Ovid Technologies (Wolters Kluwer Health)
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Human Mesenchymal Stem Cells Differentiate to a Cardiomyocyte Phenotype in the Adult Murine Heart
Background
—
Cellular cardiomyoplasty has been proposed as an alternative strategy for augmenting the function of diseased myocardium. We investigated the potential of human mesenchymal stem cells (hMSCs) from adult bone marrow to undergo myogenic differentiation once transplanted into the adult murine myocardium.
Methods and Results
—
A small bone marrow aspirate was taken from the iliac crest of healthy human volunteers, and hMSCs were isolated as previously described. The stem cells, labeled with
lacZ
, were injected into the left ventricle of CB17 SCID/
beige
adult mice. At 4 days after injection, none of the engrafted hMSCs expressed myogenic markers. A limited number of cells survived past 1 week and over time morphologically resembled the surrounding host cardiomyocytes. Immunohistochemistry revealed de novo expression of desmin, β-myosin heavy chain, α-actinin, cardiac troponin T, and phospholamban at levels comparable to those of the host cardiomyocytes; sarcomeric organization of the contractile proteins was observed. In comparison, neither cardiac troponin T nor phospholamban was detected in the myotubes formed in vitro by MyoD-transduced hMSCs.
Conclusions
—
The purified hMSCs from adult bone marrow engrafted in the myocardium appeared to differentiate into cardiomyocytes. The persistence of the engrafted hMSCs and their in situ differentiation in the heart may represent the basis for using these adult stem cells for cellular cardiomyoplasty.
Ovid Technologies (Wolters Kluwer Health) - Tập 105 Số 1 - Trang 93-98 - 2002
Acute Hemodynamic Effects of Conivaptan, a Dual V <sub>1A</sub> and V <sub>2</sub> Vasopressin Receptor Antagonist, in Patients With Advanced Heart Failure
Background
Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V
1A
(vascular and myocardial effects) and V
2
receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure.
Methods and Results
A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V
1a
/V
2
vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (−2.6±0.7, −5.4±0.7, and −4.6±0.7 mm Hg for placebo and 20 and 40 mg groups, respectively;
P
<0.05) and right atrial pressure (−2.0±0.4, −3.7±0.4, and −3.5±0.4 mm Hg for placebo and 20 and 40 mg groups, respectively;
P
<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (−11±17, 68±17, 152±19, and 176±18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively;
P
<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo.
Conclusions
In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.
Ovid Technologies (Wolters Kluwer Health) - Tập 104 Số 20 - Trang 2417-2423 - 2001
Vasopressin V <sub>2</sub> -Receptor Blockade With Tolvaptan in Patients With Chronic Heart Failure
Background—
In this study, we evaluated the effects of tolvaptan (OPC-41061), a novel, oral, nonpeptide vasopressin V
2
-receptor antagonist in patients with chronic heart failure (CHF).
Methods and Results—
This was a double-blind study investigating the effects of three doses of tolvaptan and placebo in patients with CHF. After a run-in period, 254 patients were randomly assigned to placebo (n=63) or tolvaptan [30 mg (n=64), 45 mg (n=64), or 60 mg (n=63)] once daily for 25 days. Patients were not fluid-restricted and were maintained on stable doses of furosemide. At day 1, when compared with baseline, a decrease in body weight of −0.79±0.99, −0.96±0.93, and −0.84±0.02 kg was observed in the 30-, 45-, and 60-mg tolvaptan groups, respectively, and a body weight increase of +0.32±0.46 kg in the placebo group (
P
<0.001 for all treatment groups versus placebo). Although the initial decrease in body weight was maintained during the study, no further reduction was observed beyond the first day. An increase in urine volume was observed with tolvaptan when compared with placebo (3.9±0.6, 4.2±0.9, 4.6±0.4, and 2.3±0.2 L/24 hours at day 1 for 30-, 45-, and 60-mg tolvaptan groups, and placebo, respectively;
P
<0.001). A decrease in edema and a normalization of serum sodium in patients with hyponatremia were observed in the tolvaptan group but not in the placebo group. No significant changes in heart rate, blood pressure, serum potassium, or renal function were observed.
Conclusions—
In patients with CHF, tolvaptan was well tolerated; it reduced body weight and edema and normalized serum sodium in the hyponatremic patients.
Ovid Technologies (Wolters Kluwer Health) - Tập 107 Số 21 - Trang 2690-2696 - 2003
Lower Serum Sodium Is Associated With Increased Short-Term Mortality in Hospitalized Patients With Worsening Heart Failure
Background—
The prognostic value of serum sodium in patients hospitalized for worsening heart failure has not been well defined.
Methods and Results—
The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study randomized 949 patients with systolic dysfunction hospitalized for worsening heart failure to receive 48 to 72 hours of intravenous milrinone or placebo in addition to standard therapy. In a retrospective analysis, we investigated the relationship between admission serum sodium and the primary end point of days hospitalized for cardiovascular causes within 60 days of randomization, as well as the secondary end points of in-hospital mortality, 60-day mortality, and 60-day mortality/rehospitalization. The number of days hospitalized for cardiovascular causes was higher in the lowest sodium quartile: 8.0 (4.5, 18.5) versus 6 (4, 13) versus 6 (4, 11.5) versus 6 (4, 12) days (
P
<0.015 for comparison with the lowest quartile). Lower serum sodium was associated with higher in-hospital and 60-day mortality: 5.9% versus 1% versus 2.3% versus 2.3% (
P
<0.015) and 15.9% versus 6.4% versus 7.8% versus 7% (
P
=0.002), respectively. There was a trend toward higher mortality/rehospitalization for patients who were in the lowest sodium quartile. Multivariable-adjusted Cox proportional hazards analysis showed that serum sodium on admission, when modeled linearly, predicted increased 60-day mortality: sodium (per 3-mEq/L decrease) had a hazard ratio of 1.18 with a 95% CI of 1.03 to 1.36 (
P
=0.018).
Conclusions—
In patients hospitalized for worsening heart failure, admission serum sodium is an independent predictor of increased number of days hospitalized for cardiovascular causes and increased mortality within 60 days of discharge.
Ovid Technologies (Wolters Kluwer Health) - Tập 111 Số 19 - Trang 2454-2460 - 2005
Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Those With Absent Coronary Artery Calcium: Multi-Ethnic Study of Atherosclerosis
Background:
The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up.
Methods:
We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes.
Results:
We studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32–3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01–2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06–2.33).
Conclusions:
Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.
Ovid Technologies (Wolters Kluwer Health) - Tập 145 Số 4 - Trang 259-267 - 2022
Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Special Report From the American Heart Association and American College of Cardiology Risk assessment is a critical step in the current approach to primary prevention of atherosclerotic cardiovascular disease. Knowledge of the 10-year risk for atherosclerotic cardiovascular disease identifies patients in higher-risk groups who are likely to have greater net benefit and lower number needed to treat for both statins and antihypertensive therapy. Current US prevention guidelines for blood pressure and cholesterol management recommend use of the pooled cohort equations to start a process of shared decision-making between clinicians and patients in primary prevention. The pooled cohort equations have been widely validated and are broadly useful for the general US clinical population. But, they may systematically underestimate risk in patients from certain racial/ethnic groups, those with lower socioeconomic status or with chronic inflammatory diseases, and overestimate risk in patients with higher socioeconomic status or who have been closely engaged with preventive healthcare services. If uncertainty remains for patients at borderline or intermediate risk, or if the patient is undecided after a patient–clinician discussion with consideration of risk enhancing factors (eg, family history), additional testing with measurement of coronary artery calcium can be useful to reclassify risk estimates and improve selection of patients for use or avoidance of statin therapy. This special report summarizes the rationale and evidence base for quantitative risk assessment, reviews strengths and limitations of existing risk scores, discusses approaches for refining individual risk estimates for patients, and provides practical advice regarding implementation of risk assessment and decision-making strategies in clinical practice.
Ovid Technologies (Wolters Kluwer Health) - Tập 139 Số 25 - 2019
Abnormal Epicardial Coronary Resistance in Patients With Diffuse Atherosclerosis but “Normal” Coronary Angiography
Background
Coronary arteries without focal stenosis at angiography are generally considered non–flow-limiting. However, atherosclerosis is a diffuse process that often remains invisible at angiography. Accordingly, we hypothesized that in patients with coronary artery disease, nonstenotic coronary arteries induce a decrease in pressure along their length due to diffuse coronary atherosclerosis.
Methods and Results
Coronary pressure and fractional flow reserve (FFR), as indices of coronary conductance, were obtained from 37 arteries in 10 individuals without atherosclerosis (group I) and from 106 nonstenotic arteries in 62 patients with arteriographic stenoses in another coronary artery (group II). In group I, the pressure gradient between aorta and distal coronary artery was minimal at rest (1±1 mm Hg) and during maximal hyperemia (3±3 mm Hg). Corresponding values were significantly larger in group II (5±4 mm Hg and 10±8 mm Hg, respectively; both
P
<0.001). The FFR was near unity (0.97±0.02; range, 0.92 to 1) in group I, indicating no resistance to flow in truly normal coronary arteries, but it was significantly lower (0.89±0.08; range, 0.69 to 1) in group II, indicating a higher resistance to flow. In 57% of arteries in group II, FFR was lower than the lowest value in group I. In 8% of arteries in group II, FFR was <0.75, the threshold for inducible ischemia.
Conclusion
Diffuse coronary atherosclerosis without focal stenosis at angiography causes a graded, continuous pressure fall along arterial length. This resistance to flow contributes to myocardial ischemia and has consequences for decision-making during percutaneous coronary interventions.
Ovid Technologies (Wolters Kluwer Health) - Tập 104 Số 20 - Trang 2401-2406 - 2001
TIMI Frame Count
Background
Although the Thrombolysis in Myocardial Infarction (TIMI) flow grade is a valuable and widely used qualitative measure in angiographic trials, it is limited by its subjective and categorical nature.
Methods and Results
In normal patients and patients with acute myocardial infarction (MI) (TIMI 4), the number of cineframes needed for dye to reach standardized distal landmarks was counted to objectively assess an index of coronary blood flow as a continuous variable. The TIMI frame-counting method was reproducible (mean absolute difference between two injections, 4.7±3.9 frames, n=85). In 78 consecutive normal arteries, the left anterior descending coronary artery (LAD) TIMI frame count (36.2±2.6 frames) was 1.7 times longer than the mean of the right coronary artery (20.4±3.0) and circumflex counts (22.2±4.1,
P
<.001 for either versus LAD). Therefore, the longer LAD frame counts were corrected by dividing by 1.7 to derive the corrected TIMI frame count (CTFC). The mean CTFC in culprit arteries 90 minutes after thrombolytic administration followed a continuous unimodal distribution (there were not subpopulations of slow and fast flow) with a mean value of 39.2±20.0 frames, which improved to 31.7±12.9 frames by 18 to 36 hours (
P
<.001). No correlation existed between improvements in CTFCs and changes in minimum lumen diameter (
r
=−.05,
P
=.59). The mean 90-minute CTFC among nonculprit arteries (25.5±9.8) was significantly higher (flow was slower) compared with arteries with normal flow in the absence of acute MI (21.0±3.1,
P
<.001) but improved to that of normal arteries by 1 day after thrombolysis (21.7±7.1,
P
=NS).
Conclusions
The CTFC is a simple, reproducible, objective, and quantitative index of coronary flow that allows standardization of TIMI flow grades and facilitates comparisons of angiographic end points between trials. Disordered resistance vessel function may account in part for reductions in flow in the early hours after thrombolysis.
Ovid Technologies (Wolters Kluwer Health) - Tập 93 Số 5 - Trang 879-888 - 1996
Histologic evidence for small-vessel coronary artery disease in patients with angina pectoris and patent large coronary arteries. We studied six patients who suffered from angina pectoris but had angiographically patent major coronary arteries. Two of the patients suffered also from congestive heart failure. Three patients had supraventricular tachyarrhythmias. Three patients had conduction disturbances. During coronary angiography the patients had significantly reduced flow velocity of angiographic contrast medium compared with that in a control group. Echocardiographic and Doppler flow studies showed a tendency for symmetrical thickening of the left ventricular wall, enlargement of the right ventricle, and reduced compliance of both ventricles. Right ventricular endomyocardial biopsy revealed pathologic small coronary arteries with fibromuscular hyperplasia, hypertrophy of the media, myointimal proliferation, and endothelial degeneration. Capillaries had swollen endothelial cells encroaching on the lumen. Myocardial hypertrophy, lipofuscin deposition, and patchy fibrosis were also observed. These cases show that small-vessel coronary artery disease can cause classic angina pectoris. The diagnosis can be suspected when the coronary angiogram shows large patent arteries with slow flow of the angiographic contrast medium and it can be confirmed by endomyocardial biopsy.
Ovid Technologies (Wolters Kluwer Health) - Tập 74 Số 5 - Trang 964-972 - 1986
Intrathoracic spatial location of specified coronary segments on the normal human heart. Applications in quantitative arteriography, assessment of regional risk and contraction, and anatomic display. The clinically important coronary segmental anatomy has been described in a format useful for quantitative analysis and standardized display. We have determined the intrathoracic location and course of each of the 23 coronary artery segments and branches commonly used for clinical description of disease. Measurements were averaged from perpendicular angiographic view-pairs in 37 patients with normal-sized hearts. Each segment or branch is described by several points along its course; each point is specified in polar coordinates as the radial distance from the principal coronary ostium and by angles about the patient, corresponding to those describing rotation in c-arm radiographic systems. This computer-assisted measurement method is accurate to within +/- 0.2 cm (SD) and +/- 2 degrees in phantom studies. Coronary segment location among a group of normal-sized hearts can be specified to within +/- 1.0 cm (SD). For example, the left anterior descending coronary artery segment at the apex of the heart is 12.2 +/- 1.0 cm from the left coronary ostium, 32 +/- 4 degrees to the left of the anterioposterior axis, and at 46 +/- 7 degrees of caudal angulation. There are several clinically important applications of this new knowledge. First, this anatomic format provides the basis for estimating regional myocardial contraction and the relative size of the myocardial region at risk from a given arterial occlusion. Second, precise knowledge of "normal" segment location greatly simplifies the computation of dimensional correction factors for quantitative arteriography. Third, viewing angles most appropriate for videodensitometric assessment of lesion lumen area may be computed from these data. The theoretical basis and numerical values needed for most of the above estimates are provided. Finally, a computer program has been written to generate a three-dimensional tree-branch vascular model from these anatomic locations. This easily used interactive program aids in teaching coronary angiographic anatomy and, of importance, permits selection of viewing angles that "best" visualize the traditionally difficult parts of the coronary tree.
Ovid Technologies (Wolters Kluwer Health) - Tập 78 Số 5 - Trang 1167-1180 - 1988
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