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Background In 10% to 15% of patients with ST-segment elevation myocardial infarction (STEMI), concurrent coronary chronic total occlusion (CTO) in a non–infarct-related artery is present and is associated with increased morbidity and mortality. Objectives The EXPLORE (Evaluating Xience and Left Ventricular Function in Percutaneous Coronary Intervention on Occlusions After ST-Elevation Myocardial Infarction) trial evaluated whether patients with STEMI and concurrent CTO in a non–infarct-related artery benefit from additional percutaneous coronary intervention (PCI) of CTO shortly after primary PCI. Methods From November 2007 through April 2015, we enrolled 304 patients with acute STEMI who underwent primary PCI and had concurrent CTO in 14 centers in Europe and Canada. A total of 150 patients were randomly assigned to early PCI of the CTO (CTO PCI), and 154 patients were assigned to conservative treatment without PCI of the CTO (no CTO PCI). Primary outcomes were left ventricular ejection fraction (LVEF) and left ventricular end diastolic volume (LVEDV) on cardiac magnetic resonance imaging after 4 months. Results The investigator-reported procedural success rate in the CTO PCI arm of the trial was 77%, and the adjudicated success rate was 73%. At 4 months, mean LVEF did not differ between the 2 groups (44.1 ± 12.2% vs. 44.8 ± 11.9%, respectively; p = 0.60). Mean LVEDV at 4 months was 215.6 ± 62.5 ml in the CTO PCI arm versus 212.8 ± 60.3 ml in the no–CTO PCI arm (p = 0.70). Subgroup analysis revealed that patients with CTO located in the left anterior descending coronary artery who were randomized to the CTO PCI strategy had significantly higher LVEF compared with patients randomized to the no–CTO PCI strategy (47.2 ± 12.3% vs. 40.4 ± 11.9%; p = 0.02). There were no differences in terms of 4-month major adverse coronary events (5.4% vs. 2.6%; p = 0.25). Conclusions Additional CTO PCI within 1 week after primary PCI for STEMI was feasible and safe. In patients with STEMI and concurrent CTO, we did not find an overall benefit for CTO PCI in terms of LVEF or LVEDV. The finding that early CTO PCI in the left anterior descending coronary artery subgroup was beneficial warrants further investigation. (Evaluating Xience and Left Ventricular Function in Percutaneous Coronary Intervention on Occlusions After ST-Segment Elevation Myocardial Infarction; NTR1108)

In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI. Conclusions Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360) (J Am Coll Cardiol 2014;63:110–22) a 2014 by the American College of Cardiology Foundation

Left ventricle end diastolic pressure (LVEDP) measured during cardiac catheterization is an independent predictor of prognosis in acute myocardial infarction. We evaluated the prognostic value of postprocedural LVEDP in a large cohort of severe aortic stenosis patients treated with transcatheter

Because the real benefit of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot who develop pulmonary insufficiency remains unclear, it is necessary to analyze the evidence published around the world. We performed a systematic review of studies that reported data about the effect of PVR in patients with repaired tetralogy of Fallot that developed pulmonary insufficiency, until December 2012. The variables chosen to represent the benefit were both right ventricular (RV) and left ventricular measures, QRS duration, and functional class. The principal summary measures were difference in means with 95% confidence interval and p values (considered statistically significant when p

Patients with valvular heart disease often have left ventricular diastolic dysfunction. This review summarizes the underlying mechanisms for diastolic dysfunction in patients with mitral and aortic valve disease. In addition to load, intrinsic myocardial abnormalities occur related to changes in sarcomeric proteins, abnormal calcium handling, and fibrosis. Echocardiography is the initial modality for the diagnosis of left ventricular diastolic function. Although there are challenges to conventional Doppler parameters of diastolic function, it is often possible to arrive at a clinically useful assessment of left ventricular filling pressures using a comprehensive approach. When needed, cardiac magnetic resonance and cardiac catheterization can be obtained. Medical therapy can be of value for the treatment of diastolic dysfunction, but there is a paucity of data evaluating its clinical utility. More importantly, diastolic dysfunction usually improves with timely surgical intervention, although surgery does not always lead to normalization of function.

Left ventricular ejection fraction (EF) depends on ventricular contractility, afterload, and preload. Preload is related to end-diastolic volume (EDV) and pressure; the relationship between these 2 parameters (the end-diastolic pressure-volume relationship, EDPVR) indexes the degree of ventricular

Objectives The purpose of the present study was to translate our laboratory investigations to establish safety and efficacy of 8 weeks of chronic SC B-type natriuretic peptide (BNP) administration in human Stage C heart failure (HF). Background B-Type natriuretic peptide is a cardiac hormone with vasodilating, natriuretic, renin-angiotensin inhibiting, and lusitropic properties. We have previously demonstrated that chronic cardiac hormone replacement with subcutaneous (SC) administration of BNP in experimental HF resulted in improved cardiovascular function. Methods We performed a randomized double-blind placebo-controlled proof of concept study comparing 8 weeks of SC BNP (10 μg/kg bid) (n = 20) with placebo (n = 20) in patients with ejection fraction Results Eight weeks of chronic SC BNP resulted in a greater reduction of LV systolic and diastolic volume index and LV mass index as compared with placebo. There was a significantly greater improvement of Minnesota Living with Heart Failure score, LV filling pressure as demonstrated by the reductions of E/e' ratio, and decrease in left atrial volume index as compared with placebo. Glomerular filtration rate was preserved with SC BNP, as was the ability to activate plasma 3′,5′-cyclic guanosine monophosphate (p Conclusions In this pilot proof of concept study, chronic protein therapy with SC BNP improved LV remodeling, LV filling pressure, and Minnesota Living with Heart Failure score in patients with stable systolic HF on optimal therapy. Renin-angiotensin was suppressed, and glomerular filtration rate was preserved. Subcutaneous BNP represents a novel, safe, and efficacious protein therapeutic strategy in human HF. Further studies are warranted to determine whether these physiologic observations can be translated into improved clinical outcomes and ultimately delay the progression of HF. (Cardiac Hormone Replacement With BNP in Heart Failure: A Novel Therapeutic Strategy; NCT00252187 )

Background Bioabsorbable cardiac matrix (BCM) is a novel device that attenuates adverse left ventricular (LV) remodeling after large myocardial infarctions in experimental models. Objectives This study aimed to analyze whether BCM, compared with saline control, would result in less LV dilation and fewer adverse clinical events between baseline and 6 months. Methods In an international, randomized, double-blind, controlled trial, 303 subjects with large areas of infarction despite successful primary percutaneous coronary intervention (PCI) of ST-segment elevation myocardial infarction (STEMI) were randomized 2:1 to BCM or saline injected into the infarct-related artery 2 to 5 days after primary PCI. The primary outcome was mean change from baseline in LV end-diastolic volume index (LVEDVI) at 6 months. Secondary outcomes included change in Kansas City Cardiomyopathy Questionnaire score, 6-minute walk time, and New York Heart Association functional class at 6 months. The primary safety endpoint was a composite of cardiovascular death, recurrent MI, target-vessel revascularization, stent thrombosis, significant arrhythmia requiring therapy, or myocardial rupture through 6 months. Results In total, 201 subjects were assigned to BCM and 102 to saline control. There was no significant difference in change in LVEDVI from baseline to 6 months between the groups (mean change ± SD: BCM 14.1 ± 28.9 ml/m 2 vs. saline 11.7 ± 26.9 ml/m 2 ; p = 0.49). There was also no significant difference in the secondary endpoints. The rates of the primary safety outcome were similar between the 2 groups (BCM 11.6% vs. saline 9.1%; p = 0.37). Conclusions Intracoronary deployment of BCM 2 to 5 days after successful reperfusion in subjects with large myocardial infarction did not reduce adverse LV remodeling or cardiac clinical events at 6 months. (IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction [PRESERVATION I]; NCT01226563 )

The study published in this issue of the Journal by Maurer et al. ([1][1]) provides data which, interpreted in the context of a number of recently published studies ([2–8][2]), allow us to conclude that: 1) left ventricular (LV) end-diastolic volume (EDV) is normal in the vast majority of patients

Restrictive cardiomyopathy (RCM) is characterized by restrictive ventricular physiology in the presence of normal diastolic volume and normal ventricular wall thickness [(1)][1]. RCM is the least common cardiomyopathy and its prevalence is unknown [(1,2)][1]. Furthermore, its etiology could be

Objectives We sought to determine whether matrix metalloproteinase (MMP) inhibitor, PG-116800, reduced left ventricular (LV) remodeling after myocardial infarction (MI). Background PG-116800 is an oral MMP inhibitor with significant antiremodeling effects in animal models of MI and ischemic heart failure. Methods In an international, randomized, double-blind, placebo-controlled study, 253 patients with first ST-segment elevation MI and ejection fraction between 15% and 40% were enrolled 48 ± 24 h after MI and treated with placebo or PG-116800 for 90 days. Major efficacy end points were changes in LV volumes as determined by serial echocardiography, and clinical and safety outcomes were also collected. Results In total, 203 patients (80%) completed 90 days of treatment and had evaluable baseline and 90-day echocardiograms. The proportion of patients with anterior MI (78% vs. 81%) and primary percutaneous coronary intervention (90% vs. 91%) along with baseline LV ejection fraction (35.5% vs. 36.8%) did not differ between PG-116800-treated and placebo-treated patients. There was no difference in the change in LV end-diastolic volume index from days 0 to 90 with PG-116800 versus placebo (5.09 ± 1.45 ml/m2vs. 5.48 ± 1.41 ml/m2, p = 0.42). Changes in LV diastolic volume, LV systolic volume, LV ejection fraction, sphericity index, plus rates of death or reinfarction were not significantly improved with PG-116800. PG-116800 was well tolerated; however, there was increased incidence of arthralgia and joint stiffness without significant increase in overall musculoskeletal adverse events (21% vs. 15%, p = 0.33). Conclusions Matrix metalloproteinase inhibition with PG-116800 failed to reduce LV remodeling or improve clinical outcomes after MI.

OBJECTIVES We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition

Objectives. The purpose of this study was to determine whether contrast-enhanced transthoracic echocardiography improves the evaluation of left ventricular (LV) volumes and ejection fraction (EF).Background. Echocardiographic assessment of LV volumes and EF is widely used but may be inaccurate when the endocardium is not completely visualized. Recently the intravenous (IV) administration of perfluorocarbon microbubbles has been shown to enhance opacification of the LV cavity, but the utility of these agents to improve the echocardiographic assessment of LV systolic function is unknown.Methods. In 40 subjects (29 men and 11 women, aged 24 to 81 years) an assessment of LV volumes and EF was performed with a magnetic resonance imaging examination, followed immediately by a transthoracic echocardiogram before and after the intravenous administration of 2% dodecafluoropentane emulsion (EchoGen; Sonus Pharmaceuticals, Bothell, Washington).Results. Contrast enhanced the echocardiographic assessment of LV end diastolic volume (p < 0.02), end systolic volume (p < 0.01) and LVEF (p < 0.03). The percentage of subjects in whom the correct echocardiographic classification EF was normal, mild to moderately depressed or severely reduced improved significantly after contrast enhancement (from 71% before contrast to 94% after, p < 0.03). These findings were most striking in the subjects with two or more adjacent endocardial segments not visualized at baseline.Conclusions. Administration of an intravenous contrast agent improves the ability to accurately assess LV volumes and EF in humans. Contrast enhancement is most useful in subjects with two or more adjacent endocardial segments not seen at baseline.

Objectives. In this study we quantified the effects of a critical coronary stenosis on global systolic function using pressure-volume relations at baseline and during incremental dobutamine stress.Background. The effects of coronary stenosis have previously been analyzed mainly in terms of regional (dys)function. Global hemodynamics are generally considered normal until coronary flow is substantially reduced. However, pressure-volume analysis might reveal mechanisms not fully exposed by potentially load-dependent single-beat parameters. Moreover, no systematic analysis by pressure-volume relations of the effects of dobutamine over a wide dose range has previously been presented.Methods. In 14 dogs left ventricular volume and pressure were measured by conductance and micromanometer catheters, and left circumflex coronary flow by Doppler probes. Measurements in control and with left circumflex stenosis were performed at baseline and at five levels of dobutamine (2.5 to 20 μg/kg/min). The end-systolic pressure-volume relation (ESPVR) dP/dtMAX− vs. end-diastolic volume (dP/dtMAX− VED) and the relation between stroke work and end-diastolic volume (preload recruitable stroke work [PRSW]) were derived from data obtained during gradual caval occlusion.Results. In control, dobutamine gradually increased heart rate up to 20 μg/kg/min, the inotropic effect blunted at 15 μg/kg/min. With stenosis, the chronotropic effect was similar, however, contractile state was optimal at approximately 10 μg/kg/min and tended to go down at higher levels. At baseline, the positions of ESPVR and PRSW, but not of dP/dtMAX− VED, showed a significant decrease in function with stenosis. No differences between control and stenosis were present at 2.5 μg/kg/min; the differences were largest at 15 μg/kg/min.Conclusions. Pressure-volume relations and incremental dobutamine may be used to quantify the effects of critical coronary stenosis. The positions of these relations are more consistent and more useful indices than the slopes. The positions of the ESPVR and PRSW show a reduced systolic function at baseline, normalization at 2.5 μg/kg/min and a consistent significant difference between control and stenosis at dobutamine levels of 5 μg/kg/min and higher.

Objectives The objective of this study was to compare the physiological determinants of ejection fraction (EF)—ventricular size, contractile function, and ventricular-arterial (VA) interaction—and their associations with clinical outcomes in chronic heart failure (HF). Background EF is a potent predictor of HF outcomes, but represents a complex summary measure that integrates several components including left ventricular size, contractile function, and VA coupling. The relative importance of each of these parameters in determining prognosis is unknown. Methods In 466 participants with chronic systolic HF, we derived quantitative echocardiographic measures of EF: cardiac size (end-diastolic volume [EDV]); contractile function (the end-systolic pressure volume relationship slope [Eessb] and intercept [V0]); and VA coupling (arterial elastance [Ea]/Eessb). We determined the association between these parameters and the following adverse outcomes: 1) the combined endpoint of death, cardiac transplantation, or ventricular assist device (VAD) placement; and 2) cardiac hospitalization. Results Over a median follow-up of 3.4 years, there were 76 deaths, 52 transplantations, 14 VAD placements, and 684 cardiac hospitalizations. EF was independently associated with death, transplantation, and VAD placement (adjusted hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.8 to 5.0 comparing third and first tertiles), as were EDV (HR: 2.6; 95% CI: 1.5 to 4.2); V0 (HR: 3.6; 95% CI: 2.1 to 6.1); and Ea/Eessb (HR: 2.1; 95% CI: 1.3 to 3.3). EDV, V0, and Ea/Eessb were also associated with risk of cardiac hospitalization. Eessb was not significantly associated with any adverse outcomes in adjusted analyses. Conclusions Left ventricular size, V0, and VA coupling are associated with prognosis in systolic HF, but end-systolic elastance (Eessb) is not. Assessment of VA coupling via Ea/Eessb is an additional noninvasively derived metric that can be used to gauge prognosis in human HF.

Objectives. The objective of this study was to evaluate cardiac functional reserve in patients with syndrome X. Background. Syndrome X is characterized by stress-induced anginal pain and ST segment depression, normal findings on coronary angiography and normal left ventricular function at rest. Reduced coronary vasodilative reserve and abnormal myocardial lactate metabolism have been described in such patients. Methods. To assess left ventricular functional reserve in patients with syndrome X, continuons radionuclide monitoring of left ventricular end-diastolic volume, end-systolic volume and ejection fraction was performed in 12 patients and 13 normal control subjects during supine bicycle ergometer exercise. Results. In control subjects, end-diastolic volume increased at peak exercise from 100% to 106.5% (p < 0.01), end-systolic volume decreased from 39.1% to 22.6% (p < 0.01) and ejection fraction increased from 60.9% to 78.6% (p < 0.01). In patients with syndrome X, end-diastolic volume increased at peak exercise from 100% to 106% (p < 0.01), and end-systolic volume decreased at ST segment depression ≤0.5 mm (the ST point) from 37% to 28.8% (p < 0.01) but increased at peak exercise to 44.7% (p < 0.01 vs. the ST point). Thus, ejection increased at the ST point from 63% to 72.7% (p < 0.01) but decreased at peak exercise to 57.7% (p < 0.01 vs. the ST pint and control subjects) in proportion to the degree of ST segment depression. In nine patients (75%), ejection fraction at peak exercise was lower than baseline values. All patients and control subjects showed a rapid ejection fraction increase just after exercise during the recovery period. The degree of ejection fraction “overshoot” in patients was similar to that in control subjects, but the interval from the end of exercise to the overshoot in patients was significantly longer than that in control subjects (118 vs. 65 s, p < 0.01). Conclusions. In patients with syndrome X subjected to exercise stress, left ventricular function remained normal before the onset of ST segment depression. Once ST segment depression appeared, left ventricular function deteriorated in proportion to the degree of depression, and reduced left ventricular function persisted into the recovery period. Continuous ventricular function monitoring is thus a useful predictor of reduced left ventricular functional reserve in patients with syndrome X.

In patients with heart disease, changes in left ventricular filling pressures produce alterations in the Doppler transmitral flow velocity and isovolumetric relaxation time. This investigation explored the hypothesis that combining isovolumetric relaxation time with measurements derived from the transmitral flow velocity can be used to estimate left ventricular end-diastolic pressure. Simultaneous Doppler and left ventricular pressure recordings were obtained in 33 patients (24 men with a mean age of 58 ± 11 years) and an ejection fraction ranging from 15% to 74% (mean 55 ± 15%). The following Doppler measurements correlated significantly with left ventricular end-diastolic pressure (range 4 to 36 mm Hg): isovolumetric relaxation time (IVRT; r = − 0.73), atrial filling fraction (AFF; r = − 0.66), deceleration time (DT; r = − 0.59), ratio of early transmitral flow velocity to atrial flow velocity (E/A ratio; r = − 0.53) and time from termination of mitral flow to the electrocardiographic R wave (MAR; r = 0.37). Combining these measurements into a multilinear regression equation provided a more accurate estimate of end-diastolic pressure (LVEDP; r = 0.80; SEE = 7.4). The equation LVEDP = 46 − 0.22 IVRT − 0.10 AFF − 0.03 DT −(2 ÷ E/A) + 0.05 MAR was tested prospectively in 26 additional patients (mean age 55 ± 11 years; ejection fraction 41 ± 23%) with simultaneous Doppler and hemodynamic recordings but with the two measurements made independently, in blinded fashion, by additional observers. Estimated and measured end-diastolic pressures correlated well with each other (r = 0.86). For all patients combined (r = 0.83), the equation was 90% sensitive and specific in detecting an increased end-diastolic pressure > 15 mm Hg. Ejection fraction was ≥ 50% in 21 of 39 patients with an elevated end-diastolic pressure. In 10 patients, the equation was accurate in tracking acute changes in end-diastolic pressure induced by an intervention. Thus, the combination of mitral flow velocity measurements and isovolumetric relaxation time can provide a noninvasive estimate of filling pressures in patients with heart disease irrespective of systolic performance.

The end-systolic pressure-volume relation, the relation between stroke work and end-diastolic volume, termed the preload recruitable stroke work relation, and the relation between the peak of the first derivative of left ventricular pressure (dP/dtmax) and end-diastolic volume have been employed as linear indexes of left ventricular contractile performance in laboratory animals. The purpose of this study was to examine the relative utility of these indexes during routine cardiac catheterization in seven human subjects (mean age 48 +/- 18 [SD] years) with a normal left ventriculogram and coronary angiogram. Left ventricular pressure was recorded continuously with a micromanometer catheter, and left ventricular volume was derived from digital subtraction contrast ventriculograms obtained at 30-ms intervals. Transient occlusion of the inferior vena cava with a balloon-tipped catheter was employed to obtain beat to beat reductions in left ventricular pressure and volume over 8.7 +/- 1.7 cardiac cycles. Stroke work declined by 49 +/- 13% during vena caval occlusion, but end-systolic pressure fell by only 26 +/- 11%, and changes in dP/dtmax were small and inconsistent (12 +/- 22%). Consequently, the range of data available for determination of the preload recruitable stroke work relation greatly exceeded that for the end-systolic pressure-volume relation and the dP/dtmax-end-diastolic volume relation, and much less linear extrapolation from the measured data was required to determine the volume-axis intercept. Preload recruitable stroke work relations were highly linear (r = 0.95 +/- 0.07), and much more so than end-systolic pressure-volume relations (r = 0.79 +/- 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether modulation of systolic ventricular interaction influences right ventricular performance during right heart ischemia, the effects of septal ischemia and inotropic stimulation were studied in 15 dogs in an open chest preparation. Right coronary branch occlusions led to right ventricular dilation and free wall dyskinesia, reversed septal curvature and reduced left ventricular diastolic volume. In systole, the septum thickened but bulged paradoxically into the right ventricle generating an active but depressed right ventricular systolic pressure (28.9 ± 5.5 to 22.1 ± 4.5 mm Hg), with associated decreases in right ventricular stroke work (5.66 ± 0.94 to 1.92 ± 0.53 g m/m2) and left ventricular systolic pressure (123 ± 11 to 80 ± 10 mm Hg). Septal ischemia induced systolic septal thinning, left ventricular dilation and decreased left ventricular systolic pressure (80 ± 10 to 55 ± 10 mm Hg) and stroke work. Although the extent of paradoxic septal displacement increased, there were further dec- rements in right ventricular systolic pressure (22.1 ± 4.5 to 18.7 ± 4.3 mm Hg) and stroke work (1.92 ± 0.53 to 0.7 ± 0.2 g·m/m2). Dopamine infusion augmented left ventricular free wall contraction and increased left ventricular systolic pressure (55 ± 10 to 172 ± 17 mm Hg) and stroke work. Although systolic septal thinning persisted, the extent of paradoxic septal displacement increased strikingly and, despite continued right ventricular free wall dyskinesia, right ventricular systolic pressure increased (18.7 ± 4.3 to 39.6 ± 6.2 mm Hg) as did right ventricular stroke work (0.7 ± 0.2 to 7 ± 1.6 g·m/m2). Therefore, the magnitude of systolic interaction is an important determinant of right ventricular performance during right heart ischemia. Septal dysfunction diminishes this interaction, whereas inotropic stimulation augments this compensatory mechanism.

Two-dimensional echocardiography was used to determine the responses of left ventricular volumes, ejection fraction and segmental left ventricular motion to supine dynamic exercise in 22 professional athletes, comparing these responses with those in 22 age- and gender-matched healthy untrained individuals. End-systolic volume was significantly greater at rest and during exercise in the athletes (50 +/- 6 versus 29 +/- 4 ml and 40 +/- 5 versus 17 +/- 4 ml, respectively, p less than 0.001 for both). It decreased during exercise in all the untrained subjects, but did not change or increased in nine athletes (41%). End-diastolic volume was greater in the athletes at rest (143 +/- 12 versus 98 +/- 9 ml) and during exercise (157 +/- 14 versus 121 +/- 13 ml, p less than 0.01 for both). It increased in all the untrained subjects, but decreased or did not change in six athletes (27%). Ejection fraction was significantly lower in the athletes at rest and during exercise (65 +/- 4% versus 70 +/- 5% and 73 +/- 5% versus 86 +/- 5%, p less than 0.01 and 0.001, respectively); the values augmented normally in all the untrained subjects, but increased only by less than 5% units, did not change or decreased in nine athletes (41%). Eight athletes (36.5%) failed to demonstrate the expected symmetric hyperkinetic wall motion changes during exercise, which were seen in all the untrained subjects. No correlation was found between atypical responses to exercise and electrocardiographic patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate diagnostic accuracy and reproducibility of 320-slice dynamic volume computed tomography (CT) for measuring left ventricular end diastolic volume (EDV), left ventricular end systolic volume (ESV), stroke volume (SV) and left ventricular ejection fraction (EF) during the cardiac cycle, we

Background: Endothelial nitric oxide synthase (ENOS) is reduced in heart failure (HF). Statins upregulate NO production independent of lipid-lowering. We evaluated the ability of simvastatin (Sim) lo reverse ventricular remodeling and dysfunction by restoring coronary NO production and NO mediated regulation of apoptosis. Methods: Five month old cardiomyopathic (CMP) hamsters were divided into 2 groups Sim (n=5), and Untreated (n=5). Age-matched normal hamsters ware used as controls (n=6). Sim group received 20 “g/kg Sim daily by oral gavage for 6 weeks. Serial 2D echocardiograms were obtained at baseline and 2 week intervals. LV function and dimensions indexed lo body surface area were compared between groups. Myocardial apoptosis was evaluated by immunostaining and caspasa 3 activity assay. Myocardial ENOS expression was measured by Western blot and immunohistochemistry. Results: At baseline, CMP hamsters had lower LV shortening fraction (SF) compared to controls (17*2% vs.59+2%), higher LV diastolic volume (30*2 vs.6iO.5 ml/m*) and lower LV mass/volume ratio (0.5iO.02 vs. 0.72t0.02 “g/ml, p

Objectives. This study evaluated the feasibility of estimating pulmonary artery end-diastolic pressure from within the right ventricle. If feasible, this could have important implications for long-term hemodynamic monitoring. Background. Right ventricular pressure at the time of pulmonary valve opening closely approximates pulmonary artery end-diastolic pressure. Because maximal first derivative of right ventricular pressure (dP/dt) can be easily measured, if it occurs at or very near pulmonary valve opening, right ventricular pressure at maximal right ventricular dP/dt would be an estimation of pulmonary artery end-diastolic pressure. Methods. In 10 patients undergoing routine right and left heart catheterization, simultaneous measurements were made using micromanometers in the right ventricle and pulmonary artery at baseline, during isometric work and Valsalva maneuver. Right ventricular pressure at maximal right ventricular dP/dt was considered the estimated pulmonary artery end-diastolic pressure and was compared with the actual pulmonary artery end-diastolic pressure. Results. At baseline, estimated and actual pulmonary artery end-diastolic pressures were (mean ± SD) 17.7 ± 6.6 and 16.7 ± 6.7 mm Hg, respectively (p = NS). During isometric stress, estimated and actual pulmonary artery end-diastolic pressures were 30.4 ± 12.7 and 28.4 ± 10.1 mm Hg, respectively (p = NS). During Valsalva maneuvers, estimated and actual pulmonary artery end-diastolic pressures were 36.5 ± 17.8 and 38.0 ± 16.1 mm Hg, respectively (p = NS). Conclusions. Although more extensive testing is necessary to evaluate validity in different physiologic and pathologic situations, it appears that right ventricular pressure at maximal right ventricular dP/dt can provide accurate estimation of pulmonary artery end-diastolic pressure.

Objectives.We hypothesized that orthotopic heart transplantation with bicaval and pulmonary venous anastomoses preserves atrial contractility.Background.The standard biatrial anastomotic technique of orthotopic heart transplantation causes impaired function and enlargement of the atria. Cine magnetic resonance imaging (MRI) allows assessment of atrial size and function.Methods.We studied 16 patients who had undergone bicaval (n = 8) or biatrial (n = 8) orthotopic heart transplantation without evidence of rejection and a control group of 6 healthy volunteers. For all three groups, cine MRI was performed by combining coronal and axial gated spin echo and gradient echo cine sequences. Intracardiac volumes were calculated with the Simpson rule. Atrial emptying fraction was defined as the difference between atrial diastolic and systolic volumes, divided by atrial diastolic volume, expressed in percent. All patients had right heart catheterization.Results.Right atrial emptying fraction was significantly higher in the bicaval (mean [±SD] 37 ± 9%) than in the biatrial group (22 ± 11%, p < 0.05) and similar to that in the control group (48 ± 4%). Left atrial emptying fraction was significantly higher in the bicaval (30 ± 5%) than in the biatrial group (15 ± 4%, p < 0.05) and significantly lower in both transplant groups than in the control group (47 ± 5%, p < 0.05). The left atrium was larger in the biatrial than in the control group (p < 0.05). Cardiac index, stroke index, heart rate and blood pressure were similar in the transplant groups.Conclusions.Left and right atrial emptying fractions are significantly depressed with the biatrial technique and markedly improved with the bicaval technique of orthotopic heart transplantation. The beneficial effects of the latter technique on atrial function could improve allograft exercise performance.

Objectives. We examined the effect of shock timing within the QRS complex on cardioversion efficacy in a randomized crossover test of shocks delivered at two timing intervals relative to QRS onset. Background. The local ventricular electrogram is used in implantable cardioverter-defibrillators to synchronize cardioversion shocks to terminate ventricular tachycardia. However, the timing of the local electrogram relative to global ventricular depolarization is variable, depending on the site of ventricular tachycardia origin. Methods. Transvenous detibrillation leads were positioned in the right ventricular apex (cathode), coronary sinus and superior vena cava (anodes) of patients with sustained monomorphic ventricular tachycardia. After repeat ventricular tachycardia induction, sequential shocks with energy settings of 0.5 to 22 J were delivered simultaneously with QRS onset (QRS + 0 shock) or 100 ms after QRS onset (QRS + 100 shock). QRS onset was determined from the surface electrocardiogram. Cardioversion threshold, defined as the lowest shock energy for successful ventricular tachycardia termination, was measured for these two timings. Results. Fifteen patients (13 men, 2 women; mean [± SD] age 60.5 ± 7.7 years) completed testing. Cardioversion threshold was significantly lower with QRS + 100 shocks than QRS + 0 shocks (3.1 ± 3.5 vs. 10.5 ± 7.4 J, p < 0.01). Thirteen patients (87%) experienced ventricular tachycardia acceleration with QRS + 0 shocks, but only three patients (20%) had ventricular tachycardia acceleration using QRS + 100 shocks (p < 0.01). Of the 32 failed QRS + 0 shocks, 25 (78%) caused ventricular tachycardia acceleration, whereas only 5 (36%) of the 14 failed QRS + 100 shocks caused ventricular tachycardia acceleration (p < 0.05). Cardioversion threshold was not correlated with ventricular tachycardia cycle length, QRS duration, left ventricular ejection fraction or left ventricular diastolic volume (p = NS). Conclusions. Internal cardioversion shocks delivered late in the QRS complex during ventricular tachycardia are more effective and have a lower risk of ventricular tachycardia acceleration than those delivered near QRS onset.

Objectives. We evaluated a three-dimensional echocardiographic method for ventricular volume and surface area determination that uses polyhedral surface reconstruction. Six to eight nonparallel, unequally spaced, nonintersecting short-axis planes were positioned with a line of intersection display to overcome limitations associated with two-dimensional echocardiography. Background. Two-dimensional echocardiographic methods of ventricular volume and surface area determination are limited by assumptions about ventricular shape and image plane position. Methods. Left ventricular end-diastolic and end-systolic volumes and endocardial surface areas determined by three-dimensional echocardiography and nuclear magnetic resonance (NMR) imaging were compared in 15 normal subjects (7 men, 8 women, aged 23 to 41 years, body surface area 1.38 to 2.17 m2). Ten of these subjects also underwent two-dimensional echocardiography; and end-diastolic and end-systolic volumes were determined by the apical biplane summation of discs method and compared with results of NMR imaging. Results. Interobserver variability was 5% to 8% for three-dimensional echocardiography and 6% to 9% for NMR imaging. Both methods were in close agreement on end-diastolic volume (r = 0.92, SEE = 6.99 ml) and end-systolic volume (r = 0.81, SEE = 4.01 ml) and on end-diastolic surface area (r = 0.84, SEE = 8.25 cm2) and end-systolic surface area (r = 0.84, SEE = 4.89 cm2). Three-dimensional echocardiography and NMR imaging correlated significantly better for end-diastolic volume (r = 0.90, SEE = 7.0 ml) and end-systolic volume (r = 0.88, SEE = 3.1 ml) than did two-dimensional echocardiography and NMR imaging (r = 0.48, SEE = 20.5 ml for end-diastolic volume; r = 0.70, SEE = 5.6 ml for end-systolic volume). Conclusions. Three-dimensional echocardiography is an in vivo method of measuring left ventricular end-diastolic and end-systolic volumes and endocardial surface area with results comparable to those of NMR imaging. Additionally, three-dimensional echocardiography is superior to the two-dimensional echocardiographic apical biplane summation method because the technique eliminates geometric assumptions and image plane positioning error.

OBJECTIVE. The aim of the present study was to evaluate the hemodynamic and volume correlates of early diastolic filling and isovolumetric relaxation in patients with aortic stenosis. BACKGROUND. Left ventricular diastolic relaxation and filling have been found to be heterogeneous in patients with aortic stenosis. Potential mechanisms underlying this heterogeneity include individual differences in the severity of muscle hypertrophy or systolic dysfunction, or both, in the presence and severity of mitral regurgitation and in the level of left atrial pressure. METHODS. Right (fluid-filled) and left (high fidelity micromanometer) ventricular pressures, left ventricular volumes (contrast angiography) and transmitral inflow dynamics (Doppler echocardiography) were measured in 17 patients with isolated severe aortic stenosis (valve area less than 0.75 cm2). Measurements included left ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction, peak positive and negative first derivative of left ventricular pressure (dP/dt), the time constant of isovolumetric relaxation (tau), left ventricular end-diastolic pressure, left ventricular mass, left ventricular end-systolic stress, mean capillary wedge pressure and peak early (E) and late (A) transmitral filling velocities. Patients were subclassified according to left ventricular ejection performance at rest and mean capillary wedge pressure. RESULTS. Patients with normal ejection performance and normal mean capillary wedge pressure had a normal rate of isovolumetric left ventricular pressure decay and an abnormal diastolic filling pattern, with diastolic filling occurring primarily during atrial systole. In contrast, in patients with systolic dysfunction and elevated mean capillary wedge pressure, isovolumetric pressure decay was prolonged and diastolic filling occurred essentially during the rapid filling period, with reduced atrial contribution to left ventricular filling and a short isovolumetric relaxation period. Stepwise multiple linear regression analysis identified two variables as independent predictors of transmitral velocity profile and three variables independently predictive of the rate of left ventricular pressure decay. The single most important predictor of transmitral filling pattern was the pulmonary capillary wedge pressure (p less than 0.0001), followed by the left ventricular peak negative dP/dt (p = 0.002). The single most powerful predictor of the rate of reduction in left ventricular pressure was left ventricular mass index (p less than 0.0001), followed by end-systolic volume index (p = 0.0002) and left ventricular peak negative dP/dt (p = 0.0029). CONCLUSIONS. In patients with aortic stenosis, left ventricular filling is essentially determined by left atrial pressure, whereas isovolumetric relaxation more closely depends on the severity of muscle hypertrophy and chamber dilation.

Infarct expansion after myocardial infarction results in early ventricular enlargement and distortion of ventricular geometry. To characterize the components of late volume enlargement, biplane left ventriculography was performed in 52 patients 3 weeks and 1 year after a first anterior myocardial infarction. Biplane diastolic circumference and contractile and noncontractile segment lengths were measured. Global geometry was evaluated by using a sphericity index (angiographic volume of the ventricle divided by the volume of a sphere with the same circumference). Regional geometry was assessed by measurement of endocardial curvature, an important determinant of wall tension. End-diastolic volume was enlarged at baseline and increased at 1 year (230 +/- 42 to 244 +/- 55 ml, p = 0.01) as a result of increases in contractile segment length (34 +/- 5 to 37 +/- 5 cm, p less than 0.001) and sphericity index (0.74 +/- 0.07 to 0.76 +/- 0.08, p less than 0.001), whereas the noncontractile segment length decreased (15 +/- 6 to 12 +/- 6 cm, p less than 0.005). Curvature analysis revealed a flattening of presumably high tension concavity at the anterobasal (-6.0 +/- 4.0 to -4.5 +/- 3.7, p less than 0.01) and inferior (-4.5 +/- 2.0 to -3.6 +/- 2.1, p less than 0.005) margins of the infarct and less bulging of the anterior wall (9.4 +/- 2.5 to 8.2 +/- 2.3, p less than 0.001). Patients selected for late enlargement (diastolic volume increase greater than 20 ml, n = 19) had an increase in sphericity (0.75 +/- 0.05 to 0.80 +/- 0.08, p less than 0.005) and in diastolic circumference (54 +/- 3 to 56 +/- 4 cm, p less than 0.001) secondary to elongation of the contractile segment (32 +/- 4 to 36 +/- 4 cm, p = 0.001) at 1 year. Thus, late ventricular enlargement after anterior infarction results from an increase in contractile segment length and a change in ventricular geometry and is not a result of progressive infarct expansion. In the group of patients at high risk for late ventricular enlargement because of persistent occlusion of the infarct-related vessel, captopril therapy attenuated late volume enlargement by preventing these changes in contractile segment length and chamber geometry.

This study investigated the presence of atrial natriuretic factor in ventricular tissue obtained from humans with dilated or restrictive heart disease. In 17 patients with ventricular dilation and impaired systolic function and in 8 patients with restrictive heart disease and preserved systolic function, the presence of ventricular atrial natriuretic factor was investigated in tissue obtained by ventricular endomyocardial biopsy. The objective of the study was to determine if the ventricular presence of atrial natriuretic factor is dependent on ventricular dilation. Left ventricular end-diastolic volume index was greater in the group with dilated cardiomyopathy than in the group with restrictive cardiomyopathy (134 +/- 13 versus 78 +/- 5 ml/m2, p less than 0.05); end-diastolic pressure was elevated in the two groups (20 +/- 2 versus 25 +/- 4 mm Hg, p = NS). With the use of immunohistochemical techniques, ventricular atrial natriuretic factor was clearly detected in 15 of the 17 patients with dilated cardiomyopathy and in 6 of the 8 patients with restrictive cardiomyopathy. This study demonstrates the high prevalence of ventricular atrial natriuretic factor in living patients with either systolic or diastolic dysfunction. Whereas in the atria, stretch or dilation may be an important stimulus, atrial natriuretic factor in the ventricular chamber occurs independent of dilation.

To evaluate acute and follow-up changes in left ventricular diastolic performance, simultaneous digital left ventriculography and micromanometry were performed in 49 patients undergoing aortic balloon valvuloplasty. All patients improved symptomatically after valvuloplasty, and 26 returned 6.3 ± 1.5 months later for follow-up catheterization.Immediately after valvuloplasty, aortic valve area increased (before 0.5 ± 0.2 versus after 0.8 ± 0.2 cm2, p < 0.01), cardiac output (before 4.3 ± 1.2 versus after 4.4 ± 1.3 liters/min) and ejection fraction (before 51 ± 18% versus after 52 ± 17%) did not change and diastolic indexes worsened, signified by a decrease in peak filling rate (before 247 ± 80 versus after 226 ± 78 ml/s, p < 0.01) and increase in the time constant of isovolumetric relaxation (π) (before 78 ± 29 versus after 96 ± 40 ms, p < 0.01) and the modulus of chamber stiffness (before 0.107 ± 0.071 versus after 0.141 ± 0.083, p < 0.01).At follow-up catheterization, 16 patients continued to have symptomatic improvement (group 1) and 10 had recurrence of symptoms (group 2). Aortic valve area, cardiac output and ejection fraction at follow-up catheterization in both groups were similar and unchanged from values before valvuloplasty. However, diastolic indexes and left ventricular mass were improved compared with values before valvuloplasty in group 1 and worse in group 2 as follows: peak filling rate: group 1 ±8% versus group 2 −20%, p = 0.001; time constant of isovolumetric relaxation: group 1 −11% versus group 2 ±35%, p = 0.008; chamber stiffness: group 1 −27% versus group 2 ±26%, p = 0.001; mass: group 1 −9% versus group 2 ±6%, p = 0.004.These data indicate that 1) diastolic performance worsens immediately after valvuloplasty, consistent with the development of ischemia during balloon inflation; and 2) changes in left ventricular diastolic indexes and mass, rather than aortic valve area or systolic indexes, correlate best with symptomatic status 6 months after valvuloplasty.

The elevation of systolic pulmonary artery pressure (S-PAP) is an important prognostic variable in patients with left ventricular dysfunction (LVD). The potential determinant of pulmonary hypertension have not been consistently measured and remain ill defined. In 93 patients (age = 6B ± 13 years) with primary LVD (Ejection Fraction l50%, mean ± SO = 31 ± 10%), the S-PAP was prospectively measured using Doppler tricuspid regurgitant velocity. The correlations between S-PAP and LV diastolic volume (R = 0.19, P = NS). LVejection fraction (R = –0.23, p = 0.024). cardiac index (R = –0.22, P = 0.04). left atrial volume (R = 0.31, P = 0.002) were weak. Stronger correlations were observed with mitral regurgitant fraction (R = 0.46, p = 0.0001). effective regurgitant orifice (ERO, R = 0.48, P = 0.0001), mitral deceleration time (DT) R = –0.62, P = 0.0001) and E/A ratio (R = 0.43, P = 0.002). With multivariate analysis, the only independent predictors of S-PAP were mitral deceleration time (P = 0.0001), mitral effective regurgitant orifice IP = 0.0003) and age (P = 0.007). The S-PAP of patients with similar EF are shown below: DT g 150 (msec) DT ≤150 (msec) P EF:≤30 39 ± 13 61 ± 12 00001 EF ≤30 40 ± 10 57 ± 10 00001 ERO l15 (mm2) ERO≤ 15 (mm2) P EF:≤30 49 ± 16 60 ± 13 002 EF ≤30 40 ± 10 55 ± 11 0.0001 We conclude that in patients with primary systolic LV dysfunction, the independent determinant of pulmonary hypertension are the diastolic stiffness of LV as estimated by the mitral deceleration time and the degree of functional mitral regurgitation as measured by the effective regurgitant orifice but not by the degree of LV systolic dysfunction. These data help explain the wide variation of hemodynamic compromise in patients with similar degree of LV dysfunction.

Left ventricular (LV) contraction contributes importantly to right ventricular (RV) performance via left to right ventricular interaction (LV-RVI). To determine the magnitude of LV-RVI in human heart failure, 5 explanted hearts with dilated cardiomyopathy (DCM) were obtained at the time of transplant and restored to a beating condition using a blood perfusion system. One normal human heart, unsuitable for transplantation, was also obtained and served as control. Balloons were placed in both RV and LV With RV volume fixed at an end diastolic pressure (EDP) of 20 mmHg, LV volume was ramped from low (LV EDP = 0) to high (LV EDP = 30) and resulting changes in RV systolic pressures were plotted vs. changes in LV pressure. The slope of this line defines the LV-RVI pressure gain. An analogous procedure was used to determine RV-LVI. The figures depict representative data. In the DCM hearts mean ( ± SD) LV-RVI gain was 0.26 ± 0.06 and RV-LVI was 0.16 ± 0.12. In the control heart LV-RVI = 0.08 and RV-LVI = 0.15. LV-RVI is markedly increased in heart failure when compared to the control. This is consistent with previous reports using animal models. Conversely, RV-LVI remains unaffected by heart failure. These data, not previously available from humans, suggest that LV contribution to RV performance is significantly enhanced in chronic heart failure.

The purpose of this study is to compare left ventricular ejection fraction (LVEF) and regional wall motion (RWM) during exercise to LVEF and RWM during dobutamine infusion in the same pts. Ten pts (8 males, 2 females, mean age 56.9 ± 11.1), with known or suspected coronary disease, who had abnormal symptom-limited upright bicycle exercise first-pass radionuc1ide angiograms (FPRNA), had dobutamine FPRNA within 3 months of the exercise study and prior to any intervention or interim cardiac event. Dobutamine was given incrementally up to 40 μ g/kg/min. Atropine was given to increase heart rate as needed. FPRNA was performed by injecting 25 mCi of Tc-99m-sestamibi at the peak dobutamine dose. HR × SBP LVEF EDV ESV RWMA REF Exercise 33,100 ± 4,882 61 ± 6.2 182 ± 56 76 ± 32 10 ± 10 46 ± 6.8 Dobutamine 24,669 ± 5,571 72 ± 5.5 135 ± 44 43 ± 20 3 ± 10 67 ± 8.8 * * ** ** *** * EDV = end diastolic volume, ESV = end systolic volume, RWMA = regional wall motion abnormality, REF = regional ejection fraction of abnormal segments, SBP = systolic blood pressure, HR = heart rate * p = l 0.0001 (Ttest) ** p = 0.05(T test) *** p = 0.005 (chi-square) Exercise and dobutamine regional and global LV function are not comparable diagnostically or prognostically. Dobutamine LV function is not a surrogate for exercise LV function.

We have previously shown that diastolic dysfunction is frequent immediately after CABG. Although combined antegrade and retrograde cardioplegia (A + R) may improve myocardial protection, it can also lead to extracellular edema and microvaSCUlar injury. To assess postCABG diastolic function after A + R cardioplegia, volume manipUlation was used to create pressure-area curves before and after CABG in 20 pts. LV end diastOlic area (EDAREA) was measured by transesophageal echocardiography as an index of end diastOlic volume, and plotted against the PCWP as an estimate of mean LV diastOlic pressure. A smaller EDAREA at a similar PCWP postCABG reflects a leftward shift in the pressure-area curve and increased LV diastolic chamber stiffness. A (n = 14) A+R (n = 6) p EF(%) 52 ± 4 56 ± 4 NS Wall thickness (mm) 9.9 ± 0.1 9.3 ± 0.3 NS Bypass (min) 80 ± 5 74 ± 7 NS Pre-Post Δ PCWP (mmHg) 1 ± 1 0 ± 1 NS Pre-Post Δ EDAREA (%) -12.4 ± 23 -22.5 ± 30 0.02 Increased LV diastolic chamber stiffness occurred in all pts postCABG, but was more pronounced with both antegrade and retrograde cardioplegia. Conclusion After CABG, combined A + R cardioplegia is associated with a more prominent increase in diastolic chamber stiffness than antegrade cardioplegia alone. Recognition of worsening diastolic function with A + R may be important for optimal pt management postCABG.

A delay of left ventricular isovolumic relaxation and decrease in myocardial compliance may result in a decline of measured early filling rates in elderly subjects. Previous studies of diastolic function, however, have not excluded coronary artery disease or addressed the contribution of atrial contraction to diastole. The present study evaluated radionuclide-derived diastolic variables in 13 healthy elderly volunteers aged 75 +/- 6 years without symptoms or risk factors for coronary disease who had normal findings on the stress electrocardiogram, stress gated blood pool imaging and two-dimensional echocardiogram. Results were compared with those of a group of 10 healthy young volunteers aged 26 +/- 5 years. High count, 32 frame, double-buffered gated blood pool acquisitions were obtained at rest in the left anterior oblique view with an RR interval variation less than 5%. Left ventricular time-activity curves were analyzed and flow-volume loops for each group were constructed. In the healthy elderly: peak early diastolic filling rate is decreased, time of peak early filling and time to first third of diastolic filling are delayed, and peak late left ventricular filling rate and percent of atrial filling volume are augmented, suggesting an adaptive response of the atria to diminished left ventricular compliance.

Inflow characteristics of left and right ventricular filling were assessed in 40 patients with myocardial infarction and in 10 normal subjects by pulsed Doppler echocardiography. Patients with myocardial infarction were subdivided into four groups, focusing on the involvement of right ventricular and septal branches of the coronary arteries. Group I consisted of 11 patients with anterior infarction who showed an obstructive lesion of the proximal left anterior descending branch involving the first septal perforator with a patent right coronary artery. Group II consisted of 10 patients with inferior infarction who showed an obstructive lesion of the proximal right coronary artery involving the right ventricular branch. Group III consisted of 12 patients with both anterior and inferior infarction who showed obstructive lesions of both the proximal left anterior descending branch and the right coronary artery involving the right ventricular branch. Group IV consisted of seven patients with lateral infarction who showed an obstructive lesion of the diagonal branch or branches of the circumflex coronary artery with a patent left anterior descending branch and right coronary artery. Three measurements were performed from the trans-mitral and transtricuspidal inflow velocity patterns to assess the left and right ventricular diastolic behaviors. These measurements were: 1) acceleration half-time, 2) deceleration half-time of early diastolic rapid inflow, and 3) the ratio of the peak velocity of early diastolic rapid inflow to that of the late diastolic inflow due to the atrial contraction. Impaired diastolic filling of the left ventricle compensated by enhanced left atrial contraction was observed in patients with myocardial infarction from groups I, II, III and IV. Impaired diastolic filling of the right ventricle compensated by enhanced right atrial contraction was revealed in groups I, II and III. It is supposed that myocardial damage of the interventricular septum and a part of the right ventricular anterior wall perfused from the left anterior descending branch might be one of the causes for mildly impaired diastolic filling of the right ventricle in group I patients with a patent right coronary artery.

To determine the mechanisms of pulsus paradoxus during asthma, six subjects known to have cold air bronchial hyperreactivity were studied while in a quiescent phase of their disease. All were free of significant airway obstruction at the time of study. After placement of an esophageal balloon to estimate intrathoracic pressure, the subjects were assessed during quiet breathing, resistive airway loading and then during a stable period of airway obstruction induced by cold air. Steady state left ventricular volume and performance were measured using radionuclide ventriculography; right ventricular volume was calculated from the stroke volume ratio and right ventricular ejection fraction. Cardiac cycles were segregated according to their occurrence in inspiration or expiration using a flow signal from a pneumotachograph. Combined inspiratory and expiratory resistance produced pulsus paradoxus and changes in esophageal pressure that were similar to those during asthma and significantly greater than those during quiet breathing. These changes were accompanied by decreases in left ventricular diastolic volume and stroke volume during inspiration, and increases in these variables during expiration; right ventricular volume and stroke volume demonstrated changes reciprocal to those seen in the left ventricle. These data indicate that during periods of increase in airway resistance, abnormal pulsus paradoxus results from an exaggeration in the normal inspiratory-expiratory difference in stroke volume mediated primarily by the effects of intrathoracic pressure on ventricular preload.