Progression of aortic stenosis in elderly patients over long-term follow up.

BACKGROUND: The natural history of aortic stenosis (AS) in elderly patients remains poorly defined. In an elderly cohort over long-term follow-up, we assessed: 1) rates and predictors of hemodynamic progression and 2) composite aortic valve replacement (AVR) or death endpoint. METHODS: Consecutive Department of Veterans' Affairs patients with AS (>60 years) were prospectively enrolled between 1988 and 1994 (n=239) and followed until 2008. Patients with ≥ 2 trans-thoracic echocardiograms >6 months apart were included in the progression analysis (n=147). Baseline demographics, comorbidities and echocardiography parameters were recorded. Follow-up was censored at AVR/death. RESULTS: The age of patients was 73 ± 6 years; 82% were male. Baseline AS severity was mild (67%), moderate (23%) and severe (10%). Follow-up was 6.5 ± 4 years (range: 1-17 years). Annualized mean aortic valve gradient progression rates were: mild AS 4 ± 4 mmHg/year; moderate AS 6 ± 5 mmHg/year and severe AS 10 ± 8 mmHg/year (p<0.001). Five-year event-free survival was 66 ± 5%, 23 ± 7% and 20 ± 10% for mild, moderate and severe AS respectively. Progression to severe AS occurred in 35% and 74% of patients with mild and moderate AS respectively. Independent predictors of rapid progression were: baseline AS severity (per grade) (OR 2.6, p=0.001), aortic valve calcification (per grade) (OR 2.1, p=0.01), severe renal impairment (OR 4.0, p=0.04) and anemia (OR 2.3, p=0.05). CONCLUSIONS: In elderly patients, hemodynamic progression of AS is predicted by AS severity, renal function, aortic valve calcification and history of anemia. These factors identify patients at high risk of rapid hemodynamic progression, for whom more frequent clinical and echocardiographic surveillance is advisable.

Global longitudinal strain is a strong independent predictor of all-cause mortality in patients with aortic stenosis.

AIMS: To assess the capacity of global longitudinal strain (GLS) in patients with aortic stenosis (AS) to (i) detect the subclinical left ventricular (LV) dysfunction [LV ejection fraction (LVEF) ≥50% patients]; (ii) predict all-cause mortality and major adverse cardiac events (MACE) (all patients), and (iii) provide incremental prognostic information over current risk markers. METHODS AND RESULTS: Patients with AS (n = 146) and age-matched controls (n = 12) underwent baseline echocardiography to assess AS severity, conventional LV parameters and GLS via speckle tracking echocardiography. Baseline demographics, symptom severity class and comorbidities were recorded. Outcomes were identified via hospital record review and subject/physician interview. The mean age was 75 ± 11, 62% were male. The baseline aortic valve (AV) area was 1.0 ± 0.4 cm(2) and LVEF was 59 ± 11%. In patients with a normal LVEF (n = 122), the baseline GLS was controls -21 ± 2%, mild AS -18 ± 3%, moderate AS -17 ± 3% and severe AS -15 ± 3% (P< 0.001). GLS correlated with the LV mass index, LVEF, AS severity, and symptom class (P< 0.05). During a median follow-up of 2.1 (inter-quartile range: 1.8-2.4) years, there were 20 deaths and 101 MACE. Unadjusted hazard ratios (HRs) for GLS (per %) were all-cause mortality (HR: 1.42, P< 0.001) and MACE (HR: 1.09, P< 0.001). After adjustment for clinical and echocardiographic variables, GLS remained a strong independent predictor of all-cause mortality (HR: 1.38, P< 0.001). CONCLUSIONS: GLS detects subclinical dysfunction and has incremental prognostic value over traditional risk markers including haemodynamic severity, symptom class, and LVEF in patients with AS. Incorporation of GLS into risk models may improve the identification of the optimal timing for AV replacement.

Advances in percutaneous treatment for adult valvular heart disease.

Valvular heart disease occurs in 2-3% of the general population with an increase in prevalence with advancing age. The aetiology of valvular heart disease has evolved in recent decades with degenerative aortic and mitral valve disease supplanting rheumatic heart disease as a primary cause. The common valve lesions to be discussed in this article are aortic stenosis and mitral regurgitation. The traditional approach to calcific aortic stenosis when either symptoms or left ventricular impairment develops is surgical aortic valve replacement and it remains a treatment with excellent outcomes. In recent years there has been interest in less invasive approaches, including percutaneous and transapical aortic valve implantation. With refinements in technology these approaches are becoming a potential treatment option, primarily for high-risk patients who may otherwise be unsuitable for traditional open surgical treatment. Catheter-based approaches for mitral valve disease are also evolving. Mitral regurgitation may often be the result of mitral annular dilatation seen in patients with an enlarged left ventricle or left atrium. Percutaneous implantation of a constricting device in the coronary sinus, which lies in close proximity to the mitral annulus, results in a change to the geometry of the mitral valve and reduced regurgitation. Another technique in patients with degenerative mitral regurgitation is the endovascular edge-to-edge repair in which coaptation of the mitral valve leaflets can be improved with a percutaneously deployed clip. Small patient series indicate that these new techniques are promising. As such, advances in percutaneous interventional and surgical approaches have the potential to further improve outcomes for selected patients with valvular heart disease.

What factors influence the results of coronary artery bypass grafting in aged patients?

AIM: Early and late results were studied in order to improve the indication for coronary artery bypass grafting (CABG) and to enhance METHODS: A total of 1 973 patients aged 70 years and older who had undergone isolated CABG were studied. Elective operations (EL) were performed in 1 716 patients and 257 patients underwent urgent or emergency operations (UR/EM). Patients were divided into two groups; 104 patients aged 80 years and older (Oct. Group) and 1 869 patients of septuagenarians (Sept. Group). There were no differences between the groups in the number of diseased vessels. RESULTS: Total operative mortality rates in the Oct. and the Sept. groups were 7% and 4%, respectively. The operative mortality of elective surgery was 4% in both groups. The operative mortality of UR/EM CABG was significantly higher in the Oct. group than in the Sept. group (21% vs 6%). Operative mortality was significantly higher in patients with preoperative poor (<49%) left ventricular ejection fraction (LVEF) than in patients with higher (>50%) LVEF (6% vs 3%). Among preoperative risk factors, diabetes mellitus and peripheral vascular disease were significant contributory factors to operative death. In the follow-up study, 70% patients of the Oct. group and 72% patients of the Sept. group survived. Preoperative number of diseased vessels and number of CABG grafts did not influence the early and late CONCLUSION: Preoperative poor LVEF, diabetes mellitus and peripheral vascular disease were significant contributory factors to operative death. When feasible, CABG in octogenarians should be performed electively.

A novel approach to reconstructing the distal aortic arch.

Repair of the aortic arch remains one of the greatest challenges in cardiac surgery. This difficulty is compounded by associated descending or thoracoabdominal pathology. Options include single stage repair, two stage procedures and the ingenious elephant trunk operation where a distal trunk is left for reconnection at a subsequent operation or completion by endovascular stenting. We present a technique involving the use of horizontal interrupted buttressed sutures. This allows the distal suture line to be safely placed more distally than is generally the case, achieves reliable haemostasis and may avoid the need for a second stage procedure in some cases.

An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population.

BACKGROUND: We investigated the efficacy of an integrated system of advanced supportive care based on extracorporeal membrane oxygenation (ECMO) in older patients with an estimated mortality of more than 90% to establish whether its use is justifiable. METHODS: Treatment was provided by cardiac surgeons and critical care physicians and included the following key elements: (1) ECMO, (2) early application of continuous venovenous hemofiltration, (3) inhaled nitric oxide, (4) maintenance of perfusion pressure with norepinephrine, (5) maintenance of pulmonary blood flow by ventricular filling with intravenous colloids, (6) avoidance of early postoperative anticoagulation, (7) frequent use of transesophageal echocardiography, and (8) low tidal volume ventilation. Demographic features, intraoperative details, postoperative course, ECMO weaning rate, morbidity, survival to hospital discharge, and the quality of life of survivors were recorded. RESULTS: Seventeen consecutive patients (median age, 69 years) with refractory cardiogenic shock were studied. The median duration of ECMO was 86 hours (20 to 201 hours). Eleven patients (65%) were successfully weaned from ECMO. Seven patients (41%) survived to discharge. The major causes of morbidity were bleeding and leg ischemia. All patients who survived to discharge were alive and well at follow-up (median, 21 months) and reported a satisfactory quality of life. CONCLUSIONS: An ECMO-based approach can be used with acceptable results in the treatment of refractory cardiogenic shock, even in older patients.

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery.

BACKGROUND: The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS: Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS: Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS: Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

Treatment of traumatic false aneurysm of the thoracic aorta with endoluminal grafts.

PURPOSE: Traumatic false aneurysms of the thoracic aorta presenting at a time remote from the original injury are a rare but complex problem. The treatment of a traumatic false aneurysm by endovascular techniques may offer many advantages over conventional open surgery. METHODS AND RESULTS: Two male patients presented with traumatic false aneurysm of the thoracic aorta after being treated emergently for visceral injuries from a gunshot wound in one and an automobile accident in the other. In both cases, the aneurysm was situated so that only the T11 intercostal artery would be sacrificed by endoluminal exclusion. Commercially available endoluminal stent-grafts (Talent) were deployed successfully. Recovery in both patients was rapid and uneventful with no neurological sequelae. Spiral computed tomographic scans at 1 year indicated sustained aneurysm exclusion and satisfactory endograft position. CONCLUSIONS: A customized endoluminal stent-graft can be used with great accuracy to exclude thoracic false aneurysms, avoiding the potential complexity and morbidity of an open thoracic approach.

Pattern and significance of cerebral microemboli during coronary artery bypass grafting.

BACKGROUND: Strokes that occur during coronary artery bypass grafting are often caused by embolism. Intraoperative transcranial Doppler monitoring can detect cerebral microemboli. The aims of this study were to identify the pattern of microembolic phenomena during various stages of coronary artery bypass grafting, to verify whether numbers of high-intensity transient signals correlated with early neuropsychologic deficits, and to identify, using magnetic resonance imaging scans, whether radiologic evidence of cerebral infarction correlated with microembolic numbers during the bypass period. METHODS: Forty-one consecutive patients undergoing coronary bypass grafting with transcranial Doppler monitoring were enrolled in this study. All had preoperative and postoperative magnetic resonance imaging brain scans. A subgroup of 32 patients were studied by comparing microembolic load and early neuropsychological outcomes. RESULTS: Transcranial Doppler monitoring confirmed that most microemboli occurred during cardiopulmonary bypass. A significant early neuropsychological deficit after coronary artery bypass grafting did correspond to the total microembolic load during bypass (p = 0.008). However, patients with cerebral infarction on magnetic resonance imaging had significantly more microembolic signal during the preincision phases and not during the bypass period. CONCLUSIONS: Microembolic load during bypass is associated with early neuropsychologic deficits. In contrast, patients who show evidence of strokes during coronary artery bypass grafting have a higher microembolic load during the preincision phase than those without cerebral infarction. Differing mechanisms may be responsible for these different outcomes.

The intraoperative assessment of ascending aortic atheroma: epiaortic imaging is superior to both transesophageal echocardiography and direct palpation.

OBJECTIVES: To determine the optimal method for detecting ascending aortic atheroma intraoperatively by comparing manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging); and to assess risk factors for severe aortic atheroma. DESIGN: A longitudinal prospective study. Assessment of the atheroma by manual palpation was blinded to the results of the ultrasound images. SETTING: The study was performed in a single university tertiary referral hospital. PARTICIPANTS: One hundred consecutive patients undergoing coronary bypass or valve surgery were studied after their written, informed consent. INTERVENTIONS: Potential risk factors were evaluated by both a patient questionnaire and examination of prior hospital records. The ascending aorta was assessed by the following methods: manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging) performed by an echocardiologist. For analysis, the ascending aorta was divided into three equal segments: proximal, mid, and distal, corresponding to regions of different operative manipulations. MEASUREMENTS AND MAIN RESULTS: Age older than 70 years and hypertension were significant risk factors for severe ascending aortic atheroma with adjusted odds ratios of 3.3 (95% CI, 1.2 to 9.3) and 3.9 (95% CI, 1.3 to 12.0), respectively. There was no significant difference in atheroma detection between the two ultrasonic epiaortic probes in any segment; however, epiaortic probes were superior to manual palpation in all segments and also superior to transesophageal echocardiography in the mid and distal segments of the ascending aorta. CONCLUSIONS: Age older than 70 years and hypertension are significant risk factors for severe ascending aortic atheroma. Intraoperative detection of ascending aortic atheroma is best achieved by epiaortic ultrasound with either a linear or phased array transducer. Transesophageal echocardiography is an insensitive technique for evaluation of mid and distal ascending aortic atheroma and, therefore, of little value in guiding surgical manipulations such as cross-clamping.

Retrograde vital organ perfusion during aortic arch repair.

A technique is described for cerebral and other vital organ preservation during aortic arch repair using retrograde venous perfusion at 20 degrees C. This technique retains the excellent operating conditions of deep hypothermia and circulatory arrest. Potential benefits include shortening of the cooling and rewarming time, reduction of coagulopathy, prevention of emboli, and extension of the safe period of antegrade circulatory arrest.

A technique for the in vitro culture of human parathyroid gland tissue.

A technique for prolonged in vitro culture of human parathyroid tissue is described. Cells could be maintained in this monolayer system and were shown to continue releasing high levels of parathyroid hormone into their culture medium even after 140 days in culture. Furthermore, growth of fibroblasts, persistence of epithelial cells and parathyroid hormone release was demonstrated in cells derived from parathyroid tissue that had been cryopreserved for 2 years. The availability of viable and functioning human parathyroid tissue produced in this culture system may be of value in both auto- and allo-transplantation in patients with permanent hypoparathyroidism.

Is there still a place for carotid endarterectomy?

Carotid endarterectomy is a controversial procedure. Despite the increasing incidence of its performance, there have been as yet no prospective randomised trials which have conclusively shown its benefits for patients with carotid artery atherosclerosis. Until the results of such studies become available, a rational approach to the estimation of stroke risk in these patients can be based on an understanding of their carotid plaque morphology. Over the past 4 years we have examined plaque morphology with a B-mode duplex scanner and have been able to categorise the degree of heterogeneity of plaques into 4 types depending on the degree of plaque echolucency. We have shown good correlation between the preoperative plaque type and the operation specimen. Furthermore, we have found that the risk of symptom development correlates with the development of a more echolucent plaque. Finally, while plaque heterogeneity may be a good predictor of the risk of embolism from the plaque, other deleterious factors such as hypertension may determine the severity of the ensuing neurological event. The approach in our unit has been to operate on symptomatic patients with demonstrated high grade or heterogeneous carotid artery atherosclerosis appropriate to the patient's symptoms. We have found that most asymptomatic patients have subcritical stenoses and dense homogeneous plaques, and we treat these conservatively. On the other hand, surgery is recommended for asymptomatic patients with high grade stenoses and heterogeneous plaques. We have been able to follow this policy with a morbidity and mortality of 2.6% and 1.0% respectively.

Lectin binding patterns and monoclonal antibodies to epidermal antigens in tumours of the skin.

Monoclonal antibodies to epidermal antigens and cell surface carbohydrate markers, as defined by lectin binding, were used to analyze the cells in squamous and basal cell carcinomas of the skin (SCC and BCC). The cells in BCC failed to stain with the lectin peanut agglutinin (PNA), which stains surface carbohydrates of cells in the stratum spinosum and stratum granulosum layers of normal epidermis, confirming histological observations that the cells in BCC are incapable of differentiation beyond the basal cell stage. Conversely, the central cells in SCC did react with PNA, suggesting that they can differentiate to a stage equivalent to the stratum spinosum of epidermis. The zone immediately surrounding BCC differed from that around SCC in lectin binding and staining with antisera to laminin and fibronectin, an observation which could be connected with the failure to metastasize. It was of interest that histologically normal skin immediately adjacent to and overlying these tumours showed marked changes in reaction with markers of normal epidermis. The outer layers of this epidermis showed aberrant retention of the lower molecular weight cytokeratins marked by the monoclonal antibodies LMM2 and LMM3, and occasional strong staining of individual cells by the stratum granulosum-reactive LMM1. These changes appear to be indicative of a 'premalignant' state in these cells and the monoclonal antibodies are thus potentially useful reagents for early detection of skin malignancies.

Dopamine-induced depression of adrenergic nerve-mediated contraction of smooth muscle.

1 Dopamine (0.25-1.0 micrometer) applied extraluminally depressed vasoconstrictor responses of the perfused rabbit ear artery to low frequency adrenergic nerve stimulation. 2 The depressant effect of dopamine was prevented in the presence of haloperidol (0.1 micrometer) but not in the presence of phentolamine (0.03-0.14 micrometer). 3 Extraluminal dopamine (1 micrometer) or intraluminal injection of dopamine in amounts up to 0.025 micronmol had no dilator effect on arteries partially constricted by infusion of noradrenaline. 4 Dopamine also depressed contractile responses of guinea-pig vas deferens to low frequency adrenergic nerve stimulation. However, in this tissue the effect of dopamine was prevented by phentolamine but not affected by haloperidol. 5 In neither the rabbit ear artery nor the guinea-pig vas deferens did haloperidol increase the magnitude of responses to nerve stimulation or affect muscle sensitivity to noradrenaline. 6 We conclude that the adrenergic axons in the rabbit ear artery, but not the guinea-pig vas deferens, possess specific receptors for dopamine whose activation depresses axonal conduction or transmitter release. However, our results do not favour the view that these receptors are activated during normal transmission at physiological frequencies.