bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory markers, clinical and subclinical cardiovascular disease in older persons: the Health ABC study
Authors: Pahor Marco , Kritchevsky Steve B , Tracy Russell P , Newman Anne B , Sutton-Tyrrell Kim , Carosella Luciana , Onder Graziano , Simonsick Eleanor M , Harris Tamara B , Penninx Brenda BWJH
Published: July 2021

P37

Inflammation is a potentially important mechanism underlying cardiovascular disease (CVD). Several studies have assessed the asociations of inflammation with clinical CVD, but data on inflammation and sub-clinical CVD are limited. We assessed the association of C-reactive protein (CRP) and interleukin-6 (IL-6) with clinical and subclinical CVD in the Health and Body Composition study (Health ABC), a cohort study of 3075 well functioning older adults living in Memphis, TN, and Pittsburgh, PA. Mean±SDM age was 73.6±2.9 years, 51.5% were women and 41.7% were African American. History of heart attack, heart failure, stroke, peripheral artery disease or CV procedures was reported by 31.4% of participants. Subclinical disease (positive Rose questionnaire for angina or claudication, ECG abnormalities, or ankle brachial index <0.9 in persons with no clinical CVD) was found in 32.4% of participants. CRP (mean 2.31±3.01 μg/ml, range 0.16-54.03 μg/ml) was measured in 1370 participants, and IL-6 (mean±SDM 2.39±1.92 ng/ml, range 0.21-15.96 ng/ml) was measured in 2824 participants. After adjustment for age, gender, race, site, history of diabetes, smoking status, body-mass index, use of anti-inflammatory drugs and serum cholesterol, HDL cholesterol, creatinine and albumin, higher CRP levels were significantly associated with a higher risk of clincal CVD, but not with risk of subclinical CVD (p for trend with increasing IL-6 tertiles =0.0082 and =0.55)(see

Table). Higher IL-6 levels were significantly associated with a higher risk of both clinical and sub-clinical CVD (p for trend with increasing IL-6 tertiles <0.0001 and =0.0003).

Table 1.
Effect of HMG-Co-Reductase Inhibitor Use on 1-Year Mortality and Hospitalization Rates in Elderly Cardiovascular Disease Patients in Nursing Homes
Authors: Eaton Charles B , Lapane Kate L , Murphy John B , Hume Anne L
Published: July 2021

P43

Background:The risks and benefits of HMG-Co-Reductase Inhibitor therapy in elderly cardiovascular disease patients is not known. Aims: To compare the effects of statins on the 1-year mortality, and hospitalization rate in a cohort of elderly CVD patients. Methods: We conducted a historical cohort study using the SAGE database (1992-1997), a long-term care database linking patient clinical information with data on drug utilization, hospital discharges, and death. Among 51,599 newly admitted nursing home patients with CVD, we compared 1313 statin users to non-users matched by facility. The effects of statins on outcomes was estimated using a Cox proportional hazards model. Results: Prevalence of statin use in this CVD cohort was 2.5%. Statin use varied by age, gender, co-morbid condition,CHD risk factors, medication use, cognitive and physical function(p<.05). The number of deaths at one year was 265 in the statin users and 410 in the non-users. The 1-year all-cause mortality adjusted hazards ratio comparing statin users to non-users was HR=0.73, 95%CI (0.61-0.87). Number needed to treat(NNT)was 9. Results were similar for men and women, and for ages 65-74, 75-84, and 85 and older. Similar results were found for 1-year rates of hospitalization. Conclusion: HMG-Co-reductase inhibitor therapy appears to signficantly reduce 1-year all-cause mortality and hospitalization rates in a frail elderly population after adjusting for potential confounding.
Heart Failure After Myocardial Infarction - A Population-Based Study
Authors: Hellermann Jens P , Jacobsen Steven J , Yawn Barbara P , Weston Susan , Redfield Margaret M , Rodeheffer Richard R , Reeder Guy S , Roger Veronique L
Published: July 2021

P46

While heart failure (HF), an emerging epidemic, complicates myocardial infarction (MI), little is known on the predictors of HF post-MI, in particular the impact of reperfusion therapy. This population-based study was undertaken to examine the association between clinical characteristics and post-MI HF between 1979 and 1994. Hospitalized incident MIs were validated using enzymes, chest pain, and Minnesota coding of the ECG. Framingham criteria were used to ascertain both in- and outpatient HF. Proportional hazard regression was used to identify predictors of CHF. In the study period, 1657 patients (pts.) (mean age 67.2 ± 13.9 years, 43% women) had an incident MI. History of diabetes, hypertension and prior HF was found in 19%, 54% and 11% of pts respectively. After 5 years, 43% of pts had experienced HF. Factors independently associated with HF were (see

table). There was a 2% decline per year in occurrence of HF. Adding reperfusion therapy in the model attenuated the association between year and HF (adjusted RR for reperfusion 0.67, 95% CI 0.53, 0.84, p=0.006; adjusted for year 0.99; 95% CI 0.97, 1.01, p=0.37). Thus, while remaining frequent post-MI CHF has declined over time. Reperfusion therapy accounted for most of the effect of year.

Table 1.
Trends in Stroke Prevalence in the United States Population Age 25-74, 1971-1994.
Authors: Muntner Paul , Klag Michael J , Coresh Josef
Published: July 2021

P58

Mortality from stroke in the United States (US) has declined since 1900. Primary prevention was credited for much of this decline through the 1970s; however, observational studies have indicated that stroke incidence did not decline during the 1980s. In contrast, improvement in stroke survival has been noted in the 1970s and 1980s. The effect of these secular trends on the prevalence and number of stroke survivors in the US has not been determined. The prevalence and number of non-institutionalized stroke survivors in the US was estimated through self-report for three time periods, 1971-1975, 1976-1980, and 1988-1994, using data from the National Health and Nutrition Examination Survey (NHANES) I, II, and III, respectively. Prevalence and number of stroke survivors were analyzed for the overall US population and by age (25-59, 60-74), race (White and African-American), and sex. Estimates were limited to the US population age 25-74 years old because NHANES I and II did not interview persons 75 years of age and older. The age, race, and sex adjusted prevalence of stroke increased from 1.41 to1.69 to 1.87; an average increase of 7.5% (95% confidence interval, CI: -2%, 18%) for each 5-year period between NHANES I, II, and III. Additionally, the number of stroke survivors increased from 1.5 to 2.4 million across this same time period. The prevalence of stroke among the US population age 60-74 years of age increased from 4.2% to 5.0% to 5.2% from NHANES I to III; an average increase of 6.4% for each 5 years (95% CI: -3%, +17%) during the period analyzed. In contrast, among persons age 25-59 the prevalence of stroke was less than 1% in all three-time periods and a secular trend was not present. Although stroke prevalence increased 28% for each 5-year period among African-American females (95% CI: +3%, +56%) and +12% among White males (95% CI: -2%, +29%) it did not change among African-American males or White females. In contrast, the number of stroke survivors increased among all age, race and sex sub-groups. Despite the absence of strong trends in stroke prevalence, the number of non-institutionalized stroke survivors under age 75 years of age increased substantially.
Evidence of a Genetic Susceptibility Locus Influencing Interindividual Variation in Triglycerides: The NHLBI Family Heart Study
Authors: Arnett Donna K , Atwood Larry , Province Michael A , Coon Hilary , Pankow James
Published: July 2021

P06

Genomic regions have been linked to hypertriglyceridemia associated with familial syndromes, such as familial combined hyperlipidemia. However, there is little information regarding chromosomal regions harboring susceptibility genes for more common forms of hypertriglyceridemia. Significant linkage of triglycerides (TGs) was recently identified on chromosome 15 in Mexican Americans (LOD=3.88). As part of the NHLBI-sponsored Family Heart Study (FHS), a genome-wide linkage analysis was done to replicate this finding or to identify other quantitative trait loci for TGs. Multi-generational families were recruited (a) at excess risk of early onset myocardial infarction and (b) randomly selected from Framingham, Atherosclerosis Risk in Communities, and Utah Family Tree Studies. The largest families were selected for genomic analysis (105 families, family size=8.6). Microsatellite markers (n=369), approximately equally spaced throughout the genome (CHLC-10), were typed by the NHLBI Mammalian Genotyping Service. TGs were measured in participants fasting for at least 12 hours. TGs were adjusted for sex, age and age

2

, and log-transformed to normalize the distribution. The search for quantitative trait loci for TGs was carried out using a multipoint model-free variance components method implemented in GENEHUNTER. The mean age was 60 years and 52% were female. The mean triglyceride value in the family members was 146 (±85) mg/dl in men and 155 (±102) mg/dl in women. Evidence for linkage was identified on chromosome 4 (LOD=3.23 (p<.0003) at position 35cM from the pter). Further evidence for linkage was found on chromosome 15 (LOD=1.90 (p<.007) at position 36cM from the pter), which overlaps the genomic region identified in Mexican Americans. In conclusion, we found significant evidence for linkage of TGs to a region on chromosome 4 in families either randomly recruited or at high risk of early onset coronary heart disease. This putative locus appears to have a major influence on the interindividual variation in triglycerides. Finally, these data add support for the existence of a putative locus for TGs on chromosome 15.
Alcohol Consumption And Cardiovascular Mortality In Hypertensive Patients
Authors: Malinski Maciej K. , Sesso Howard D. , Lopez-Jimenez Francisco , Buring Julie E. , Gaziano J. Michael
Published: July 2021

P83

Background: Alcohol drinking is associated with a dose-dependent increase in blood pressure, and JNC VI advises limiting alcohol consumption in patients with hypertension. Data are sparse on relationship between alcohol consumption and mortality in hypertensive patients. We therefore assessed whether alcohol consumption is associated with decrease in total, and cardiovascular mortality among subjects with hypertension. Methods: From the enrollment cohort of 89,251 men from the Physicians’ Health Study who provided self-reported information on alcohol intake and were free of myocardial infarction, stroke, cancer or liver disease at baseline, we identified a group of 14,125 persons with a history of current or past treatment for hypertension. Results: During 75,710 person-years of follow up, there were 1,018 deaths including 579 from cardiovascular disease and 224 from cancer. In multivariate analyses that controlled for several potential confounders, moderate alcohol intake was associated with significant decrease in cardiovascular mortality (P<0.001 for linear trend). Compared with non-drinking men, those who drank 1 to 3 drinks per month had a RR for cardiovascular mortality of 0.86 (CI 0.63-1.18, P=0.35); for 1 to 6 drinks per week, the RR was 0.64 (CI 0.51-0.81, P<0.001); for >= 1 drink per day the RR was 0.57 (CI 0.44-0.72, P<0.001). RR values for all-cause mortality in the same groups were respectively 0.89 (CI 0.70-1.15, P=0.38); 0.73 (CI 0.60-0.88, P=0.001); and 0.73 (CI 0.61-0.89, P=0.0014)(P=0.0025 for linear trend). On the other hand, we found no significant association between moderate alcohol consumption and cancer mortality (P=0.68 for linear trend). Conclusion: These results suggest that light to moderate alcohol consumption is associated with a significant reduction in cardiovascular and all-cause mortality in patients with hypertension.
Genetic and Environmental Contributions to Childhood Growth in Stature and Lifetime Overweight Risk.
Authors: Czerwinski Stefan A , Williams Jeff T , Wisemandle Wayne , Towne Bradford , Demerath Ellen W , Guo Shumei S , Chumlea Wm. Cameron , Siervogel Roger M
Published: July 2021

P09

The prevalence of childhood overweight and obesity in the US continues to increase. Epidemiological studies have shown that children who mature earlier tend to have an increased risk of being overweight in adulthood. Acknowledging that measures of overweight and patterns of human growth are under moderate to strong genetic control, we examined the nature of these associations using a bivariate variance components approach to estimate the genetic and environmental correlations between lifetime overweight status and parameters of the adolescent growth spurt. Serial stature data from 490 participants in the Fels Longitudinal Study were used to derive three adolescent growth curve parameters: peak height velocity (PHV), age at PHV, and height at PHV. Three categories of lifetime overweight status were determined from over 16,000 serial observations according to age at onset of overweight: early-onset overweight (BMI >25 kg/m

2

before age 25 y), late-onset overweight (BMI >25 kg/m

2

after age 25 y), and never overweight (never having a BMI measurement >25 kg/m

2

). Those classified as overweight also needed to meet certain criteria (i.e., maintenance of BMI >25 kg/m

2

in 80% of all subsequent visits following the first presentation). Heritability estimates (h

2

) for the adolescent growth parameters are h

2

=0.54 for PHV, h

2

=0.74 for age at PHV, and h

2

=0.92 for height at PHV. Heritability estimates for lifetime overweight status range from 0.52-0.57 depending upon the age at onset categorization. Although all of the traits examined are highly heritable, preliminary analyses reveal little effect of shared genes between the adolescent growth curve parameters and the lifetime overweight status categories; the genetic correlations are low and insignificant. There is, however, a statistically significant negative environmental correlation (ρ

e

=-0.40) between age at PHV and the lifetime overweight status category contrasting never overweight with early/late overweight. These results suggest that environmental influences on the timing of the adolescent growth spurt may be more influential in predicting adult risk of overweight than shared genetic factors.
Hormone Therapy and Menopausal Symptoms Among Women Participating in a Behavioral Lifestyle Intervention: The Women’s Healthy Lifestyle Project
Authors: Boraz Miriam A. , Simkin-Silverman Laurey R , Wing Rena R. , Meilahn Elaine N. , Kuller Lewis H.
Published: July 2021

P91

The decision to take hormone replacement therapy (HRT) is a choice many women encounter when entering menopause. In light of controversy of the benefits and risks of HRT use, an important question to ask is on what basis are women taking HRT, and are they taking hormone therapy because they are at higher risk. The purpose of this study was to examine HRT use in women who are participating in a behavioral lifestyle intervention through the menopause. The Women’s Healthy Lifestyle Project (WHLP) was a 5-year randomized clinical trial designed to examine whether a behavioral lifestyle intervention could decrease the expected rise in cardiovascular risk through the menopause. A sample of 535 healthy premenopausal women, aged 44-50 years (M=47 + 1.9) participated in the study. The intervention was highly successful in buffering risk elevation through the 54-month visit. The control group gained 5.2 lb over the 54 month study and the intervention group remained 0.18 lb below baseline (p=.00). The intervention group’s LDLc increased by 3.5 mg/dl, and the control group’s LDLc increased by 8.9 mg/dl (p=.01). At the 54-month visit, there was no difference between the intervention and control groups in menopausal status, with 34.7% of the women postmenopausal. There was no difference between intervention and control groups with regard to HRT use, with 31.2% of the total sample reporting use of HRT. Further, there was no difference in menopausal symptoms between treatment groups. The women started HRT an average of 6 months after they missed a period. Analysis was done to examine predictors of HRT use in this group of women. Baseline cardiovascular risk factors did not predict HRT use at the 54-month visit. Moreover, the number of menopausal symptoms did not predict HRT use at 54 months. There was little difference between the women who were taking HRT and the women who were not taking HRT. There was a high use of HRT in this group of healthy, well-educated women. But an intensive lifestyle intervention did not change the use of HRT.
Interleukin-6 and heart rate in a population-based sample:
Authors: Tracy Russell P , Newman Anne B , Williamson Jeff D , Harris Tamara B , Cummings Steve R
Published: July 2021

0022

Inflammatory cytokines enhance the spontaneous beating rate of cardiac myocytes. We hypothesize that higher levels of interleukin-6 (IL-6) may be associated with a higher resting heart rate in a population-based sample. IL-6 (mean±SEM 2.39±0.5 ng/ml, range 0.21-15.96 ng/ml, n=2824) was measured in Health ABC, a cohort study of 3075 well functioning older adults living in Memphis, TN, and Pittsburgh, PA (age 73.6±0.3 years, 51.5% women, 41.7% African American). Heart rate was calculated from electrocardiogram strips recorded at the baseline clinic visit after 15 min resting in supine position. Participants with arrhythmias or conduction anomalies were excluded. After adjustment for demographics, body-mass index, smoking, history of cardiovascular disease, and use of digoxin, beta-blockers, calcium antagonists, anti-inflammatory drugs and antiarrhythmic drugs, higher log (IL-6) was significantly correlated with a higher heart rate (β=.17, p<0.001, n=2377). Such an association was significant in all race and gender strata (white men β=0.17, p<0.001; white women β=0.13, p=0.001; black men β=0.18, p<0.001; black women β=0.18, p<0.001). The overall il-6/heart rate association was even more evident when the analyses were restricted to the participants who had no history of cardiovascular disease and were not using any these cardiovascular drugs (β=0.21, p<0.001, n=1196). The

table shows heart rate according to IL-6 quintiles. Circulating IL-6 was strongly and independently correlated with resting heart rate. Circulating IL-6 is a possible biological mediator that may contribute to explain the increased mortality associated with high heart rate.

Table 1.
Long-Term (29 Years) Results of Reconstructive Surgery in Rheumatic Mitral Valve Insufficiency
Authors: Chauvaud Sylvain , Fuzellier Jean-François , Berrebi Alain , Deloche Alain , Fabiani Jean-Noël , Carpentier Alain
Published: July 2021

Background

Results of conservative surgery are well established in degenerative mitral valve (MV) insufficiency. However, there are controversies in rheumatic disease. This study is the evaluation of one center for rheumatic MV insufficiency based on a functional approach.

Methods and Results

From 1970 to 1994, 951 patients with rheumatic MV insufficiency were operated on with the reconstructive techniques elaborated by Alain Carpentier. Aortic valve diseases were excluded. Mean age was 25.8 years (4 to 75), and sinus rhythm was present in 63%. The functional classification used was type I, normal leaflet motion, 71 patients (7%); type II, prolapsed leaflet, 311 patients (33%); and type III, restricted leaflet motion, 345 patients (36%). The combined lesion of prolapse of the anterior leaflet and restriction of the posterior was present in 224 patients (24%). Surgical techniques used were implantation of a prosthetic ring in 95%, shortening of the chords and leaflet enlargement with autologous pericardium, and commissurotomy. Hospital mortality rate was 2%. The mean follow-up was 12 years (maximum, 29 years): 8618 patients per year. Actuarial survival was 89±19% at 10 years and 82±18% at 20 years. The rate of thromboembolic events was 0.4% patients per year (33 events), with 3 deaths. Freedom from reoperation was 82±19% at 10 years and 55±25% at 20 years. The main cause (83%) of reoperation was progressive fibrosis of the MV. The actuarial rate of reoperation was 2% patients per year and was correlated to the degree of preoperative fibrosis.

Conclusions

Conservative surgery of rheumatic MV insufficiency has a low hospital mortality rate and an acceptable rate of reoperation. The results are excellent regarding the minimal risk of thromboembolic events.
Factors Related to Pleural Effusions After Fontan Procedure in the Era of Fenestration
Authors: Fedderly Raymond T. , Whitstone Beth N. , Frisbee Stephanie J. , Tweddell James S. , Litwin S. Bert
Published: July 2021

Background

Significant pleural effusions after the Fontan operation prolong hospital stay, may increase the risk of infection, and may necessitate a pleurodesis procedure.

Methods and Results

From February 1991 to April 2000, 98 consecutive patients under the age of 18 years underwent the fenestrated Fontan procedure at Children’s Hospital of Wisconsin. Ninety-four patients who survived at least 30 days after surgery were retrospectively evaluated for the following factors: age, ventricular morphology (right single ventricle, left single ventricle [RV/LV]), fenestration open (FO) or closed (FC) at end of operation, intracardiac Fontan (IF) or extracardiac Fontan (EF), days with chest tube output per day >5, 10, and/or 20 mL · kg
−1
· d
−1
(CTO5, CTO10, and CTO20, respectively), need for pleurodesis, length of hospital stay (LOS), operation during winter respiratory viral season of November through March (ReVS+, ReVS−), and pre-Fontan mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). In univariate analysis, the ReVS+ patients had prolonged LOS, greater chest tube output, and more pleurodesis (
P
<0.05), and PAP was related to CTO5 and CTO10 but not to CTO20 or LOS. No significant differences were found in LOS, CTO5, CTO10, CTO20, and need for pleurodesis between patients in RV/LV, FO/FC, IF/EF, or PVR groups. Patients <4 years of age had more instances of CTO20 (
P
<0.05). When we used ordinary least squares regression analysis with age, FO or FC, RV or LV, PAP, and ReVS+ or ReVS− to predict each of CTO5, CTO10, CTO20, and LOS, only ReVS+ or ReVS− and age were statistically significant in all models.

Conclusions

Use of the Fontan procedure during the respiratory viral season appeared to be related to significant, prolonged pleural effusions and longer hospitalizations.
Impact of Inspired Gas Mixtures on Preoperative Infants With Hypoplastic Left Heart Syndrome During Controlled Ventilation
Authors: Tabbutt Sarah , Ramamoorthy Chandra , Montenegro Lisa M. , Durning Suzanne M. , Kurth C. Dean , Steven James M. , Godinez Rodolfo I. , Spray Thomas L. , Wernovsky Gil , Nicolson Susan C.
Published: July 2021

Background

Management strategies for preoperative infants with hypoplastic left heart syndrome (HLHS) include increased inspired nitrogen (hypoxia) and increased inspired carbon dioxide (hypercarbia). There are no studies directly comparing these 2 therapies in humans. This study compares the impact of hypoxia versus hypercarbia on oxygen delivery, under conditions of fixed minute ventilation.

Methods and Results

Ten anesthetized and paralyzed preoperative infants with HLHS were evaluated in a prospective, randomized, crossover trial comparing hypoxia (17% F
io
2
) with hypercarbia (2.7% F
ico
2
). Each patient was treated in a random order (10 minutes per condition) with a recovery period (15 to 20 minutes) in room air. Arterial (Sa
o
2
) and superior vena caval (Sv
o
2
) co-oximetry and cerebral oxygen saturation (Sc
o
2
) measurements were made at the end of each condition and recovery period. Sc
o
2
was measured by near infrared spectroscopy. Hypoxia significantly decreased both Sa
o
2
(−5.2±1.1%,
P
=0.0014) and Sv
o
2
(−5.6±1.7%,
P
=0.009) compared with baseline, but arteriovenous oxygen saturation (AV
o
2
) difference (Sa
o
2
−Sv
o
2
) and Sc
o
2
remained unchanged. Hypercarbia decreased Sa
o
2
(−2.6±0.6%,
P
=0.002) compared with baseline but increased both Sc
o
2
(9.6±1.8%,
P
=0.0001) and Sv
o
2
(6±2.2%,
P
=0.022) and narrowed the AV
o
2
difference (−8.5±2.3%,
P
=0.005). Both hypoxia and hypercarbia decreased the balance between pulmonary and systemic blood flow (Qp:Qs) compared with baseline.

Conclusions

In preoperative infants with HLHS, under conditions of anesthesia and paralysis, although Qp:Qs falls in both conditions, oxygen delivery is unchanged during hypoxia and increased during hypercarbia. These data cannot differentiate cerebral from systemic oxygen delivery.
Time Course of Aortic Valve Function and Root Dimensions After Subcoronary Ross Procedure for Bicuspid Versus Tricuspid Aortic Valve Disease
Authors: Schmidtke Claudia , Bechtel Matthias , Hueppe Michael , Sievers Hans-H.
Published: July 2021

Background

The freestanding aortic root, which is the currently preferred operative technique for pulmonary autografts, is reported to dilate and potentially promote aortic insufficiency, which has led to a controversial debate on the appropriate surgical technique, especially for congenital bicuspid aortic valve disease. Desirable data on the time course of valve function and root dimensions for the alternative subcoronary technique comparing bicuspid and tricuspid aortic valve disease are scarce.

Methods and Results

Echocardiographic examinations of 31 patients with congenital bicuspid aortic valve disease (group A; age 50.5±11.0 years) and 51 patients with acquired tricuspid aortic valve disease (group B; age 48.1±15.7 years) who were operated on between June 1994 and August 1998 were performed twice postoperatively. At first and second follow-up, respectively, maximum (mean) pressure gradients were 6.0±2.0 (3.6±1.0) and 5.1±2.1 (2.9±1.1) mm Hg in group A and 6.5±3.5 (3.9±1.9) and 5.0±1.7 (2.9±1.0) mm Hg in group B (
P
>0.05 between groups). In group A, grade 0 aortic insufficiency at first and second follow-up occurred in 8 and 7 patients, respectively, grade 0-I in 12 and 9 patients, grade I in 9 and 11 patients, grade I-II in 1 and 0 patients, and grade II in 1 and 4 patients; in group B, grade 0 aortic insufficiency occurred in 16 and 18 patients, grade 0-I in 16 and 8 patients, grade I in 17 and 21 patients, grade I-II in 0 and 1 patient, and grade II in 0 and 1 patient (
P
>0.05). Aortic insufficiency decreased in 10 patients (17%). However, there was an overall tendency for aortic insufficiency to increase over time (n=23, 38%), although it remained subclinical. Aortic root dimensions did not differ between groups and were constant during follow-up.

Conclusions

This study provides some evidence that the function of the subcoronary pulmonary autograft in bicuspid aortic valve disease is excellent, with stable root dimensions, and is not different from that of tricuspid aortic valves at least up to 5.5 years postoperatively, which suggests the subcoronary technique should be reconsidered.
Intracoronary Infusion of Skeletal Myoblasts Improves Cardiac Function in Doxorubicin-Induced Heart Failure
Authors: Suzuki Ken , Murtuza Bari , Suzuki Noriko , Smolenski Ryszard T. , Yacoub Magdi H.
Published: July 2021

Background

Skeletal myoblast transplantation is promising for the treatment of end-stage heart failure. Direct intramyocardial injection is useful for local cell delivery but may not be effective in global dissemination of cells into the heart, which would be advantageous in treating generalized cardiac dysfunction as in dilated cardiomyopathy. We hypothesized that intracoronary infusion of myoblasts would disseminate cells more effectively, leading to functional improvement in global heart failure.

Methods and Results

Heart failure was induced by the intraperitoneal administration of doxorubicin (total dose 15 mg/kg) in rat. One million primary skeletal myoblasts were then infused via the coronary arteries of an excised, failing doxorubicin-treated heart. After incubation under increased intracoronary pressure, the hearts were subsequently transplanted into syngeneic recipients. For the control group, doxorubicin-treated hearts were infused with medium only and transplanted. Four weeks after transplantation, Langendorff perfusion demonstrated that both maximum dP/dt (2797.6±103.3 versus 2326.9±133.1 mm Hg/s,
P
=0.01) and minimum dP/dt (−2067.4±88.1 versus −1718.8±91.3 mm Hg/s,
P
=0.02) were improved in myoblast-transplanted hearts compared with medium-infused hearts. This was associated with a sharper slope of the left ventricular developed pressure-volume curve and a reduced slope of the end-diastolic pressure-volume relation in the myoblast-transplanted hearts. Immunohistochemistry for skeletal myosin heavy chain showed that globally disseminated myoblasts had survived and differentiated into multinucleated myotubes that had aligned with the cardiac fiber axis within host myocardium. No significant myocardial infarction was observed.

Conclusions

We demonstrated the feasibility and efficiency of skeletal myoblast transplantation via the intracoronary route as a promising strategy for improving cardiac function in global heart failure.
Is Skeletal Myoblast Transplantation Clinically Relevant in the Era of Angiotensin-Converting Enzyme Inhibitors?
Authors: Pouzet Bruno , Ghostine Saïd , Vilquin Jean-Thomas , Garcin Isabelle , Scorsin Marcio , Hagège Albert A. , Duboc Denis , Schwartz Ketty , Menasché Philippe
Published: July 2021

Background

There is compelling experimental evidence that autologous skeletal muscle (SM) cell transplantation improves postinfarction cardiac function. This study assessed whether this benefit is still manifested in the clinically relevant setting of a treatment by ACE inhibitors.

Methods and Results

A myocardial infarction was created in 99 rats by coronary artery ligation. They were divided into 4 groups. Two groups did not receive any drug and were intramyocardially injected 7 days after the infarct with either culture medium alone (control rats, n=16) or autologous SM cells (2.3×10
6
myoblasts) previously expanded ex vivo for 7 days (myoblasts, n=24). Two other groups received the ACE inhibitor perindoprilat (1 mg · kg
−1
· d
−1
), started the day of the infarct and continued uninterruptedly thereafter, and underwent time-matched procedures, that is, they were intramyocardially injected at 7 days after infarction with either culture medium alone (ACE inhibitors, n=22) or autologous SM cells (2.5×10
6
myoblasts) previously expanded ex vivo for 7 days (ACE inhibitors+myoblasts, n=37). Left ventricular function was assessed by 2D echocardiography. At the end of the 2-month study, left ventricular ejection fraction (%, mean±SEM) was increased in all groups (myoblasts, 37.4±1.2; ACE inhibitors, 31.6±1.7; ACE inhibitors+myoblasts, 43.9±1.4) compared with that in control rats (19.8±0.7) (
P
<0.0001). The improvement in ejection fraction was similar in the ACE inhibitor and the myoblast groups (31.6±1.7 versus 37.4±1.2,
P
=0.0636). However, in the ACE inhibitor+myoblast group, this improvement was greater than that seen in hearts receiving either treatment alone (43.9±1.4 versus 31.6±1.7 in the ACE inhibitor group and 43.9±1.4. versus 37.4±1.2 in the myoblast group,
P
<0.0001 and
P
=0.0084, respectively).

Conclusions

These data provide further support for the clinical relevance of autologous SM cell transplantation in that its cardioprotective effects are additive to those observed with ACE inhibitors.
Protection From Reperfusion Injury After Cardiac Transplantation by Inhibition of Adenosine Metabolism and Nucleotide Precursor Supply
Authors: Smolenski Ryszard T. , Raisky Olivier , Slominska Ewa M. , Abunasra Haitham , Kalsi Kameljit K. , Jayakumar Jay , Suzuki Ken , Yacoub Magdi H.
Published: July 2021

Background

Adenosine (Ado) triggers numerous protective mechanisms in the heart that may attenuate ischemia-reperfusion injury in cardiac grafts. We aimed to establish whether sustained increase in endogenous Ado production by the combined application of Ado metabolism inhibitors and nucleotide precursors attenuates reperfusion injury in transplanted hearts.

Methods and Results

Rat hearts were collected after the infusion of St Thomas’ Hospital cardioplegic solution, stored at 4°C for 4 hours, and heterotopically transplanted into the abdomen of recipient rats. A solution containing Ado deaminase inhibitor erythro-9(2-hydroxy-3-nonyl)adenine, Ado kinase inhibitor 5′-aminoadenosine, and nucleotide precursors adenine and ribose was administered at the time of reperfusion in the treated group, whereas saline was administered to control animals. After 1 or 24 hours, mechanical function of the transplanted hearts was evaluated in an ex vivo perfusion system followed by the determination of myocardial ATP with related metabolites and measurement of the activity of neutrophil-specific enzyme myeloperoxidase in cardiac homogenates. After 24 hours of reperfusion, maximum left ventricular developed pressure increased from 87.0±6.8 mm Hg (mean±SEM) in controls to 118.1±8.2 mm Hg in the treated group (
P
<0.05), ATP increased from 11.0±0.8 μmol/g dry wt in controls to 15.1±1.2 μmol/g dry wt in the treated group (
P
<0.01), and myeloperoxidase activity decreased from 2.23±0.60 U/g wet wt in controls to 0.58±0.12 U/g wet wt in the treated group (
P
<0.001). No differences in cardiac function, ATP, or myeloperoxidase activity were observed between the treated group and controls after 1 hour of reperfusion.

Conclusions

The administration of Ado metabolism inhibitors with nucleotide precursors causes a sustained increase in endogenous Ado production and exerts a potent protective effect against reperfusion injury in transplanted hearts. Improved cardiac function and elevated ATP concentration were accompanied by complete amelioration of neutrophil infiltration in treated hearts, suggesting that reduction in postischemic inflammation could be an important mechanism of this protective effect.
Does Histocompatibility Affect Homograft Valve Function After the Ross Procedure?
Authors: Bechtel J.F. Matthias , Bartels Claus , Schmidtke Claudia , Skibba Wim , Müller-Steinhardt Michael , Klüter Harald , Sievers Hans-Hinrich
Published: July 2021

Background

Homograft valves have been shown to be immunogenic, but it is unknown whether this affects valve function. Therefore, we prospectively studied the degree of histoincompatibility (defined as the number of human leukocyte antigen [HLA] mismatches between valve donor and recipient) and the response of the recipient (measured by antibodies against HLA) in relation to echocardiographic parameters of homograft valve function after the Ross procedure.

Methods and Results

Twenty-six patients (mean age 41±14 years; 20 males, 6 females) and the cryopreserved pulmonary homograft valves that were implanted during a Ross procedure were typed for HLA-A, HLA-B, and HLA-DR. After a mean follow-up of 15±6 months, 14 (54%) of the patients were anti–HLA class I antibody positive. In all but 1 patient, these antibodies were shown to be donor specific. During follow-up, there was a significant increase of the maximal (+6.2±7.1 mm Hg) and mean (+3.2±4.3 mm Hg) transhomograft pressure gradients but not of homograft regurgitation. Neither the number of HLA mismatches nor antibody status was found to have significant impact on homograft valve function. In a multivariate analysis, smaller homograft size (
P
=0.001) and younger recipient age (
P
=0.044) were shown to be significantly associated with increased transhomograft pressure gradients.

Conclusions

Implantation of a cryopreserved pulmonary homograft during the Ross procedure can induce a specific humoral response. We observed a significant increase of the transhomograft pressure gradients within 15±6 months after surgery. For this period, we were unable to demonstrate a relationship between this increase and the degree of histoincompatibility.
Effects of Hematocrit on Cerebral Microcirculation and Tissue Oxygenation During Deep Hypothermic Bypass
Authors: Duebener Lennart F. , Sakamoto Takahiko , Hatsuoka Shin-ichi , Stamm Christof , Zurakowski David , Vollmar B. , Menger Michael D. , Schäfers Hans-Joachim , Jonas Richard A.
Published: July 2021

Background

One rationale for hemodilution during hypothermic cardiopulmonary bypass (CPB) has been improved microcirculation. However, the optimal degree of hemodilution remains unclear. We therefore studied cerebral microcirculation and tissue oxygenation in a new intravital microscopic model at 3 different hematocrit (Hct) values.

Methods and Results

Three groups of 5 piglets with a cranial window over the parietal cortex underwent cooling at Hct of 10%, 20%, or 30%, followed by 1-hour deep hypothermic circulatory arrest (DHCA) and rewarming on CPB. For assessment of functional capillary density (FCD), plasma was labeled with fluorescein-isothiocyanate-dextran. Rhodamine-stained leukocytes were observed in postcapillary venules with analysis for adhesion and rolling. NADH, a natural intracellular fluorophore that increases during ischemia, was measured densitometrically during bypass and DHCA. FCD did not significantly differ from baseline during cooling in any group. However, during early reperfusion (5 minutes) after DHCA, the FCD was significantly higher in the Hct 30% group than in the Hct 10% group. Leukocyte adherence decreased in all groups during CPB and was only moderately increased at the end of the experiment. However, severe hemodilution (Hct 10%) was associated with a significantly greater number of rolling leukocytes relative to Hct 30%.

Conclusions

Higher Hct does not impair cerebral microcirculation and reduces white cell/endothelial activation after deep hypothermic bypass and circulatory arrest. Severe hemodilution (Hct 10%) results in evidence of inadequate cerebral tissue oxygenation during the cooling phase of CPB. This study suggests that Hct of 30% is preferable relative to lower Hct values during hypothermic CPB, particularly if DHCA is used.
Plasma Levels of Metalloproteinases-3 and -9 as Markers of Successful Abdominal Aortic Aneurysm Exclusion After Endovascular Graft Treatment
Authors: Sangiorgi Giuseppe , D’Averio Rita , Mauriello Alessandro , Bondio Monya , Pontillo Marina , Castelvecchio Serenella , Trimarchi Santi , Tolva Valerio , Nano Giovanni , Rampoldi Vincenzo , Spagnoli Luigi Giusto , Inglese Luigi
Published: July 2021

Background

Structural alterations of aortic wall resulting from degradation of matrix proteins by matrix metalloproteinases (MMPs) characterize abdominal aortic aneurysms (AAAs). No studies have compared circulating levels of MMPs after endovascular graft (EVG) exclusion in comparison with open surgical repair (OSR) in patients affected by AAA.

Methods and Results

An abdominal angiography and CT scan were performed in all patients at the time of enrollment. A spiral CT scan was performed at 6 months to detect presence of endoleaks. MMP-3 and MMP-9 levels were measured before EVG (n=30) and OSR (n=15) treatments and at 1, 3, and 6 months of follow-up by a sandwich ELISA technique. Healthy volunteers (n=10) were used as control subjects. Immunohistochemical staining for MMP-9 and MMP-3 was performed on tissue samples from surgical cases. Both MMP-9 and MMP-3 mean basal levels were significantly higher in patients affected by AAA than in control subjects (32.3±20.7 ng/mL for EVG and 28±9.9 ng/mL for OSR versus 8.9±2.5 ng/mL, 2
P
<0.05; 18.3±9.7 ng/mL and 26.7±10.8 ng/mL versus 8.2±5.3 ng/mL, 2
P
<0.001). In the OSR group, both MMP-9 and MMP-3 mean levels decreased after surgery (28±9.9 ng/mL at basal versus 14.7±6.6 ng/mL at 6 months, 2
P
<0.001; 26.7±10.8 versus 12±5.3 ng/mL; 2
P
<0.001). In the EVG group, a statistically significant difference at 6-month follow-up in MMP-9 and MMP-3 mean plasma values was detected in patients who had endoleakage in comparison with patients without endoleakage (44.3±20.7 versus 14.6±7.0 ng/mL, 2
P
<0.005; 25±11.5 versus 10.3±5.4 ng/mL, 2
P
<0.005).

Conclusions

After EVG exclusion, MMP-9 and MMP-3 levels decreased to a level similar to that of patients undergoing OSR. In addition, a lack of decrease in MMP levels after EVG exclusion may help in identifying patients who will have endoleakage and consequent aneurysm expansion caused by continuous sac pressurization during follow-up.
Heat Shock Protein 70 Gene Transfection Protects Mitochondrial and Ventricular Function Against Ischemia-Reperfusion Injury
Authors: Jayakumar Jay , Suzuki Ken , Sammut Ivan A. , Smolenski Ryszard T. , Khan Mak , Latif Najma , Abunasra Haitham , Murtuza Bari , Amrani Mohamed , Yacoub Magdi H.
Published: July 2021

Background

Upregulation of heat shock protein 70 (HSP70) is beneficial in cardioprotection against ischemia-reperfusion injury, but the mechanism of action is unclear. We studied the role of HSP70 overexpression through gene therapy on mitochondrial function and ventricular recovery in a protocol that mimics clinical donor heart preservation.

Methods and Results

Hemagglutinating virus of Japan (HVJ)-liposome technique was used to transfect isolated rat hearts via intracoronary infusion of either the HSP70 gene (HSP group, n=16) or no gene (CON group, n=16), which was heterotopically transplanted into recipient rats. Four days after surgery, hearts were either perfused on a Langendorff apparatus for 30 minutes at 37°C (preischemia studies [n=8/group]) or perfused for 30 minutes at 37°C, cardioplegically arrested for 4 hours at 4°C, and reperfused for 30 minutes at 37°C (postischemia studies [n=8/group]). Western blotting and immunohistochemistry confirmed HSP70 upregulation in the HSP group. Postischemic mitochondrial respiratory control indices (RCIs) were significantly better preserved in HSP than in CON hearts: NAD
+
-linked RCI values were 9.54±1.1 versus 10.62±0.46 before ischemia (NS) but 7.98±0.69 versus 1.28±0.15 after ischemia (
P
<0.05), and FAD-linked RCI values were 6.87±0.88 versus 6.73±0.93 before ischemia (NS) but 4.26±0.41 versus 1.34±0.13 after ischemia (
P
<0.05). Postischemic recovery of mechanical function was greater in HSP than in CON hearts: left ventricular developed pressure recovery was 72.4±6.4% versus 59.7±5.3% (
P
<0.05), maximum dP/dt recovery was 77.9±6.6% versus 52.3±5.2% (
P
<0.05), and minimum dP/dt recovery was 72.4±7.2% versus 54.8±6.9% (
P
<0.05). Creatine kinase release in coronary effluent after reperfusion was 0.20±0.04 versus 0.34±0.06 IU · min
−1
· g wet wt
−1
(
P
<0.05) in HSP versus in CON hearts.

Conclusions

HSP70 upregulation protects mitochondrial function after ischemia-reperfusion injury; this was associated with improved preservation of ventricular function. Protection of mitochondrial function may be important in the development of future cardioprotective strategies.
Time Course of Functional Recovery of Stunned and Hibernating Segments After Surgical Revascularization
Authors: Bax Jeroen J. , Visser Frans C. , Poldermans Don , Elhendy Abdou , Cornel Jan H. , Boersma Eric , van Lingen Arthur , Fioretti Paolo M. , Visser Cees A.
Published: July 2021

Background

Recovery of function is possible in patients with ischemic cardiomyopathy when left ventricular dysfunction is caused by stunning or hibernation. It is plausible that recovery of function after revascularization may take a longer time in hibernating myocardium compared with stunned myocardium. Accordingly, the time courses of functional recovery in hibernating and stunned myocardium were compared.

Methods and Results

Patients (n=26) with ischemic cardiomyopathy undergoing surgical revascularization were studied; regional perfusion (resting
201
Tl single-photon emission CT), glucose utilization (
18
F-2-deoxyglucose single-photon emission CT), and contractile function (2D echocardiography) were assessed before revascularization. Dysfunctional segments with normal perfusion/glucose utilization were considered to be stunned, and dysfunctional segments with reduced perfusion/preserved glucose utilization were considered to be hibernating. Contractile function was reevaluated 3 months (early) and 14 months (late) after revascularization. Of the 266 dysfunctional segments, 57 (22%) were stunned, 62 (23%) were hibernating, and 147 (55%) were scar tissue. In stunned myocardium, contractile function improved significantly at 3 months, without further improvement at 14 months; 61% of the stunned segments improved at 3 months, and 9% improved at 14 months. In hibernating myocardium, contractile function improved at 3 months, with a further improvement at 14 months; 31% of the hibernating segments improved at 3 months, and 61% showed (additional) recovery at 14 months.

Conclusions

Stunned myocardium is likely to demonstrate early recovery of function, whereas hibernating myocardium may take a longer time to (fully) recover in function after revascularization.
Influence of Atrial Fibrillation on Outcome Following Mitral Valve Repair
Authors: Lim Eric , Barlow Clifford W. , Hosseinpour A. Reza , Wisbey Christopher , Wilson Kate , Pidgeon Willis , Charman Susan , Barlow John B. , Wells Francis C.
Published: July 2021

Background

To investigate the outcome of patients in atrial fibrillation (AF) following mitral valve repair, clinical and echocardiographic follow-up was undertaken in 400 consecutive patients who underwent mitral valvuloplasty from 1987 to 1999.

Methods and Results

The main indications for surgery were degenerative (81.4%), endocarditis (7.1%), rheumatic (6.6%), ischemic (4.6%), and traumatic (0.3%) mitral valve disease. After excluding 6 paced patients and 1 patient in nodal rhythm, we compared the outcomes of 152 patients in AF against 241 patients in sinus rhythm. For patients in AF versus those in sinus rhythm, more AF patients were older (mean age 67.2±8.8 versus 61.9±11.8 years, respectively;
P
<0.001), more were assigned to a poorer New York Heart Association (NYHA) class (77.6% versus 66.0% in NYHA III/IV, respectively;
P
=0.01), and more demonstrated impaired ventricular function (78.9% versus 46.2% with moderate or severe impairment, respectively;
P
<0.001). For patients in AF versus those in sinus rhythm, there was no difference in 30-day mortality (2.0% versus 2.1%, respectively;
P
=0.95), repair failure (5.4% versus 3.6%, respectively;
P
=0.41), stroke (5.4% versus 2.2%, respectively;
P
=0.11), or endocarditis (2.3% versus 0.9%, respectively;
P
=0.27) on follow-up at a median of 2.8 years (interquartile range 1.1 to 6.0). On echocardiography, the proportion of patients with mild regurgitation or worse was 13.3% (AF patients) versus 10.8% (patients in sinus rhythm) (
P
=0.70). Patients in AF versus those in sinus rhythm had lower survival at 3 years (83% versus 93%, respectively) and 5 years (73% versus 88%, respectively). Univariate analysis identified factors affecting survival as AF (
P
=0.002), age >70 years (
P
=0.041), and poor ventricular function (
P
<0.001). However, by use of a multivariate model, only poor ventricular function remained significant (
P
=0.01).

Conclusions

AF does not affect early outcome or durability of mitral repair. The onset of AF may be indicative of disease progression because of its association with poor left ventricular function.