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Biomedical subjects

Brian P Griffin

Publications and source records attributed to Brian P Griffin.

At least 19 recordsLinked to original sources

Mitral valve surgery in the adult Marfan syndrome patient.

BACKGROUND: Because mitral valve dysfunction in adults with Marfan syndrome is poorly characterized, this study compares mitral valve pathophysiology and morphology with that of myxomatous mitral disease, documents types of mitral valve operations, and assesses long-term survival and durability of mitral valve surgery in Marfan patients. METHODS: From May 1975 to June 2000, 27 adults with Marfan syndrome underwent mitral valve surgery. Their valve pathophysiology and morphology was compared with that of 119 patients with myxomatous mitral disease undergoing surgery from September 1995 to March 1999. Survival and repair durability were assessed at follow-up. RESULTS: Compared with myxomatous disease patients, Marfan patients had less posterior leaflet prolapse (44% versus 70%, p = 0.01), more bileaflet (44% versus 28%, p = 0.09) and anterior leaflet prolapse (11% versus 3%, p = 0.07), and presented earlier for surgery (age 41 +/- 12 years versus 57 +/- 13, p < 0.0001). Marfan patients had longer and thinner leaflets. Mitral valve repair was performed less frequently in Marfan (16 of 27, 59%) than myxomatous disease patients (112 of 119, 94%). There were no hospital deaths; at 10 years, survival was 80% and freedom from reoperation 96%, with only 1 reoperation among the 16 repairs. CONCLUSIONS: Mitral valve pathophysiology and morphology differ between Marfan and myxomatous mitral valve diseases. Valve repair in Marfan patients is durable and gives acceptable long-term results, even in adults who present with advanced mitral valve pathology. With increasing use of the modified David reimplantation operation and sparing of the aortic valve, mitral valve repair is a greater imperative, particularly since we have not had to reoperate on any Marfan patients with reimplantations.

Adult↗

Preoperative cholesterol levels do not predict explant for structural valve deterioration in patients undergoing bioprosthetic aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Structural valve deterioration (SVD) is the most common cause of bioprosthetic valve failure. Coronary disease risk factors, including hypercholesterolemia, might predict SVD. Here, the relationship was examined between preoperative cholesterol levels and SVD in patients undergoing bioprosthetic aortic valve replacement (AVR). METHODS: A total of 7,150 patients (mean age 68 +/- 12 years) was identified who underwent bioprosthetic AVR at the Cleveland Clinic Foundation, between January 1975 and December 2002. Preoperative and postoperative variables were retrieved from a prospective, computerized database. A parametric method was used to estimate the distribution of valve explants; a multivariable risk factor model was then developed to include patient demographics, cardiac and non-cardiac comorbidities, valve type and interactions. The primary end-point was explant for SVD. All explants were examined, and observations were censored at the time of any explant or death. Bootstrap analysis was used to validate the model. RESULTS: Among 7,150 patients, 208 had explants for SVD. Mean preoperative total cholesterol (TC) was 203 +/- 48 mg/dl, HDL-cholesterol 45 +/- 15 mg/dl, and LDL-cholesterol 121 +/- 41 mg/dl. The average follow up was 3.7 years, and 1,169 patients (16%) were followed for more than eight years. In multivariable analysis, only younger age (p < 0.0001), greater body weight (p < 0.0001), elevated serum creatinine level (p = 0.0004) and use of a pericardial valve (p = 0.04) predicted SVD. Neither preoperative cholesterol nor its fractions predicted valve explant for SVD (log-rank p = 0.19) Moreover, no cardiovascular risk factors were predictive of SVD. CONCLUSION: Preoperative cholesterol levels do not predict SVD in patients undergoing bioprosthetic AVR. Whether long-term hypercholesterolemia or statin therapy impacts SVD requires further investigation.

Aged↗

Natural history of valvular regurgitation using side-by-side echocardiographic analysis in anorexigen-treated subjects.

In 1997, the US Food and Drug Administration (FDA) reported valvular regurgitation (aortic regurgitation [AR] mild or greater and/or mitral regurgitation [MR] moderate or greater) in 32.8% of patients treated with anorexigens. This study sought to determine the natural history of valvular regurgitation in patients who were included in the FDA's original report. This was a nonrandomized, natural history study of these subjects. Cohort I consisted of 155 of 186 patients (83%) who were reported to the FDA. Cohort II consisted of a similar group of 311 patients who were not included. Initial echocardiograms were obtained for medical indications before the study initiation, and study echocardiograms were standardized and obtained at 3-month intervals. Level III echocardiographers performed blinded, side-by-side comparison of the first and last study echocardiograms at a core laboratory. Cohorts I and II consisted of predominantly female, middle-aged, obese subjects. At enrollment, patients in cohorts I and II had mild or greater AR (17.9%, 13.5%) and moderate or greater MR (3.3%, 4.0%), respectively, which was less than in the FDA's report. At follow-up, there were no statistically significant changes in the degree of valvular regurgitation in either cohort when the first and last study echocardiograms were read side by side. In conclusion, this natural history follow-up study demonstrates that MR and AR in long-term anorexigen-treated patients was less than reported to the FDA, did not progress, and remained echocardiographically stable during the 10-month duration of the study.

Appetite Depressants↗

Apparently normal mitral valves in patients with heart failure demonstrate biochemical and structural derangements: an extracellular matrix and echocardiographic study.

OBJECTIVES: This study assessed apparently normal mitral valves from patients with congestive heart failure (CHF) using biochemical and echocardiographic measures of extracellular matrix (ECM) and anatomy. BACKGROUND: Mitral regurgitation (MR) is frequently found in patients with CHF. This MR is considered purely functional, yet animal studies suggest that altered left ventricular (LV) function leads to increased cellularity and fibrosis of the mitral valve. Therefore, we hypothesized that patients with CHF might have partly organic MR, via dysfunctional valvular remodeling. METHODS: Mitral valves from transplant recipient hearts of patients with CHF (23 dilated, 14 ischemic) were analyzed for deoxyribonucleic acid (DNA), collagen, glycosaminoglycan (GAG), and water concentrations and compared with autopsy controls. Cardiac dimensions and functional parameters (measured from recent echocardiograms) were compared with biochemical parameters using a repeated measures generalized linear model. RESULTS: The mitral valves in CHF had up to 78% more DNA (p <0.03), 59% more GAGs (p <0.02), and 15% more collagen (p <0.007), but 7% less water (p <0.05) than normal. The absence of anterior leaflet redundancy was associated with these deranged biochemical measures (p <0.03). Associations were found between leaflet thickness and DNA concentration (+, p=0.003), annular diameter and chordal collagen (+, p=0.03), and water concentration and both left atrial diameter (-, p=0.008) and LV collagen concentration (-, p=0.04). CONCLUSIONS: Mitral valves in CHF are biochemically different from normal, with ECM changes that are influenced by the altered cardiac dimensions. This remodeling suggests that MR in patients with CHF may not be purely functional, and that these valves are not "normal."

Adult↗

Ischemic and viable myocardium in patients with non-Q-wave or Q-wave myocardial infarction and left ventricular dysfunction: a clinical study using positron emission tomography, echocardiography, and electrocardiography.

OBJECTIVES: We investigated whether patients with non-Q-wave myocardial infarction (NQMI) have more ischemic viable myocardium (IVM) than patients with Q-wave myocardial infarction (QMI). BACKGROUND: Non-Q-wave myocardial infarction is associated with higher incidences of cardiac events than QMI, suggesting more myocardium at risk in NQMI. METHODS: To identify myocardial ischemia, hibernation, and scar, the resting and stress (82)rubidium perfusion and F-18 fluorodeoxyglucose metabolic positron emission tomographic imaging (PET) was performed in 64 consecutive patients with NQMI (n = 21) or QMI (n = 43). Echocardiography was performed for assessment of left ventricular function and wall motion index (WMI). The relationships between PET, echocardiographic, and electrocardiographic findings were analyzed. RESULTS: There were no significant differences in left ventricular ejection fraction (LVEF) between NQMI and QMI groups (28 +/- 10% vs. 25 +/- 11%, p > 0.05). Ischemic and viable myocardium was more common in NQMI than in QMI (91% vs. 61%, p < 0.05). The total amount of IVM was significantly higher in NQMI than in QMI (6.5 +/- 5.2 vs. 2.9 +/- 2.8 segments, p < 0.001). Neither the number of Q waves, residual ST-segment depression of >or=0.5 mm or elevation of >or=1 mm, nor LVEF and WMI were significant predictors for IVM. Wall motion index correlated with scar segments (r = 0.54, p < 0.001) and LVEF (r = -0.67, p < 0.001). CONCLUSIONS: Ischemic and viable myocardium is common in patients with NQMI and left ventricular dysfunction, suggesting that aggressive approaches should be taken to salvage the myocardium at risk in such patients.

Case-Control Studies↗

Biomechanical and echocardiographic characterization of flail mitral leaflet due to myxomatous disease: further evidence for early surgical intervention.

BACKGROUND: Flail mitral leaflet (FML) is a common complication of mitral valve prolapse, often leading to severe mitral regurgitation (MR) and left ventricular dysfunction. In the absence of timely surgical correction, survival is significantly impaired. Early recognition of FML and identification of risk factors is important because early intervention increases the chances of survival. METHODS: We studied 123 patients undergoing mitral valve surgery for severe MR caused by myxomatous disease. Chart review, echocardiography, and tensile testing were performed. RESULTS: Thirty-eight patients had FML, and 85 patients had non-flail mitral leaflet (non-FML). Patients with FML were younger (53.7 +/- 1.8 vs 59.3 +/- 1.4 years, P =.02), had more severe MR (3.89 +/- 0.04 vs 3.76 +/- 0.04, P =.02), were less likely to be in New York Heart Association class III or IV heart failure (5% vs 20%, P =.037), and were less likely to have bileaflet mitral valve prolapse (5% vs 38%, P <.001) than non-FML patients. Valve tissue from patients with FML had less stiff chordae (23.5 +/- 3.6 vs 59.1 +/- 11.7 Mpa, P =.006) that tended to have a lower failure stress (3.8 +/- 0.9 vs 9.6 +/- 2.2 Mpa, P =.07) and had more extensible leaflets (56.4% +/- 7.9% vs 42.9% +/- 2.7% strain, P =.04) compared with that of non-FML patients. CONCLUSIONS: The development of FML may result from intrinsic tissue abnormalities and is associated with a distinct subset of the myxomatous population. Identification of such clinical characteristics in this population and knowledge of an implicit mechanical abnormality of valve tissue may further the argument for early surgical correction.

Chordae Tendineae↗

Association between apolipoprotein E alleles and calcific valvular heart disease.

BACKGROUND: Studies on apolipoprotein E (apoE) alleles have reported an increased risk of coronary heart disease in patients with the apoE4 allele. Given the risk factor and histological similarities between coronary and calcific valvular heart disease (aortic stenosis [AS] and mitral annular calcification [MAC]), we postulated that apoE alleles might be associated with the development of these valvular lesions. METHODS AND RESULTS: We evaluated the association between apoE alleles and calcific valvular lesions in 802 patients undergoing transthoracic echocardiography using logistic regression analyses. No difference was noted in genotype distribution (P=0.59) or prevalence of apoE4 between those with or without MAC (30% versus 27%, respectively; P=0.57). Compared with patients without AS, the genotype distribution of patients with AS differed significantly (P=0.03), with increasing prevalences of the apoE 4 allele (27% in those without versus 40% in those with AS; P=0.01). In multivariate analyses adjusting for age, gender, low-density lipoprotein cholesterol levels, and coronary artery disease, increasing age and the apoE4 allele were significant independent predictors of AS (odds ratio, 1.94; 95% confidence interval, 1.01 to 3.71; P=0.046), whereas the apoE4 allele was not predictive of MAC. CONCLUSIONS: These findings support extension of the importance of the apoE4 allele beyond atherosclerosis and Alzheimer's disease to calcific AS.

Aged↗

Importance of ischemic and viable myocardium for patients with chronic ischemic mitral regurgitation and left ventricular dysfunction.

The objective of this investigation is to determine the importance of ischemic viable myocardium for clinical outcomes in patients with severe chronic ischemic mitral regurgitation and severe left ventricular dysfunction undergoing surgical correction of mitral regurgitation. The study included 54 patients with left ventricular ejection fraction of 27 +/- 9%. Positron emission tomography was performed preoperatively for the identification of ischemic viable myocardium. The patients with a large amount of ischemic viable myocardium (> or =5 segments) had significantly lower 6-month mortality rates than those with less viable myocardium (0 to 4 segments) after the surgery.

Cause of Death↗

Glycosaminoglycan profiles of myxomatous mitral leaflets and chordae parallel the severity of mechanical alterations.

OBJECTIVES: This biochemical study compared the extracellular matrix of normal mitral valves and myxomatous mitral valves with either unileaflet prolapse (ULP) or bileaflet prolapse (BLP). BACKGROUND: Myxomatous mitral valves are weaker and more extensible than normal valves, and myxomatous chordae are more mechanically compromised than leaflets. Despite histological evidence that glycosaminoglycans (GAGs) accumulate in myxomatous valves, previous biochemical analyses have not adequately examined the different GAG classes. METHODS: Leaflets and chordae from myxomatous valves (n = 41 ULP, 31 BLP) and normal valves (n = 27) were dried, dissolved, and assayed for deoxyribonucleic acid, collagen, and total GAGs. Specific GAG classes were analyzed with selective enzyme digestions and fluorophore-assisted carbohydrate electrophoresis. RESULTS: Biochemical changes were more pronounced in chordae than in leaflets. Myxomatous leaflets and chordae had 3% to 9% more water content and 30% to 150% higher GAG concentrations than normal. Collagen concentration was slightly elevated in the myxomatous valves. Chordae from ULP had 62% more GAGs than those from BLP, primarily from elevated levels of hyaluronan and chondroitin-6-sulfate. CONCLUSIONS: The GAG classes elevated in the myxomatous chordae are associated with matrix microstructure and elastic fiber deficiencies and may influence the hydration-related "floppy" nature of these tissues. These abnormalities may be related to the reported mechanical weakness of myxomatous chordae. The biochemical differences between ULP and BLP confirm previous mechanical and echocardiographic distinctions.

Adult↗

Calcific aortic stenosis: another face of atherosclerosis?

Calcific aortic stenosis is not the result of decades of wear and tear alone. Rather, it is being increasingly recognized as an inflammatory, atheromatous, and potentially modifiable disease. Exciting new research suggests that medical therapies may soon be available to retard its progression and reduce the need for surgery.

Aortic Valve Stenosis↗

Incidence and echocardiographic features of congenital unicuspid aortic valve in an adult population.

BACKGROUND AND AIM OF THE STUDY: Although well described in pediatric populations, series of congenital unicuspid aortic valves in adults are limited and mainly arise from surgical reports. Also, the incidence of this rare congenital anomaly has never been estimated in an adult echocardiographic population. METHODS: Between January 1990 and May 2002, the authors' echocardiographic database was systematically reviewed to identify adult patients with congenital unicuspid aortic valve. Echocardiographic studies were reviewed off-line to define morphologic characteristics and evaluate ascending aortic dimensions. RESULTS: Twenty-one adult patients with congenital unicuspid aortic valve were identified, resulting in an estimated incidence in the referral population of approximately 0.02%. Aortic stenosis was the predominant associated hemodynamic lesion; on average, this required surgical intervention during the third decade of life. All valves were unicommissural with a posteriorly positioned commissural attachment. Of particular clinical importance, coexisting ascending aortic dilatation was found in almost half of the cohort (48%), despite the younger patient age. CONCLUSION: Adult congenital unicuspid aortic valve is a rare cardiac anomaly, even in a large referral population. On average, patients will present for cardiac surgery in their third decade of life. Aortic dilatation in association with unicuspid aortic valves should be well recognized and routinely assessed in the initial evaluation and follow up of these patients.

Adult↗

Clinical, echocardiographic, and biomechanical differences in mitral valve prolapse affecting one or both leaflets.

Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation necessitating surgical correction. Unileaflet prolapse (ULP), usually involving the posterior leaflet, is more common than bileaflet prolapse (BLP), which is more difficult to repair. Little is known about clinical, echocardiographic, and biomechanical differences between ULP and BLP. In this study, biomechanical testing was performed on mitral valve leaflets and chordae obtained at operation for severe mitral regurgitation. Preoperative clinical characteristics and echocardiographic measurements were obtained on surgical patients (ULP = 88, BLP = 37). Men outnumbered women by a factor of 4:1 in ULP, and by 3:1 in BLP. Patients with BLP were younger (53.2 +/- 1.7 vs 59.5 +/- 1.1 years) than those with ULP, and this difference was greater in women (48.9 +/- 2.5 vs 62.9 +/- 2.2 years). BLP patients were less likely to be hypertensive, and more likely to undergo valve replacement rather than repair. Echocardiography showed that BLP leaflets were longer and thicker than ULP leaflets. The severity of mitral regurgitation was similar in both groups, although ULP patients had a much higher incidence of flail leaflets (45% vs 5% in BLP). Mechanical strength of chordae was greater in BLP than in ULP, although leaflet strength was similar. The increased chordal strength in BLP may be responsible for less flail. In patients with MVP and severe mitral regurgitation requiring surgery, ULP and BLP are distinct entities with substantial differences in the population affected, in echocardiographic manifestations including prevalence of flail, in chordal mechanics, and in the likelihood of surgical repair.

Biomechanical Phenomena↗

Endocarditis after mitral valve repair.

BACKGROUND: Native valve endocarditis is frequently managed with antibiotics alone, but prosthetic valve endocarditis usually requires an early operation. What is the best treatment of endocarditis after mitral valve repair? METHODS: From 1986 to 2000, 22 patients were treated for endocarditis affecting a previously repaired mitral valve. Causes of mitral valve dysfunction that led to repair were degenerative (11 patients), ischemic (5 patients), endocarditic (3 patients), rheumatic (2 patients), and functional (1 patient). Endocarditis was active in 21 patients and healed in 1. Interval from initial mitral valve repair to onset of endocarditis ranged from 1 week to 10.3 years (median, 6 months). Pathology included leaflet vegetation (15), annuloplasty vegetation (4), leaflet perforation (5), and abscess (3). Mean follow-up was 3.9 +/- 3.3 years. RESULTS: Fifteen patients underwent repeat mitral valve operations with freedom from mitral valve reoperation of 65%, 41%, and 26% at 30 days, 1 year, and 5 years after onset of endocarditis. After a high early hazard, risk of reoperation fell to 10.8% per year. Seven patients, all with a leaflet vegetation, were treated with antibiotics alone. Antibiotics eradicated infection in all; however all had mitral regurgitation 2+ to 4+. Survival was 96%, 74%, and 68% at 30 days, 1 year, and 5 years. Endocarditis recurred in 1 patient (92% free of event). CONCLUSIONS: Most patients that have endocarditis develop after mitral valve repair require reoperation. However if infection is limited to a leaflet, early reoperation may be unnecessary because antibiotics alone can eradicate infection.

Adolescent↗