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John A Elefteriades

Publications and source records attributed to John A Elefteriades.

At least 19 recordsLinked to original sources
PubMed2006

Health related quality of life after mitral valve repairs and replacements.

BACKGROUND: The decision to replace or repair mitral valves is often a difficult decision, and outcomes from the patients' perspective should guide decision-making. We investigated whether the change in health related quality of life (HRQOL) after mitral valve surgery is different after valve repairs compared with replacements. METHODS: We prospectively studied 25 patients with mitral valve replacement and 45 patients with valve repairs performed in 1998-99. We measured HRQOL at baseline and at 18 months using the Medical Outcomes Trust Short Form 36-item Health Survey (SF-36) questionnaire. We compared mean HRQOL scores of the groups with age-adjusted U.S. population scores. We used analysis of covariance to determine a change in HRQOL within groups (repair or replacement) and if the change in HRQOL was different between the groups. RESULTS: We found few differences between the groups, with more men and simultaneous coronary artery bypass graft surgery in the valve repair group and more prior operation in the valve replacement group. HRQOL improved after surgery in most domains, and was comparable to age-adjusted U.S. norms in the valve repair group. In the multivariable analysis, mitral valve repair recipients reported higher social functioning compared with patients who received valve replacement (p = 0.04). We did not find other statistically significant differences. However, the adjusted improvements in the component scales of physical functioning (PCS) and mental functioning (MCS) were substantial in the valve repair group (mean changes: PCS = 6.8, p = 0.003; MCS = 8.1, p = 0.014) and less pronounced in the replacement group (mean changes: PCS = 3.6, p = 0.09; MCS = 4.3, fsp = 0.16). CONCLUSIONS: While many considerations influence the decision to repair or replace mitral valves, these findings suggest that repair may be better from the health status perspective. Further studies are necessary to validate this finding.

Aged↗
PubMed2006

Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysms.

BACKGROUND: Optimal operative decision making in thoracic aortic aneurysms requires accurate information on the risk of complications during expectant management. Cumulative and yearly risks of rupture, dissection, and death before operative repair increase with increasing aortic size, but previous work has not addressed the impact of relative aortic size on complication rates. METHODS: Our institutional database contains data on 805 patients followed up serially with thoracic aortic aneurysms. Body surface area information was obtained on 410 patients (257 male, 153 female). We calculated a new measure of relative aortic size, the "aortic size index," and examined its ability to predict complications in these patients. RESULTS: Increasing aortic size index was a significant predictor of increasing rates of rupture (p = 0.0014) as well as the combined endpoint of rupture, death, or dissection (p < 0.0001). Using aortic size index, patients were stratified into three risk groups: less than 2.75 cm/m2 are at low risk (approximately 4% per year), 2.75 to 4.24 cm/m2 are at moderate risk (approximately 8% per year), and those above 4.25 cm/m2 are at high risk (approximately 20% per year). CONCLUSIONS: This study confirms that (1) thoracic aortic aneurysm is a lethal disease, (2) relative aortic size is more important than absolute aortic size in predicting complications, and (3) a novel measurement of relative aortic size allows for the stratification of patients into three levels of risk, enabling appropriate surgical decision-making.

Adolescent↗
PubMed2006

Familial thoracic aortic aneurysms and dissections--incidence, modes of inheritance, and phenotypic patterns.

BACKGROUND: We examined the genetic nature and phenotypic features of thoracic aortic aneurysms (TAAs) and dissections in a large cohort of patients. METHODS: Interviews were conducted with 520 patients with TAAs and their pedigrees were compiled to identify family members with aneurysms. Study patients were divided into three groups: 101 non-Marfan patients, in 88 pedigrees, had a family pattern for TAA (familial group), 369 had no family pattern (sporadic group), and 50 had Marfan syndrome (MFS). We determined incidence of familial clustering, age at presentation, rate of aneurysm growth, incidence of hypertension, correlation of aneurysm sites among kindred, and pedigree inheritance patterns. RESULTS: An inherited pattern for TAA was present in 21.5% of non-MFS patients. The predominant inheritance pattern was autosomal dominant (76.9%), with varying degrees of penetrance and expressivity. The familial TAA group was significantly younger than the sporadic group (p < 0.0001), but not as young as the MFS group (p < 0.0001) (mean ages, 58.2 versus 65.7 versus 27.4 years). Among all 197 probands and kindred with aneurysm, 131 (66.5%) had TAA, 49 (24.9%) had abdominal aortic aneurysm (AAA), and 17 (8.6%) had cerebral or other aneurysms. Ascending aneurysm paired most commonly with ascending, and descending with abdominal. Abdominal aortic aneurysms (AAAs) and hypertension were more often associated with descending than with ascending TAAs (p < 0.001). Aortic growth rate was highest for the familial group (0.21 cm/y), intermediate for the sporadic group (0.16 cm/y), and lowest for the Marfan group (0.1 cm/y; p < 0.01). CONCLUSIONS: TAAs are frequently familial diseases. The predominant mode of inheritance is autosomal dominant. Familial TAAs have a relatively early age of onset. Aneurysms in relatives may be seen in the thoracic aorta, the abdominal aorta, or the cerebral circulation. Screening of first-order relatives of probands with TAA is essential. Familial TAAs tend to grow at a higher rate, exemplifying a more aggressive clinical entity.

Adult↗
PubMed2005

Hyperplastic cellular remodeling of the media in ascending thoracic aortic aneurysms.

BACKGROUND: Progressive medial degeneration and atrophy is thought to be a cause of ascending thoracic aortic aneurysms in the elderly. Extensive apoptosis of vascular smooth muscle cells (VSMCs) has been demonstrated in the media of abdominal aortic aneurysms. We investigated whether medial atrophy from loss of VSMCs occurs in primary ascending thoracic aortic aneurysms. METHODS AND RESULTS: Morphometric analysis of 28 nonaneurysmal ascending thoracic aortas and 29 ascending thoracic aortic aneurysms was performed by directly measuring the thickness of their vascular layers and by indirectly calculating the area of their vascular compartments. The cellular and matrix composition of the media was assessed at the structural, protein, and transcript levels. Despite thinning of the media secondary to vascular dilatation, there was an overall increase in the medial area of aneurysms. VSMC density was preserved, implying cellular hyperplasia as a result of the increased medial mass. There was decreased expression of matrix proteins, despite sustained synthesis of these molecules, which was associated with evidence of increased matrix degradation. The remodeling and expansion of the media was most evident in comparisons between nonaneurysmal aortas versus smaller aneurysms and did not evolve further in larger aneurysms. CONCLUSIONS: The mechanisms for luminal enlargement in thoracic and abdominal aortic aneurysms differ significantly with regard to the survival of VSMCs and atrophy of the media but share common pathophysiology involving degeneration of the matrix. Hyperplastic cellular remodeling of the media in ascending thoracic aortic aneurysms may be an initial adaptive response to minimize increased wall stress resulting from vascular dilatation.

Aorta↗
PubMed2005

Transmural inflammation by interferon-gamma-producing T cells correlates with outward vascular remodeling and intimal expansion of ascending thoracic aortic aneurysms.

Arterial pathology manifests as aneurysmal or obstructive disease depending on changes in lumen size due to vascular remodeling (change in vessel external diameter) and/or intimal expansion. Recent clinical and experimental observations in abdominal aortic aneurysms have led to the emerging dogma that Th2-dominant immune responses result in expansive vascular remodeling and luminal ectasia, whereas Th1 immune responses cause intimal hyperplasia and luminal stenosis. We tested this hypothesis by descriptive analyses of 31 non-aneurysmal and 29 aneurysmal ascending thoracic aortic specimens. Approximately half the aneurysms were distinguished by transmural inflammation. The remaining aneurysms and all the non-aneurysmal aortas had a similar leukocytic infiltrate that spared the inner media. Aneurysm tissue had increased expression of the prototypical Th1 cytokine, interferon (IFN)-gamma, and undetectable Th2 cytokines. Specimens with inner media infiltration displayed robust production of IFN-gamma, induction of the IFN-gamma-inducible chemokines IP-10 and Mig, and recruitment of lymphocytes bearing their cognate receptor CXCR3. Transmural inflammation and IFN-gamma production were associated with increased aortic external diameter, intimal thickening, preserved vascular smooth muscle cell density, and decreased matrix proteins. Th1, but not Th2, immune responses have a positive correlation with both outward vascular remodeling and intimal expansion of ascending thoracic aortic aneurysms.

Adolescent↗
PubMed2005

Symptoms plus family history trump size in thoracic aortic aneurysm.

A 43-year-old woman presented with chest pain of unclear cause. The patient's mother and brother had suffered aortic dissection. Echocardiography had shown mild dilatation of the ascending aorta at 4.0 cm. Echocardiogram and magnetic resonance imaging were negative for dissection. The patient was taken to the operating room on the basis of her painful symptoms and her family history. Unexpectedly, a localized dissection was found in the ascending aorta (see Fig 2), which was too small for imaging detection. Without preemptive surgery, full-fledged dissection would have likely occurred with attendant short and long-term consequences. This case emphasizes that size criteria pertain to asymptomatic patients, and symptomatic patients with aneurysm require resection regardless of size.

Adult↗
PubMed2005

Mechanical deterioration underlies malignant behavior of aneurysmal human ascending aorta.

OBJECTIVE: The human ascending aorta becomes markedly prone to rupture and dissection at a diameter of 6 cm. The mechanical substrate for this malignant behavior is unknown. This investigation applied engineering analysis to human ascending aortic aneurysms and compared their structural characteristics with those of normal aortas. METHODS: We measured the mechanical characteristics of the aorta by direct epiaortic echocardiography at the time of surgery in 33 patients with ascending aortic aneurysm undergoing aortic replacement and in 20 control patients with normal aortas undergoing coronary artery bypass grafting. Six parameters were measured in all patients: aortic diameter in systole and diastole, aortic wall thickness in systole and diastole, and blood pressure in systole and diastole. These were used to calculate mechanical characteristics of the aorta from standard equations. Aortic distensibility reflects the elastic qualities of the aorta. Aortic wall stress reflects the disrupting force experienced within the aortic wall. Incremental elastic modulus indicates loss of elasticity reserve. RESULTS: Aortic distensibility falls to extremely low levels as aortic dimension rises toward 6 cm (3.02 mm Hg(-1) for small aortas versus 1.45 mm Hg(-1) for aortas larger than 5 cm, P < .05). Aortic wall stress rises to 157.8 kPa for the aneurysmal aorta, compared with 92.5 kPa for normal aortas. For 6-cm aortas at pressures of 200 mm Hg or more, wall stress rises to 857 kPa, nearly exceeding the known maximal tensile strength of human aneurysmal aortic wall. Incremental elastic modulus deteriorates (1.93 +/- 0.88 MPa vs 1.18 +/- 0.21 MPa, P < .05) in aneurysmal aortas relative to that in normal aortas. CONCLUSION: The mechanical properties of the aneurysmal aorta deteriorate dramatically as the aorta enlarges, reaching critical levels associated with rupture by a diameter of 6 cm. This mechanical deterioration provides an explanation in engineering terms for the malignant clinical behavior (rupture and dissection) of the aorta at these dimensions. This work adds to our fundamental understanding of the biology of aortic aneurysms and promises to permit future application of engineering measurements to supplement aneurysm size in clinical decision making in aneurysmal disease.

Aorta↗
PubMed2005

Indications, timing, and prognosis of operative repair of aortic dissections.

Since the first description of aortic dissection in the 1700s, the understanding and treatment of this catastrophic disease has evolved. Aortic dissections are identified as a tear in the aortic intima and inner layer of the media that allows for blood flow within the aortic wall. The area of the vessel involved determines its classification. The classification, in turn, helps to predict outcomes, which allows for appropriate treatment planning. The goal of this article is to outline the operative indications and timing for Stanford type A and type B dissections, based on prior reported data and our own clinical experience with 176 patients treated surgically at the Yale Center for Thoracic Aortic Disease. With this data we will revisit the importance of looking at each patient individually to devise an appropriate operative plan, with the knowledge that treatment for type A dissections is operative and treatment for type B dissections is medical unless patients present with actual or impending rupture, malperfusion, or failure of medical management.

Adolescent↗
PubMed2005

Phantom aortic valve pressure gradient: discrepancies between cardiac catheterization and Doppler echocardiography.

We present a case of a patient scheduled for mitral valve replacement and possible aortic valve replacement. On Doppler examination, her peak transaortic pressure gradient measured on three separate occasions (pre-, intra-, and postoperatively) was approximately 60 mm Hg. In contrast, the peak-to-peak pressure gradient (cardiac catheterization) was 11 mm Hg. This latter gradient was confirmed in the operating room by direct simultaneous measurement of the pressures in the left ventricle and ascending aorta. Potential causes for this discrepancy are discussed, among which the "pressure recovery phenomenon" is considered the most important.

Aged↗
PubMed2004

Immunohistochemical testing for Helicobacter pylori infection in ascending aortic aneurysms and penetrating aortic ulcers.

Evidence implicating Helicobacter pylori (H. pylori) in coronary artery disease and aneurysmal lesions is controversial. No published data have related H. pylori infection to ascending aortic aneurysms and penetrating ulcers, although both of these lesions may have an infectious components in their initiating process. We sought to investigate possible H. pylori infection in 54 human specimens of 42 aortic aneurysms and 12 penetrating ulcers. No evidence of H. pylori was found in these specimens.

Adult↗
PubMed2004

Femoral cannulation is safe for type A dissection repair.

BACKGROUND: Recently, surgeons have embraced axillary artery cannulation for type A aortic dissection repair out of concern for malperfusion phenomena with traditional femoral artery cannulation. My colleagues and I sought to determine whether these concerns are justified. METHODS: Records of 86 consecutive patients (51 men and 35 women; age, 30 to 86 years; mean, 62 years) undergoing surgical repair for acute type A dissection were reviewed. Cannulation site, specific operative repair, and complications related to cannulation were noted. RESULTS: Seventy-nine cannulations were performed in the femoral artery (47 left, 23 right, and 9 unspecified), 3 in the axillary artery (1 left and 2 right), and 4 in the ascending aorta or arch. Deep hypothermic arrest was used in 64 operations. Seven involved re-sternotomy. Seventy patients had supracoronary grafts (2 with valve replacement and 10 with valve resuspension), and 16 underwent aortic root replacement. Fourteen patients were in shock from cardiac tamponade. Eighty patients survived the operation, and 71 were hospital survivors. Malperfusion on initiation of cardiopulmonary bypass was noted in 3 patients. In 1, the original cannulation site was the ascending aorta, and the cannula was moved to the femoral artery for correction. In 2, the original cannulation site was the femoral artery, and the cannula was moved to the ascending aorta. Malperfusion on clamping of the aorta or on resumption of aortic flow was noted in no patient. Postoperative ischemia of any vascular bed was noted locally only in 3 (cannulated) lower extremities. CONCLUSIONS: Straight femoral cannulation for all phases of type A dissection repair is appropriate and yields excellent clinical results. The anticipated malperfusion events are actually rare (2 of 79 with femoral artery cannulation, or 2.5%).

Acute Disease↗
PubMed2004

Increased tissue microarray matrix metalloproteinase expression favors proteolysis in thoracic aortic aneurysms and dissections.

BACKGROUND: Little information is available regarding the role of matrix metalloproteinases (MMPs) in thoracic aortic aneurysms and dissections. We applied tissue microarray analysis to determine MMP profiles in a large group of surgically resected thoracic aneurysms and dissections. METHODS: Specimens from 47 patients undergoing a variety of surgical procedures for thoracic aneurysm (n = 30) and dissection (n = 17) were included. Expression of MMP-1, MMP-2, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were assessed by aortic tissue microarray immunostaining. Matrix metalloproteinase and TIMP expression in aortic tissue was compared with seven control aortic specimens, free of any vascular disease. RESULTS: Expression of MMP-1 and MMP-9 was significantly increased in aneurysm and aortic dissection patients compared with control specimens (p < 0.05). Expression of TIMP-2 was significantly increased in the entire patient group, compared with control specimens (p < 0.05). Aortic dissection patients had higher MMP-2 and MMP-9 expression than aortic aneurysm patients in areas of disease. Compared with control patients, the MMP-9 to TIMP-1 ratio (a relative index of proteolytic state) was increased in both the aortic aneurysm and dissection groups (p < 0.05). CONCLUSIONS: The increased MMP expression in aortic aneurysms and dissections indicates a metamorphosis in the aneurysm wall toward increased proteolysis compared with the normal aorta. Furthermore, we find even higher MMP-2 and MMP-9 presence in aortic dissection. In both aneurysms and dissections, this transformation to a proteolytic state likely plays an important pathophysiologic role in the development and progression of the aortic disease. The recognition of this pathophysiologic mechanism raises the potential for drug therapy to interrupt the cascade of events.

Aged↗
PubMed2004

Tissue microarray detection of matrix metalloproteinases, in diseased tricuspid and bicuspid aortic valves with or without pathology of the ascending aorta.

OBJECTIVE: The degeneration of bicuspid aortic valve and its frequent association with ascending aortic pathology, point to a still unidentified genetic tissue defect with unknown mediators. Metalloproteinases (MMPs) are lytic enzymes that have been strongly implicated in aneurysm formation. The purpose of this study was to detect the presence of these enzymes in aortic valvular tissue in healthy and diseased aortic valves with or without the presence of synchronous ascending aortic pathology. METHODS: Aortic valve specimens from 26 aortic valve replacement patients as well as 4 healthy control tricuspid aortic valves were included. 10 patients had bicuspid aortic valves, and 16 had tricuspid aortic valves. Half of our patient population had a concomitant aortic procedure for aortic pathology. The study detected MMPs 1,2 and 9 as well as their Tissue inhibitors (TIMPs) 1 and 2. MMP and TIMP detection was accomplished with the construction of a tissue micro array and immunohistochemistry. CONCLUSIONS: MMP-9 expression was significantly higher in bicuspid aortic valves compared to normal valves (P<0.05). When compared to the tricuspid valve group, MMP-9 mean value was significantly higher in bicuspid valves (P<0.05). When the entire rest of the valve group (n=4+16, i.e. control and tricuspid valve groups) was compared to the bicuspid valve group, bicuspid valves had significantly higher MMP-2, and MMP-9 (P<0.01) expression. TIMP expression also changed in diseased valves, among different patient groups. This increased proteolytic presence in bicuspid aortic valves may attribute to the observed decreased elastin and collagen content, and their resultant functional failure.

Aortic Aneurysm↗
PubMed2004

Quality of life after aortic valve replacement with tissue and mechanical implants.

OBJECTIVES: We sought to determine whether changes in quality of life at 18 months following aortic valve replacement differ depending on the use of tissue valves or mechanical valves. METHODS: We prospectively studied 73 patients with tissue valve replacements and 53 patients with mechanical valve replacements performed from April 1998 through March 1999 at Yale-New Haven Hospital. Quality of life was measured at baseline and at 18 months using the Medical Outcomes Trust Short Form 36-Item Health Survey. RESULTS: Baseline unadjusted mean quality-of-life scores were lower in tissue valve recipients than in mechanical valve recipients and, for both groups, were generally lower than US population norms. At 18 months postoperatively, quality-of-life scores were greatly improved in both groups and were comparable to population norms (ie, within one-half a standard deviation). After adjusting for baseline quality of life, age, and other prognostic factors in an analysis of covariance, improvements in quality-of-life scores for tissue valve recipients versus mechanical valve recipients were similar. Of 10 (8 domains and 2 summary) scales examined, the only significant difference between the 2 groups was for the improvement in role limitations due to physical problems (Role Physical), which was more favorable in patients with mechanical valve implants (P =.04). CONCLUSIONS: The use of tissue valve implants versus mechanical valve implants has little influence on improvement in quality of life at 18 months following aortic valve replacement. Thus, decisions about whether to choose a tissue valve or mechanical valve implant should depend upon other factors such as rates of complications and differences in the life span of the implants.

Aged↗