bluuebunny/crossref_metadata_2025 huggingface dataset:
Electron Beam Computed Tomography Detects Coronary Artery Disease in Fit Asymptomatic Middle-Aged Individuals
Authors: Zoltick Jerel M , Feuerstein Irwin M. , Brazaitis Michael P. , Vaitkus Mark A , Barko William F
Published: July 2021

P25

Electron Beam Computed Tomography (EBCT) is used to detect coronary artery calcification (CAC), a marker of atherosclerosis. The EBCT was used to determine the presence of CAC in a population of very fit individuals. EBCT determined the calcification scores in 436 asymptomatic individuals (400 males 36 females, mean age 43.5±3.2 yrs, range 33 to 56 yrs). All underwent extensive cardiovascular and fitness evaluations including medical, fitness and nutritional histories; lipid profiles, fasting blood sugars, homocysteine, and lipoprotein(a) levels. Individuals underwent a physical examination, resting electrocardiogram, measurements of strength and flexibility, a maximal symptom-limited treadmill test, and a direct measurement of maximal oxygen consumption. CAC was detected by EBCT scan (3 mm thick, ECG-triggered, axial images) and quantified using the Agatston scoring technique. EBCT scores ranged from 0 to 2112 and were classified into standard categories - insignificant atherosclerosis: calcium <10 (n=364 83.3%); mild atherosclerosis: calcium 10-99 (n=31 13.5%); moderate atherosclerosis: calcium 100-399 (n=7 1.6%); and marked atherosclerosis: calcium >399 (n=7 1.6%). CAC was more likely in individuals who had an elevated LDL-Chol level (p≤.001) and CHOL/HDL ratio (p≤.001), but there was wide variance. Factors that had little or no correlation included fitness parameters as determined by strength measurements, aerobic capacity or bodyfat determination. Individuals with family history of early CAD had tendency for the development of CAC but again there was wide variation in the severity of the calcium score. Of the four individuals who had CAC scores over 1000, two subsequently sustained a myocardial infarction despite previous normal maximal exercise treadmill tests. In this group exercise thallium studies were not predictive for future events. It is difficult to detect CAD in fit, asymptomatic middle-aged individuals. EBCT is helpful in defining a high risk CAD group that is not readily determined by standard risk factors.
Calcium channel blocker use and gastrointestinal tract bleeding among older adults
Authors: Kaplan Robert C , Heckbert Susan R , Koepsell Thomas D , Rosendaal Frits R , Furberg Curt D , Cooper Lawton S , Psaty Bruce M
Published: July 2021

P56

Previous studies suggest that calcium channel blockers (CCBs) may be associated with bleeding complications. We examined the association between CCB use and hospitalization for gastrointestinal (GI) tract bleeding among hypertensive older adults in the Cardiovascular Health Study (CHS). Within the CHS population of adults >=65 years old, a cohort of pharmacologically-treated hypertensive individuals was identified (n=2,189 at baseline). Hospitalized GI tract bleeding events during follow-up (n=121) were identified using computerized data and validated using medical records. Information on medication use and other risk factors for bleeding was assessed at yearly examinations. The adjusted hazard ratio (HR) was estimated using Cox proportional hazards regression with time-dependent predictor variables. Compared with use of other antihypertensive medications, use of CCBs was associated with a HR of 1.37 (95 % confidence interval (CI) = 0.95-1.98) for any hospitalized GI tract bleeding, after adjustment for age and cardiovascular disease status. Further adjustment for other known risk factors for GI tract bleeding had little effect. The HRs associated with each of the major CCB subclasses and release formulations were similar. Subjects who used the lowest daily doses of CCBs had the highest risk. The HR associated with CCB use was 1.32 for upper GI tract bleeding (95% CI = 0.82-2.13), 1.19 for lower GI tract bleeding (95% CI = 0.64-2.23), 1.49 for peptic ulcer-related bleeding (95% CI = 0.70-3.20), and 1.98 for “life-threatening” bleeding (95% CI = 1.08-3.63). In this study, the HR associated with CCB use was consistent with a moderately elevated risk of hospitalized GI tract bleeding but was not significantly different from the null. Ongoing clinical trials will help to clarify whether CCBs cause bleeding complications.
A Nonlinear Association of Serum Cholesterol Level with Incident Coronary Heart Disease in Elderly Men
Authors: Rodriguez Beatriz L , Abbott Robert D , Masaki Kamal H , Schatz Irwin J , Chen Randi , Yano Katsuhiko , Curb Jess D
Published: July 2021

P62

Increased serum cholesterol has been found to be a direct risk factor for coronary heart disease (CHD) in middle aged individuals in epidemiologic follow-up studies. However, this relationship has not been consistently reproduced in elderly populations. From 1991-93, 2424 elderly (71-93 years old) Japanese American men from the Honolulu Heart Program cohort, who did not have prevalent CHD and who were not on cholesterol lowering drugs, were examined. The subsequent 6-year follow-up provided an opportunity to closely examine the relationship between their baseline cholesterol and their incidence of CHD as determined by surveillance and a physician panel review. The study revealed a significant non-linear association of the baseline cholesterol with the incidence of CHD (p=0.033). Among the 1524 elderly men with cholesterol values below 200mg/dl the age adjusted CHD rate decreased as the mean cholesterol level increased. In those with cholesterol levels of greater than or equal to 200mg/dl (900) the age adjusted CHD rates increased with increasing level of cholesterol. The lowest CHD rates were seen in men with cholesterol levels between 200 and 219 mg/dl. Multivariate adjustment for other know risk factors (BMI, smoking, hypertension, diabetes, and HDL), decreased the strength of this non-linear relationship but it remained significant (p=0.049). A measure of frailty (10% weight loss since an exam 20 years before) further reduced the strength of the cholesterol relationship slightly but did so by reducing the magnitude of the cholesterol/CHD relationship in both those higher cholesterol (positive relationship) and those with lower cholesterol (negative relationship). Thus it is unlikely that frailty can fully explain the reverse cholesterol/CHD relationship seen in those with lower cholesterol levels. In this study the majority of men already had cholesterol levels below the standard cutpoint of 200mg/dl and had the opposite pattern of risk as elderly men with cholesterols above that cutpoint. This would indicate that further data is needed before recommending lowering of cholesterol to levels below 200mg/dl in older individuals.
Does the adverse effect of excess body weight on cardiovascular disease decline with age?
Authors: Moore Lynn L. , Bradlee M. Loring , D’Agostino Ralph B. , Ellison R. Curtis
Published: July 2021

P65

Excess body weight increases CVD risk but some studies suggest that this effect declines with age. We addressed this question using >40 years of data from The Framingham Study. In general, we found that the incidence of CVD increased with advancing age and BMI. To evaluate the age-specific effects of BMI on CVD risk, we used two types of estimates--rate ratios (RR) and rate differences (RD). After adjusting for potential confounding by age, sex, education, activity, smoking, and alcohol, the RR of CVD associated with obesity (BMI ≥30 vs. BMI <22) generally declined with age (RR=2.2, 2.4, 1.8, 1.5, and 1.4, for those in their 30s, 40s, 50s, 60s, and 70s, respectively). The RR associated with moderate overweight (BMI 26-29 vs. BMI <22) also declined with age, ranging from a RR of 1.8 (95% CI: 1.4-2.3) for the youngest subjects to a slight protective effect (RR=0.93, 95% CI: 0.71-1.2) in the oldest. The RD represents the number of excess cases of CVD attributable to a given body weight. Among the obese, the RD did not decline with age (with 12.0, 15.6, 13.7, 12.7, and 16.9 excess cases of CVD/1000 person-years in the respective age categories). Thus, the excess risk of CVD attributable to obesity (BMI ≥30) was constant across five decades of adult life. In contrast, more modest amounts of overweight were not associated with an excess risk of CVD among men and women over the age of 60.

Table 1.
Heart Rate Recovery after Submaximal Exercise Test and 20 Year All-Cause Mortality Test in Asymptomatic Russian and American Men: The Lipid Research Clinics Study
Authors: Vaidean Georgeta D , Deev Alexander , Abolafia Jeffrey , Shestov Dmitri , Davis Edward C
Published: July 2021

P76

Background. Heart Rate Recovery at two minutes post exercise (HRR2) was reported to be a predictor of death in the US-Lipid Research Clinics (LRC) Study. Objective. To extend study of HRR2 to the USSR-LRC population, with higher mortality rates and cardiovascular (CVD) risk factor levels. Design and methods. Among the LRC cohorts, using a standardized protocol, HRR2 after a treadmill submaximal test and CVD risk factors was measured in 1294 Russian and 1589 American men ages 39-60 years, free of coronary disease at baseline, not taking cardio-active drugs, followed for an average of 17.5 years for all cause mortality. Kaplan-Meier curves and stratified Cox proportional hazard models were employed for analysis. Results.There were 391 (30.2%) deaths in the Russian and 232 (14.6%) in the American men, and mean HRR2 was 59.6 bpm (95% CI 58.3-60.3) and 53.2 (CI 52.6-53.8) respectively. All cause mortality increased monotonically with decreasing HRR2 and was predicted by HRR2 adjusting for age, physical fitness, ST-T response, cholesterol and blood pressure, and alcohol intake in both samples. For each 15 bpm (1 SD) decrease in HRR2 the crude hazard rate ratio was 1.61 (95% CI 1.37, 1.89) in Russian and 1.37 (1.23, 1.51) in American men among smokers; upon adjustment the values were 1.34 (95% CI 1.16-1.56) and 1.39 (1.13-1.70) respectively. Conclusion. Delay in the recovery of heart rate after a submaximal exercise test was associated with all cause mortality, statistically independent of cardiovascular risk factors in both Russian and American men.The extension of these associations to a higher risk population, suggests the potential utility of HRR2 for CVD risk assessment.
Exercise Effect on Risk Factor Score Differs Between Genders in a Rural Cohort
Authors: Marx Herbert J. , Erb Tara , Jenkins Paul L. , Nafziger Anne N. , Lewis Carol
Published: July 2021

P95

Physical inactivity is classified as a predisposing risk factor (RF) in the AHA/ACC Scientific Statement on Assessment of Cardiovascular Risk. Whether the mechanism relates to intensification of “causal” RF or is independent is uncertain. Also, the quantity and intensity of exercise needed to reverse that risk effect remain unclear. The recent Harvard Alumni Study update suggests that in males (M) vigorous activity was associated with lower cardiovascular (CV) risk, but moderate to light activity was not. Whether the same applies to females (F) is not known. We evaluated the effect of exercise on the AHA/ACC risk factor score (RFS) in 173 M and 217 F (ages 20 to 69 years) with no known CV disease in 3 rural counties in New York State. Each subject completed a behavioral RF survey and had a physical exam plus laboratory tests at baseline and again 5 years later. Degree and frequency of work and recreational activity were assessed. Strenuous activity on ≥4 days/week was termed vigorous exercise (VE). In our cohort, 59% of M and 67% of F did not exercise vigorously compared to 60% of American adults nationally. M who did VE had significantly lower RFS at baseline than those who did not (No VE) and maintained this difference in RFS 5 years later. However, among F there was no difference in RFS between the VE and No VE groups at baseline or follow-up (see

table). We conclude that the lower CV risk in M associated with VE may be mediated at least in part through influence on causal RF. However, if VE confers benefit in F, a different mechanism must be involved.

Table 1.
CHD Risk Factors In African-Americans
Authors: Jones Daniel W , Chambless Lloyd E , Folsom Aaron R , Hutchinson Richard G , Sharrett Richey A , Tyroler H A , Taylor Herman A
Published: July 2021

0017

Few studies have reported the incidence of coronary heart disease and its relationship to risk factors in African-Americans. As part of the Atherosclerosis Risk in Communities Study, baseline risk factors were tested as predictors of incident coronary heart disease over 7-10 years of follow-up, 1987-1997, in four U.S. communities (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland). The sample included 14,026 men and women (2,298 black women [BW]; 5,686 white women [WW]; 1,396 black men [BM]; and 4,682 white men [WM] aged 45-64 who were free of clinical coronary heart disease at baseline. Age-adjusted incidence rates for the 7-10 year period (95% confidence interval) for coronary heart disease were BW 5.0(4.1-6.1), WW 4.0(3.5-4.6), BM 10.7(8.9-12.8), and WM 12.6(11.5-13.8). In multivariate analysis, traditional risk factors were generally predictive in blacks as in whites. Hypertension was a particularly strong risk factor in black women, with hazard rate ratios (HR) being: BW 4.12, WW 2.0, BM 1.85, and WM 1.59. Diabetes was predictive, but HRs were somewhat less in blacks than in whites: BW 1.88, WW 3.34, BM 1.70, and WW 2.14. LDL cholesterol was similarly predictive in all race/gender groups, HR 1.19-1.36 per S.D. LDL cholesterol increment. HDL cholesterol appeared somewhat more protective in whites than in blacks. Although black/white differences in risk factor associations exist, there were more similarities than differences in coronary heart disease risk factors and incidence. Findings from this study, along with clinical trial evidence showing efficacy, support aggressive management of traditional risk factors in blacks as in whites. Understanding of the intriguing racial differences in risk factor prediction may be an important part of further understanding the causes of coronary heart disease and may lead to better methods of prevention and treatment.
Homocysteine Predicts Incident Isolated Systolic Hypertension in Older Adults
Authors: Wildman Rachel P , Kuller Lewis H
Published: July 2021

0019

Untreated isolated systolic hypertension (ISH) indicates arterial stiffening and carries a risk for both stroke and cardiovascular disease. Elevated plasma homocysteine, a metabolite of the essential amino acid methionine, has been linked to vascular stiffness. 187 normotensive (defined as systolic blood pressure (SBP) < 160 mmHg and diastolic blood pressure < 90 mmHg) men and women (mean age 71.29 + 6.3 yrs) were followed for an average of 7 years for incident ISH. ISH was defined as a SBP ≥160 mmHg (while maintaining a DBP of < 90 mmHg) at least one time at 3 year follow-up visits, or the initiation of antihypertensive therapy. The mean baseline systolic and diastolic blood pressures (DBP) were 127 and 69 mmHg, respectively. Over the 7 year period, 59(31.5%) participants developed ISH, 76% qualified by antihypertensive use, and 24% by blood pressure values. The Kaplan Meier Estimate of 7 year survival free from ISH was 67% (95% CI: 61%, 74%). The relationship between incident ISH and the traditional cardiovascular risk factors, creatinine, homocysteine, and carotid artery intima-media wall thickness (IMT) was assessed by Cox proportional hazards regression. The strongest predictor of incident ISH was baseline SBP. For participants with baseline SBPs of < 130, 130-139, and 140+ mmHg, the corresponding 7 year survival free from ISH was 80% (95% CI: 73%, 88% ), 53% (95%CI: 38%, 67%), and 44% (95% CI: 26%, 62%). Factors independently associated with time to ISH were higher triglycerides (upper tertile,RR=2.0, p=0.012), homocysteine levels (> 12.0 μmol/l, RR=2.2, p=0.005), and baseline SBP (per 10 mmHg,RR=1.4, p=0.003). The results were similar when the analysis was restricted to the 157 participants with a baseline SBP of < 140 mmHg. Baseline IMT was found to be univariately related to time to ISH (RR per each 1.0 mm increment=3.0; p=0.016). In multivariate analysis, this association remained independent of triglycerides and homocysteine, but not baseline SBP (RR per each 1.0 mm increment=2.5; p=0.049). In conclusion, among normotensive older adults, 32% can be expected to develop ISH over a 7 year period, and higher triglyceride and homocysteine levels are risk factors.
Relative Lymphocytopenia and Outcome of Myocardial Infarction.
Authors: Roger Veronique L. , Gabriel Sherine E. , Killian Jill , Reeder Guy S. , Jacobsen Steven J.
Published: July 2021

0024

Background: There is evidence for the role of inflammation in the pathogenesis of coronary disease. Relative lymphocytopenia was reported for the diagnosis of myocardial infarction (MI), but little is known about its prognostic value. This study was undertaken to test the hypothesis that relative lymphocytopenia was associated with cardiac events (defined as recurrent MI, congestive heart failure or cardiac death) after MI among Olmsted County residents. Methods: MIs were validated using standard epidemiological criteria using enzymes, chest pain and Minnesota coding of the ECG. The entire community medical record, available via the Rochester Epidemiology Project, was reviewed to determine incident status and ascertain outcomes. Relative lymphocytopenia was defined as percent lymphocytes<20, 3%. Results: Between 1979 and 1994, an incidence cohort of 1653 validated MIs (mean age 67 ± 14, 43% women) was assembled. At the time of index MI, relative lymphocytopenia was present in 51% of the cases. After a mean follow-up of 6.9 ± 5.4 years, 471 pts had experienced recurrent MIs, 849 pts CHF and 602 cardiac deaths occurred. The 5-year event-free survival was 35% for cases with relative lymphocytopenia vs 52% for those without(p<0.001). After adjustment for age and current smoking, relative lymphocytopenia was associated with a 21% increase in the risk of cardiac event (RR 1.21, 95% CI 1.1-1.4; p=0.003). Conclusion: Relative lymphocytopenia is associated with cardiac events after incident MI. These data support the role of inflammation in the outcome of coronary disease.
Coronary calcification detected by electron-beam computed tomography and non-coronary measures of atherosclerosis:
Authors: Witteman Jacqueline CM
Published: July 2021

0004

Coronary calcification as detected by electron-beam tomography (EBT) is a measure of coronary atherosclerosis. We investigated whether coronary artery calcium is associated with non-coronary measures of atherosclerosis, using data from the population-based Rotterdam Study. Participants in the third phase of the study were invited to undergo EBT scanning for detection of coronary calcifications. EBT scans were obtained from 2263 participants (47% men, mean age (SD), 71.3 (5.7)). Quantification of coronary calcifications was performed using Agatston’s method, and resulted in a calcium score. Calcium scores were available for 1874 subjects. Measures of non-coronary atherosclerosis included presence of aorta calcification detected by X-ray, presence of plaques in carotid arteries and intima-media thickness of the common carotid artery, both detected by ultrasonography, and ankle to brachial blood pressure index as a measure of peripheral arterial disease. Three calcium score categories were considered: 0 - 100, 101 - 500, and >500. The calcium score showed a graded association with the measures of non-coronary atherosclerosis. Using logistic regression analysis, age and sex adjusted odds ratios for aorta calcification were 3.2 (95% confidence interval, 2.0 - 5.2) in subjects with calcium score 101 - 500 and 12.0 (7.6 - 18.9) in subjects with calcium score > 500, when compared to subjects in the lowest calcium score category. The corresponding odds ratios for carotid plaques were 2.4 (1.6 - 3.5) and 5.8 (3.9 - 8.6). In a general linear model adjusted for age and sex, mean intima-media thickness increased with increasing calcium score category, while mean ankle to brachial blood pressure index decreased. These results indicate that known measures of non-coronary atherosclerosis are strongly related to coronary atherosclerosis, as measured by EBT calcium.
Sudden Cardiac Death in US Young Adults, 1989-1996
Authors: Zheng Zhi-Jie , Croft Janet B. , Giles Wayne H. , Mensah George A.
Published: July 2021

0007

Anecdotal evidence and case reports indicate that sudden cardiac death (SCD) occurs in adolescents and young adults. To investigate the epidemiologic pattern and secular trend of SCD among ages 15-34 years, we analyzed US Multiple Causes of Death data from 1989 to 1996. SCD is defined as death due to cardiac disease (ICD-9 codes: 390-398, 402 and 404-429)that occurred out of hospital or in emergency room. This definition has been used in prior studies with reasonable accuracy. Mortality rates were calculated using mid-year population estimates as the denominators, and standardized to 1970. In 1996, 3,000 sudden cardiac deaths occurred for this specific age group, which reflects a 10% increase from 1989 (n=2,719). The leading underlying causes of SCD were ischemic heart disease (ICD codes 410-414, and 429.2), and arrhythmias or cardiomyopathies (ICD codes 425-427), each accounting for 35% of all SCDs. SCD mortality rates were twice as high in men as in women, and increased with age. From 1989 to 1996, age-standardized SCD mortality rates increased in both men (+10%) and women (+31%) (

Figure). Although SCD is relatively rare in US adolescents and young adults, the increased trend of SCD mortality warrants further investigation. This is the first national surveillance report on SCD in young adults.

Figure 1.
The Diet, Exercise and Weight Loss Intervention Trial (DEW-IT)
Authors: Miller Edgar R , Young Deborah R , Erlinger Thomas P , Jehn Megan L , Charleston Jeanne , Appel Lawrence J
Published: July 2021

0009

Background - Certain lifestyle modifications (weight loss, sodium reduction, adoption of the DASH diet, and increased exercise) when administered separately, can lower blood pressure. However, the effects on blood pressure of combining all of these therapies in adults on blood pressure lowering medications is unknown. Methods - In a randomized controlled feeding study, 44 hypertensive obese adults, taking a single daily blood pressure lowering medication, were randomized for 9 weeks to a lifestyle or monitoring group. The lifestyle group was fed a hypocaloric version of the DASH diet (high in fruits, vegetables and low-fat dairy products) with reduced sodium (100 mmol/day). This group also exercised at moderate intensity 3 times per week. The monitoring group received information only. The primary outcome was change in 24 hour ambulatory blood pressure. Results - 43 of 44 completed the study. Net mean weight loss in the lifestyle group was 12.3 pounds. Compared with the monitoring group, the lifestyle group had significant reductions in 24 hour blood pressures with greatest reductions occurring while awake (

TABLE). Conclusions -A comprehensive lifestyle intervention is extremely effective at lowering blood pressure in hypertensive adults taking blood pressure lowering medications.

Table 1.
Development of Robotic Enhanced Endoscopic Surgery for the Treatment of Coronary Artery Disease
Authors: Kappert Utz , Schneider Jens , Cichon Romuald , Gulielmos Vassilios , Tugtekin Sems-Malte , Nicolai Joachim , Matschke Klaus , Schueler Stephan
Published: July 2021

Background

The introduction of robotic enhanced surgery demanded stepwise development of performed procedures on the basis of growing experience of the operating team.

Methods and Results

Between May 1999 and January 2001, this new wrist-enhanced instrumentation was used in 201 patients (156 men and 45 women, median age 64±10.5 years, left ventricular ejection fraction 68±12.4%). During the development of robotic enhanced CABG, the patients were divided into 3 groups. Group A (n=156) consisted of patients in whom the robotic system was used to harvesting the left or right internal mammary artery, or both, whereas the anastomoses were performed directly through a small chest incision. In group B (n=37), the harvest of the internal mammary arteries and the coronary anastomoses were performed totally endoscopically. In a third early group C, patient (n=8) were treated with robotic enhanced CABG via a median sternotomy already preoperatively planned, whereas gradual step-by-step application of robotic instrumentation and its feasibility were assessed. The survival rate was 99.4%. One patient (0.6%) died due to pneumonia on postoperative day 16. Conversion rate to median sternotomy was 5%. The left and right internal mammary artery conduits could be successfully harvested in 98% and 100%, respectively. The time of dissection of the left internal mammary artery could be significantly reduced alone by increasing experience. All patients were discharged from the hospital after a mean of 7 days. In 9 patients (4.5%), bleeding required reexploration.

Conclusions

The introduction of this new surgical tool enables the development of new endoscopic procedures. Our results gained during the development of robotic enhanced CABG motivate us to establish a set standard for the totally endoscopic treatment of patients with 1-vessel coronary artery disease.
Late Outcome After Arterial Switch Operation for Transposition of the Great Arteries
Authors: Losay J. , Touchot A. , Serraf A. , Litvinova A. , Lambert V. , Piot J.D. , Lacour-Gayet F. , Capderou A. , Planche C.
Published: July 2021

Background

Early and midterm results of the arterial switch operation (ASO) in transposition of the great arteries (TGA) are good, but late outcome data in large populations are still few.

Methods and Results

Twelve hundred patients had an ASO for TGA between 1982 and 1999, with prospective follow-up of 1095 survivors. Outcome measures included late death, reoperation, aortic insufficiency (AI), pulmonary stenosis (PS), and coronary anomaly. Median follow-up was 4.9 years (range 0.5 to 17 years). Late death occurred in 32 patients; survival was 88% at both 10 and 15 years. The hazard function for death declined rapidly, with no deaths after 5 years. Late mortality was correlated with reintervention and major events in the intensive care unit. Reoperation was performed in 103 patients, more often in complex TGA; the cause was mainly PS. Freedom from reintervention was 82% at 10 and 15 years, with a hazard function that declined rapidly but slowly increased after 3 years. At the last follow-up, PS was present in 3.9% of patients, and grade II or more AI was present in 3.2%, with a cumulative incidence of 9% at 15 years. Among the 278 patients who had a coronary arteriography, 8% had coronary lesions. Normal left ventricle and sinus rhythm were seen in 96.4% and 98.1%, respectively.

Conclusions

Fifteen years after ASO, late mortality was low, with no deaths after 5 years; reoperation, mainly owing to PS, occurred throughout the follow-up. AI and coronary obstruction are rare but warrant further follow-up. Good left ventricular function and sinus rhythm are maintained.
Neurodevelopmental Outcomes in Children After the Fontan Operation
Authors: Forbess Joseph M. , Visconti Karen J. , Bellinger David C. , Jonas Richard A.
Published: July 2021

Background

Previous studies of patients after the Fontan operation have reported IQ scores lower than population norms. In the past decade, changes have occurred both in surgical methods used and in the patient population undergoing Fontan palliation. The present study examined the impact of these changes on neurodevelopmental outcomes after Fontan.

Methods and Results

Neuropsychological tests were administered to 27 five-year-old children after Fontan. Mean age at repair was 2 years 4 months. The present sample was compared with an earlier Fontan group (EFG) of 133 patients who underwent surgery in the 1970s and 1980s. Mean age at repair for the EFG was 7 years 3 months. Compared with EFG, the present study sample was younger at Fontan (
P
=0.0001) and more likely to have undergone a Norwood procedure (
P
=0.02), a pre-Fontan bidirectional cavopulmonary anastomosis (
P
<0.001), and Fontan fenestration (
P
=0.001). Although mean full-scale, verbal, and performance IQ scores were within 1 SD (15 points) of the population mean of 100 (93±16, 95±15, and 91±17, respectively), mean full-scale and performance IQ scores were significantly lower than this population mean (
P
=0.03 and
P
=0.01, respectively).

Conclusions

Compared with a historical cohort of Fontan patients from this institution, a staged approach to Fontan earlier in life is not detrimental to neurodevelopmental outcome. Neurodevelopmental outcomes in children after Fontan are in the normal range, but performance remains lower than the general population.
Survival Benefit of the Implantable Cardioverter-Defibrillator in Patients on the Waiting List for Cardiac Transplantation
Authors: Sandner Sigrid E. , Wieselthaler Georg , Zuckermann Andreas , Taghavi Shahrokh , Schmidinger Herwig , Pacher Richard , Ploner Meinhard , Laufer Guenther , Wolner Ernst , Grimm Michael
Published: July 2021

Background

The implantable cardioverter-defibrillator (ICD) effectively reduces sudden cardiac death in patients with severe LV dysfunction. Effect of ICD therapy on total mortality in patients on the waiting list for cardiac transplantation is still uncertain.

Methods and Results

We retrospectively analyzed 854 unselected consecutive patients (ICD therapy, n=102; 11.9%) on the waiting list for cardiac transplantation between January 1992 and March 2000. Actuarial 12-month total mortality rate on the waiting list was 24.2%; sudden cardiac death was the predominant mode of death (66.7% of total deaths). Kaplan-Meier analysis revealed improved survival for ICD (total mortality, 13.2%) compared with non-ICD (total mortality, 25.8%) patients (log rank,
P
=0.03). No event of sudden death occurred in ICD patients, whereas in non-ICD patients, 12-month sudden death rate was 20.1% (
P
=0.0001). Nonsudden death rates did not differ between ICD and non-ICD patients (
P
=0.16). A Cox proportional hazards model demonstrated that absence of an ICD was a powerful independent predictor of total mortality (
P
=0.02; relative risk, 2.22; 95% confidence interval, 1.16 to 4.17) and sudden cardiac death (
P
<0.0001; infinite relative risk) on the waiting list.

Conclusions

ICD therapy, because it prevents sudden cardiac death, significantly improves survival on the waiting list for cardiac transplantation. The present study supports the use of ICDs as a bridge to transplantation in patients who are at risk of sudden cardiac death. Prospective randomized trials are needed to evaluate the potential benefit of prophylactic ICD therapy as a bridge to transplantation in all patients on cardiac transplant waiting lists.
Reliability of Tissue Doppler Wall Motion Monitoring After Heart Transplantation for Replacement of Invasive Routine Screenings by Optimally Timed Cardiac Biopsies and Catheterizations
Authors: Dandel Michael , Hummel Manfred , Müller Johannes , Wellnhofer Ernst , Meyer Rudolf , Solowjowa Natalia , Ewert Ralf , Hetzer Roland
Published: July 2021

Background

Invasive screenings at predefined time intervals for acute rejection and transplant coronary artery disease (TxCAD) are standard procedures. However, cardiac biopsies and catheterizations are distressing and risky for the patients and are also costly. We assessed the reliability of pulsed-wave tissue Doppler imaging (PW-TDI) for the timing of invasive examinations in heart recipients in an attempt to avoid unnecessary endomyocardial biopsies (EMBs) and catheterizations.

Methods and Results

PW-TDI obtained at the basal left ventricular posterior wall before 408 EMBs and 293 catheterizations was tested for its diagnostic value regarding rejection and TxCAD with the use of International Society of Heart and Lung Transplantation biopsy grading, coronary angiography, and intravascular ultrasound as standards. Early diastolic peak wall motion velocity and relaxation time showed high sensitivities for clinically relevant rejection diagnosis (90.0% and 93.3%, respectively). The negative and positive predictive values for rejection of diastolic parameter changes appeared high enough (up to 96% and 92%, respectively) to allow a reliable noninvasive PW-TDI monitoring with efficiently timed, instead of routinely scheduled, EMBs. At definite cutoff values for systolic parameters, the probability for TxCAD reached 92% to 97%. The Fisher classification functions allowed TxCAD exclusion with 80% probability.

Conclusions

Without diastolic parameter changes, acute rejection can be practically excluded, and serial PW-TDI can save patients from routine EMBs. The high specificity and negative predictive value for TxCAD of reduced systolic peak velocities and extended systolic time allow optimized timed catheterizations. Peak systolic velocity and systolic time allow diagnostic classifications that enable patients without known TxCAD but with high risk for catheterization to be spared routine angiographies.
Upregulation of Bcl-2 Through Caspase-3 Inhibition Ameliorates Ischemia/Reperfusion Injury in Rat Cardiac Allografts
Authors: Grünenfelder Jürg , Miniati Douglas N. , Murata Seiichiro , Falk Volkmar , Hoyt E. Grant , Kown Murray , Koransky Mark L. , Robbins Robert C.
Published: July 2021

Background

Oxidative stress after ischemia/reperfusion of cardiac allografts leads to cytokine production. Bcl-2, an inhibitor of apoptosis, also has strong antioxidant properties. Caspase-3 is known to cleave bcl-2. This study tests the hypothesis that bcl-2 is downregulated while tumor necrosis factor-α (TNF-α) levels increase after cardiac transplantation. Furthermore, the use of caspase-3 inhibition was investigated as a strategy for preserving myocardial bcl-2 and mitochondrial cytochrome c after transplantation.

Methods and Results

PVG-to-ACI rat heterotopic cardiac transplantations were performed in 4 groups designed with 30 minutes’ ischemia and 4 or 8 hours of reperfusion (n=4 per group). Treatment consisted of DEVD-CHO 500 μg IP per animal to donor and recipient 2 hours before transplantation and 250 μg IC into allograft. Controls were treated with saline. Grafts were analyzed by reverse transcription–polymerase chain reaction for bcl-2 mRNA, by ELISA for TNF-α, for myeloperoxidase activity, and by Western blot for cytochrome c. In untreated groups, bcl-2 mRNA decreased significantly over time, whereas TNF-α increased significantly at 4 hours (
P
=0.003) and returned to baseline after 8 hours’ reperfusion (
P
=NS compared with normal hearts). Treatment with caspase-3 inhibitor showed significant upregulation of bcl-2 mRNA expression after 4 and 8 hours of reperfusion (
P
<0.001 versus control), with a concomitant decrease in TNF-α to baseline levels. Myeloperoxidase activity in all groups was no different from that of normal hearts. Mitochondrial cytochrome c release increased in both control and treatment groups.

Conclusions

Bcl-2 is actively downregulated and TNF-α is upregulated in this model of cardiac allograft ischemia/reperfusion. Furthermore, the caspase-3 pathway is linked to this process, and blockade of caspase-3 can ameliorate reperfusion injury by upregulating bcl-2 and inhibiting TNF-α without affecting cytochrome c release.
Modified Ultrafiltration Reduces Morbidity After Adult Cardiac Operations
Authors: Luciani Giovanni Battista , Menon Tiziano , Vecchi Barbara , Auriemma Stefano , Mazzucco Alessandro
Published: July 2021

Background

Extracorporeal circulation contributes to morbidity after open-heart surgery by causing a systemic inflammatory reaction. Modified ultrafiltration is a technique able to remove the fluid overload and inflammatory mediators associated with use of cardiopulmonary bypass. It has been shown to reduce morbidity after cardiac operations in children, but the impact on adult cardiac procedures is unknown.

Methods and Results

Five hundred seventy-three consecutive adult patients were prospectively randomized to either ultrafiltration after cardiopulmonary bypass (treatment) or to no ultrafiltration (control). Parsonnet score was used to assess the severity of the patients’ clinical conditions. Analysis was done with Student’s
t
test or Mann-Whitney
U
test for continuous variables and Fisher’s exact test or Pearson’s χ
2
for discrete variables. Hospital mortality was 2.5% (7 of 284) in the treatment group versus 3.8% (11 of 289) in the control group (
P
=0.357). Hospital morbidity was lower in treated patients (66 of 284 [23.2%] versus 117 of 289 [40.5%],
P
=0.0001). Cardiac morbidity was similar (26 of 284 [9.1%] versus 35 of 289 [12.1%],
P
=0.251), whereas significantly lower rates of respiratory (20 of 284 [7.0%] versus 36 of 289 [12.5%],
P
=0.029), neurological (5 of 284 [1.8%] versus 14 of 289 [4.8%],
P
=0.039), and gastrointestinal (0 of 284 versus 4 of 289 [1.4%],
P
=0.044) complications were found in treated patients. Transfusion requirements were also lower in treated patients (1.66±2.6 versus 2.25±3.8 U/patient,
P
=0.039). Duration of intensive care (39.9±49.2 versus 46.3±72.8 hours,
P
=0.218) and hospital stay (7.6±3.5 versus 7.9±4.4 days,
P
=0.372) were comparable.

Conclusions

Modified ultrafiltration after cardiopulmonary bypass is associated with a lower prevalence of early morbidity and lower blood transfusion requirements. The impact on length of hospital stay needs further analysis. Routine application of modified ultrafiltration after adult cardiac operations is warranted.
Passive Containment and Reverse Remodeling by a Novel Textile Cardiac Support Device
Authors: Konertz Wolfgang F. , Shapland J. Edward , Hotz Holger , Dushe Simon , Braun Jan Peter , Stantke Katrin , Kleber Franz Xaver
Published: July 2021

Background

Progressive remodeling and dilation of cardiac chambers is responsible in part for myocardial dysfunction in chronic heart failure. Preclinical studies with suitable animal models indicate that a passive cardiac constraint device can promote reverse remodeling, with improvement in cardiac function. We hypothesize that such a device could provide benefit for stable heart failure patients in New York Heart Association (NYHA) class II and III .

Methods and Results

From April 1999 to March 2000, 27 patients received Acorn’s Cardiac Support Device (CSD) during an initial safety/feasibility study. In 11 patients, the only surgical measure was CSD placement. Most patients suffered from idiopathic cardiomyopathy; 4 were in NYHA class II, one was in class II/III, and 6 were in class III. All were stable on intensive medical treatment. The CSD, a textile polyester device, was fitted snugly around the heart during surgery. All patients survived surgery and recovered smoothly. Three months after surgery, 56% of patients were in NYHA class I, 33% were in class II, and 11% were in class II/III. Echocardiography showed an improvement in left ventricular ejection fraction from an average of 22% to 28% and 33% at 3 and 6 months, respectively. Simultaneously, the left ventricular end-diastolic dimension decreased from 74 mm to 68 mm and 65 mm, respectively. Mitral valve regurgitation (on a scale of 0 to 4+) decreased from 1.3 to 0.7 by 3 months. Quality-of-life indices correlated with the apparent reversal of ventricular remodeling. Preoperative cardiac medications remained virtually unchanged after implant.

Conclusions

In the short- and intermediate-term, CSD implantation seems to ameliorate symptoms and improve cardiac and functional performance in heart failure patients. Worldwide randomized trials are currently underway.
Angiotensin II Type 2 Receptor Mediates Vascular Smooth Muscle Cell Apoptosis in Cystic Medial Degeneration Associated With Marfan’s Syndrome
Authors: Nagashima Hirotaka , Sakomura Yasunari , Aoka Yoshikazu , Uto Kenta , Kameyama Kin-ichi , Ogawa Motoko , Aomi Shigeyuki , Koyanagi Hitoshi , Ishizuka Naoko , Naruse Mitsuhide , Kawana Masatoshi , Kasanuki Hiroshi
Published: July 2021

Background

Cystic medial degeneration (CMD) is a histological abnormality that is common in the aortic diseases associated with Marfan’s syndrome (MFS). Although little known about the mechanism underlying CMD, several recent reports have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a substantial role in CMD. On the other hand, angiotensin II (Ang II) has been reported to play an important role in the regulation of VSMC growth and apoptosis via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R).

Methods and Results

To elucidate the role of Ang II signaling via the Ang II receptors in CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of Ang II in MFS aortas (n=10) and control aortas (n=12). Furthermore, we examined the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was significantly decreased (
P
<0.01) and AT2R expression was significantly increased (
P
<0.001) in MFS aortas compared with control aortas, and tissue Ang II concentration was significantly higher in CMD than in the control condition (
P
<0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum deprivation-induced VSMC apoptosis (
P
<0.05), although the AT1R blocker did not inhibit apoptosis in cultured aortic media from MFS patients.

Conclusions

Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have clinical value in the prevention and treatment of CMD.
Overexpression of Interleukin-1 Receptor Antagonist Provides Cardioprotection Against Ischemia-Reperfusion Injury Associated With Reduction in Apoptosis
Authors: Suzuki Ken , Murtuza Bari , Smolenski Ryszard T. , Sammut Ivan A. , Suzuki Noriko , Kaneda Yasufumi , Yacoub Magdi H.
Published: July 2021

Background

Interleukin-1 (IL-1) plays a role in mediating acute inflammation during ischemia-reperfusion (I/R) injury in the heart, which leads to both necrosis and apoptosis of cardiomyocytes. IL-1 receptor antagonist (IL-1ra) is known to inhibit the effects of IL-1α and IL-1β, resulting in attenuated inflammatory injury, and to protect cells from IL-1β–induced apoptosis in vitro. We hypothesized that IL-1ra overexpression would provide cardioprotection by reducing inflammation-mediated myocardial damage including apoptosis after I/R injury in vivo.

Methods and Results

Rat hearts were transfected with human secreted–type IL-1ra gene by intracoronary infusion of Hemagglutinating Virus of Japan liposome and were heterotopically transplanted. IL-1ra overexpression in these hearts was confirmed by enzyme immunoassay and immunohistochemistry. Myocardial tolerance of the transplanted heart was evaluated with the use of a novel system in which the heart, existing within the recipient’s abdomen, was given 30 minutes of ischemia by left coronary artery occlusion and 24 hours of reperfusion. Consequently, infarct size was decreased in IL-1ra–transfected hearts compared with control-transfected ones (26.9±3.2% versus 46.2±3.0%,
P
=0.001), corresponding to lower myocardial myeloperoxidase activity (2.20±0.69 versus 6.82±1.19 U/g wet wt,
P
<0.001) and decreased neutrophil infiltration in histological study. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and DNA-laddering studies demonstrated that cardiomyocyte apoptosis was attenuated in IL-1ra–transfected hearts (21.4±3.3 versus 41.4±3.4%,
P
=0.002), correlating with reduced post I/R upregulation of Bax, Bak, and caspase-3.

Conclusions

IL-1ra introduced by gene transfection protected myocardium from I/R injury by attenuating the inflammatory response, which was associated with decreased apoptosis. This suggests a potentially important role of IL-1/IL-1ra in myocardial I/R injury and the value of IL-1ra-gene therapy for myocardial preservation.
Relationship Between Early Diastolic Intraventricular Pressure Gradients, an Index of Elastic Recoil, and Improvements in Systolic and Diastolic Function
Authors: Firstenberg Michael S. , Smedira Nicholas G. , Greenberg Neil L. , Prior David L. , McCarthy Patrick M. , Garcia Mario J. , Thomas James D.
Published: July 2021

Background

Early diastolic intraventricular pressure gradients (IVPGs) have been proposed to relate to left ventricular (LV) elastic recoil and early ventricular “suction.” Animal studies have demonstrated relationships between IVPGs and systolic and diastolic indices during acute ischemia. However, data on the effects of improvements in LV function in humans and the relationship to IVPGs are lacking.

Methods and Results

Eight patients undergoing CABG and/or infarct exclusion surgery had a triple-sensor high-fidelity catheter placed across the mitral valve intraoperatively for simultaneous recording of left atrial (LA), basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were compared with those with similar LA pressures and heart rates obtained after bypass. From each LV waveform, the time constant of LV relaxation (τ), +dP/dt
max
, and −dP/dt
max
were determined. Transesophageal echocardiography was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased after bypass (before bypass 1.64±0.79 mm Hg; after bypass 2.67±1.25 mm Hg;
P
<0.01). Significant improvements were observed in ESV, as well as in apical and basal +dP/dt
max
, −dP/dt
max
, and τ (each
P
<0.05). Overall, IVPGs correlated inversely with both ESV (IVPG=−0.027[ESV]+3.46,
r
=−0.64) and EDV (IVPG=−0.027[EDV]+4.30,
r
=−0.70). Improvements in IVPGs correlated with improvements in apical τ (Δτ =5.93[ΔIVPG]+4.76,
r
=0.91) and basal τ (Δτ =2.41[ΔIVPG]+5.13,
r
=−0.67). Relative changes in IVPGs correlated with changes in ESV (ΔESV=−0.97[%ΔIVPG]+23.34,
r
=−0.79), EDV (ΔEDV=−1.16[%ΔIVPG]+34.92,
r
=−0.84), and EF (ΔEF=0.38[%ΔIVPG]−8.39,
r
=0.85).

Conclusions

Improvements in LV function also increase IVPGs. These changes in IVPGs, suggestive of increases in LV suction and elastic recoil, correlate directly with improvements in LV relaxation and ESV.