted February 1, 2010.
- American College of Cardiology Foundation
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- Aortic Valve Stenosis (AS)
- Aortic Regurgitation (AR)
- Bicuspid AV (BAV)
- Mitral Stenosis (MS)
- Mitral Regurgitation
- Tricuspid Regurgitation (TR)
- Infective Endocarditis (IE)
- European Society of Cardiology's Guidelines on the Prevention, Diagnosis, and Treatment of IE (New Version 2009) (46)
- Transcatheter Valve Therapy (TVT)
- Prosthetic Heart Valves
- Valve Prosthesis-Patient Mismatch (VP-PM)