Diagnostic accuracy study of routine echocardiography for bicuspid aortic valve: a retrospective study and meta-analysis.

BACKGROUND: Transthoracic echocardiography (TTE) is the standard procedure to distinguish tricuspid aortic valve (TAV) from bicuspid aortic valve (BAV). Published studies assessed the accuracy of TTE for BAV under ideal conditions. Conversely, we aimed at assessing accuracy of TTE for BAV under routine conditions. METHODS: This retrospective, cross-sectional study of 216 adults included 132 men aged 62±14 years. Of these, 108 had BAV and 108 were age-matched individuals with TAV. All diagnoses were confirmed at surgery. We assessed TTE in two patient groups. First, in the (I) group of all 216 individuals, where we assessed accuracy for BAV according to the original diagnoses as documented by the primary investigators during original TTE examination. Second, we assessed accuracy for BAV according to expert re-evaluation in (II) all 158 TTE with availability of original recordings. Third, we performed a meta-analysis of published results on the accuracy of TTE for BAV according to PRISMA standards. RESULTS: Sensitivity, specificity and accuracy of (I) primary investigators was 46.3%, 97.2, and 71.8% as compared to (II) expert re-evaluation with 59.7%, 93%, and 77.8%, respectively. Sensitivity was significantly higher at re-evaluation (P<0.001). TTE at a non-tertiary care center (P=0.012), presence of aortic aneurysm (P=0.001) and presence of severe aortic valve calcification (P=0.003) predicted an inaccurate diagnosis of BAV. Conversely, meta-analysis of published TTE studies identified a pooled sensitivity of 87.7% and a pooled specificity of 88.3% for BAV. CONCLUSIONS: The current study shows that TTE yields almost ideal diagnostic accuracy when ideal investigators examine ideal patients. However, the study also shows that TTE yields suboptimal diagnostic accuracy under routine conditions. TTE in non-tertiary care settings, concomitant aortic aneurysm, and presence of severe aortic valve calcification predict an inaccurate diagnosis of BAV.

Mitral valve prolapse syndrome and MASS phenotype: Stability of aortic dilatation but progression of mitral valve prolapse.

BACKGROUND: Mitral valve prolapse syndrome (MVPS) and MASS phenotype (MASS) are Marfan-like syndromes that exhibit aortic dilatation and mitral valve prolapse. Unlike in Marfan syndrome (MFS), the presence of ectopia lentis and aortic aneurysm preclude diagnosis of MVPS and MASS. However, it is unclear whether aortic dilatation and mitral valve prolapse remain stable in MVPS or MASS or whether they progress like in MFS. METHODS: This retrospective longitudinal observational study examines clinical characteristics and long-term prognosis of 44 adults with MVPS or MASS (18 men, 26 women aged 38 ± 17 years) as compared with 81 adults with Marfan syndrome (MFS) with similar age and sex distribution. The age at final contact was 42 ± 15 years with mean follow-up of 66 ± 49 months. RESULTS: At baseline, ectopia lentis and aortic sinus aneurysm were absent in MVPS and MASS, and systemic scores defined by the revised Ghent nosology were lower than in MFS (all P < .001). Unlike in MFS, no individual with MVPS and MASS developed aortic complications (P < .001). In contrast, the incidence of endocarditis (P = .292), heart failure (P = .644), and mitral valve surgery (P = .140) was similar in all syndromes. Cox regression analysis identified increased LV end-diastolic (P = .013), moderate MVR (P = .019) and flail MV leaflet (P = .017) as independent predictors of mitral valve surgery. CONCLUSIONS: The study provides evidence that MVPS and MASS are Marfan-like syndromes with stability of aortic dilatation but with progression of mitral valve prolapse. Echocardiographic characteristics of mitral valve disease rather than the type of syndrome, predict clinical progression of mitral valve prolapse.

Blood transfusion is associated with impaired outcome after transcatheter aortic valve implantation.

OBJECTIVES: We sought to evaluate the relationship of blood transfusion after transcatheter aortic valve implantation (TAVI) and mid-term outcome to improve patient selection and periprocedural treatment. BACKGROUND: Increasing evidence suggests a negative influence of blood transfusion on outcomes of patients with cardiovascular diseases. While the adverse impact of bleeding events on survival has been documented after TAVI, data on the impact of postoperative blood transfusions are scarce. METHODS: TAVI was performed in 700 consecutive patients; 14.7% of TAVI patients suffered from bleeding or access site complications and were excluded from analysis to minimize confounding. Outcomes were analyzed with emphasis on blood transfusions and according to the Valve Academic Research Consortium definitions. Median follow-up duration was 364 days. Multivariable analyses were performed to identify predictors for transfusion and 1-year mortality. RESULTS: 33.0% of patients received blood transfusions after TAVI, irrespective of access choice. Blood transfusions were associated with a higher baseline risk profile (median logistic EuroSCORE 21.0 vs. 17.0%), increased rates of postoperative complications and impaired survival (21.2 vs. 36.1% all-cause 1-year mortality). Transfusion was an independent predictor of mortality at 1 year (OR 2.78 [CI 1.59-4.86]). Low body mass index (OR 0.94 [0.89-1.0]), low baseline hemoglobin (OR 0.39 [0.33-0.47]) and combined anticoagulation/antiplatelet therapy were identified as independent predictors of blood transfusion after TAVI. CONCLUSIONS: Blood transfusions were frequently required after TAVI even in the absence of overt bleeding or access site complications and were identified as an independent predictor of impaired mid-term outcome. Optimization of baseline factors, strict blood conservation strategies, and individualized antiplatelet or anticoagulant regimens may improve outcome after TAVI.

Single-centre experience with next-generation devices for transapical aortic valve implantation.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) has become an established procedure in patients with aortic stenosis and high surgical risk. Experience with first-generation transcatheter heart valves (THVs) is broad but limitations, e.g. paravalvular regurgitation, have been demonstrated. Much hope rests on the recently Conformité Européenne mark approved next-generation devices to improve results in these patients. However, apart from the initial approval studies, clinical data with these new devices are still scarce. We aimed to assess short-term outcomes of 200 consecutive patients who underwent transapical TAVI with next-generation THV at our institution. METHODS: Transapical TAVI was performed in 200 consecutive patients 80.5±6.7 years old (38.5% female) at high surgical risk (log EuroSCORE 20.2±16.5%). Devices implanted were the Engager (Medtronic, Inc., Minneapolis, MN, USA; n=50), JenaValve (JenaValve Technology, Munich, Germany; n=88) and Symetis Acurate (Symetis SA, Ecublens, Switzerland; n=62) THV that were selected by the heart team on an individual basis. Data at baseline, during the procedure and follow-up were analysed according to standardized Valve Academic Research Consortium end points. Median follow-up was 219 days. RESULTS: Implantation was successful in 96.5% of cases. Valve function improved significantly with an increase in effective orifice area from 0.8±0.4 to 1.8±0.3 cm2 and a reduction in mean transvalvalvular gradients from 34.0±17.0 to 11.2±5.4 mmHg. Paravalvular regurgitation was none or trace in 70.3% of patients, Grade 1 in 26.1%, and Grade 2 in 3.5%. No patients developed aortic regurgitation>Grade 2. Major access site complications occurred in 6.5%, major stroke in 1.5% and stage-3 kidney injury in 2.5% of patients. A permanent pacemaker was implanted in 20.5% of patients overall and in 8.0% for a complete heart block. At 30-day follow-up 72.8% of patients were in New York Heart Association class I or II (10.5% at baseline). Overall survival was 91.5% at 30 days and 73.9% at 1 year. CONCLUSIONS: In a real-world clinical setting, next-generation transapical THV yielded positive haemodynamic results. The incidence of relevant paravalvular regurgitation was scarce in this group and clinical outcomes were encouraging during short-term follow-up. Long-term follow-up is required to investigate the durability of these new devices.

The main pulmonary artery in adults: a controlled multicenter study with assessment of echocardiographic reference values, and the frequency of dilatation and aneurysm in Marfan syndrome.

BACKGROUND: Echocardiographic upper normal limits of both main pulmonary artery (MPA) diameters (MPA-d) and ratio of MPA to aortic root diameter (MPA-r) are not defined in healthy adults. Accordingly, frequency of MPA dilatation based on echocardiography remains to be assessed in adults with Marfan syndrome (MFS). METHODS: We enrolled 123 normal adults (72 men, 52 women aged 42 ± 14 years) and 98 patients with MFS (42 men, 56 women aged 39 ± 14 years) in a retrospective cross-sectional observational controlled study in four tertiary care centers. We defined outcome measures including upper normal limits of MPA-d and MPA-r as 95 quantile of normal persons, MPA dilatation as diameters > upper normal limits, MPA aneurysm as diameters >4 cm, and indication for surgery as MPA diameters >6 cm. RESULTS: MPA diameters revealed normal distribution without correlation to age, sex, body weight, body height, body mass index and body surface area. The upper normal limit was 2.6 cm (95% confidence interval (CI) =2.44-2.76 cm) for MPA-d, and 1.05 (95% CI = .86-1.24) for MPA-r. MPA dilatation presented in 6 normal persons (4.9%) and in 68 MFS patients (69.4%; P < .001), MPA aneurysm presented only in MFS (15 patients; 15.3%; P < .001), and no patient required surgery. Mean MPA-r were increased in MFS (P < .001), but ratios >1.05 were equally frequent in 7 normal persons (5%) and in 8 MFS patients (10.5%; P = .161). MPA-r related to aortic root diameters (P = .042), reduced left ventricular ejection fraction (P = .006), and increased pulmonary artery systolic pressures (P = .040). No clinical manifestations of MFS and no FBN1 mutation characteristics related to MPA diameters. CONCLUSIONS: We established 2.6 cm for MPA-d and 1.05 for MPA-r as upper normal limits. MFS exhibits a high prevalence of MPA dilatation and aneurysm. However, patients may require MPA surgery only in scarce circumstances, most likely because formation of marked MPA aneurysm may require LV dysfunction and increased PASP.

Valve-in-valve implantation of a novel and small self-expandable transcatheter heart valve in degenerated small surgical bioprostheses: the Hamburg experience.

BACKGROUND: Transcatheter valve-in-valve (VIV) implantation has emerged as a novel treatment option in patients with degenerated aortic bioprostheses and high surgical risk. However, VIV implantation in small aortic bioprostheses using first generation TAVI devices has frequently resulted in high postprocedural gradients and small effective orifice areas. Recently, an updated version of the self-expandable Medtronic CoreValve prosthesis, which is particularly suitable for small aortic annuli, has become available. We report on the feasibility and early results of VIV implantation using this novel device in a series of patients with degenerated small aortic bioprostheses. METHODS AND RESULTS: 16 patients from two Hamburg hospitals (age range 72-92 years) underwent implantation of a 23-mm CoreValve Evolut (Medtronic, Minneapolis, MN, USA) transcatheter heart valve into failing aortic bioprostheses with internal diameters below 21 mm. All patients were considered high risk for surgical aortic valve replacement after evaluation by an interdisciplinary heart team mean (logistic EuroSCORE range 9.0-88%). Implantation was successful without relevant remaining aortic regurgitation or signs of stenosis and a marked reduction in postprocedural gradientswas observed in 14 out of 16 patients. The mean gradient was reduced from from 34 mm Hg (SEM 10 mm Hg) to 14 mm Hg (SEM 6 mm Hg). No major device- or procedure-related adverse events occurred during 30-day follow up and clinical improvement was observed. CONCLUSIONS: Failing aortic bioprostheses with small internal diameters continue to be a challenging pathology for TAVI due to the risk of high residual gradients and small aortic orifice areas. This report provides first evidence that the 23-mm CoreValve Evolut, a novel self-expanding prosthesis, provides an improved treatment option in these specific patients due to its low profile which resulted in promising early results. © 2013 Wiley Periodicals, Inc.

The challenge of valve-in-valve procedures in degenerated Mitroflow bioprostheses and the advantage of using the JenaValve transcatheter heart valve.

AIMS: Recently, the feasibility of valve-in-valve procedures using current first-generation transcatheter heart valves (THV) in cases of structural valve degeneration has been reported as an alternative to conventional open repeat valve replacement. By design, certain biological valve xenografts carry a high risk of coronary ostia occlusion due to lateral displacement of leaflets after valve-in-valve procedures. In the present report we aimed to prove feasibility and safety of transapical valve-in-valve implantation of the JenaValve THV in two cases of degenerated Mitroflow bioprostheses. METHODS AND RESULTS: We herein report two cases of successful transapical valve-in-valve procedures using a JenaValve THV implanted in Sorin Mitroflow bioprostheses for structural valve degeneration. Both patients were alive and in good clinical condition at 30 days from the procedure. However, increased transvalvular gradients were noted in both cases. CONCLUSIONS: Transcatheter valve-in-valve implantation of a JenaValve THV is a valid alternative for patients with degenerated Mitroflow bioprostheses of sufficient size and in the presence of short distances to the coronary ostia who are too ill for conventional repeat open heart surgery. Increased pressure gradients have to be expected and weighed against the disadvantages of other treatment options when planning such a procedure.

Transapical transcatheter aortic valve implantation without prior balloon aortic valvuloplasty: feasible and safe.

OBJECTIVES: Currently, preimplant balloon aortic valvuloplasty (BAV) is considered a prerequisite for successful subsequent transapical transcatheter aortic valve implantation (TA-TAVI) using balloon-expandable devices. However, cerebral embolization has been shown to originate at least in part from BAV procedures. Omitting BAV may therefore reduce neurological events after TAVI and facilitate the procedure while yielding non-inferior haemodynamic and clinical outcomes. METHODS: From May 2011 through December 2012, a total of 50 consecutive patients were treated by TA-TAVI without preimplant BAV (TA-TAVI(-BAV), study group) using the Edwards Sapien XT device (54% male, age 78 ± 8 years, logistic European System for Cardiac Operative Risk Evaluation I 21 ± 14%). Data were prospectively entered into a dedicated database, retrospectively analysed and compared with a consecutive series of conventional TA-TAVI using the same device (control group, n = 50). Reporting of data followed Valve Academic Research Consortium definitions. RESULTS: Overall device success rate was 94% (47/50) and 86% (43/50) in study and control groups, respectively (P = 0.32). Procedure time was similar in the study group compared with the control group (88 ± 31 vs 91 ± 25 min, P = 0.60), while significantly less contrast was used (138 ± 68 vs 183 ± 78 ml, P < 0.001). Post-procedural peak and mean transvalvular gradients were 16 ± 7 and 8 ± 3 mmHg, respectively, in the study group with similar values in the control group (19 ± 9 and 9 ± 5 mmHg, P = 0.08 and P = 0.09, respectively). Residual paravalvular leakage (PVL) grade 2 was present in 2 and 8% in study and control groups, respectively (P = 0.36), with no PVL >grade 2 in any patient. Rates of 30-day mortality and periprocedural stroke were 4 and 10% (P = 0.44) and 2 and 6% (P = 0.62), respectively. CONCLUSIONS: TA-TAVI(-BAV) is feasible and safe and has become ur default technique for patients allocated to TA-TAVI with balloon-expandable devices. This approach resulted in less contrast agent used and facilitated the procedure without compromising valve performance. Possible beneficial effects of this approach on the incidence of cerebrovascular events, other periprocedural complications or haemodynamic valve performance need to be verified in larger patient numbers before general recommendations can be made.

Predictors and outcomes after transcatheter aortic valve implantation using different approaches according to the valve academic research consortium definitions.

OBJECTIVES: We report the results of a large single-center study evaluating predictors and outcomes after transcatheter aortic valve implantation (TAVI) with different devices and access routes according to the Valve Academic Research Consortium (VARC). BACKGROUND: The widespread adoption of TAVI warrants a systematic analysis of outcomes. Only few comprehensive data exist comparing different approaches as selected by a heart team. METHODS: TAVI was performed in 326 consecutive patients (mean age 80.6 ± 7.1 years, 55.5% female) at high risk for surgery with balloon-expandable and self-expanding devices through transfemoral or transapical access. Data were analyzed according to VARC endpoints; predictors of mortality were identified. RESULTS: All-cause mortality was 10.1% (30 days) and 29.9% (1 year) overall and comparable with regard to valve or access choice (P = 0.295) despite different risk profiles at baseline. Device success and 30-day safety endpoints were achieved in 87.1 and 21.2%. Myocardial infarction [hazard ratio (HR) 6.52], stage-2 and -3 acute kidney injury (HR 2.52 and 6.80) and major access site complications (HR 1.96) were independent predictors of 1-year all-cause mortality. Device success had a protective effect (HR 0.58). Baseline predictors included body mass index <20 kg/m(2) (HR 3.20), NYHA class IV (HR 1.87), left ventricular ejection-fraction <30% (HR 2.30), higher STS-PROM scores (HR 1.05 per percent), and age (group 75-85 years, HR 0.47). CONCLUSIONS: Comparable results were achieved with different devices and access routes in a heart team approach. Baseline and perioperative predictors of all-cause mortality were identified, contributing to the refinement of patient and device selection criteria for TAVI.

A heart team's perspective on interventional mitral valve repair: percutaneous clip implantation as an important adjunct to a surgical mitral valve program for treatment of high-risk patients.

OBJECTIVE: Surgical mitral valve repair carries an elevated perioperative risk in the presence of severely reduced ventricular function and relevant comorbidities. We sought to assess the feasibility of catheter-based mitral valve repair using a clip-based percutaneous edge-to-edge repair system in selected patients at high surgical risk with mitral regurgitation grade 3 or worse. METHODS: Between 2002 and January 2011, 202 consecutive patients without prior mitral valve surgery (age 75 ± 9 years; 63% were male) with symptomatic functional (65%), degenerative (27%), or mixed (8%) mitral regurgitation were treated with a percutaneous clip system for approximation of the anterior and posterior mitral leaflets. Risk for mitral valve surgery was considered high in terms of a mean logistic European System for Cardiac Operative Risk Evaluation of 44% (range, 21%-54%). Preprocedural left ventricular ejection fraction was 35% or less in 36% of patients. An interdisciplinary heart team of cardiologists and cardiac surgeons discussed all patients. RESULTS: Percutaneous clip implantation was successful in 186 patients (92%). Patients were treated with 1 clip (n = 125; 62%), 2 clips (n = 64; 32%), or 3 or more clips (n = 7; 3%). Reduction in mitral regurgitation from pre- to postprocedure was significant (P < .0001) and remained stable within the first 12 months in the majority of patients. Thirty-day mortality was 3.5% (7/202 patients). Hospital stay was 12 ± 10 days, and median intensive care unit stay was 1 day (range, 0-45 days). Eleven patients required surgical valve repair/replacement at a median of 38 days (0-468 days) after percutaneous clip implantation. CONCLUSIONS: Clip-based percutaneous mitral valve repair is a safe, low-risk, and effective therapeutic option in symptomatic patients with a high risk for surgery and does not exclude later surgical repair.

Impact of patient-prosthesis mismatch after transcatheter aortic valve-in-valve implantation in degenerated bioprostheses.

OBJECTIVE: Transcatheter valve-in-valve implantation is evolving as an alternative to reoperative valve replacement in high-risk patients with degenerated bioprostheses. Nevertheless, hemodynamic performance is limited by the previously implanted xenograft. We report our experience with patient-prosthesis mismatch (PPM) after valve-in-valve implantation in the aortic position. METHODS: Eleven patients (aged 79.3 ± 6.1 years) received transapical implantation of a balloon-expandable pericardial heart valve into a degenerated bioprosthesis (size, 23.9 ± 1.6 mm; range, 21-27 mm) in the aortic position. All patients were considered high risk for surgical valve replacement (logistic European System for Cardiac Operative Risk Evaluation, 31.8% ± 24.1%). Severe PPM was defined as an indexed effective orifice area less than 0.65 cm(2)/m(2), determined by discharge echocardiography. RESULTS: Severe PPM was evident in 5 patients (group 1) and absent in 6 patients (group 2). Mean transvalvular gradients decreased from 29.2 ± 15.4 mm Hg before implantation to 21.2 ± 9.7 mm Hg at discharge (group 1) and from 28.2 ± 9.0 mm Hg before implantation to 15.2 ± 6.5 mm Hg at discharge (group 2). Indexed effective orifice area increased from 0.5 ± 0.1 cm(2)/m(2) to 0.6 ± 0.1 cm(2)/m(2) and from 0.6 ± 0.3 cm(2)/m(2) to 0.8 ± 0.3 cm(2)/m(2). Aortic regurgitation decreased from grade 2.0 ± 1.1 to 0.4 ± 0.5 overall. No differences in New York Heart Association class improvement or survival during follow-up were observed. One patient required reoperation for symptomatic PPM 426 days after implantation. CONCLUSIONS: Valve-in-valve implantation can be performed in high-risk surgical patients to avoid reoperation. However, PPM frequently occurs, making adequate patient selection crucial. Small bioprostheses (<23 mm) should be avoided. Implantation into 23-mm xenografts can be recommended only for patients with a body surface area less than 1.8 m(2). Larger prostheses seem to carry a lower risk for PPM. Although no delay in clinical improvement was seen at short-term, 1 PPM-related surgical intervention raises concern regarding long-term performance.

Predictors of outcome of mitral valve prolapse in patients with the Marfan syndrome.

Mitral valve prolapse has a prevalence of 2% to 3% in the general population, with adverse outcomes such as mitral valve regurgitation (MVR), heart failure, and endocarditis. Predictors of outcomes are used in idiopathic mitral valve prolapse for the timing of surgery, but such predictors are unknown in Marfan syndrome. Therefore, a population-based cohort study of 112 patients (49 male, 63 female; mean age 34 ± 15 years) with classic Marfan syndrome and mitral valve prolapse with moderate or less MVR at baseline was conducted. During 4.6 ± 3.6 years of follow-up, progression of MVR was observed in 41 patients and valve-related events, which comprised mitral valve endocarditis (7 events), heart failure (5 events), and mitral valve surgery (25 events), were observed in 31 patients. Multivariate Cox proportional-hazards regression analysis identified a flail mitral leaflet (hazard ratio [HR] 3.262, 95% confidence interval [CI] 1.406 to 7.566, p = 0.006) and increased indexed end-systolic left ventricular diameters (HR 1.113, 95% CI 1.043 to 1.188, p = 0.001) as independent predictors of progression of MVR. Similarly, mitral valve-related events were independently predicted by a flail mitral leaflet (HR 5.343, 95% CI 2.229 to 12.808, p <0.001), and mild (HR 14.336, 95% CI 1.873 to 109.755, p = 0.01) or moderate (HR 16.849, 95% CI 2.205 to 128.76, p = 0.006) degree of MVR. Conversely, aortic dilatation, dural ectasia, and sporadic mode of inheritance were not associated with outcome. In conclusion, the same clinical determinants that predict outcomes in idiopathic mitral valve prolapse also predict outcomes in mitral valve prolapse associated with Marfan syndrome.

Frequency of sleep apnea in adults with the Marfan syndrome.

Obstructive and central sleep apneas are treatable disorders, which contribute to cardiovascular morbidity in older adults. Younger adults with Marfan syndrome may also be at risk for sleep apnea, but the relation between cardiovascular complications and sleep apnea is unknown. We used MiniScreen8 portable monitoring devices for polygraphy in 68 consecutive adults with Marfan syndrome (33 men, 35 women, 41 +/- 14 years old) to investigate frequency of sleep apnea and its relation to cardiovascular morbidity. The apnea-hypopnea index (AHI) was 6 to 15/hour in 14 subjects (mild sleep apnea, 21%), and AHI was >15/hour in 7 subjects (moderate or severe sleep apnea, 10%). Among established risk factors for sleep apnea, only older age (Spearman rho = 0.35, p = 0.004) and body mass index (rho = 0.26, p = 0.03) were associated with increased AHI. Of all cases of apnea, 12 +/- 27 were obstructive, 11 +/- 25 central, and 3 +/- 9 mixed. AHI was associated with decreased left ventricular ejection fraction (rho = -0.33, p = 0.01), increased N-terminal pro-brain natriuretic peptide levels (rho = 0.35, p = 0.004), enlarged descending aortic diameters (rho = 0.44, p = 0.001), atrial fibrillation (phi = 0.43, p = 0.002), and mitral valve surgery (phi = 0.34, p = 0.02). Of these, left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide levels, atrial fibrillation, and mitral valve surgery were associated with AHI independently of age and body mass index. We found similar associations with oxygen desaturation index. In conclusion, sleep apnea exhibits increased frequency in Marfan syndrome and is not predicted by classic risk factors. Obstructive and central sleep apneas may relate to cardiovascular disease variables.

Augmentation index relates to progression of aortic disease in adults with Marfan syndrome.

BACKGROUND: Noninvasive applanation tonometry (APT) is useful to assess aortic stiffness and pulse wave reflection. Moreover, APT can predict outcome in many conditions such as arterial hypertension. In this study, we test whether APT measurements relate to progression of aortic disease in Marfan syndrome (MFS). METHODS: We performed APT in 50 consecutive, medically treated adults with MFS (19 men and 31 women aged 32 +/- 13 years), who had not undergone previous cardiovascular surgery. During 22 +/- 16 months of follow-up, 26 of these patients developed progression of aortic disease, which we defined as progression of aortic root diameters >or=5 mm/annum (18 individuals), aortic surgery >or=3 months after APT (seven individuals), or onset of acute aortic dissection any time after APT (one individual). RESULTS: Univariate Cox regression analysis suggested an association of aortic disease progression with age (P = 0.001), total cholesterol levels (P = 0.04), aortic root diameter (P = 0.007), descending aorta diameter (P = 0.01), aortic root ratio (P = 0.02), and augmentation index (AIx@HR75; P < 0.006). Multivariate Cox regression analysis confirmed an independent impact on aortic disease progression exclusively for baseline aortic root diameters (hazard ratio = 1.347; 95% confidence interval (CI) 1.104-1.643; P = 0.003) and AIx@HR75 (hazard ratio = 1.246; 95% CI 1.029-1.508; P = 0.02). In addition, Kaplan-Meier survival curve analysis illustrated significantly lower rates of aortic root disease progression both with lower AIx@HR75 (P = 0.025) and with lower pulse wave velocity (PWV) values (P = 0.027). CONCLUSIONS: We provide evidence that APT parameters relate to aortic disease progression in medically treated patients with MFS. We believe that APT has a potential to improve risk stratification in the clinical management of MFS patients.

Tissue Doppler imaging identifies myocardial dysfunction in adults with Marfan syndrome.

BACKGROUND: Successful prevention of aortic complications has lead to improved survival of Marfan syndrome (MFS). With increasing age, however, ventricular arrhythmia and heart failure are emerging as life-threatening manifestations of myocardial dysfunction. HYPOTHESIS: We sought to investigate whether echocardiography with tissue Doppler imaging (TDI) identifies myocardial dysfunction in adults with MFS. METHODS: We performed two-dimensional (2-D) and Doppler echocardiography with TDI in 141 individuals with suspected MFS and competent heart valves, including 28 persons with MFS who had not undergone surgery and 86 healthy controls without inherited connective tissue disorders. RESULTS: Demographic profile, 2-D, mitral and pulmonary venous flow indices, and left ventricular ejection fractions were similar in both groups. Conversely, isovolumic relaxation time (p < 0.001) and deceleration time of E velocity (p = 0.005) were longer, and atrial reversal velocities (p = 0.02), and systolic and early diastolic TD velocities were slower in MFS than in controls (p = 0.01). Multiple linear regression analysis excluded association of reduced systolic and early diastolic TD velocities with mitral valve prolapse or other clinical or echocardiographic features of MFS. CONCLUSIONS: Our study identifies reduced systolic and early diastolic TD velocities in adults with MFS. Further studies are mandatory to elucidate whether TD velocities predict arrhythmia and heart failure in MFS.

Emergency stent-graft placement in thoracic aortic dissection and evolving rupture.

BACKGROUND: Even with rapid diagnosis and effective medical treatment mortality in type B aortic dissection with evidence of extraaortic leakage of blood remains high. Considering a mortality rate of 29% to 50% associated with emergency surgical repair, the concept of endovascular stent-graft placement may become a life-saving option in impending or evolving rupture by endovascular sealing of the entry tear and subsequent abortion of leakage. METHODS: The concept was tested by comparing short-term and 1-year outcomes of 11 patients after emergency endovascular stent-graft placement with historic-matched control patients subjected to conventional therapy. All patients had acute type B dissection complicated by loss of blood into periaortic spaces. RESULTS: Emergency stent-graft placement was successful without periprocedural morbidity, aborted leakage, and ensured reconstruction of the dissected aorta; at a mean follow-up of 15 +/- 6 months no death had occurred in the stent-graft group whereas four patients had died with conventional treatment (p < 0.05). CONCLUSION: With appropriate logistics and expertise, type B aortic dissection with leakage and evolving rupture may benefit from nonsurgical reconstruction of the dissected segment by endovascular stent grafts.

Value of intravascular ultrasound for endovascular stent-graft placement in aortic dissection and aneurysm.

BACKGROUND: Endovascular stent-graft placement is a new concept for the treatment of aortic dissection and aneurysm. Intravascular ultrasound (IVUS) with established diagnostic features may be instrumental in guiding endovascular procedures. METHODS: We performed IVUS and digital angiography before, during, and after implantation of 47 stent grafts in 40 patients with Stanford type B dissection (26 patients, 28 stent grafts), thoracic aneurysm (9 patients, 11 stent grafts), and abdominal aneurysm (5 patients, 8 stent grafts). RESULTS: IVUS could clearly identify the aortic anatomy and differentiate between true and false lumen in all cases of dissection. In four patients with type B dissection extending from the thoracic to the abdominal aorta the true lumen was exclusively identified by IVUS, and thus, essential for safe execution of the procedure. In another patient stent-graft placement in the aorta was optimized by covering a second entry detected by IVUS, but undetected by angiography. The site of stent implantation, the true and false lumen, as well as entry and reentry were always identified in both thoracic and abdominal aorta. In comparison with angiography, IVUS information led to additional balloon molding due to incomplete stent apposition in seven cases. CONCLUSIONS: As an adjunctive imaging modality IVUS is likely to improve stent-graft placement in aortic type B dissection, especially in patients with abdominal extension.

Intramural hematoma of the aorta: predictors of progression to dissection and rupture.

BACKGROUND: Aortic intramural hematoma (IMH) is a variant of overt aortic dissection. The predictors of progression of IMH to dissection and rupture are still unknown, and strategies for management are not established. METHODS AND RESULTS: A multicenter study was conducted comprising 66 patients with IMH and hospital admission

Angiotensin-converting enzyme insertion/deletion polymorphism does not influence the restenosis rate after coronary stent implantation.

BACKGROUND: Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relationship between the ACE gene polymorphism and the restenosis rate after coronary stent implantation. METHODS: As a substudy of the optimization with intracoronary ultrasound (ICUS) to reduce stent restenosis (OPTICUS) study, we analyzed ACE serum levels and the ACE gene polymorphism in 154 patients at 9 different centers. All patients underwent elective coronary stent implantation in a stenosis of a major coronary vessel. Balloon inflations were repeated until a satisfactory result was achieved in on-line quantitative coronary angiography or ICUS fulfilling the OPTICUS study criteria. After follow-up of 6 months, all patients underwent reangiography under identical projections as the baseline procedure. A blinded quantitative analysis of the initial procedure as well as the follow-up examinations were performed by an independent core laboratory. ACE gene polymorphism and ACE serum activity were measured at the 6-month follow-up in a double-blinded setting. RESULTS: With respect to the ACE gene polymorphism, there were three subgroups: DD genotype (48 patients), ID (83 patients) and II (23 patients). The subgroups did not differ in regard to age, gender, extent of coronary artery disease, stenosis length, initial degree of stenosis or degree of stenosis after stent implantation. In all, 39 patients (25.3%) had significant restenosis: 12 DD patients (25.0%), 18 ID patients (21.7%) and 9 II patients (39.1%) (odds ratio 2.164, 95% confidence interval 0.853-5.493). We obtained the following results for ACE serum levels: 0.53 micromol/l/s in the DD subgroup, 0.29 micromol/l/s in the ID subgroup and 0.09 micromol/l/s in the II subgroup (p < 0.001). Multivariate logistic regression analysis of the influence of ACE gene polymorphism on the restenosis rate after coronary stent implantation adjusted for lesion length (>12 mm), ACE inhibitor or hydroxymethylglutaryl coenzyme A reductase (CSE) inhibitor treatment, age, male gender, diabetes mellitus, hypertension, high cholesterol, family history, smoking and three-vessel disease did not uncover any statistic significance. CONCLUSIONS: In contrast to other study groups, we were unable to disclose that the DD polymorphism of the ACE gene was associated with a higher rate of restenosis after coronary stent implantation in this multicenter study. In addition, patients with higher ACE serum levels did not show a higher restenosis rate in this trial. We conclude that the pathogenesis of restenosis is a multifactorial process involving various genetic and nongenetic factors.

Predictors of aneurysmal formation after surgical correction of aortic coarctation.

OBJECTIVES: We sought to identify the predictors of aneurysmal formation after surgical correction of aortic coarctation. BACKGROUND: In 9% of patients, aneurysms develop late after corrective surgery of coarctation of the aorta, with a 36% mortality rate if left untreated. However, the predictors of postsurgical aneurysmal formation are unknown. METHODS: Of 25 aortic aneurysms requiring corrective surgery 152 +/- 78 months after the initial coarctation repair, 8 were located in the ascending aorta (type A) and 17 at the site of previous repair (local type). Seventy-four patients without progression of the aortic diameter within 189 +/- 71 months after coarctation repair were used for categorical data analysis in an attempt to identify the predictors of postsurgical aneurysmal formation. RESULTS: Advanced age at coarctation repair (p = 0.004) and patch graft technique (p < 0.0005) independently predicted local aneurysmal formation. Type A aneurysm was univariately associated with the presence of a bicuspid aortic valve (p = 0.02), advanced age at coarctation repair (p = 0.044) and a high preoperative peak systolic pressure gradient of 74 +/- 21 mm Hg (p = 0.041). Conversely, multivariate analysis confirmed only the presence of a bicuspid aortic valve (p = 0.015) as an independent predictor of type A aneurysm. Receiver operating characteristic curve analysis revealed that 72% of patients with a postsurgical aneurysm had an operation at age 13.5 years or more, whereas 69% with no postsurgical aneurysm had an operation at a younger age. CONCLUSIONS: Use of the patch graft technique and late correction of coarctation can predict aneurysmal formation at the site of coarctation repair, although patients with a bicuspid aortic valve may be at risk for an aneurysm developing in the ascending aorta, particularly after late repair of aortic coarctation with high preoperative pressure gradients.