Optical Coherence Tomography Assessment in Patients Treated With Rotational Atherectomy Versus Modified Balloons: PREPARE-CALC OCT.

[Figure: see text].

Impact of Calcified Lesion Complexity on the Success of Percutaneous Coronary Intervention With Upfront High-Speed Rotational Atherectomy or Modified Balloons - A Subgroup-Analysis From the Randomized PREPARE-CALC Trial.

BACKGROUND/PURPOSE: In the randomized PREPARE-CALC trial, lesion preparation of calcified lesions with upfront rotational atherectomy (RA) prior to drug-eluting stent (DES) implantation resulted in higher acute success as compared to a provisional modified balloon (MB) strategy. We aimed to investigate the impact of calcified lesion complexity on the treatment effect with either MB or RA. METHODS/MATERIALS: Two hundred patients were randomized to lesion preparation with either MB or RA. The study population was stratified according to lesion complexity into at least one type-C lesion or into exclusively non-type-C lesions. Endpoints were strategy success, need for bail-out RA, acute lumen gain, and late lumen loss (LLL) at 9 months. RESULTS: In total, 143 patients were graded as type-C (45% patients were allocated to MB), whereas 57 patients were graded as non-type-C (61% patients were allocated to MB). In patients with at least one type-C lesion, strategy success with RA was higher than with MB (97% vs 72%, p < 0.001), but superiority of RA was not observed in patients with non-type-C lesions (100% vs 97%, p = 1.00; pinteraction = 0.001). The need for bail-out RA was higher in patients with type-C lesions (n = 15) as compared with non-type-C lesions (n = 1). Acute lumen gain, LLL, and target lesion revascularization at 9 months were not dependent on lesion complexity and upfront lesion preparation strategy. CONCLUSIONS: In patients with calcified non-type-C lesions, the treatment strategy with RA or MB before DES implantation results in comparable success rates, whereas in type-C lesions upfront RA appears to be the superior upfront strategy.

Revascularisation or medical therapy in elderly patients with acute anginal syndromes: the RINCAL randomised trial.

BACKGROUND: Historically the elderly have been under-represented in non-ST-elevation myocardial infarction (NSTEMI) management trials. AIMS: The aim of this trial was to demonstrate that an intervention-guided strategy is superior to optimal medical therapy (OMT) alone for treating NSTEMI in elderly individuals. METHODS: Patients (≥80 years, chest pain, ischaemic ECG, and elevated troponin) were randomised 1:1 to an intervention-guided strategy plus OMT versus OMT alone. The primary endpoint was a composite of all-cause mortality and non-fatal myocardial reinfarction at 1 year. Ethics approval was obtained by the institutional review board of every recruiting centre. RESULTS: From May 2014 to September 2018, 251 patients (n=125 invasive vs n=126 conservative) were enrolled. Almost 50% of participants were female. The trial was terminated prematurely due to slow recruitment. A Kaplan-Meier estimate of event-free survival revealed no difference in the primary endpoint at 1 year (invasive 18.5% [23/124] vs conservative 22.2% [28/126]; p=0.39). No significant difference persisted after Cox proportional hazards regression analysis (hazard ratio 0.79, 95% confidence interval 0.45-1.35; p=0.39). There was greater freedom from angina at 3 months (p<0.001) after early intervention but this was similar at 1 year. Both non-fatal reinfarction (invasive 9.7% [12/124] vs conservative 14.3% [18/126]; p=0.22) and unplanned revascularisation (invasive 1.6% [2/124] vs conservative 6.4% [8/126]; p=0.10) occurred more frequently in the OMT alone cohort. CONCLUSIONS: An intervention-guided strategy was not superior to OMT alone to treat very elderly NSTEMI patients. The trial was underpowered to demonstrate this definitively. Early intervention resulted in fewer cases of reinfarction and unplanned revascularisation but did not improve survival.

5-Year Outcomes After TAVR With Balloon-Expandable Versus Self-Expanding Valves: Results From the CHOICE Randomized Clinical Trial.

OBJECTIVES: The purpose of this study was to evaluate clinical and echocardiographic outcome data of the CHOICE (Randomized Comparison of Transcatheter Heart Valves in High Risk Patients with Severe Aortic Stenosis: Medtronic CoreValve Versus Edwards SAPIEN XT) trial at 5 years. BACKGROUND: The CHOICE trial was designed to compare device performance of a balloon-expandable (BE) transcatheter heart valve (THV) versus a self-expanding (SE) THV. METHODS: The CHOICE trial is an investigator-initiated trial that randomized 241 high-risk patients with severe symptomatic aortic stenosis and an anatomy suitable for treatment with both BE and SE THVs to transfemoral transcatheter aortic valve replacement with either device. The primary endpoint was device success. Patients were followed up to 5 years, with assessment of clinical outcomes, and echocardiographic evaluation of valve function and THV durability. RESULTS: After 5 years, there were no statistically significant differences between BE and SE valves in the cumulative incidence of death from any cause (53.4% vs. 47.6%; p = 0.38), death from cardiovascular causes (31.6% vs. 21.5%; p = 0.12), all strokes (17.5% vs. 16.5%; p = 0.73), and repeat hospitalization for heart failure (28.9% vs. 22.5%; p = 0.75). SE patients had larger prosthetic valve area (1.6 ± 0.5 cm2 vs. 1.9 ± 0.5 cm2; p = 0.02) with a lower mean transprosthetic gradient (12.2 ± 8.7 mm Hg vs. 6.9 ± 2.7 mm Hg; p = 0.001) at 5 years. No differences were observed in the rates of paravalvular regurgitation. Clinical valve thrombosis occurred in 7 BE patients (7.3%) and 1 SE patient (0.8%; p = 0.06), and moderate or severe structural valve deterioration in 6 BE patients (6.6%) and no SE patient (0%; p = 0.018). The rate of bioprosthetic valve failure was low and not significantly different between both groups (4.1% vs. 3.4%; p = 0.63). CONCLUSIONS: Five-year follow-up of patients in the CHOICE trial revealed clinical outcomes after transfemoral transcatheter aortic valve replacement with early-generation BE and SE valves that were not statistically significantly different, with limited statistical power. Forward flow hemodynamics were significantly better with the SE valve. Moderate or severe structural valve deterioration was uncommon but occurred more frequently with the BE valve. (A Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: The CHOICE Trial [CHOICE]; NCT01645202).

High-Speed Rotational Atherectomy Versus Modified Balloons Prior to Drug-Eluting Stent Implantation in Severely Calcified Coronary Lesions.

BACKGROUND: Balloon dilatation or debulking seems to be essential to allow successful stent implantation in calcified coronary lesions. Compared with standard balloon predilatation, debulking using high-speed rotational atherectomy (RA) is associated with higher initial procedural success albeit with higher in-stent late lumen loss at intermediate-term follow-up. Whether modified (scoring or cutting) balloons (MB) could achieve similar procedural success compared with RA is not known. In addition, whether new-generation drug-eluting stents could counterbalance the excessive neointimal proliferation triggered by RA remains to be determined. METHODS AND RESULTS: We randomly assigned patients with documented myocardial ischemia and severely calcified native coronary lesions undergoing percutaneous coronary intervention to a strategy of lesion preparation using MB or RA followed by drug-eluting stent implantation. Stenting was performed using a third-generation sirolimus-eluting stent with a bioabsorbable polymer. The trial had 2 primary end points: strategy success (defined as successful stent delivery and expansion with attainment of <20% in-stent residual stenosis in the presence of TIMI [Thrombolysis in Myocardial Infarction] 3 flow without crossover or stent failure; powered for superiority) and in-stent late lumen loss at 9 months (powered for noninferiority). Two hundred patients were enrolled at 2 centers in Germany (n=100 in each treatment group). The mean age of the study population was 74.9±7.0 years; 76% were men, and 33.5% had diabetes mellitus. Strategy success was significantly more common in the RA group (81% versus 98%; relative risk of failure with an MB- versus RA-based strategy, 9.5; 95% CI, 2.3-39.7; P=0.0001), but mean fluoroscopy time was longer (19.6±13.4 versus 23.9±12.2 minutes; P=0.03). At 9 months, mean in-stent late lumen loss was 0.16±0.39 mm in the MB group and 0.22±0.40 mm in the RA group ( P=0.21, P=0.02 for noninferiority). Target lesion revascularization (7% versus 2%; P=0.17), definite or probable stent thrombosis (0% versus 0%; P=1.00), and target vessel failure (8% versus 6%; P=0.78) were low and not significantly different between the MB and RA groups. CONCLUSIONS: Lesion preparation with upfront RA before drug-eluting stent implantation is feasible in nearly all patients with severely calcified coronary lesions, is more commonly successful as a primary strategy compared with MB, and is not associated with excessive late lumen loss. A strategy of provisional MB remains feasible, safe, and effective as long as bailout RA is readily available and may offer the advantages of compatibility with smaller sized catheters and less irradiation. Both strategies are associated with excellent clinical outcome at 9 months. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02502851.

1-Year Outcomes After Transcatheter Aortic Valve Replacement With Balloon-Expandable Versus Self-Expandable Valves: Results From the CHOICE Randomized Clinical Trial.

BACKGROUND: The use of a balloon-expandable transcatheter heart valve previously resulted in a greater rate of device success compared with a self-expandable transcatheter heart valve. OBJECTIVES: The aim of this study was to evaluate clinical and echocardiographic outcome data at longer term follow-up. METHODS: The investigator-initiated trial randomized 241 high-risk patients with symptomatic severe aortic stenosis and anatomy suitable for treatment with both balloon- and self-expandable transcatheter heart valves to transfemoral transcatheter aortic valve replacement with either device. Patients were followed-up for 1 year, with assessment of clinical outcomes and echocardiographic evaluation of valve function. RESULTS: At 1 year, the rates of death of any cause (17.4% vs. 12.8%; relative risk [RR]: 1.35; 95% confidence interval [CI]: 0.73 to 2.50; p = 0.37) and of cardiovascular causes (12.4% vs. 9.4%; RR: 1.32; 95% CI: 0.63 to 2.75; p = 0.54) were not statistically significantly different in the balloon- and self-expandable groups, respectively. The frequencies of all strokes (9.1% vs. 3.4%; RR: 2.66; 95% CI: 0.87 to 8.12; p = 0.11) and repeat hospitalization for heart failure (7.4% vs. 12.8%; RR: 0.58; 95% CI: 0.26 to 1.27; p = 0.19) did not statistically significantly differ between the 2 groups. Elevated transvalvular gradients during follow-up were observed in 4 patients in the balloon-expandable group (3.4% vs. 0%; p = 0.12); all were resolved with anticoagulant therapy, suggesting a thrombotic etiology. More than mild paravalvular regurgitation was more frequent in the self-expandable group (1.1% vs. 12.1%; p = 0.005). CONCLUSIONS: Despite the higher device success rate with the balloon-expandable valve, 1-year follow-up of patients in CHOICE (Randomized Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: Medtronic CoreValve Versus Edwards SAPIEN XT Trial), with limited statistical power, revealed clinical outcomes after transfemoral transcatheter aortic valve replacement with both balloon- and self-expandable prostheses that were not statistically significantly different. (A Comparison of Transcatheter Heart Valves in High Risk Patients With Severe Aortic Stenosis: The CHOICE Trial; NCT01645202).

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of late graft failure after lung transplantation. The objective was to determine whether de novo donor human leukocyte antigen (HLA)-specific antibodies (DSA) are associated with the development of BOS or patient survival. Data were analyzed from 188 lung transplant recipients with a follow-up period up to 8 years. METHODS: HLA antibody monitoring was performed at 3-month intervals post-transplant at routine outpatient clinic attendances and during the investigation of any acute deterioration. HLA antibody data were available for 148 patients; 66 (45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA and 28 (19%) non-donor-specific HLA antibodies. RESULTS: De novo DSA was associated with development of BOS Stage 1 (BOS1; hazard ratio [HR] = 2.302, p = 0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo persistent DSA correlated strongly with shorter time to onset of BOS3 (HR = 6.506, p = 0.0001). There was a significant reduction in patient survival associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival. CONCLUSIONS: De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies.

Atrial fibrillation burden estimates derived from intermittent rhythm monitoring are unreliable estimates of the true atrial fibrillation burden.

BACKGROUND: Estimates of atrial fibrillation (AF) burden (AFB) derived from intermittent rhythm monitoring (IRM) are increasingly being used as an outcome measure after therapeutic interventions; however, their accuracy has never been validated. The aim of this study was to compare IRM-derived AFB estimates to the true AFB as measured by implantable continuous monitoring (CM) devices. METHODS: Rhythm histories from 647 patients (mean AFB: 12 ± 22%; 687 patient·years) with CM devices were analyzed. IRM of various frequencies and durations were simulated and the obtained IRM-derived AF burdens were compared to the true AFB measured by CM. RESULTS: The relative error of the IRM burden estimates was dependent on the IRM length (P < 0.001), frequency of IRM (P < 0.001), the true AFB (P < 0.001), and its temporal aggregation (AF density, P < 0.001). In paroxysmal AF patients, the relative error even with aggressive IRM strategies was >80% of the true AFB. The relative error decreased with higher true AF burdens, lower AF densities, and higher IRM frequency or duration (P < 0.001). However, even in patients with high AF burdens and/or low AF densities, IRM estimates of AFB significantly deviated from the true AFB (relative error >20%, P < 0.001) and resulted in a substantial measurement error. CONCLUSION: IRM-derived AFB estimates are unreliable estimators of the true AFB. Particularly for paroxysmal AF patients, IRM-derived AFB estimates should not be used to evaluate outcomes after AF interventions.

How often should we monitor for reliable detection of atrial fibrillation recurrence? Efficiency considerations and implications for study design.

OBJECTIVE: Although atrial fibrillation (AF) recurrence is unpredictable in terms of onset and duration, current intermittent rhythm monitoring (IRM) diagnostic modalities are short-termed and discontinuous. The aim of the present study was to investigate the necessary IRM frequency required to reliably detect recurrence of various AF recurrence patterns. METHODS: The rhythm histories of 647 patients (mean AF burden: 12 ± 22% of monitored time; 687 patient-years) with implantable continuous monitoring devices were reconstructed and analyzed. With the use of computationally intensive simulation, we evaluated the necessary IRM frequency to reliably detect AF recurrence of various AF phenotypes using IRM of various durations. RESULTS: The IRM frequency required for reliable AF detection depends on the amount and temporal aggregation of the AF recurrence (p<0.0001) as well as the duration of the IRM (p<0.001). Reliable detection (>95% sensitivity) of AF recurrence required higher IRM frequencies (>12 24-hour; >6 7-day; >4 14-day; >3 30-day IRM per year; p<0.0001) than currently recommended. Lower IRM frequencies will under-detect AF recurrence and introduce significant bias in the evaluation of therapeutic interventions. More frequent but of shorter duration, IRMs (24-hour) are significantly more time effective (sensitivity per monitored time) than a fewer number of longer IRM durations (p<0.0001). CONCLUSIONS: Reliable AF recurrence detection requires higher IRM frequencies than currently recommended. Current IRM frequency recommendations will fail to diagnose a significant proportion of patients. Shorter duration but more frequent IRM strategies are significantly more efficient than longer IRM durations. CLINICAL TRIAL REGISTRATION URL: Unique identifier: NCT00806689.

Patient age at the Ross operation in children influences aortic root dimensions and aortic regurgitation.

BACKGROUND: The Ross operation provides the advantage of growth potential of the pulmonary autograft in the aortic position. However, development of autograft dilatation and regurgitation may occur. We sought to assess the progression of autograft diameters and aortic regurgitation (AR) with regard to patient age at the time of the Ross operation. METHODS: Autograft echo dimensions from 48 children <16 years of age at the time of the Ross operation, who had follow-up echocardiograms at <20 years of age, were analyzed using hierarchical multilevel modeling. The z values of autograft dimensions were calculated according to the normal aortic dimensions. Mean follow-up was 5.1 ± 3.3 years. The mean age at the time of the Ross operation was 10.0 ± 4.3 years. RESULTS: The mean z values of all patients showed a significant increase with follow-up time at the sinus (0.5 ± 0.1/year, P < .001) and the sinotubular junction (0.7 ± 0.2/year, P < .001) but not at the annulus (0.1 ± 0.1/year, P = .59). There was no significant difference in the z values of sinus and the sinotubular junction between younger and older children at implantation and with time. The initial annulus z value was significantly larger in younger children (P < .0001), whereas the annual increase was significantly higher in older children (P = .021). Age at operation has no impact on the initial AR grade (P = .60). The AR tends to increase more quickly in older patients (P = .040). Sinus and sinotubular junction dilate with time, regardless of patient age. CONCLUSIONS: Young children show larger initial annulus sizes than older children. However, annulus diameters tend to normalize in young children, whereas they increase in older children. Autograft regurgitation develops slowly, but significantly, and predominantly in older children. Stabilizing measures to prevent autograft root dilatation are warranted in adolescents, but they are not required in young children.

A comprehensive evaluation of rhythm monitoring strategies for the detection of atrial fibrillation recurrence: insights from 647 continuously monitored patients and implications for monitoring after therapeutic interventions.

BACKGROUND: Intermittent rhythm monitoring (IRM) to detect atrial fibrillation (AF) recurrence is employed to evaluate the success of therapeutic interventions. In a large population of patients with continuous monitoring (CM), we investigated the sensitivity of various frequencies and durations of IRM strategies on the detection of AF recurrence, the dynamics behind AF recurrence detection, and we describe measures to evaluate temporal AF recurrence. METHODS AND RESULTS: Rhythm histories of 647 patients (mean AF burden, 0.12±0.22; median, 0.014; 687 patient-years) with implantable CM devices were reconstructed and analyzed. With the use of computationally intensive simulation, the sensitivity of IRM of various frequencies and durations on the identification of AF recurrence was evaluated. Prolonged-duration IRM was superior to shorter IRM (P<0.0001). However, even with aggressive IRM strategies, AF recurrence was not detected in a great proportion of patients. The temporal AF burden aggregation (AF density) was directly related to IRM sensitivity (P<0.0001). Even at similar AF burdens, patients with high-density AF required higher-frequency or prolonged-duration IRM to achieve the same sensitivity as in low-density AF (P<0.0001). Patients with high-density, low-burden AF benefit the most from CM for detection of AF recurrence. CONCLUSIONS: IRM follow-up is significantly inferior to CM. IRM strategies will not identify AF recurrence in a great proportion of patients at risk. Temporal AF characteristics play a significant role in AF recurrence detection with the use of IRM. For the scientific, evidence-based evaluation of AF treatments, CM should be strongly recommended. Prospective studies are required to evaluate whether CM to guide clinical management can also improve patient outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00806689.

Major adverse cardiac and cerebrovascular events after the Ross procedure: a report from the German-Dutch Ross Registry.

BACKGROUND: The purpose of the study is to report major cardiac and cerebrovascular events after the Ross procedure in the large adult and pediatric population of the German-Dutch Ross registry. These data could provide an additional basis for discussions among physicians and a source of information for patients. METHODS AND RESULTS: One thousand six hundred twenty patients (1420 adults; 1211 male; mean age, 39.2±16.2 years) underwent a Ross procedure between 1988 and 2008. Follow-up was performed on an annual basis (median, 6.2 years; 10 747 patient-years). Early and late mortality were 1.2% (n=19) and 3.6% (n=58; 0.54%/patient-year), respectively. Ninety-three patients underwent 99 reinterventions on the autograft (0.92%/patient-year); 78 reinterventions in 63 patients on the pulmonary conduit were performed (0.73%/patient-year). Freedom from autograft or pulmonary conduit reoperation was 98.2%, 95.1%, and 89% at 1, 5, and 10 years, respectively. Preoperative aortic regurgitation and the root replacement technique without surgical autograft reinforcement were associated with a greater hazard for autograft reoperation. Major internal or external bleeding occurred in 17 (0.15%/patient-year), and a total of 38 patients had composite end point of thrombosis, embolism, or bleeding (0.35%/patient-year). Late endocarditis with medical (n=16) or surgical treatment (n=29) was observed in 38 patients (0.38%/patient-year). Freedom from any valve-related event was 94.9% at 1 year, 90.7% at 5 years, and 82.5% at 10 years. CONCLUSIONS: Although longer follow-up of patients who undergo Ross operation is needed, the present series confirms that the autograft procedure is a valid option to treat aortic valve disease in selected patients. The nonreinforced full root technique and preoperative aortic regurgitation are predictors for autograft failure and warrant further consideration. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00708409.

Validation of a prediction score model to distinguish acute coronary syndromes from other conditions causing raised cardiac troponin T levels.

OBJECTIVE: Serum cardiac troponins can be elevated in acute coronary syndromes (ACS) and other non-ACS conditions. We investigated the usefulness of a prediction score model comprising clinical variables to distinguish patients with ACS from other non-ACS conditions. METHODS: Two independent, non-randomized observational cohorts (groups 1 and 2) were examined, comprising consecutive patients who were admitted to a university teaching hospital and found to have a raised serum troponin T level (>or=0.01 microg/l). The international definition was used to confirm acute myocardial infarction. Multivariate logistic regression identified clinical variables in the first cohort, which were used to construct a score model for distinguishing between ACS and non-ACS, and this score was re-evaluated in the second cohort. RESULTS: Of the 313 patients in group 1, a score model was formulated using logarithm troponin T, ischaemic chest pain, ST depression and atrial fibrillation or flutter. Using a score of more than or equal to 1.5, sensitivity and specificity for predicting non-ACS were 0.81 and 0.84. The area under the curve was 0.900 (95% confidence interval 0.867-0.934). Sensitivity and specificity for predicting non-ACS among the 341 patients in group 2 using the same model and a score of more than or equal to 1.5 were 0.76 and 0.89, respectively, and the area under the curve was 0.918 (confidence interval 0.887-0.945). CONCLUSION: A prediction score model using simple clinical variables has been validated, and this can help clinicians in distinguishing patients with ACS from other non-ACS conditions.

The Ross operation - a feasible and safe option in the setting of a bicuspid aortic valve?

OBJECTIVES: The Ross operation in the setting of a bicuspid aortic valve (BAV) remains controversial. Using data from the German Ross Registry, we sought to investigate the effect of the presence of a BAV on autograft function and diameters over time after the Ross operation compared with the presence of a tricuspid aortic valve (TAV). METHODS: A total of 1277 patients (mean age 42.2 + or - 15.3 years) with intra-operatively documented aortic valve morphology during the Ross operation were analysed in the present study (sub-coronary technique, n=648, root replacement technique, n=629 patients). A BAV was present in 70.9% of patients. Clinical and echocardiographic follow-up was performed preoperatively and at pre-specified intervals (mean follow-up 5.7 + or - 3.8 years, 6806 patient-years). Hierarchical multilevel modelling techniques were used for the statistical analysis of serial measurements and comparisons among groups. RESULTS: Initial neo-aortic regurgitation was lower in the BAV group (0.52 vs 0.62 aortic insufficiency (AI) grades, p=0.008), whereas the annual increase of it did not differ among groups. In both surgical techniques, no significant development of neo-aortic regurgitation (<0.02 AI grades per year) could be detected. Initial aortic annulus and sinus dimensions did not differ in the presence of a BAV. However, BAV patients developed a higher degree of annulus and sinus dilatation over time (0.20mm per year vs 0.06 mm per year, p=0.003; 0.24 vs 0.11 mm per year, p=0.013). This effect persisted when allowing for the two different surgical techniques. Baseline sinotubular junction (STJ) diameters did not differ among groups and annual increase thereof was similar (29.15 mm vs 28.9 mm, p=0.69; 0.44 mm vs 0.35 mm, p=0.15). CONCLUSIONS: For the observed time period, postoperative neo-aortic regurgitation after the Ross procedure did not differ between patients with a BAV or a TAV. Root dimensions, although clinically not relevant, increased in both valve entities supporting surgical reinforcement strategies. We cannot consider a BAV as a contraindication for the Ross operation.

Autograft reinforcement to preserve autograft function after the ross procedure: a report from the german-dutch ross registry.

BACKGROUND: Autograft reinforcement interventions (R) during the Ross procedure are intended to preserve autograft function and improve durability. The aim of this study is to evaluate this hypothesis. METHODS AND RESULTS: 1335 adult patients (mean age:43.5+/-12.0 years) underwent a Ross procedure (subcoronary, SC, n=637; root replacement, Root, n=698). 592 patients received R of the annulus, sinotubular junction, or both. Regular clinical and echocardiographic follow-up was performed (mean:6.09+/-3.97, range:0.01 to 19.2 years). Longitudinal assessment of autograft function with time was performed using multilevel modeling techniques. The Root without R (Root-R) group was associated with a 6x increased reoperation rate compared to Root with R (Root+R), SC with R (SC+R), and without R (SC-R; 12.9% versus 2.3% versus 2.5%.versus 2.6%, respectively; P<0.001). SC and Root groups had similar rate of aortic regurgitation (AR) development over time. Root+R patients had no progression of AR, whereas Root-R had 6 times higher AR development compared to Root+R. In SC, R had no remarkable effect on the annual AR progression. The SC technique was associated with lower rates of autograft dilatation at all levels of the aortic root compared to the Root techniques. R did not influence autograft dilatation rates in the Root group. CONCLUSIONS: For the time period of the study surgical autograft stabilization techniques preserve autograft function and result in significantly lower reoperation rates. The nonreinforced Root was associated with significant adverse outcome. Therefore, surgical stabilization of the autograft is advisable to preserve long-term autograft function, especially in the Root Ross procedure.

Neoaortic root diameters and aortic regurgitation in children after the Ross operation.

BACKGROUND: For children who require aortic valve replacement, the Ross operation provides a unique advantage of growth potential of the pulmonary autograft in the aortic position. This study assessed the progression of autograft root diameters and its effect on aortic regurgitation (AR). METHODS: Neoaortic echo dimensions from 48 children (<16 years) undergoing Ross operation who had follow-up echocardiograms before age 20 were analyzed (mean follow-up, 5.1 +/- 3.3 years). RESULTS: The mean age at the time of the Ross operation was 10.0 +/- 4.3 years. Mean z values of the neoaortic annulus (1.5 +/- 0.4), sinus (2.5 +/- 0.4), and sinotubular junction (2.6 +/- 0.9) when the autograft was implanted were significantly larger compared with normal values (p < 0.001, all). The mean z values significantly increased with follow-up at the level of the sinus (0.5 +/- 0.1/year, p < 0.001) and the sinotubular junction (0.7 +/- 0.2, p < 0.001), but not at the level of the annulus (0.1 +/- 0.1, p = 0.59). AR increased with follow-up time (0.07 +/- 0.02 grade/year, p < 0.001). AR increased with sinotubular junction diameter (p = 0.028), but there was not significant evidence of an association with annulus diameter (p = 0.25) or sinus diameter (p = 0.40). CONCLUSIONS: Children undergoing Ross operation have larger neoaortic root dimensions than healthy children. Growth of the annulus matches somatic growth. The diameters of the sinus and the sinotubular junction increase significantly relative to somatic growth. The latter may explain the development of AR.

Homograft performance in children after the Ross operation.

BACKGROUND: The Ross operation may be the ideal aortic valve replacement in pediatric patients. However, reoperations for replacement of the homograft in the pulmonary position are inevitable. This study determined influencing factors for the development of homograft stenosis and regurgitation in pediatric Ross patients. METHODS: Follow-up echocardiograms of 116 children (86 boys) undergoing Ross operations at a mean age, 9.3 +/- 4.9 years were analyzed using hierarchic multilevel modeling. Mean duration of the echocardiographic follow-up was 5.3 +/- 4.2 years (609 patient-years, 398 examinations). RESULTS: Median homograft diameter z value was 0.3 (range -2.2 to +7.3). Mean homograft pressure gradient at implantation was 5.0 mm Hg with a significant increase of 4.2 mm Hg/y (p < 0.001) within the first 2 years and a steady state thereafter. Older donor age was significantly associated with lower mean pressure gradient at implantation (p = 0.037). Larger z value had no significant influence on the annual increase of pressure gradient (p = 0.87). Mean grade of regurgitation at implantation was 0.9, without significant annual increase (0.02 grade/y, (p = = 0.32). Older recipient (p = 0.005) and donor age (p < 0.0001) were significantly associated with lower mean regurgitation at implantation. Larger z value was associated with a higher annual increase of regurgitation (p = 0.014). CONCLUSIONS: Relevant midterm homograft regurgitation is rare in children after the Ross operation. However, a significant annual increase occurs in the pressure gradient that cannot be influenced by larger graft size. Homograft oversizing may lead to a higher annual increase of regurgitation.

A reevaluation of the role of IgM Non-HLA antibodies in cardiac transplantation.

BACKGROUND: Preexisting IgG antibodies to donor human leukocyte antigens (HLA) are a risk factor for rapid allograft rejection. However, non-HLA antibodies, of the IgM class, also called autoreactive antibodies, are not believed to affect graft survival. The aim of this study was to determine the incidence and clinical relevance of pretransplant lymphocytotoxic non-HLA IgM antibodies on long-term cardiac allograft survival. METHODS: A retrospective study of 616 adult recipients of cardiac allografts, transplanted at this center between 1991 and 2003, has been performed. Antibodies in pretransplant sera were initially defined using complement-dependent cytotoxicity assays, and subsequently analyzed for HLA specificities using solid phase assays. RESULTS: HLA antibodies were present in 69 of 616 heart recipients (58 IgG, 11 IgM); in 22 of these, the antibodies were donor-specific. Non-HLA IgM antibodies were detected in 59 of 616 recipients who did not have HLA-specific antibodies; these patients had a 1, 2, 5, and 10 year survival of 55.9%, 54.2%, 49.9%, and 43.3% compared with 75.8%, 73.7%, 66.6%, and 52.8% for those without antibodies (P=0.0085 log-rank test). Multivariate analysis demonstrated pretransplant non-HLA IgM antibodies to be an independent risk factor for mortality (P=0.0001). Myocardial histology of postmortem heart and cardiac biopsies suggested an association with ischemic damage and "primary" allograft failure. CONCLUSIONS: We propose the hypothesis that the presence of cytotoxic IgM antibodies to non-HLAs before heart transplantation maybe a risk factor for early allograft failure.

Autograft regurgitation and aortic root dimensions after the Ross procedure: the German Ross Registry experience.

BACKGROUND: Autograft regurgitation and root dilatation after the Ross procedure is of major concern. We reviewed data from the German Ross Registry to document the development of autograft regurgitation and root dilatation with time and also to compare 2 different techniques of autograft implantation. METHODS AND RESULTS: Between 1990 and 2006 1014 patients (786 men, 228 women; mean age 41.2+/-15.3 years) underwent the Ross procedure using 2 different implantation techniques (subcoronary, n=521; root replacement, n=493). Clinical and serial echocardiographic follow up was performed preoperatively and thereafter annually (mean follow up 4.41+/-3.11 years, median 3.93 years, range 0 to 16.04 years; 5012 patient-years). For statistical analysis of serial echocardiograms, a hierarchical multilevel modeling technique was applied. Eight early and 28 late deaths were observed. Pulmonary autograft reoperations were required in 35 patients. Initial autograft regurgitation grade was 0.49 (root replacement 0.73, subcoronary 0.38) with an annual increase of grade 0.034 (root replacement 0.0259, subcoronary 0.0231). Annulus and sinus dimensions did not exhibit an essential increase over time in both techniques, whereas sinotubular junction diameter increased essentially by 0.5 mm per year in patients with root replacement. Patients with the subcoronary implantation technique showed nearly unchanged dimensions. Bicuspid aortic valve morphology did not have any consistent impact on root dimensions with time irrespective of the performed surgical technique. CONCLUSIONS: The present Ross series from the German Ross Registry showed favorable clinical and hemodynamic results. Development of autograft regurgitation for both techniques was small and the annual progression thereof is currently not substantial. Use of the subcoronary technique and aortic root interventions with stabilizing measures in root replacement patients seem to prevent autograft regurgitation and dilatation of the aortic root within the timeframe studied.

A critical reappraisal of the Ross operation: renaissance of the subcoronary implantation technique?

BACKGROUND: The autograft procedure, an option in aortic valve replacement, has undergone technical evolution. A considerable debate about the most favorable surgical technique in the Ross operation is still ongoing. Originally described as a subcoronary implant, the full root replacement technique is now the most commonly used technique to perform the Ross principle. METHODS AND RESULTS: Between June of 1994 and June of 2005, the original subcoronary autograft technique was performed in 347 patients. Preoperative, perioperative, and follow-up data were collected and analyzed. Mean patient age at implantation was 44+/-13 years (range 14 to 71 years; 273 male, 74 female). Bicuspid valve morphology was present in 67%. The underlying valve disease was aortic regurgitation in 111 patients, stenosis in 46 patients, combined lesion in 188 patients, and active endocarditis in 22 patients (in 2 patients without stenosis or regurgitation). Concomitant procedures were performed in 130 patients. Clinical and echocardiographic follow-up visits were obtained annually (mean follow up 3.9+/-2.7 years, 1324 patient-years; completeness of follow-up 99.4%). The in-hospital mortality rate was 0.6% (n =2), and the late mortality was 1.7% (n=6), with 5 noncardiac deaths (4 cancer, 1 multiorgan failure after noncardiac surgery) and 1 cardiac death (sudden death). At last follow-up, 94% of the surviving patients were in New York Heart Association class I. Ross procedure-related valvular reoperations were necessary in 9 patients: Three received autograft explants, 5 received homograft explants, and 1 received a combined auto- and homograft explant. At last follow-up visit, autograft/homograft regurgitation grade II was present in 5/10 patients and grade III in 4/0. Maximum/mean pressure gradients were 7.4+/-6.2/3.7+/-2.1 mm Hg across the autograft and 15.3+/-9.4/7.6+/-5.0 mm Hg across the right ventricular outflow tract, respectively. Aortic root dilatation was not observed. Freedom from any valve-related intervention was 95% at 8 years (95% confidence interval 91% to 99%). CONCLUSIONS: Midterm follow-up of autograft procedures according to the original Ross subcoronary approach proves excellent clinical and hemodynamic results, with no considerable reoperation rates. Revival of the original subcoronary Ross operation should be taken into account when considering the best way to install the Ross principle.