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Context: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy.Objective: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina.Design, Setting, and Patients: A phase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011.Intervention: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group).Main Outcome Measures: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory.Results: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n = 61 in BMC group and n = 31 in placebo group). Changes in LVESV index (-0.9 mL/m(2) [95% CI, -6.1 to 4.3]; P = .73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P = .17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P = .84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement.Conclusion: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT.Trial Registration: clinicaltrials.gov Identifier: NCT00824005. [ABSTRACT FROM AUTHOR]

Objective: To study the potential usefulness of the 6-minute walk test, a self-paced submaximal exercise test, as a prognostic indicator in patients with left ventricular dysfunction.Design: Data were collected during a prospective cohort study, the Studies of Left Ventricular Dysfunction (SOLVD) Registry Substudy.Setting: Twenty tertiary care hospitals in the United States, Canada, and Belgium.Participants: A stratified random sample of 898 patients from the SOLVD Registry who had either radiological evidence of congestive heart failure and/or an ejection fraction of 0.45 or less were enrolled in the substudy and underwent a detailed clinical evaluation including a 6-minute walk test. Patients were followed up for a mean of 242 days.Outcome Measures: Mortality and hospitalization.Results: During follow-up, 52 walk-test participants (6.2%) died and 252 (30.3%) were hospitalized. Hospitalization for congestive heart failure occurred in 78 participants (9.4%), and the combined endpoint of death or hospitalization for congestive heart failure occurred in 114 walk-test participants (13.7%). Compared with the highest performance level, patients in the lowest performance level had a significantly greater chance of dying (10.23% vs 2.99%; P = .01), of being hospitalized (40.91% vs 19.90%; P = .002), and of being hospitalized for heart failure (22.16% vs 1.99%; P < .0001). In a logistic regression model, ejection fraction and distance walked were equally strong and independent predictors of mortality and heart failure hospitalization rates during follow-up.Conclusion: The 6-minute walk test is a safe and simple clinical tool that strongly and independently predicts morbidity and mortality in patients with left ventricular dysfunction. [ABSTRACT FROM AUTHOR]

Background: Sublingual nitroglycerin (SL NTG) is useful for treating acute decompensated heart failure, possibly by increasing splanchnic capacitance and reducing left ventricular (LV) preload. We evaluated a radionuclide method to study these effects, initially in subjects without heart failure., Methods and Results: Red blood cells were labelled by an in vitro method. Abdominal and chest images were obtained at rest, showing relative regional blood volumes. The abdomen was then re-imaged during progressive escalation of intrathoracic pressure using continuous positive airway pressure to assess baseline splanchnic capacitance (pressure-volume relationship, PVR) and compliance (slope of PVR). The procedure was repeated after 0.6 mg SL NTG, followed by chest images. Relative splanchnic blood volume increased at rest after SL NTG (P < .002), signifying an increase in splanchnic capacitance. The slope of the splanchnic PVR decreased in proportion to the baseline PVR (P = .0014), signifying increased compliance. The relative pulmonary blood volume decreased in proportion to the increase in splanchnic blood volume (P = .01)., Conclusions: A semi-quantitative radionuclide method demonstrated the effect of SL NTG for increasing splanchnic capacitance and compliance, with a proportional decrease in pulmonary blood volume. These data may be applied to quantitatively evaluate the importance of splanchnic vasodilation as a mechanism of LV preload reduction in the treatment of heart failure., Clinical Trials Registration: NCT02425566., (© 2021. American Society of Nuclear Cardiology.)

Coronary artery disease is a leading cause of morbidity and mortality worldwide. Noninvasive imaging tests play a significant role in diagnosing coronary artery disease, as well as risk stratification and guidance for revascularization. Myocardial perfusion imaging, including single photon emission computed tomography and positron emission tomography, has been widely employed. In this review, we will review test accuracy and clinical significance of these methods for diagnosing and managing coronary artery disease. We will further discuss the comparative usefulness of other noninvasive tests-stress echocardiography, coronary computed tomography angiography, and cardiac magnetic resonance imaging-in the evaluation of ischemia and myocardial viability., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: We sought to clarify the role of ventriculo-arterial (V-A) coupling in the treatment of nonischemic dilated cardiomyopathy (NIDCM) by adding a mineralocorticoid receptor antagonist (MRA) to conventional anti-failure therapy., Methods and Results: We employed cardiac magnetic resonance imaging to quantify left ventricular (LV) contractility and V-A coupling in normal subjects at rest (n = 11) and in patients with NIDCM (n = 12) before and after long term anti-failure therapy, in which MRA was added to conventional anti-failure therapy. After ≥6 months' treatment in NIDCM patients, LV volumes and mass decreased, and the LV ejection fraction increased from a median of 24% (17, 27) (interquartile range IQR) to 47 (42, 52) (P < 0.002), with a marked reduction in arterial elastance (Ea) from 2.89 mmHg/mL (2.34, 4.0) to 1.50 (1.29, 1.95) (P < 0.002), similar to Ea of normal subjects, 1.53 (1.34, 1.67) (P > 0.05). The V-A coupling ratio, Ea/end-systolic elastance (single-beat method), decreased by -1.08 (-1.96, -0.55), (P = 0.003), as did Ea/end-systolic pressure/end-systolic pressure ratio, -0.54 (0.35, 0.87), (P = 0.002). The preload recruitable stroke work (PRSW) increased as did PRSW indexed for Ea (both P = 0.002), which reflected 'total circulatory performance'., Conclusions: In NIDCM, adding MRA to conventional anti-failure therapy markedly improved LV ejection fraction and reduced peripheral vascular resistance, due to both improved LV contractility and especially to enhanced V-A coupling, as Ea decreased to normal. Total circulatory performance was a sensitive indicator of both LV pump performance and the arterial loading conditions., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Mineralocorticoid receptor antagonist (MRA) treatment produces beneficial left ventricular (LV) remodeling in nonischemic dilated cardiomyopathy (NIDCM). This study addressed the timing of maximal beneficial LV remodeling in NIDCM when adding MRA., Materials and Methods: We studied 12 patients with NIDCM on stable β-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor-blocking therapy who underwent cardiac magnetic resonance imaging before and after 6-31 months of continuous MRA therapy., Results: At baseline, the LV ejection fraction (LVEF) was 24% (19-27); median [interquartile range]. The LV end-systolic volume index (LVESVI) was 63 ml (57-76) and the LV stroke volume index (LVSVI) was 19 ml (14-21), all depressed. After adding MRA to the HF regimen, the LVEF increased to 47% (42-52), with a decrease in LVESVI to 36 ml (33-45) and increase in LVSVI to 36 ml (28-39) (for each, P  < 0 .0001). Using generalized least squares analysis, the maximal beneficial remodeling (defined by maximal increase in LVEF, the maximal decrease in LVESVI and maximal increase in LVSVI) was achieved after approximately 12-16 months of MRA treatment., Conclusions: Adding MRA to a standard medical regimen for NIDCM resulted in beneficial LV remodeling. The maximal beneficial remodeling was achieved with 12-16 months of MRA therapy. These results have implications for the timing of other advanced therapies, such as placing internal cardioverter-defibrillators., (Copyright © 2018. Published by Elsevier Inc.)

Background: The myocardial longitudinal relaxation time (T1) on cardiac magnetic resonance imaging (CMR) can quantify myocardial fibrosis in the presence or absence of visually detectable late gadolinium (Gd) enhancement (LGE). Mineralocorticoid receptor antagonist (MRA) treatment produces beneficial remodeling in nonischemic dilated cardiomyopathy (NIDCM). We assessed the hypothesis that interstitial myocardial fibrosis measured with the use of CMR predicts left ventricular (LV) beneficial remodeling in NIDCM after heart failure (HF) treatment including MRAs., Methods and Results: Twelve patients with NIDCM, on stable beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor-blocking therapy, were studied before and after 6-29 months of treatment with MRAs, by means of CMR assessment of LV structure, function, and T1 from standard Look-Locker sequences (T1 LL ). All patients had depressed cardiac function, dilated left ventricles, and no visual LGE. After adding MRA to HF treatment, the LV ejection fraction increased and the LV end-systolic volume index (LV end-systolic volume/m 2 ) decreased in all patients (P < .0001). This this was inversely proportional to the baseline myocardial T1 LL (r = -0.65; P = .02)., Conclusion: Myocardial T1 LL , in the absence of visually detectable LGE, was quantitatively related to the degree of beneficial LV remodeling achieved in response to adding MRA to a HF regimen., (Published by Elsevier Inc.)

Objective: To evaluate the reproducibility of first-pass contrast-enhanced cardiac MR (CMR) myocardial perfusion imaging in patients with non-ischaemic dilated cardiomyopathy (NIDCM)., Design: Prospective observational study., Setting: Single centre, tertiary care hospital., Participants: 6 outpatient participants with NIDCM., Outcome: Reproducibility of semiquantitative myocardial perfusion analysis by CMR., Method: 6 patients with NIDCM were studied twice using first-pass of contrast transit through the left ventricular (LV) myocardium with a saturation-recovery gradient echo sequence at rest and during adenosine-induced hyperaemia. The anterior wall was divided into endocardial (Endo) and epicardial (Epi) segments. The Myocardial Perfusion Index (MPI) was calculated as the myocardial signal augmentation rate normalised to the LV cavity rate. The Myocardial Perfusion Reserve Index (MPRI) was calculated as hyperaemic/resting MPI., Results: Between study 1 and 2, median MPI was similar for resting Endo (0.076 vs 0.077), hyperaemic Endo (0.143 vs 0.143), resting Epi (0.073 vs 0.074), and hyperaemic Epi (0.135 vs 0.134). Median MPRI was similar for Endo (1.84 vs 1.87) and Epi (1.90 vs 2.00). Combining Endo and Epi MPI (N=12), there was excellent agreement between Study 1 and 2 for resting MPI (r=0.998, intraclass correlation coefficient (ICC) 0.998, coefficients of variation (CoV) 1.4%), hyperaemic MPI (r=0.979, ICC 0.963, CoV 3.3%) and MPRI (r=0.989, ICC 0.94, CoV 3.8%)., Conclusions: Resting and hyperaemic myocardial perfusion using a normalised upslope analysis during adenosine CMR is a highly reproducible technique in patients with NIDCM., Trial Registration Number: Clinical Trials.Gov ID NCT00574119., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Left ventricular (LV) energy supply-demand imbalance is postulated to cause "energy starvation" and contribute to heart failure (HF) in nonischemic dilated cardiomyopathy (NIDCM). Using cardiac magnetic resonance (CMR) and [(11)C] acetate positron emission tomography (PET), we evaluated LV perfusion and oxidative metabolism in NIDCM and the effects of spironolactone on LV supply-demand relations., Methods and Results: Twelve patients with NIDCM underwent CMR and PET at baseline and after ≥6 months of spironolactone therapy added to a standard HF regimen. The myocardial perfusion reserve index (MPRI) was calculated after gadolinium injection during adenosine, as compared to rest. The monoexponential clearance rate of [(11)C] acetate (kmono) was used to calculate the work metabolic index (WMI), an index of LV mechanical efficiency, and kmono/RPP (rate-pressure product), an index of energy supply/demand. At baseline, the subendocardium was hypoperfused versus the subepicardium (median MPRI, 1.63 vs. 1.80; P<0.001), but improved to 1.80 (P<0.001) after spironolactone. The WMI increased (P=0.001), as did kmono/RPP (P=0.003). These improvements were associated with reverse remodeling, increased LV ejection fraction, and decreases in LV mass and systolic wall stress (all P<0.002)., Conclusions: NIDCM is associated with subendocardial hypoperfusion and impaired myocardial oxidative metabolism, consistent with energy starvation. Antifailure therapy improves parameters of energy starvation and is associated with augmented LV performance., Clinical Trial Registration Url: http://www.clinicaltrials.gov/ Unique identifier: ID NCT00574119., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Cardiac magnetic resonance (CMR) and [(11)C]acetate positron emission tomography (PET) were used to assess the hypothesis that patients with nonischemic dilated cardiomyopathy (NIDCM) have decreased subendocardial perfusion reserve and impaired oxidative metabolism, consistent with the concept of "energy starvation" in heart failure (HF)., Methods and Results: CMR myocardial perfusion was evaluated in 13 NIDCM patients and 15 control subjects with coronary risk factors and normal myocardial perfusion. The NIDCM patients underwent [(11)C]acetate PET. The myocardial perfusion index (MPI) was calculated as the normalized rate of myocardial signal augmentation following gadolinium contrast injection. Hyperemic transmural, subendocardial, and subepicardial MPI were reduced in NIDCM compared with control subjects [0.13 vs 0.18 (P < .001), 0.13 vs 0.17 (P < .001), and 0.13 vs 0.17 (P = .008), respectively]. The subendocardial perfusion reserve was 1.59 ± 0.21 vs 1.86 ± 0.32 for the subepicardium (P = .002), demonstrating reduced perfusion reserve. The myocardial oxidative metabolic rate (kmono) per unit demand (rate-pressure product) was reduced in proportion to perfusion reserve (P = .02) CONCLUSIONS: Impaired subendocardial perfusion reserve in NIDCM confirmed results previously attained only in animal models. Impaired perfusion and impaired oxidative metabolism are consistent with subendocardial energy starvation in HF., (Published by Elsevier Inc.)

Aims: Recombinant Neuregulin (NRG)-1β has multiple beneficial effects on cardiac myocytes in culture, and has potential as a clinical therapy for heart failure (HF). A number of factors may influence the effect of NRG-1β on cardiac function via ErbB receptor coupling and expression. We examined the effect of the NRG-1β isoform, glial growth factor 2 (GGF2), in rats with myocardial infarction (MI) and determined the impact of high-fat diet as well as chronicity of disease on GGF2 induced improvement in left ventricular systolic function. Potential mechanisms for GGF2 effects on the remote myocardium were explored using microarray and proteomic analysis., Methods and Results: Rats with MI were randomized to receive vehicle, 0.625 mg/kg, or 3.25 mg/kg GGF2 in the presence and absence of high-fat feeding beginning at day 7 post-MI and continuing for 4 weeks. Residual left ventricular (LV) function was improved in both of the GGF2 treatment groups compared with the vehicle treated MI group at 4 weeks of treatment as assessed by echocardiography. High-fat diet did not prevent the effects of high dose GGF2. In experiments where treatment was delayed until 8 weeks after MI, high but not low dose GGF2 treatment was associated with improved systolic function. mRNA and protein expression analysis of remote left ventricular tissue revealed a number of changes in myocardial gene and protein expression altered by MI that were normalized by GGF2 treatment, many of which are involved in energy production., Conclusions: This study demonstrates that in rats with MI induced systolic dysfunction, GGF2 treatment improves cardiac function. There are differences in sensitivity of the myocardium to GGF2 effects when administered early vs. late post-MI that may be important to consider in the development of GGF2 in humans.

Cell-based therapies are being developed for myocardial infarction (MI) and its consequences (e.g., heart failure) as well as refractory angina and critical limb ischemia. The promising results obtained in preclinical studies led to the translation of this strategy to clinical studies. To date, the initial results have been mixed: some studies showed benefit, whereas in others, no benefit was observed. There is a growing consensus among the scientific community that a better understanding of the fate of transplanted cells (e.g., cell homing and viability over time) will be critical for the long-term success of these strategies and that future studies should include an assessment of cell homing, engraftment, and fate as an integral part of the trial design. In this review, different imaging methods and technologies are discussed within the framework of the physiological answers that the imaging strategies can provide, with a special focus on the inherent regulatory issues., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to examine the effects of vasopressin V2 receptor antagonism with tolvaptan on the changes in left ventricular (LV) volumes over time., Background: Vasopressin levels may be increased in patients with heart failure (HF) and may be a factor driving the progression of HF., Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the effect of long-term administration of the vasopressin V2-receptor antagonist tolvaptan (30 mg/day) on reducing left ventricular end-diastolic volume (LVEDV) compared with placebo in patients with HF and reduced systolic function, using quantitative radionuclide ventriculography at baseline, repeated after 1 year of therapy, and repeated again approximately 1 week after withdrawal of study drug., Results: A total of 120 patients were randomized to tolvaptan and 120 were randomized to placebo. In the placebo group, there was no change in LVEDV over the course of follow-up (change of 0.0 +/- 10.0 ml/m2). After 1 year of tolvaptan, there was a small reduction in LV volume (decrease of 1.8 +/- 10.7 ml/m2); the between-group difference was not significant (p = 0.21). During the course of the trial, there were 6 deaths (5%) and 21 HF hospitalizations (18%) in the tolvaptan group, compared with 11 deaths (9%) and 34 HF hospitalizations (28%) in the placebo group. In a time-to-event analysis, there was a significant favorable effect of tolvaptan on the composite of mortality or heart failure hospitalization (p < 0.03 by log-rank test)., Conclusions: In a well-treated population of stable HF patients, there was no significant effect of tolvaptan therapy on LV volumes observed during 1 year of therapy. Nonprespecified natural history data favored therapy with tolvaptan, with a reduction in the combined end point of mortality and heart failure hospitalization observed. (Multicenter, Randomized, Double-Blind, Placebo Controlled, Efficacy Study on the Effects of Tolvaptan on Left Ventricular Dilatation in Congestive Heart Failure Patients; http://clinicaltrials.gov/ct/show/NCT00043758?order=1; NCT00043758).

Background: The purpose of this study was to compare stress supine single photon emission computed tomography (SPECT) imaging with attenuation correction (AC) via computed tomography-based attenuation maps with stress prone SPECT imaging with regard to the rate of equivocal interpretation of rest/stress myocardial perfusion imaging., Methods and Results: Interpretations for 324 consecutive patients referred for rest/stress myocardial perfusion imaging were performed by use of the following sets of poststress SPECT images: supine with no AC (NC), supine NC/AC, supine NC/prone, and all images. The number of equivocal studies decreased with additional imaging: supine NC, 40%; supine NC/prone, 18%; supine NC/AC, 11%; and all images, 8%. The supine NC/AC sets of images reduced the number of defects to a greater extent than the supine NC/prone images for all patients (P = .01), men (P = .002), and women (P = .425). For the inferior (but not the anterior) wall, the percent decrease in defects with supine NC/AC images was lower as compared with supine NC/prone images., Conclusion: Interpretation with all images resulted in the fewest equivocal studies. The supine NC/AC images reduced the number of equivocal studies to a greater extent than the supine NC/prone images. AC and prone imaging were more helpful in men than women and were more helpful to resolve inferior than anterior wall defects. Adding prone imaging to supine imaging without and with AC does not significantly alter the number of equivocal interpretations.

Background: Nonischemic dilated cardiomyopathy (NIDCM) is associated with left ventricular remodeling, hypertrophy, and mitochondrial metabolic abnormalities in vitro. We evaluated the hypothesis that energy supply, as judged by the rate of myocardial oxidative metabolism, is inadequate to meet oxygen demand in patients with NIDCM compared with normal subjects., Methods and Results: We used positron emission tomography to determine the myocardial carbon 11 acetate decay rate (kmono) as an index of energy supply, and we compared kmono with the rate-pressure product (RPP) as an index of metabolic demand in 7 patients with NIDCM and 7 normal subjects. The mean kmono value (SEM) was 0.060 +/- 0.006 min(-1) in NIDCM patients versus 0.054 +/- 0.002 in normal subjects (P = not significant). The RPP was 9949 +/- 931 beats/min.mm Hg in NIDCM patients and 6521 +/- 476 in normal subjects (P = .007). The relationship of kmono to this index of demand (kmono/RPP) was 6.2 x 10(-6) in NIDCM patients but was 8.5 x 10(-6) in normal subjects (P = .003). Thus RPP, as an index of myocardial oxygen demand, was poorly matched by the rate of oxidative metabolism in those patients with NIDCM. The kmono was closely related to RPP in normal subjects (r = 0.83, P = .02) but not in NIDCM patients. Furthermore, there was no significant relationship between kmono and wall stress as another index of oxygen demand., Conclusions: These results are consistent with a mitochondrial metabolic abnormality in heart failure. This metabolic mismatch detected by positron emission tomography may contribute to the pathophysiology of congestive heart failure and left ventricular remodeling.

Objectives: This study was conducted to define the frequency of internal carotid stenosis in African American patients with ischemic heart disease (IHD)., Methods: We recruited 101 African American patients with IHD from a university medical center for carotid duplex examination., Results: The frequency of >30%, >50%, and >70% stenosis was 21%, 11%, and 5%, respectively. Age >60 years (21% vs 3%, P < .01) and diabetes mellitus (22% vs 5%, P < .01) were predictors of unilateral stenosis of >50% and remained significant on multivariate testing., Conclusion: African American patients with established IHD have higher rates of extracranial carotid stenosis than community dwelling African American subjects and comparable rates with other populations.

Background: Web-based home care monitoring systems can assess medication compliance, health status, quality of life, and physiologic parameters. They may help overcome some of the limitations associated with current congestive heart failure management models., Objectives: This pilot study compared the effects of a self-care and medication compliance device, linked to a Web-based monitoring system, to the effects of usual care alone on compliance with recommended self-care behaviors; medication taking; quality of life; distance walked during a 6-minute walk test; and New York Heart Association Functional Class. We also assessed patient experiences living with the compliance device., Methods: We enrolled 18 patients with Functional Class II-III congestive heart failure in an urban VA Medical Center. The patients were randomized into 2 groups. Group A received usual care plus the compliance device. Group B (controls) received usual care only. Data were collected using the compliance device, the Heart Failure Self-Care Behavior Scale, pill counts, 6-minute walk test, and the Minnesota Living with Heart Failure Questionnaire at baseline and at 3 months follow-up., Results: At baseline and at 3 months, there were no differences between the compliance device group and the usual care group in self-care behaviors, pill counts, 6-minute walk-test distance, or Functional Class. However, quality of life improved significantly from baseline to 3-month follow-up (ANOVA, P =.006). This difference was due to an improvement in quality of life for the monitor group (P =.002) but not the usual care only group (P =.113). Patients in the compliance device group had a 94% medication compliance rate, 81% compliance with daily blood pressure monitoring, and 85% compliance with daily weight monitoring as compared to 51% for blood pressure monitoring and 79% for weight monitoring in the usual care group (P = NS)., Conclusion: These are promising pilot results that, if replicated in a larger sample, may significantly improve care and outcomes for patients with heart failure.

Background: The determinants of exercise performance are multifactorial and incompletely understood in patients with symptomatic left ventricular (LV) dysfunction, with much less information regarding asymptomatic LV dysfunction. This study assessed the hemodynamics and neurohormonal factors influencing exercise performance in patients with LV ejection fractions > or =0.35, both symptomatic and asymptomatic, enrolled in Studies of LV Dysfunction., Methods and Results: We studied 103 patients enrolled prospectively in Studies of LV Dysfunction before randomized therapy; 38 were symptomatic and 65 had no or minimal symptoms. By using rest-exercise gated equilibrium radionuclide ventriculography and cuff blood pressure, we assessed the heart rate, LV and right ventricular (RV) volumes and ejection fractions, total peripheral resistance, the LV peak systolic pressure/end systolic volume ratio as an index of contractility, and plasma renin and norepinephrine at rest and during maximal graded supine bicycle ergometer exercise. Changes between rest and exercise were evaluated as indices of cardiovascular reserve. The cumulative workload ranged from 120 to 2,100 watt-min. At rest, the LV ejection fraction was 0.30 in asymptomatic patients and 0.25 in symptomatic patients, respectively (P < .0004). During exercise, asymptomatic patients had greater increases in heart rate, systolic blood pressure, LV ejection fraction, and cardiac output than symptomatic patients (P > or = .05). Combining all patients, the strongest univariate correlates of exercise workload were the ability to increase heart rate (r = 0.70), the pressure/volume ratio (r = 0.63), and systolic blood pressure (r = 0.55), and to decrease the total peripheral resistance (r = -0.47) with moderate correlations for the ability to increase LV and RV ejection fractions (r = 0.33 and 0.35, respectively) (P < .0008). By multivariate analysis, workload was modeled best by the changes in four factors: heart rate, systolic blood pressure, and the LV and RV ejection fractions (R2 = 0.54, P < .001)., Conclusion: Exercise performance and its hemodynamics differed in patients with symptomatic and asymptomatic LV dysfunction. Rather than features at rest, the reserve capacities for increasing heart rate, systolic blood pressure, and the LV and RV ejection fractions were the predominant cardiac mechanisms related to greater exercise performance.

Patients with heart failure and left ventricular systolic dysfunction exhibit increased adrenergic activity but blunted adrenergic responsiveness. We studied patients enrolled in the Studies of Left Ventricular Dysfunction, examining exercise responses of heart rate (HR) and plasma norepinephrine (PNE). Eighty-seven patients were studied before randomization; 65 of these were examined 1 year after randomization to placebo or enalapril. Compared with prevention trial (asymptomatic) patients, patients in the treatment trial (symptomatic) had higher resting HR and PNE levels and less increase in HR with a greater increase in PNE with exercise. Acute administration of enalapril increased the resting HR in patients in the prevention trial only but had no significant effect on PNE. After 1 year of therapy, patients in the prevention trial exhibited no change. Within the treatment trial, the placebo group displayed both a higher peak PNE and increase in PNE with exercise than did the enalapril group, whose HR response was maintained in spite of a reduction of exercise PNE. We conclude that (1) compared with asymptomatic patients, symptomatic patients with reduced left ventricular ejection fraction manifest greater resting and exercise adrenergic activity, with blunted HR response; and (2) in symptomatic patients, 1 year of enalapril treatment effected an augmented HR response to adrenergic stimulation, supporting an interaction between the renin/angiotensin and adrenergic nervous systems. Normalization of adrenergic tone and response likely contributes to the benefits of long-term angiotensin-converting enzyme inhibitor therapy.

Objectives: We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non-Q wave myocardial infarction (MI)., Background: Although the ECG is the most widely used test for evaluating patients with unstable angina and non-Q wave MI, little prospective information is available on its value in predicting outcome in the current era of aggressive medical and interventional therapy., Methods: ECGs with the qualifying episode of pain were analyzed in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, a prospective study of patients admitted to the hospital with unstable angina or non-Q wave MI., Results: New ST segment deviation > or = 1 mm was present in 14.3% of 1,416 enrolled patients, isolated T wave inversion in 21.9% and left bundle branch block (LBBB) in 9.0%. By 1-year follow-up, death or MI occurred in 11% of patients with > or = 1 mm ST segment deviation compared with 6.8% of patients with new, isolated T wave inversion and 8.2% of those with no ECG changes (p < 0.001 when comparing ST with no ST segment deviation). Two other high risk groups were identified: those with only 0.5-mm ST segment deviation and those with LBBB, whose rates of death or MI by 1 year were 16.3% and 22.9%, respectively. On multivariate analysis, ST segment deviation of either > or = 1 mm or > or = 0.5 mm remained independent predictors of death or MI by 1 year., Conclusions: The admission ECG is very useful in risk stratifying patients with non-Q wave MI. The new criteria of not only > or = 1-mm ST segment deviation but also > or = 0.5-mm ST segment deviation or LBBB identify high risk patients, whereas T wave inversion does not add to the clinical history in predicting outcome.

Objective: To investigate the natural history and response to treatment of patients with unstable angina or non-Q-wave myocardial infarction (MI)., Design: Inception cohort., Setting: Patients in general community, primary care, or referral hospitals., Patients: All patients with an episode of unstable exertional chest pain or chest pain at rest presumed to be ischemic in origin lasting 5 minutes or more but without persisting ST-segment elevation greater than 30 minutes or the development of Q-waves were identified and enumerated in 18 participating hospitals. A subset of enumerated patients was selected to be followed prospectively using specific sampling strategies that would provide adequate numbers of black, women, and elderly (aged > or = 75 years) patients for comparison with their respective counterparts., Main Outcome Measures: The primary analysis compared the incidence of death or MI at 42 days after entry into the prospective study according to race, sex, and age. Other outcomes considered were recurrent ischemia and the combined outcomes of death, MI, or recurrent ischemia by 42 days after entry., Results: A total of 8676 admissions with unstable angina or non-Q-wave MI were enumerated and, of these, 3318 patients were selected for the prospective study. The direct adjusted mean age of 3318 patients was 63.8 years. There were 943 blacks and 2375 nonblacks. Compared with nonblacks, blacks were less likely to be treated with intensive anti-ischemic therapy for their qualifying anginal episode and less likely to undergo invasive procedures (risk ratio [RR], 0.65%; 95% confidence interval [CI], 0.58 to 0.72; P<.001). However, of those who underwent angiography (45% of blacks and 61% of nonblacks), blacks had less extensive and severe coronary stenoses than nonblacks. The incidence of death and MI was similar for blacks and nonblacks, but blacks had a lower incidence of recurrent ischemia. There were 1678 men and 1640 women. Women were less likely than men to receive intensive anti-ischemic therapy and less likely to undergo coronary angiography (RR, 0.71; 95% CI, 0.65 to 0.78; P<.001). Women had less severe and extensive coronary disease and were less likely to undergo revascularization, yet had a similar risk of experiencing an adverse cardiac event by 6 weeks. There were 2490 patients aged 75 years or less and 828 patients aged more than 75 years. Elderly patients received less aggressive anti-ischemic therapy and were less likely to undergo coronary angiography than their younger counterparts. Elderly patients had more severe and extensive coronary disease but fewer revascularization procedures than younger patients and experienced a much higher incidence of adverse cardiac events both in hospital and by 6 weeks., Conclusions: Among patients presenting with acute ischemic chest pain without persistent ST-segment elevation, blacks appeared to have less severe coronary disease, received revascularization less frequently, and had less recurrent ischemia compared with nonblacks. Women were also found to have less severe coronary disease and were treated less intensely than men, but experienced similar outcomes. Elderly patients had more severe coronary disease than younger patients on coronary angiography, but were more likely to be treated medically, and they experienced far more adverse outcomes. These data suggest that more aggressive strategies should be directed to those patients with the greatest likelihood of adverse outcomes.

Background: Patients with heart failure and reduced left ventricular (LV) ejection fraction (EF) manifest progressive LV dilatation, which is prevented by angiotensin converting enzyme (ACE) inhibitors. In patients with asymptomatic LV systolic dysfunction, in whom there is less activation of the renin-angiotensin system, ventricular remodeling might be less rapid and the benefit of ACE inhibitors less discernible., Methods and Results: One hundred eight patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial, with left ventricular ejection fraction < or = 0.35 but without clinical heart failure, underwent radionuclide ventriculograms, and 49 underwent left heart catheterizations. Measurements were made before and after double-blinded randomization to enalapril (2.5 to 20 mg/d) or placebo. Repeated-measures analysis of all time points showed significant differences for change in end-diastolic volume (EDV) between enalapril and placebo groups. Significant difference between the enalapril and placebo groups (P < .05) was present for change in EDV at 1 year within the catheterization study and at a mean of 25 months within the radionuclide study. Radionuclide EDV increased in placebo patients (119 +/- 28 to 124 +/- 33 mL/m2, mean +/- SD) and decreased in enalapril patients (120 +/- 25 to 113 +/- 25 mL/m2). Differences between the two groups were significantly less than previously described in patients with symptomatic heart failure (P < .02), with less increase in LV volumes in the placebo group and less decrease in volumes in the enalapril group., Conclusions: Chronic ACE inhibitor treatment slows or reverses LV dilatation in patients with asymptomatic LV systolic dysfunction. Compared with symptomatic patients, asymptomatic patients manifest a slower rate of spontaneous LV dilatation and less reduction in LV volumes by enalapril.

We have shown that positron emission scintigraphy detects changes in the uptake of 18-F 2-deoxyglucose and 13-N ammonia by the acutely rejecting myocardium in a nonworking model of heterotopic heart transplantation in the rat. We developed a new working model of heterotopic heart transplantation to determine the possible relevance of these changes to clinical transplantation. Moderate aortic valvular regurgitation was produced allowing the heterotopic left ventricle to fill and eject. Rejecting allografts and nonrejecting isografts (controls) were studied 4 days after transplantation. Histologically, isografts were normal and all allografts showed mild acute rejection. Decay-corrected uptakes of 18-F 2-deoxyglucose and 13-N ammonia reflect glucose metabolism and blood flow, respectively. Values are presented as percent of injected dose per gram of tissue. Uptake of 18-F 2-deoxyglucose was higher in rejecting allografts compared with nonrejecting isografts (3.0 +/- 1.8 versus 1.1 +/- 0.4; p = 0.024). Ammonia uptake was elevated in allografts compared with isografts (2.2 +/- 0.5 versus 1.3 +/- 0.5; p = 0.023). Uptakes of 18-F 2-deoxyglucose and 13-N ammonia are higher in mildly rejecting allografts, implying increased glucose utilization and blood flow during acute rejection. These data support our earlier findings of changes in myocardial metabolism in the absence of diminishing blood flow in acutely rejecting hearts. This model may lead to a better understanding of the physiology and metabolism of acute rejection.

Background: In patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure., Methods and Results: We examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5-20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p less than 0.01), end-systolic volume (ESV; p less than 0.005), and EF (p less than 0.05). These effects resulted from increases in EDV (mean +/- SD, 136 +/- 27 to 151 +/- 38 ml/m2) and ESV (103 +/- 24 to 116 +/- 24 ml/m2) in the placebo group and decreases in EDV (140 +/- 44 to 127 +/- 37 ml/m2) and ESV (106 +/- 42 to 93 +/- 37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25 +/- 0.07 to 0.29 +/- 0.08 (p less than 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p less than 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p less than 0.01 versus enalapril), increasing from 59.2 +/- 8.0 to 67.8 +/- 7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo., Conclusions: In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload.

The hemodynamic determinants of clinical status in patients with left ventricular (LV) systolic dysfunction have not been established. In the present study, preload reserve--LV distension during exercise--was related to clinical status, and the effect of acute angiotensin-converting enzyme inhibition was examined in 97 patients with ejection fraction less than or equal to 0.35 enrolled in the trial, Studies of Left Ventricular Dysfunction (SOLVD). Sixty-one asymptomatic patients (group I) were compared with 36 patients with symptomatic heart failure (group II). Radionuclide LV volumes were measured at rest and during maximal cycle exercise. Group II patients had higher resting heart rates, end-diastolic and end-systolic volumes, and lower ejection fractions (all p less than 0.005). During exercise, only patients in group I had increased stroke volume (from 35 +/- 8 to 39 +/- 11 ml/m2 [mean +/- SD; p less than 0.0005]) due to an increase in end-diastolic volume (from 119 +/- 29 to 126 +/- 29 ml/m2 [p less than 0.0005]), contributing to a greater increase in LV minute output (p less than 0.0001, group I vs group II). After administration of intravenous enalapril (1.25 mg), LV end-diastolic volume response to exercise was augmented in group II (rest, 140 +/- 42; exercise, 148 +/- 43 ml/m2; p less than 0.0005) and LV output response increased slightly (p less than 0.05). Thus, in patients with asymptomatic systolic dysfunction, recruitment of preload during exercise is responsible for maintaining a stroke volume contribution to the cardiac output response.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of patients presenting with significant cardiac arrhythmias depends greatly on the initial clinical assessment; underlying cardiovascular disorders must be evaluated because they often are the substrate or trigger of arrhythmias. Electrophysiologic testing may be used to guide therapy with antiarrhythmic drugs or with devices such as the automatic implantable cardioverter/defibrillator; in selected patients, arrhythmias may be ablated surgically or with percutaneous catheter techniques. Advances in clinical cardiac electrophysiology have resulted in successful therapy or cure of many patients with symptomatic or life-threatening cardiac arrhythmias.

In acute myocardial infarction, beta-adrenergic blockade might depress left ventricular contractility or improve contractility by reducing ischemia. Gated equilibrium radionuclide ventriculography and cuff blood pressure were employed in 10 patients to assess the left ventricular systolic pressure/volume (P/V) ratio as an index of contractility before and after intravenous metoprolol 9.3 +/- 2.5 hr after onset of infarction. In 13 normal subjects, the baseline left ventricular PV ratio was 3.5 and the left ventricular ejection fraction (LVEF) was 70%, both greater than the patients with infarction. In the patients after blockade, the systolic blood pressure decreased (p = 0.02), and the left ventricular end-systolic volume increased (p = 0.003), thus decreasing the P/V ratio from 1.7 to 1.4 (p = 0.003), while the ejection fraction (EF) was unchanged (55% versus 52%). The right ventricular ejection fraction (RVEF) decreased from 50% to 43% (p = 0.004). Thus, radionuclide ventriculography demonstrated that left ventricular contractility was reduced in patients with acute myocardial infarction and that beta-adrenergic blockade further decreased left ventricular contractility and right ventricular performance.

Severe autonomic failure is usually characterized by both supine hypertension and orthostatic hypotension. Inadequate preload reserve, insufficient arterial resistance and abnormal cardiac performance have been postulated to contribute to the hypotension. To clarify these mechanisms, left ventricular performance and contractility were assessed using radionuclide ventriculography and systolic pressure-volume relations when supine and with graded head-up tilt in 11 patients with autonomic failure. Results were compared with those of 12 normal subjects, using phenylephrine infusion for pharmacologic afterload augmentation after autonomic blockade with atropine and propranolol. In a subset of four patients with autonomic failure, systolic pressure-volume relations were similar by both the tilt and phenylephrine methods. In autonomic failure, end-diastolic volume, end-systolic volume and stroke volume decreased with progressive degrees of tilt (p less than or equal to 0.007 for each). The supine radionuclide ejection fraction and cardiac output were similar to those of normal subjects (69% versus 68% and 5.4 versus 4.9 liters/min, respectively, p = NS). However, the slopes of the pressure-volume relations and the supine pressure/volume ratio in autonomic failure were much greater than normal (8.8 versus 2.5, and 6.3 versus 3.6 mm Hg/ml, respectively, p less than or equal to 0.04 for both). The baseline total peripheral resistance was greater than normal (24.9 versus 17.4 mm Hg.min-1/liter, p = 0.01), but the resistance at maximal tilt failed to increase (20.8 +/- 6.1 units). Plasma norepinephrine concentrations were lower than normal. Thus, patients with autonomic failure had hypercontractile left ventricular performance when assessed by pressure-volume relations, and their hearts were well matched to the elevated peripheral resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

To examine the manner in which changes in diastolic performance can contribute to the effect of vasodilation in patients with left ventricular (LV) systolic dysfunction, we examined the effect of acute inhibition of angiotensin converting enzyme with intravenous enalaprilat on early LV diastolic filling. We studied 43 patients with congestive heart failure and depressed LV systolic function (mean ejection fraction +/- SD, 0.24 +/- 0.06), performing radionuclide ventriculography before and after administration of 1.25 mg intravenous enalaprilat. We measured the effect of enalaprilat on the maximum rate of early LV diastolic filling normalized in four different ways and related these changes to both LV and right ventricular (RV) volumes. Enalaprilat induced a small but statistically significant reduction in LV end-systolic volume and increase in LV ejection fraction. For the entire patient group, there was no significant change in LV peak filling rate after enalaprilat administration. For individual patients, however, the effect of enalaprilat on peak filling rate was related to resting RV end-diastolic and end-systolic volumes. In patients with enlarged RV end-diastolic volumes (greater than or equal to 120 ml/m2), mean peak filling rate increased from 1.38 +/- 0.6 to 1.71 +/- 0.6 end-diastolic volumes (EDV)/sec and from 244 +/- 131 to 297 +/- 162 ml/sec/m2 after enalaprilat administration, whereas no change in mean peak filling rate was observed in patients with nondilated RVs. These observations were present regardless of the method of normalizing peak filling rate. Thus, the response of LV peak filling rate to enalaprilat is influenced by the presence of RV dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

The end-systolic pressure-volume relation is employed to evaluate left ventricular contractility. In clinical studies, pharmacologic vasoconstriction is used to increase left ventricular systolic pressure to assess pressure-volume relations. However, the effect of vasoconstrictors on the ventricular contractile state is not well characterized. The effects of methoxamine and phenylephrine on systemic arterial pressure and left ventricular contractility in rabbits were studied with three protocols. In protocol 1, anesthetized rabbits (n = 10) were injected with incremental doses of methoxamine and phenylephrine intravenously. Methoxamine (4 mg) increased the mean arterial pressure by 50 +/- 12% (mean +/- SE) (n = 5, p = 0.001). Phenylephrine (0.2 mg) increased mean arterial pressure by 82 +/- 14% (n = 5, p = 0.004). In protocol 2, isolated blood-perfused hearts were injected with incremental doses of these drugs in the ascending aorta in amounts approximately equal to the concentrations injected in the intact rabbits. Methoxamine (2 mg) reduced isovolumic peak systolic left ventricular pressure by 43 +/- 9% (n = 7, p = 0.003), whereas phenylephrine (0.1 mg) increased the isovolumic pressure by 24 +/- 9% (n = 7, p less than 0.05). These responses indicated an enhanced contractile state with phenylephrine and a reduced contractile state with methoxamine. Pretreatment with propranolol blunted the effect of phenylephrine on isovolumic pressure (n = 6, p less than 0.02). In protocol 3, cross-circulation experiments allowed study of the effect of these drugs on isovolumic left ventricular pressure in the isolated heart and simultaneously on the systemic arterial pressure in the intact anesthetized rabbit (support rabbit).(ABSTRACT TRUNCATED AT 250 WORDS)

Radionuclide and contrast ventriculography were evaluated for their ability to estimate myocardial ischemia. In 14 closed-chest, sedated dogs, a small and larger region of ischemia were produced by inflating balloon occluders on the left anterior descending coronary artery. The systemic arterial pressure, atrial-paced heart rate, global ejection fraction by radionuclide and contrast ventriculography, regional wall-motion abnormalities (as the percentage of abnormally contracting segments), and regional myocardial blood flow (using the microsphere technique) were measured during an initial control period, two separate ischemic periods, and a final control period. The regional ischemic weights based on myocardial blood flow ranged from 0 to 38.5 g and were grouped as zero, small (range 0 to less than 10 g, mean 3.40 g), and large regions of ischemia (greater than 10 g, mean 24.8 g). Regional wall-motion abnormalities were sensitive qualitative indicators of ischemia. Receiver operating characteristic analysis showed that both ventriculographic methods were highly sensitive, specific, and accurate for detecting regional ischemia. Contrast ventriculography was slightly superior for detecting small regions less than 4 g, but the methods were equal for regions greater than 4 g. The arterial pressure and heart rate were unchanged during ischemia. For small regions of ischemia, the global ejection fraction did not fall using either the contrast or radionuclide technique, but it fell significantly when large regions were produced. There was a quantitative relationship between the percentage of abnormally contracting segments and the grams of myocardial ischemia (for radionuclide ventriculography, r = 0.65, P = 0.003, and for contrast ventriculography, r = 0.75, P less than 0.001), but for many small regions of ischemia, wall-motion changes were greater than anticipated, suggesting hypofunction of the continguous normal tissue. This study demonstrated that both radionuclide and contrast ventriculography were quite sensitive and specific for detecting measured amounts of regional ischemia. The functional changes resulting from ischemia are quantitatively related to the extent of regional ischemia, small areas resulting in regional wall motion abnormalities, and large areas producing both reduced global ejection fraction and wall motion changes.

Ventricular dysfunction induced by dipyridamole would be evidence of myocardial ischemia in patients with limited ability to undergo standard exercise testing. Radionuclide ventriculography before and after intravenous dipyridamole infusion was compared with the results of exercise radionuclide ventriculography in a prospective study of 31 patients undergoing coronary angiography. Among these patients, 21 (68%) had significant coronary artery disease (greater than or equal to 50% stenosis), 19 (61%) had severe coronary disease (greater than or equal to 70% stenosis) and 10 (32%) were "normal" (less than 50% stenosis). The left ventricular ejection fraction was calculated, and regional wall motion was scored on a 6 unit scale. In the normal patients, the ejection fraction (+/- SEM) increased 5.6 +/- 2% (units) during exercise and 7.9 +/- 1 units after dipyridamole (both p less than or equal to 0.004 compared with that during rest). However, in patients with coronary artery disease, the ejection fraction failed to increase during exercise or after dipyridamole. In the patients with coronary artery disease, regional wall motion decreased by 4.1 +/- 0.5 units during exercise (p less than 0.003) and by 1.8 units after dipyridamole (p less than 0.02). Receiver operating characteristic analysis demonstrated general comparability between the sensitivity and specificity of exercise and dipyridamole ventriculography, with "optimal" operating points that favored choosing high sensitivity for the former and high specificity for the latter. Specific subsets of patients with severe coronary atherosclerosis were analyzed with use of these criteria. In patients with severe stenosis (greater than or equal to 70%), the sensitivity of dipyridamole ventriculography was 67% compared with 89% for exercise ventriculography. However, at these levels of sensitivity, the specificity of dipyridamole ventriculography was 92% compared with 67% for exercise ventriculography. In this and other subsets of patients, the specificity of dipyridamole ventriculography exceeded that of exercise ventriculography. Thus, it is concluded that dipyridamole radionuclide ventriculography is moderately sensitive and highly specific for detecting severe coronary atherosclerosis. This technique provides a widely applicable, useful alternative to exercise ventriculography in the diagnosis of coronary atherosclerosis in patients who have limited exercise tolerance.

Anterior myocardial infarction (MI) was produced in conscious dogs to evaluate the relationships among: a) cardiac technetium-99m stannous pyrophosphate (TcPPi) accretion, b) creatine phosphokinase (CPK) depletion, and c) postmortem MI weight, infarct structure, and histology. In vitro, there was a close relationship between measured MI weight and MI weight calculated by the TcPPi accretion (r = 0.96) or CPK depletion (r = 0.93) in representative "cross-sectional" MI samples. Cardiac TcPPi accretion and CPK depletion showed a curvilinear relationship over the spectrum of tissue samples. Adjacent to infarcts, there was marked TcPPi uptake and modest CPK depletion where histology suggested ischemia without infarction. Within infarcts, microscopically visible calcium was rare in this series, suggesting little intracellular calcium accumulation, insensitivity of the von Kossa staining technique, and/or other cellular mechanisms to account for Tc-PPi uptake in this conscious dog model without reperfusion.

The mechanical properties of the right and left ventricles (RV and LV) have previously been studied separately. However, because of differences in RV and LV architecture, geometry, and muscle mass, it is not obvious how the properties of the two chambers would relate to each other. This study compared the time courses of RV and LV isovolumic pressure waves (LVP, RVP, respectively) measured simultaneously in the same heart. We compared RVP and LVP in each of five isolated, supported canine hearts after pentobarbital anesthesia. RV and LV volumes were varied independently so that on various beats peak LVP exceeded, equaled, or was less than peak RVP. There was a delay of approximately 35 ms between the onset of LV and RV pressure waves with atrial pacing, but only 5 ms with ventricular pacing. LVP and RVP were measured and digitized at a sampling rate of 200 Hz. Pressure waves were offset and rescaled by their respective amplitudes so that for each beat the pressure wave had a minimum value of 0% at end diastole and a maximum value of 100% at end systole. RVP was then shifted in time so that its upstroke was synchronous with that of the LVP at the point of 50% of maximal developed pressure. The rescaled, time-shifted RVP was plotted as a function of the rescaled LVP for each point of the cardiac cycle, and the relation between the two was quantified by their root mean square difference (Drms). Drms averaged 2.3 +/- 1.5% (SD) for the first half of contraction, 1.5 +/- 0.4% for the second half of contraction, and 4.6 +/- 1.6% during relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional wall motion (RWM) abnormalities are sensitive indicators of left ventricular (LV) dysfunction, but quantitation of RWM with gated radionuclide ventriculography (RVG) has been limited, particularly in the left anterior oblique (LAO) projection. Regional LV performance was studied in 18 patients undergoing LAO RVG immediately prior to contrast ventriculography (CVG). Wall motion was analyzed by semiautomated and visual methods using several coordinate systems. For semiautomated methods, RVG and CVG wall motion were closely related in the two 90 degrees polar sectors at the apex and posterior wall (r = .85) and in the five 45 degrees polar sectors from midseptum through posterior wall (r = .82). The basal sectors on RVG had weak relationship to CVG, due to adjacent vascular structures. Semiautomated and visual grades for polar sectors on both CVG and RVG were closely related (r = .88- .94). Measured regional wall motion on LAO RVG compared favorably with near-simultaneous CVG in nonoverlapping portions of the LV and allowed objective quantitation of regional LV performance.

Recent randomized clinical trials have shown that total mortality and cardiovascular mortality are reduced by the early intravenous administration of beta-blockers to patients suspected of suffering from acute myocardial infarction. These trials were conducted on patients meeting strict entry criteria. In order to assess this therapy when applied to a broader range of myocardial infarction patients, we performed a Phase IV study of metoprolol in acute myocardial infarction. The study was designed to test whether early (less than 8 hours from onset of chest pain) intervention by practicing physicians with open label intravenous metoprolol for cases of suspected acute myocardial infarction achieved mortality results similar to those obtained in large randomized clinical trials. We studied 3824 patients treated by 741 physicians representing a broad spectrum of clinical practice in the United States. Seventy-two percent of the patients entered into the study had confirmed myocardial infarction (39% anterior, 39% inferior, 22% other locations) and 85% of all individuals treated tolerated the full intravenous dose of 15 mg of metoprolol. The 15 day total mortality and cardiovascular mortality rates were 4.9% and 4.5%; 90 day mortality rates were 6.9 and 5.9%. Patients with anterior infarctions had a significantly greater cumulative mortality rate than patients with other types of infarctions. Marked bradycardia (heart rate less than 45 beats per minute) in the first 8 hours post treatment occurred in 4.7% cases and hypotension (systolic blood pressure less than 90 mm Hg) occurred in 9.8% of cases. When compared with the results of the Göteborg and MIAMI trials of metoprolol, it appears that there is no appreciable increase in mortality or morbidity when metoprolol is used in the community practice of acute coronary care.

Global left ventricular performance (ejection fraction) and regional function were studied by rest-exercise radionuclide ventriculography in 36 patients before and after (23 +/- 8.5 wk) they had coronary artery bypass surgery for stable angina pectoris. The exercise ejection fraction was less than the resting ejection fraction before surgery (n = 36,p = 0.006), but not after surgery. The degree of postoperative improvement correlated with the degree of preoperative dysfunction (r = 0.55, n = 36, p less than 0.001). Improvement was most likely to occur if exercise-induced dysfunction was present preoperatively (n = 15,p = 0.001), even with old myocardial infarction. Regional dysfunction during preoperative exercise was also likely to improve postoperatively (n = 18, p = 0.001). Protocol design is important in determining the results and their interpretation. Matching postoperative exercise loads to preoperative loads and using regional analysis with two imaging projections improved judgment of the results. Regional dysfunction was commoner than global dysfunction and was less sensitive to workloads than was ejection fraction. This study shows that coronary artery bypass surgery can improve left ventricular performance on exercise if preoperative tests indicate the presence of ischemia-induced dysfunction.

Myocardial thallium scintigraphy was performed in four subjects with variant angina and in one subject with isolated, fixed coronary obstruction. Three subjects with variant angina had short episodes of ischemic ST-segment elevation that lasted 20--100 seconds. Thallium scintigrams demonstrated excess uptake in regions judged to be ischemic by angiographic and electrocardiographic criteria. Two subjects, one with variant angina and the other with a fixed coronary lesion, had prolonged episodes of ischemia that lasted 390--900 seconds. Both had reduced thallium uptake in the ischemic regions. We conclude that myocardial reactive hyperemia is the cause of excess thallium uptake in patients with variant angina who have short episodes of myocardial ischemia.

Technetium-99m-stannous pyrophosphate scintiphotos were evaluated for diagnosing and quantitating myocardial infarct (MI) extension in sedated dogs. Infarction and extension were produced by serial left anterior descending coronary artery ligations at 0 and 48 hours. We compared serial scintiphoto data with regional myocardial blood flow (MBF) (microsphere technique) and infarct histopathology. In eight control dogs, the scintigraphic MI area was stable at 24, 48, and 72 hours. In each of 11 dogs undergoing extension, the MI area increased after the 48-hour occlusion, averaging a 48.9% increase (p less than 0.001). Grossly, most extensions were mixtures of confluent necrosis and moderate (patchy) necrosis. MBF to confluent infarct tissue decreased significantly, allowing the documentation of extension by totaling the grams of newly flow-deprived tissue, but patchy infarct tissue had little flow deprivation, making it difficult to quantitate this type of extension accurately by flow criteria alone. Rarely, extension could be diagnosed using conventional histologic criteria. We concluded that the scintiphoto MI area was related quantitatively to infarct weight in both control and extension. However, it was not possible to determine that an increase in the MI scintiphoto area was an accurate predictor of the degree of extension using independent flow or pathologic criteria.

Pulmonary extravascular volume or lung water (PEV), arterial blood gases, and cardiac hemodynamics were measured in 88 patients with acute myocardial infarction. A progressive increase in PEV and a decrease in arterial oxygen tension (PaO2) were observed from Class I (uncomplicated) patients to Class III (frank pulmonary edema) patients. Heart rate and pulmonary wedge pressure (Pw) rose and cardiac index declined with increasing severity of heart failure by clinical classification. There was a significant correlation between PEV and Pw independent of clinical class (r = 0.47, p less than 0.01). PaO2 had a negative correlation with Pw (r = -0.28, p less than 0.01) as well as PEV (r = -0.26, p less than 0.02). We conclude therefore that increased pulmonary hydrostatic pressure secondary to pulmonary venous hypertension in patients with acute myocardial infarction is a major determinant of interstitial edema. At higher values of PEV, PaO2 was lower. The mechanism of hypoxemia in the presence of excessive lung water may be due to multiple factors, including small airway dysfunction and intrapulmonary shunting.