Rizwan Attia

Use of transcatheter heart valves for a valve-in-valve implantation in patients with degenerated aortic bioprosthesis: Technical considerations and results

OBJECTIVE Transcatheter aortic valve implantation has been used to treat high-risk patients with bioprosthetic valve degeneration (valve-in-valve). We report our experience with transcatheter aortic valve implantation in the treatment of degenerated biologic aortic valve prostheses and discuss factors that can influence the outcome. METHODS From February 2009 to October 2011, 278 patients underwent transcatheter aortic valve implantation, of whom 23 underwent a valve-in-valve procedure with the Edwards Sapien valve to treat a failing bioprostheses in the aortic position. Eight of these valves were stentless bioprostheses. Thirteen patients had valve failure resulting predominantly from stenosis, and the remaining resulting from regurgitation. RESULTS Mean age was 76.9 ± 14.4 years. The mean logistic EuroSCORE was 31.8% ± 20.3% and the Society of Thoracic Surgeons score was 7.6% ± 5.4%. All patients were New York Heart Association class III or IV. The majority of the operations (21/23) were performed via the transapical route. Procedural success was 100%, although 1 patient with a degenerated homograft needed immediate placement of a second valve because of low placement of the first. The reduction in the mean gradient was 31.2 ± 17.06 mm Hg to 9.13 ± 4.9 mm Hg. In those patients with predominant aortic regurgitation (9/23), reduction in aortic regurgitation was achieved in all. The median length of stay was 11.7 days (range, 3-44 days). In-hospital and/or 30-day mortality was 0%. CONCLUSIONS Valve-in-valve is a safe and feasible alternative to treat high-risk patients with failing aortic bioprostheses. The early results are excellent, with improvement seen in hemodynamics.

In patients undergoing thoracic surgery is paravertebral block as effective as epidural analgesia for pain management

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: in patients undergoing thoracic surgery is paravertebral block (PVB) as effective as epidural analgesia for pain management? Altogether >184 papers were found using the reported search, seven of which represented the best evidence to answer the clinical question. All studies agreed that PVB is at least as effective as epidural analgesia for pain control post-thoracotomy. In one paper, the visual analogue pain score (VAS) at rest and on cough was significantly lower in the paravertebral group (P=0.02 and 0.0001, respectively). Pulmonary function, as assessed by peak expiratory flow rate (PEFR), was significantly better preserved in the paravertebral group. The lowest PEFR as a fraction of preoperative control was 0.73 in the paravertebral group in contrast with 0.54 in the epidural group (P<0.004). Oximetric recordings were better in the paravertebral group (96%) compared to the epidural group (95%) (P=0.0001). Another article reported that statistically significant differences (forced vital capacity 46.8% for PVB and 39.3% for epidural group P<0.05; forced expiratory volume in 1 s (FEV(1)) 48.4% in PVB group and 35.9% in epidural group, P<0.05) were reached in day 2 and continued until day 3. Plasma concentrations of cortisol, as marker of postoperative stress, increased markedly in both groups, but the increment was statistically different in favour of the paravertebral group (P=0.003). Epidural block was associated with frequent side-effects [urinary retention (42%), nausea (22%), itching (22%) and hypotension (3%) and, rarely, respiratory depression (0.07%)]. Additionally, it prolonged operative time and was associated with technical failure or displacement (8%). Epidurals were also related to a higher complication rate (atelectasis/pneumonia) compared to the PVB (2 vs. 0). PVB was found to be of equal efficacy to epidural anaesthesia, but with a favourable side effect profile, and lower complication rate. The reduced rate of complication was most marked for pulmonary complications and is accompanied by quicker return to normal pulmonary function. We conclude intercostal analgesia, in the form of PVB, can be at least as effective as epidural analgesia.

TIE2-expressing monocytes/macrophages regulate revascularization of the ischemic limb

A third of patients with critical limb ischemia (CLI) will eventually require limb amputation. Therapeutic neovascularization using unselected mononuclear cells to salvage ischemic limbs has produced modest results. The TIE2‐expressing monocytes/macrophages (TEMs) are a myeloid cell subset known to be highly angiogenic in tumours. This study aimed to examine the kinetics of TEMs in patients with CLI and whether these cells promote neovascularization of the ischemic limb. Here we show that there are 10‐fold more circulating TEMs in CLI patients, and removal of ischemia reduces their numbers to normal levels. TEM numbers in ischemic muscle are two‐fold greater than normoxic muscle from the same patient. TEMs from patients with CLI display greater proangiogenic activity than TIE2‐negative monocytes in vitro. Using a mouse model of hindlimb ischemia, lentiviral‐based Tie2 knockdown in TEMs impaired recovery from ischemia, whereas delivery of mouse macrophages overexpressing TIE2, or human TEMs isolated from CLI patients, rescued limb ischemia. These data suggest that enhancing TEM recruitment to the ischemic muscle may have the potential to improve limb neovascularization in CLI patients.

Role of miR-195 in aortic aneurysmal disease.

Rationale: Abdominal aortic aneurysms constitute a degenerative process in the aortic wall. Both the miR-29 and miR-15 families have been implicated in regulating the vascular extracellular matrix. Objective: Our aim was to assess the effect of the miR-15 family on aortic aneurysm development. Methods and Results: Among the miR-15 family members, miR-195 was differentially expressed in aortas of apolipoprotein E–deficient mice on angiotensin II infusion. Proteomics analysis of the secretome of murine aortic smooth muscle cells, after miR-195 manipulation, revealed that miR-195 targets a cadre of extracellular matrix proteins, including collagens, proteoglycans, elastin, and proteins associated with elastic microfibrils, albeit miR-29b showed a stronger effect, particularly in regulating collagens. Systemic and local administration of cholesterol-conjugated antagomiRs revealed better inhibition of miR-195 compared with miR-29b in the uninjured aorta. However, in apolipoprotein E–deficient mice receiving angiotensin II, silencing of miR-29b, but not miR-195, led to an attenuation of aortic dilation. Higher aortic elastin expression was accompanied by an increase of matrix metalloproteinases 2 and 9 in mice treated with antagomiR-195. In human plasma, an inverse correlation of miR-195 was observed with the presence of abdominal aortic aneurysms and aortic diameter. Conclusions: We provide the first evidence that miR-195 may contribute to the pathogenesis of aortic aneurysmal disease. Although inhibition of miR-29b proved more effective in preventing aneurysm formation in a preclinical model, miR-195 represents a potent regulator of the aortic extracellular matrix. Notably, plasma levels of miR-195 were reduced in patients with abdominal aortic aneurysms suggesting that microRNAs might serve as a noninvasive biomarker of abdominal aortic aneurysms.

A guide to fluoroscopic identification and design of bioprosthetic valves: A reference for valve‐in‐valve procedure

Surgical aortic valve replacement remains the therapy of choice in majority of patients with aortic stenosis. Bioprosthetic heart valves are often preferred over mechanical valves as they preclude the need for anticoagulation with its associated risks of bleeding and thromboembolism. However, bioprosthetic heart valves undergo structural deterioration and eventually fail. Reoperation is the standard treatment for structural failure of the bioprosthetic valve, stenosis or regurgitation but can carry a significant risk, especially in elderly patients with multiple comorbidities. Transcatheter aortic valve implantation has recently been established as a feasible alternative to conventional valve surgery for the management of high‐risk elderly patients with aortic stenosis. This treatment modality has also been shown to be of benefit in the management of degenerated aortic bioprosthesis as a valve‐in‐valve procedure. The success of this procedure depends on a good understanding of the failing bioprostheses. This not only includes the device design but its radiological/fluoroscopic appearance and how it correlates with the implanted valve, as transcatheter aortic valve implantation is performed under fluoroscopic guidance. Here we illustrate the fluoroscopic appearance of 11 commercially available surgical bioprostheses and two commercially available transcatheter heart valves and discuss important aspects in their design which can influence outcome of a valve‐in‐valve procedure. We have also collated relevant information on the aspects of the design of a bioprosthetic valve, which are relevant to the valve‐in‐valve procedure.

Magnetic Resonance T1 Relaxation Time of Venous Thrombus Is Determined by Iron Processing and Predicts Susceptibility to Lysis

Background— The magnetic resonance longitudinal relaxation time (T1) changes with thrombus age in humans. In this study, we investigate the possible mechanisms that give rise to the T1 signal in venous thrombi and whether changes in T1 relaxation time are informative of the susceptibility to lysis. Methods and Results— Venous thrombosis was induced in the vena cava of BALB/C mice, and temporal changes in T1 relaxation time correlated with thrombus composition. The mean T1 relaxation time of thrombus was shortest at 7days following thrombus induction and returned to that of blood as the thrombus resolved. T1 relaxation time was related to thrombus methemoglobin formation and further processing. Studies in inducible nitric oxide synthase (iNOS−/−)–deficient mice revealed that inducible nitric oxide synthase mediates oxidation of erythrocyte lysis–derived iron to paramagnetic Fe3+, which causes thrombus T1 relaxation time shortening. Studies using chemokine receptor-2–deficient mice (Ccr2−/−) revealed that the return of the T1 signal to that of blood is regulated by removal of Fe3+ by macrophages that accumulate in the thrombus during its resolution. Quantification of T1 relaxation time was a good predictor of successful thrombolysis with a cutoff point of <747 ms having a sensitivity and specificity to predict successful lysis of 83% and 94%, respectively. Conclusions— The source of the T1 signal in the thrombus results from the oxidation of iron (released from the lysis of trapped erythrocytes in the thrombus) to its paramagnetic Fe3+ form. Quantification of T1 relaxation time appears to be a good predictor of the success of thrombolysis.

Transaortic Transcatheter Aortic Valve Implantation: Step-by-Step Guide.

Transcatheter aortic valve implantation (TAVI) is currently used to treat high-risk and inoperable patients with aortic stenosis. The established routes of access are retrograde transfemoral (TF) and antegrade transapical (TA). Transubclavian and transaortic (TAo) routes have been described. We have performed TAo-TAVI with the Edwards Sapien prosthesis (Edwards Lifesciences, Irvine, CA) with the Ascendra I delivery system. From 2010 we have used the Sapien XT prosthesis with the Ascendra II delivery system. In this article we describe in detail the technical aspects of performing TAo TAVI.

Which patients might be suitable for a septal occluder device closure of postinfarction ventricular septal rupture rather than immediate surgery

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: which patients might be suitable for a transcatheter closure (TCC) of their postinfarction ventricular septal rupture (VSR) rather than immediate surgery? Thirty papers were found using the reported search, five of which represented the best evidence to answer the clinical question. The main limitations were the paucity of level 1 evidence on this topic. Only one study provided a prospective series as part of a registry; the remaining were retrospective cohort analyses. Although multivariate analysis may adequately control for measurable biases, unmeasured bias may still exist and influence the results. All studies agreed that timing of intervention is critical in determining the outcome. Patients preoperative haemodynamic status was a major determinant of postoperative survival. Successful outcome after TCC was in patients with simple defects, <15 mm in diameter that were in the sub-acute (>3.5 weeks) or chronic stage following acute myocardial infarct (AMI). Procedural success rate varied from 73.6% to 91%. Three of five studies looking at TCC closure concluded that procedural success does not necessarily translate to improved outcome. TCC in the acute setting (within four weeks of AMI) led to a high mortality (18%-65%) and increased incidence of complications (up to 41%). These included device embolization, major residual shunting, left ventricular rupture and malignant arrhythmias. One recent study correlated mortality to residual VSR [odds ratio (OR) 0.071, P=0.02], increased time from myocardial infarction to VSR diagnosis (OR 0.757, P=0.04) and increased time from VSR diagnosis to treatment (OR 0.758, P=0.04). The overwhelming recommendations were for immediate surgical intervention in cases of large VSR≥15 mm or where another indication for surgery exists. Three of five studies commented on a lack of a suitable device for PIVSR closure, with highest technical success with the Amplatzer device. In conclusion, small or medium PIVSR (<15 mm) can be treated definitively with Amplatzer closure in the sub-acute and chronic setting with comparable mortality to surgery. In the acute setting where surgery is deemed prohibitive TCC may provide a bridge to stabilize patients with shunt reduction, prior to surgery. The standard of treatment in large defects and PIVSRs in the acute setting remains early surgery.

Is there a role for HbA1c in predicting mortality and morbidity outcomes after coronary artery bypass graft surgery

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was is there a role for HbA1c in predicting morbidity and mortality outcomes after coronary artery bypass surgery? Eleven studies presented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The studies presented analyse the relationship between preoperative HbA1c levels and postoperative outcomes following coronary artery bypass graft (CABG) in diabetic, non-diabetic or mixed patient groups. Four studies found significant increases in early and late mortality at higher HbA1c levels, regardless of a preoperative diagnosis of diabetes. One study demonstrated that 30-day survival outcomes were significantly worse in patients with previously undiagnosed diabetes and elevated HbA1c compared with those with good control [HbA1c >6%; odds ratio 1.53, confidence interval (CI) (1.24-1.91); P = 0.0005]. However, four studies of early mortality outcomes in diabetic patients only showed no significant differences between patients with normal and those with deranged HbA1c levels (P = 0.99). There were mixed reports on morbidity outcomes. Three studies identified a significant increase in infectious complications in patients with poorly controlled HbA1c, two of which were irrespective of previous diabetic status [deep sternal wound infection (P = 0.014); superficial sternal wound infection (P = 0.007) and minor infections (P = 0.006) in poorly controlled diabetics only]. Four studies presented outcomes for total length of stay (LOS). Three of these papers looked specifically at diabetic patients, of which two found no significant differences in length of stay between good and poor preoperative glycaemic control [LOS: P = 0.59 and 0.86 vs P < 0.001]. However, elevated HbA1c vs normal HbA1c was associated with prolonged stay in hospital and in intensive care unit (ICU) in patients irrespective of previous diabetic status [total LOS (P < 0.001)]. Elevated HbA1c levels were also a significant predictor of reduced intraoperative insulin sensitivity in diabetic patients (R = -0.527; P < 0.001). Furthermore, higher HbA1c levels were associated with a reduced incidence of postoperative atrial fibrillation (P = 0.001). We conclude that elevated HbA1c is a strong predictor of mortality and morbidity irrespective of previous diabetic status. In particular, the mortality risk for CABG is quadrupled at HbA1c levels >8.6%. Some studies have called into question the predictive value of HbA1c on short-term outcomes in well-controlled diabetics; however, long-term outcomes in this population have not been reported.

Fluoroscopic guide to an ideal implant position for Sapien XT and CoreValve during a valve-in-valve procedure.

OBJECTIVES This study sought to provide a guide to the fluoroscopic appearances of various valve-in-valve (VIV) combinations by deploying a transcatheter heart valve (THV) within a degenerated surgical heart valve (SHV) in an ideal position. BACKGROUND VIV procedures are being increasingly performed with substantial experience acquired in treating degenerated SHV in the aortic position with Sapien/Sapien XT (Edwards Lifesciences Ltd., Irvine, California) and CoreValve/Evolute (Medtronic Inc., Minneapolis, Minnesota) valves. Although less invasive than conventional surgery, securing the THV in an optimal position within the SHV determines the success of this novel treatment. METHODS For VIV implantation, we selected appropriate Sapien XT and CoreValve/Evolute sizes depending on the internal diameter of the SHV. Implantation was performed in vitro. In case of the Sapien XT valve, it was deployed 4 to 5 mm below the sewing ring of the SHV, whereas the CoreValve/Evolute was deployed 5 mm below the level of the sewing ring. Photographs and fluoroscopic images of the various VIV combinations were obtained in side profile to study the ideal position and end-on profile to study the circularity of the THV. RESULTS Fluoroscopic images obtained in side profile highlighted the differences in various VIV combinations, as all SHV are unique in their fluoroscopic appearances. Also, all THV implants in various VIV combinations achieved a nearly circular shape. CONCLUSIONS To achieve an optimal result when considering VIV, it is important to be familiar with the structure and fluoroscopic appearances of the failed SHV, the THV used, and their combination.