Severe aortic stenosis and coronary artery disease

Coronary artery disease (CAD) and aortic stenosis (AS) share pathophysiological mechanisms and risk factors. Moreover, the prevalence of CAD increases among elderly patients with severe AS since disease progression is strongly associated with age for both CAD and AS. These factors contribute to the frequent coexistence of CAD and AS. Patients with concomitant AS and CAD are characterised by higher baseline risk profiles with a larger number of comorbidities as compared to patients with isolated AS. Therefore, adequate therapeutic strategies are crucial for the treatment of these patients. The number of patients undergoing concomitant coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) doubled during the last decade. Moreover, the development and rapid integration of transcatheter aortic valve implantation (TAVI) into clinical practice in western European countries has further extended invasive treatment of AS to elderly high-risk patients not considered suitable candidates for SAVR, frequently presenting with CAD. The aim of this review article is to provide an overview on CAD prevalence, impact on clinical outcomes, and treatment strategies in patients with severe AS requiring SAVR or TAVI.

European experience with the second-generation Edwards SAPIEN XT transcatheter heart valve in patients with severe aortic stenosis: 1-year outcomes from the SOURCE XT Registry

OBJECTIVES The SOURCE XT Registry (Edwards SAPIEN XT Aortic Bioprosthesis Multi-Region Outcome Registry) assessed the use and clinical outcomes with the SAPIEN XT (Edwards Lifesciences, Irvine, California) valve in the real-world setting. BACKGROUND Transcatheter aortic valve replacement is an established treatment for high-risk/inoperable patients with severe aortic stenosis. The SAPIEN XT is a balloon-expandable valve with enhanced features allowing delivery via a lower profile sheath. METHODS The SOURCE XT Registry is a prospective, multicenter, post-approval study. Data from 2,688 patients at 99 sites were analyzed. The main outcome measures were all-cause mortality, stroke, major vascular complications, bleeding, and pacemaker implantations at 30-days and 1 year post-procedure. RESULTS The mean age was 81.4 ± 6.6 years, 42.3% were male, and the mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 20.4 ± 12.4%. Patients had a high burden of coronary disease (44.2%), diabetes (29.4%), renal insufficiency (28.9%), atrial fibrillation (25.6%), and peripheral vascular disease (21.2%). Survival was 93.7% at 30 days and 80.6% at 1 year. At 30-day follow-up, the stroke rate was 3.6%, the rate of major vascular complications was 6.5%, the rate of life-threatening bleeding was 5.5%, the rate of new pacemakers was 9.5%, and the rate of moderate/severe paravalvular leak was 5.5%. Multivariable analysis identified nontransfemoral approach (hazard ratio [HR]: 1.84; p < 0.0001), renal insufficiency (HR: 1.53; p < 0.0001), liver disease (HR: 1.67; p = 0.0453), moderate/severe tricuspid regurgitation (HR: 1.47; p = 0.0019), porcelain aorta (HR: 1.47; p = 0.0352), and atrial fibrillation (HR: 1.41; p = 0.0014), with the highest HRs for 1-year mortality. Major vascular complications and major/life-threatening bleeding were the most frequently seen complications associated with a significant increase in 1-year mortality. CONCLUSIONS The SOURCE XT Registry demonstrated appropriate use of the SAPIEN XT THV in the first year post-commercialization in Europe. The safety profile is sustained, and clinical benefits have been established in the real-world setting. (SOURCE XT Registry; NCT01238497).

Heart valve sound of various mechanical composite grafts, and the impact on patients' quality of life

The closing sounds of mechanical heart valves can be disturbing for patients and their closest relatives. Although some investigations into mechanical heart valve sounds have been performed, the particularities of the valve sound when it is attached to a vascular prosthesis to replace the aortic root and the ascending aorta has not been studied to date. The study aim was to compare the closing sounds of three various mechanical composite graft prostheses, and to analyze the impact of such sounds on the patients' quality of life.

Clinical outcomes of patients with severe aortic stenosis at increased surgical risk according to treatment modality

Objectives The aim of this study was to assess the role of transcatheter aortic valve implantation (TAVI) compared with medical treatment (MT) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) at increased surgical risk. Background Elderly patients with comorbidities are at considerable risk for SAVR. Methods Since July 2007, 442 patients with severe AS (age: 81.7 ± 6.0 years, mean logistic European System for Cardiac Operative Risk Evaluation: 22.3 ± 14.6%) underwent treatment allocation to MT (n = 78), SAVR (n = 107), or TAVI (n = 257) on the basis of a comprehensive evaluation protocol as part of a prospective registry. Results Baseline clinical characteristics were similar among patients allocated to MT and TAVI, whereas patients allocated to SAVR were younger (p < 0.001) and had a lower predicted peri-operative risk (p < 0.001). Unadjusted rates of all-cause mortality at 30 months were lower for SAVR (22.4%) and TAVI (22.6%) compared with MT (61.5%, p < 0.001). Adjusted hazard ratios for death were 0.51 (95% confidence interval: 0.30 to 0.87) for SAVR compared with MT and 0.38 (95% confidence interval: 0.25 to 0.58) for TAVI compared with MT. Medical treatment (<0.001), older age (>80 years, p = 0.01), peripheral vascular disease (<0.001), and atrial fibrillation (p = 0.04) were significantly associated with all-cause mortality at 30 months in the multivariate analysis. At 1 year, more patients undergoing SAVR (92.3%) or TAVI (93.2%) had New York Heart Association functional class I/II as compared with patients with MT (70.8%, p = 0.003). Conclusions Among patients with severe AS with increased surgical risk, SAVR and TAVI improve survival and symptoms compared with MT. Clinical outcomes of TAVI and SAVR seem similar among carefully selected patients with severe symptomatic AS at increased risk.

Deleterious outcome of No-React-treated stentless valved conduits after aortic root replacement: why were warnings ignored?

OBJECTIVE: The implantation of a composite graft is the treatment of choice for patients with aortic root disease if the valve cannot be preserved and the patient is not a suitable candidate for a Ross procedure. Several years ago, the Shelhigh NR-2000C (Shelhigh, Inc, Millburn, NJ) was introduced in Europe. Being a totally biologic conduit and considering the lack of homografts, the graft seemed an ideal conduit for patients with destructive endocarditis, as well as for older patients who were not suitable candidates for oral anticoagulation. METHODS: From 2001 until 2006, the Shelhigh NR-2000C stentless valved conduit was implanted in 115 patients for various aortic root pathologies. The conduit consists of a bovine pericardial straight graft with an incorporated porcine stentless valve. Aortic root repair was performed during standard cardiopulmonary bypass and mild hypothermia in the majority of patients. Deep hypothermic circulatory arrest combined with selective antegrade cerebral perfusion was used when the repair extended into the arch. RESULTS: Seven patients with uncomplicated early outcome presented with unexpected sudden disastrous findings at the level of the aortic root, although 1-year follow-up computed tomographic scans were normal. Four of these patients underwent emergency operations because of desintegration of the graft, along with rupture of the aortic root. Retrospectively, the main findings were persistent fever or subfebrility over months and a halo-like enhancement on computed tomographic scans. Extensive microbiologic examinations were performed without finding a causative organism. CONCLUSION: The use of the Shelhigh aortic stentless conduit can no longer be advocated, and meticulous follow-up of patients in whom this device has been implanted has to be recommended.

Persistent diastolic dysfunction late after valve replacement in severe aortic regurgitation

BACKGROUND: Regression of left ventricular (LV) hypertrophy with normalization of diastolic function has been reported in patients with aortic stenosis late after aortic valve replacement (AVR). The purpose of the present study was to evaluate the effect of AVR on LV function and structure in chronic aortic regurgitation early and late after AVR. METHODS AND RESULTS: Twenty-six patients were included in the present analysis. Eleven patients with severe aortic regurgitation were studied before, early (21 months) and late (89 months) after AVR through the use of LV biplane angiograms, high-fidelity pressure measurements, and LV endomyocardial biopsies. Fifteen healthy subjects were used as controls. LV systolic function was determined from biplane ejection fraction and midwall fractional shortening. LV diastolic function was calculated from the time constant of LV relaxation, peak filling rates, and myocardial stiffness constant. LV structure was assessed from muscle fiber diameter, interstitial fibrosis, and fibrous content. LV muscle mass decreased significantly by 38% early and 55% late after surgery. Ejection fraction was significantly reduced preoperatively and did not change after AVR (P=NS). LV relaxation was significantly prolonged before surgery (89+/-28 ms) but was normalized late after AVR (42+/-14 ms). Early and late peak filling rates were increased preoperatively but normalized postoperatively. Diastolic stiffness constant was increased before surgery (22+/-6 versus 9+/-3 in control subjects; P=0.0003) and remained elevated early and late after AVR (23+/-4; P=0.002). Muscle fiber diameter decreased significantly after AVR but remained increased at late follow-up. Interstitial fibrosis was increased preoperatively and increased even further early but decreased late after AVR. Fibrosis was positively linearly correlated to myocardial stiffness and inversely correlated to LV ejection fraction. CONCLUSIONS: Patients with aortic regurgitation show normalization of macroscopic LV hypertrophy late after AVR, although fiber hypertrophy persists. These changes in LV myocardial structure late after AVR are accompanied by a change in passive elastic properties with persistent diastolic dysfunction.

The role of the sinuses of Valsalva in aortic root flow dynamics and aortic root surgery: evaluation by magnetic resonance imaging

BACKGROUND AND AIM OF THE STUDY: Combined replacement of the aortic valve and ascending aorta using a composite graft represents the standard treatment for dilated aortic root with concomitant structural damage of the aortic valve, especially when the aortic valve cannot be preserved. Unfortunately, hemodynamic changes associated with prosthetic replacement of the aortic root have not been fully elucidated. The study aim was to compare hemodynamics within the replaced aortic root using either a prosthetic vascular graft with bulges mimicking the sinuses of Valsalva and including a stented pericardial valve, or a straight xenopericardial conduit and a stentless porcine valve. METHODS: Between July 2004 and March 2006, a total of 35 patients (mean age 65.2 years: range: 32-80 years) was enrolled into the present study. Aortic root replacement was performed in nine patients with a Valsalva graft (Gelweave Valsalva; Vascutek, Renfrewshire, UK) including a stented pericardial valve, and in 19 patients with a xenopericardial conduit containing a stentless porcine valve. All patients underwent postoperative magnetic resonance imaging (MRI). A control group of seven patients allowed for comparison with native aortic root hemodynamics. RESULTS: Maximum flow-velocity above the aortic valve as one marker of compliance of the aortic root was slightly higher in patients with a Valsalva graft compared to native aortic roots (1.9 m/s versus 1.3 m/s, p = 0.001), but was significantly lower than in patients with the xenopericardial graft without neo-sinuses (1.3 m/s versus 2.4 m/s, p < 0.001). CONCLUSION: The pre-shaped bulges in the prosthetic Valsalva graft effectively mimic the native sinuses of Valsalva, improve compliance of the aortic root, and result in a more physiologic flow pattern, as demonstrated by postoperative MRI.

Fatal aortic endocarditis associated with community-acquired Serratia marcescens infection in a dog

A 12 yr old Dalmatian was referred for evaluation of acute lethargy, fever, neurologic signs, and a recently ausculted heart murmur. Echocardiography in combination with blood cultures resulted in a diagnosis of nonhospital-acquired Serratia marcescens bacteremia and aortic valve endocarditis. Despite early diagnosis and aggressive therapy, the dog failed to respond to antimicrobials and died within 6 hr after admission. Necropsy findings included aortic valve endocarditis, septicemia, and diffuse thromboembolic disease. There was no history of pre-existing underlying disease or immunosuppressive therapy, and the dog had not been hospitalized before referral.

In Vitro Testing of a Temporary Catheter-Based Aortic "Parachute" Valve

Recently developed technologies allow aortic valve implantation off-pump in a beating heart. In this procedure, the native, stenotic aortic valve is not removed, but simply crushed by a pressure balloon mounted on a percutaneous catheter. Removal of the native aortic cusps before valve replacement may reduce the incidence of annular or cuspal calcium embolization and late perivalvular leaks and increase implantable valve size. However, a temporary valve system in the ascending aorta may be necessary to maintain hemodynamic stability by reducing acute aortic regurgitation and left ventricular volume overload. This study evaluates the hemodynamic effects of a wire-mounted, monoleaflet, temporary valve apparatus in a mechanical cardiovascular simulator. Aortic flow, systemic pressure and left ventricular pressure were continuously monitored. An intraluminal camera obtained real-time proximal and distal images of the valve in operation. Insertion of the parachute valve in the simulator increased diastolic pressure from 7 to 38 mm Hg. Cardiac output increased from 2.08 to 4.66 L/min and regurgitant volume decreased from 65 to 23 mL. In conclusion, placement of a temporary valve in the ascending aorta may help maintain hemodynamic stability and improve off-pump aortic valve replacement.

Long-term outcome of elderly patients with severe aortic stenosis as a function of treatment modality

OBJECTIVE To assess long-term clinical outcomes of consecutive high-risk patients with severe aortic stenosis according to treatment allocation to transcatheter aortic valve implantation (TAVI), surgical aortic valve replacement (SAVR) or medical treatment (MT). METHODS Patients with severe aortic stenosis were consecutively enrolled into a prospective single centre registry. RESULTS Among 442 patients (median age 83 years, median STS-score 4.7) allocated to MT (n=78), SAVR (n=107), or TAVI (n=257) all-cause mortality amounted to 81%, 37% and 43% after a median duration of follow-up of 3.9 years (p<0.001). Rates of major adverse cerebro-cardiovascular events were lower in patients undergoing SAVR or TAVI as compared with MT (SAVR vs MT: HR 0.31, 95% CI 0.21 to 0.46) (TAVI vs MT: HR 0.34, 95% CI 0.25 to 0.46), with no significant difference between SAVR and TAVI (HR 0.88, 95% CI 0.62 to 1.25). Whereas SAVR (HR 0.39, 95% CI 0.24 to 0.61), TAVI (HR 0.37, 95% CI 0.26 to 0.52), and female gender (HR 0.72, 95% CI 0.53 to 0.99) were associated with improved survival, body mass index ≤20 kg/m(2) (HR 1.60, 95% CI 1.04 to 2.47), diabetes (HR 1.48, 95% CI 1.03 to 2.12), peripheral vascular disease (HR 2.01, 95% CI 1.44 to 2.81), atrial fibrillation (HR 1.74, 95% CI 1.28 to 2.37) and pulmonary hypertension (HR 1.43, 95% CI 1.03 to 2.00) were identified as independent predictors of mortality. CONCLUSIONS Among high-risk patients with severe aortic stenosis, long-term clinical outcome through 5 years was comparable between patients allocated to SAVR or TAVI. In contrast, patients with MT had a dismal prognosis.

Coronary artery disease in patients undergoing TAVI: why, what, when and how to treat.

Coronary artery disease (CAD) and aortic valve stenosis (AS) are frequently coexisting. It has been reported that CAD is present in 40% of patients with AS undergoing surgical aortic valve replacement, and in up to 60% of patients with AS undergoing transcatheter aortic valve implantation (TAVI). Elderly patients with CAD and AS are characterised by higher baseline risk profiles as compared to patients with isolated AS, increasing the complexity of their therapeutic management. In patients with CAD and AS the combination of coronary artery bypass grafting (CABG) and surgical aortic valve replacement has been shown to improve survival. Therefore, CABG is recommended in patients with CAD and AS undergoing surgical aortic valve replacement according to current guidelines of the European Society of Cardiology (ESC) and of the American College of Cardiology Foundation/American Heart Association (ACCF/AHA). Conversely, whether the presence of CAD has any prognostic implications in elderly patients with severe AS undergoing TAVI is still a matter of debate. Of note, according to the most recent ESC guidelines on myocardial revascularisation, percutaneous revascularisation should be considered in patients undergoing TAVI with a stenosis >70% in proximal coronary segments (class IIa, level of evidence C). The aim of this article is to provide an overview of evidence supporting the need for coronary revascularisation in patients with severe AS and CAD undergoing TAVI, and to summarise optimal timing and treatment modalities for percutaneous coronary interventions in these patients.

Transcatheter mitral valve implantation (TMVI) using the Edwards FORTIS device.

Transcatheter aortic valve implantation (TAVI) has demonstrated the feasibility of treating valvular heart disease with transcatheter therapy. On the back of this success, various transcatheter concepts are being evaluated to treat other valvular disease, especially mitral regurgitation (MR). The concepts currently approved to treat MR replicate surgical mitral valve repair. However, most of them cannot eliminate MR completely. Similar to TAVI, a transcatheter mitral valve implantation may provide a valuable alternative. The FORTIS transcatheter mitral valve (Edwards Lifesciences, Irvine, CA, USA) is a self-expanding device implanted via a transapical approach. We describe our experience and early results in the first five patients treated on compassionate grounds. We also describe the details of the device, selection criteria and technical details of implantation.

Treatment of aortic stenosis with a self-expanding transcatheter valve: the International Multi-centre ADVANCE Study.

AIM Transcatheter aortic valve implantation has become an alternative to surgery in higher risk patients with symptomatic aortic stenosis. The aim of the ADVANCE study was to evaluate outcomes following implantation of a self-expanding transcatheter aortic valve system in a fully monitored, multi-centre 'real-world' patient population in highly experienced centres. METHODS AND RESULTS Patients with severe aortic stenosis at a higher surgical risk in whom implantation of the CoreValve System was decided by the Heart Team were included. Endpoints were a composite of major adverse cardiovascular and cerebrovascular events (MACCE; all-cause mortality, myocardial infarction, stroke, or reintervention) and mortality at 30 days and 1 year. Endpoint-related events were independently adjudicated based on Valve Academic Research Consortium definitions. A total of 1015 patients [mean logistic EuroSCORE 19.4 ± 12.3% [median (Q1,Q3), 16.0% (10.3, 25.3%)], age 81 ± 6 years] were enrolled. Implantation of the CoreValve System led to a significant improvement in haemodynamics and an increase in the effective aortic valve orifice area. At 30 days, the MACCE rate was 8.0% (95% CI: 6.3-9.7%), all-cause mortality was 4.5% (3.2-5.8%), cardiovascular mortality was 3.4% (2.3-4.6%), and the rate of stroke was 3.0% (2.0-4.1%). The life-threatening or disabling bleeding rate was 4.0% (2.8-6.3%). The 12-month rates of MACCE, all-cause mortality, cardiovascular mortality, and stroke were 21.2% (18.4-24.1%), 17.9% (15.2-20.5%), 11.7% (9.4-14.1%), and 4.5% (2.9-6.1%), respectively. The 12-month rates of all-cause mortality were 11.1, 16.5, and 23.6% among patients with a logistic EuroSCORE ≤10%, EuroSCORE 10-20%, and EuroSCORE >20% (P< 0.05), respectively. CONCLUSION The ADVANCE study demonstrates the safety and effectiveness of the CoreValve System with low mortality and stroke rates in higher risk real-world patients with severe aortic stenosis.

Hemodynamic Performance of Edwards Intuity Valve in a Compliant Aortic Root Model

Numerous designs of bioprosthetic valves exist. The sutureless surgical valve is a newer design concept which combines elements of the transcatheter valve technology with surgical valves. This design aims at shorter and easier implantation. It was the aim of this study to perform hemodynamic and kinematic measurements for this type of valves to serve as a baseline for following studies which investigate the effect of the aortic root on the valve performance. To this end, the Edwards Intuity aortic valve was investigated in a new in vitro flow loop mimicking the left heart. The valve was implanted in a transparent, compliant aortic root model, and the valve kinematics was investigated using a high speed camera together with synchronized hemodynamic measurements of pressures and flows. The valve closure was asynchronous (one by one leaflet), and the valve started to close before the deceleration of the fluid. The aortic root model showed a dilation of the sinuses which was different to the ascending aorta, and the annulus was found to move towards the left ventricle during diastole and towards the aorta during systole.

Long-term follow-up after implantation of the Shelhigh® No-React® complete biological aortic valved conduit†.

OBJECTIVES Long-term follow-up reports after implantation of the Shelhigh® (Shelhigh, Inc., NJ, USA) No-React® aortic valved conduit used for aortic root replacement do not exist. METHODS Between November 1998 and December 2007, the Shelhigh® No-React® aortic valved conduit was implanted in 291 consecutive patients with a mean age of 69.6 ± 9.1 years, and 33.7% were female (n = 98). Indications were annulo-aortic ectasia (n = 202), aortic valve stenosis combined with ascending aortic aneurysm (n = 67), acute type A aortic dissection (n = 29), endocarditis (n = 26) and other related pathologies (n = 48) including 62 patients with previous cardiac surgery. Data from two cardiac institutions were analysed retrospectively using SPSS (SPSS Software IBM, Inc., 2014, NY, USA). RESULTS Operative mortality was 10% (n = 29). Main cause of death was cardiac failure in 15 patients (51.8%), neurological events in 6 patients (20.7%), respiratory failure in 4 patients (13.8%), bleeding complications in 2 patients (6.9%) and gastrointestinal ischaemia in 2 cases (6.9%). There were 262 hospital survivors and all were entered in the follow-up study (100% complete). During the long-term follow-up (mean 70.3 ± 53.1 in months), a total of 126/262 patients (44.3%) died. Main causes of death in patients after discharge were cardiac (n = 37, 14.1%), neurological (n = 15, 5.7%) respiratory (n = 12, 4.6%), endocarditis (n = 12, 4.6%) and peripheral vascular disease (n = 5, 1.9%). In 29 (11.1%) patients, the cause of death could not be determined. Reoperation was required in 25 (8.6%) patients due to infection of the conduit (n = 9), aortoventricular disconnection (n = 4), pseudoaneurysm formation (n = 4) and structural valve degeneration (n = 8). Reoperations were performed 5.0 ± 3.8 (range 0.1-11.7) years after index surgery. CONCLUSIONS The Shelhigh® No-React® aortic valved conduit showed satisfactory short-term operative results. However, the long-term follow-up revealed a relatively high rate of deaths, which may be explained by the epidemiology of the patient group, but a substantial proportion of deaths could not be clarified. The overall rate of reoperation (8.6%) during the mid-term follow-up is worrisome and the failures due to aortoventricular disconnection, endocarditis and pseudoaneurysm formation remain unexplained. The redo-procedures were technically demanding. We recommend close follow-up of patients with the Shelhigh® No-React® aortic valved conduit, because besides classical structural valve degeneration, unexpected findings may be observed.