Biomedical subjects

William C Little

Publications and source records attributed to William C Little.

36 records · Page 2Linked to original sources

PubMed2005

The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure.

BACKGROUND: Despite its high prevalence, optimal therapy for diastolic heart failure (DHF) has not been determined. Alagebrium chloride (ALT-711) is a novel compound that breaks glucose crosslinks and may improve ventricular and arterial compliance. METHODS AND RESULTS: A total of 23 patients, mean age 71 years, with stable DHF, ejection fraction (EF) >50%, were enrolled in a 16-week, open-label trial of alagebrium 420 mg per day. Assessments included: peak exercise oxygen consumption, aortic distensibility, and left ventricular EF and mass by magnetic resonance imaging, Doppler diastolic filling, and quality of life by the Minnesota Living with Heart Failure questionnaire. One patient discontinued treatment because of a myocardial infarction after 12 days of treatment, and a second died suddenly after 10 weeks of treatment. Thus 21 patients completed the study. Left ventricular mass was 124 +/- 35 g at baseline and decreased to 119 +/- 34 g at follow up ( P = .036). This was accompanied by a decrease in the ratio of Doppler early diastolic flow velocity to Doppler early diastolic mitral annulus velocity (E') from 10.6 +/- 2.7 to 9.4 +/- 1.9 ( P = .076) and an increase in E' from 7.3 +/- 1.2 to 8.4 +/- 1.7 cm/s ( P = .045). The Minnesota Living with Heart Failure total score improved from 41 +/- 21 to 32 +/- 21 ( P = .01). There were no changes in EF (64 +/- 4% at baseline), blood pressure, peak exercise oxygen consumption, and aortic distensibility. CONCLUSION: Sixteen weeks of treatment with the glucose crosslink breaker, alagebrium, resulted in a decrease in left ventricular mass and improvements in left ventricular diastolic filling and quality of life in patient with DHF.

Aged↗

PubMed2004

Levosimendan improves LV systolic and diastolic performance at rest and during exercise after heart failure.

The new myofilament Ca2+ sensitizer levosimendan (LSM) is a positive inotropic and vasodilatory agent. Its beneficial effects have been demonstrated at rest in congestive heart failure (CHF). However, its effect during exercise (Ex) in CHF is unknown. We assessed the effects of LSM on left ventricular (LV) dynamics at rest and during Ex in eight conscious, instrumented dogs with pacing-induced CHF. After CHF, with dogs at rest, LSM decreased arterial elastance (Ea) and increased LV contractile performance as assessed by the slope of LV pressure-volume (P-V) relation. LSM caused a >60% increase in the peak rate of mitral flow (dV/dtmax) due to decreases in minimal LV pressure and the time constant of LV relaxation (tau). LV arterial coupling, quantified as the ratio of end-systolic elastance (Ees) to Ea, was increased from 0.47 to 0.85%. LV mechanical efficiency, determined as the ratio of stroke work to total P-V area, was improved from 0.54 +/- 0.09 to 0.61 +/- 0.07. These beneficial effects persisted during Ex after CHF. Compared with CHF Ex dogs, treatment with LSM prevented Ex-induced abnormal increases in mean left atrial pressure and end-diastolic pressure and decreased Ees/Ea. With LSM treatment during CHF Ex, the early diastolic portion of the LV P-V loop was shifted downward with decreased minimal LV pressure and tau values and a further augmented dV/dtmax. Ees/Ea improved, and mechanical efficiency further increased from 0.61 +/- 0.07 to 0.67 +/- 0.07, which was close to the value reached during normal Ex. After CHF, LSM produced arterial vasodilatation; improved LV relaxation and diastolic filling; increased contractility, LV arterial coupling, and mechanical efficiency; and normalized the response to Ex.

Animals↗

PubMed2004

Relation of anemia to diastolic heart failure and the effect on outcome.

We evaluated the frequency and importance of anemia in 137 patients with heart failure and a normal ejection fraction (diastolic heart failure). We found that anemia is common in these patients and is associated with greater elevations in serum B-type natriuretic peptide, more severe diastolic dysfunction, and a worse prognosis.

Aged↗

PubMed2004

Early mitral deceleration and left atrial stiffness.

Left ventricular (LV) filling deceleration time (DT) is determined by the sum of atrial and ventricular stiffnesses (KLA + KLV). If KLA, however, is close to zero, then DT would reflect KLV only. The purpose of this study was to quantify KLA during DT. In 15 patients, KLV was assessed, immediately after cardiopulmonary bypass, from E wave DT as derived from mitral tracings obtained by transesophageal echocardiography and computed according to a validated formula. In each patient, a left atrial (LA) volume curve was also obtained combining mitral and pulmonary vein (PV) cumulative flow plus LA volume measured at end diastole. Time-adjusted LA pressure was measured simultaneously with Doppler data in all patients. KLA was then calculated during the ascending limb of the V loop and during DT. LA volume decreased by 7.3 +/- 6.5 ml/m2 during the first of mitral DT, whereas LV volume increased 9.4 +/- 8.4 ml/m2 (both P < 0.001). There was a small amount of blood coming from the PV during the same time interval, with the cumulative flow averaging 3.2 +/- 2.4 ml/m(2) (P < 0.001). Mean LA pressure was 10.0 +/- 5.1 mmHg, and it did not change during DT [from 7.8 +/- 4.3 to 8.0 +/- 4.3 mmHg, not significant (NS)], making KLA, which averaged 0.46 +/- 0.39 mmHg/ml during the V loop, close to zero during DT [KLA(DT): from -0.002 +/- 0.08 to -0.001 +/- 0.031 mmHg/ml, NS]. KLV, as assessed noninvasively from DT, averaged 0.25 +/- 0.32 mmHg/ml. In conclusion, notwithstanding the significant decrement in LA volume, KLA does not change and can be considered not different from zero during DT. Thus KLA does not affect the estimation of KLV from Doppler parameters.

Acceleration↗

PubMed2004

Endogenous beta3-adrenoreceptor activation contributes to left ventricular and cardiomyocyte dysfunction in heart failure.

The objective of the present study was to test the hypothesis that endogenous beta(3)-adrenoreceptor (AR) activation contributes to left ventricular (LV) and cardiomyocyte dysfunction in heart failure (CHF). Stimulation of the beta(3)-AR inhibits cardiac contraction. In the failing myocardium, beta(3)-ARs are upregulated, suggesting that stimulation of beta(3)-ARs may contribute to depressed cardiac performance in CHF. We assessed the functional significance of endogenous beta(3)-AR activation in 10 conscious dogs before and after pacing-induced CHF. Under normal conditions, L-748,337, a specific beta(3)-AR antagonist, produced a mild increase in LV contractile performance assessed by the slope (E(es)) of the LV pressure-volume relation (18%, 6.2 +/- 0.9 vs. 7.3 +/- 1.2 mmHg/ml, P < 0.05) and the improved LV relaxation time constant (tau; 28.4 +/- 1.9 vs. 26.8 +/- 1.0 ms, P < 0.05). After CHF, the plasma norepinephrine concentration increased eightfold, and L-748,337 produced a larger increase in E(es) (34%, 3.8 +/- 0.7 vs. 5.1 +/- 0.8 mmHg/ml, P < 0.05) and a greater decrease in tau (46.4 +/- 4.2 vs. 41.0 +/- 3.9 ms, P < 0.05). Similar responses were observed in isolated myocytes harvested from LV biopsies before and after CHF. In the normal myocyte, L-748,337 did not cause significant changes in contraction or relengthening. In contrast, in CHF myocytes, L-748,337 produced significant increases in contraction (5.8 +/- 0.9 vs. 6.8 +/- 0.9%, P < 0.05) and relengthening (33.5 +/- 4.2 vs. 39.7 +/- 4.0 microm/s, P < 0.05). The L-748,337-induced myocyte response was associated with improved intracellular Ca(2+) concentration regulation. In CHF myocytes, nadolol caused a decrease in contraction and relengthening, and adding isoproterenol to nadolol caused a further depression of myocyte function. Stimulation of beta(3)-AR by endogenous catecholamine contributes to the depression of LV contraction and relaxation in CHF.

Adrenergic beta-Antagonists↗

PubMed2004

Effect of candesartan and verapamil on exercise tolerance in diastolic dysfunction.

Diastolic dysfunction may be exacerbated by increased systolic blood pressure (SBP) during exercise. Ang II may contribute to this process. We performed a randomized, double-blind, crossover study of two weeks of candesartan (16 mg) and verapamil (SR 160 mg). The 21 subjects were 64 +/- 10 years old with ejection fraction greater than 50%, no ischemia, mitral flow velocity E/A less than 1, normal resting SBP (< 150 mm Hg), and SBP greater than 200 mm Hg during exercise. Exercise tolerance was assessed using a Modified Bruce Protocol at baseline and after each two-week treatment period, separated by a two-week washout period. Quality of life (QOL) was assessed using the Minnesota Living with Heart Failure questionnaire. During exercise, Ang II levels increased from 29 +/- 18 to 33 +/- 18 pg/ml (P < 0.05). SBP during exercise was 213 +/- 9 mm Hg at baseline and similarly reduced by candesartan (198 +/- 18, P < 0.01) and verapamil (197 +/- 14, P < 0.01). With candesartan, exercise time increased from 793 +/- 182 seconds to 845 +/- 163 seconds (P < 0.05), and QOL improved from 11 +/- 14 to 5 +/- 6 (P < 0.05). In contrast, verapamil did not significantly improve exercise time or QOL. In patients with mild diastolic dysfunction at rest and a hypertensive response to exercise, both Ang II receptor blockade and verapamil blunted the hypertensive response to exercise. Ang II blockade increased exercise tolerance and improved QOL.

Antihypertensive Agents↗

PubMed2003

Relation of cardiac prognosis to segment location with apical left ventricular ischemia.

Previously, we have shown that myocardial ischemia induced during intravenous dobutamine in the distal segments composing the left ventricular apex is associated with a heightened risk of future myocardial infarction or cardiac death. In this study, we find this heightened risk is present independent of the location of the distal segment within the left ventricular apex.

Adult↗

PubMed2003

Feasibility to detect severe coronary artery stenoses with upright treadmill exercise magnetic resonance imaging.

We performed treadmill exercise magnetic resonance imaging in 27 patients with exertional chest pain who were referred for contrast coronary angiography to determine the feasibility of this method to identify severe coronary artery stenoses. The sensitivity and specificity for detecting >70% coronary artery luminal diameter narrowings on contrast coronary angiography were 79% and 85%, respectively.

Adenosine↗

PubMed2003

The cardiovascular effects of erythropoietin.

Erythropoietin is a hypoxia-induced hormone that is essential for normal erythropoiesis. The production of recombinant human erythropoietin (rHuEpo) has revolutionized the treatment of anemia associated with chronic renal failure and chemotherapy, and has been used as prophylaxis to prevent anemia after surgery. The erythropoietin receptor is widely distributed in the cardiovascular system, including endothelial cells, smooth muscle cells and cardiomyocytes. Epo has potentially beneficial effects on the endothelium including anti-apoptotic, mitogenic and angiogenic activities. On the other hand, some reports suggest that rHuEpo may have pro-thrombotic or platelet-activating effects. Hypertension develops in 20-30% of renal patients treated with rHuEpo. Many patients with heart failure have anemia. Despite some potential adverse effects, early studies in heart failure patients with anemia suggest that rHuEpo therapy is safe and effective in reducing left ventricular hypertrophy, enhancing exercise performance and increasing ejection fraction. Further studies are warranted to define the role of rHuEpo in chronic heart failure and other cardiovascular settings.

Anemia↗

PubMed2003

Diastolic mitral annular velocity during the development of heart failure.

OBJECTIVES: We sought to investigate the mechanism of reduced diastolic mitral annular velocity with diastolic dysfunction, despite elevated left atrial (LA) pressure. BACKGROUND: The peak rate of left ventricular (LV) early diastolic filling (E) and velocity of the mitral annulus due to long-axis lengthening (E(M)) are reduced in mild diastolic dysfunction. With more severe dysfunction, E increases in response to increased LA pressures. In contrast, E(M) decreases, despite increased LA pressure. METHODS: We studied eight dogs instrumented to measure LA pressure, LV pressure, and internal dimensions during the progressive development of heart failure (HF) produced by rapid pacing. RESULTS: Early diastolic filling decreased after four days of pacing from 114 +/- 32 to 88 +/- 22 ml/s (p < 0.05), but with more severe HF, it progressively increased to 155 +/- 32 ml/s (p < 0.05). In contrast, E(M) progressively decreased from 44 +/- 12 mm/s during the control period to 24 +/- 8 mm/s after four weeks (p < 0.05). Although E(M) was related to the time constant of LV relaxation (tau) (R(2) = 0.85), E was not. The latter occurred coincident with termination of the early diastolic LA to LV pressure gradient during all conditions. In contrast, with increasing HF, E(M) was progressively delayed after LA to LV pressure crossover by 37 +/- 12 ms (p < 0.05). The time from E to E(M) was related to tau (R(2) = 0.97). CONCLUSIONS: With slowed relaxation during the development of HF, E(M) is reduced and delayed so that it occurs after early, rapid filling. Thus, with slowed relaxation, E(M) does not respond to the early diastolic LA to LV pressure gradient, because it occurs when LV pressure is greater than or equal to LA pressure.

Animals↗

PubMed2003

Restick following initial Angioseal use.

The Angioseal hemostatic device is currently in widespread use for arterial closure after both diagnostic and interventional procedures. Resticking of the artery in which an Angioseal device has been placed has been discouraged for up to 90 days after the initial device placement because of theoretical concerns of disruption or dislodgment of the hemostatic plug. However, no data are available to address this concern. We evaluated the incidence of vascular complications following restick of the artery in which an Angioseal device had been deployed </= 90 days previously in 181 patients. Restick occurred 1-7 days after device placement in 80 patients, 8-30 days in 34 patients, and 31-90 days in 66 patients. There were no major bleeding, vascular repair, vessel occlusion, or embolizations. Three large hematomas (1.7%) were noted. These data suggest that restick can be performed safely after initial Angioseal deployment.

Aged↗

PubMed2003

Tachycardia exacerbates abnormal left ventricular-arterial coupling in heart failure.

The purpose of this study was to assess the effect of heart rate on left ventricular (LV)-arterial coupling and LV mechanical efficiency before and after heart failure (CHF). The production of LV stroke work (SW) and mechanical efficiency depends on the coupling of the LV and arterial system. The response of LV-arterial coupling to tachycardia may be altered in heart failure. We compared the response of LV-arterial coupling to increased heart rate (HR) in six conscious, instrumented dogs before and after pacing-induced CHF. Coupling was quantified as E(ES)/ E(A), where E(ES) is the slope of end-systolic pressure ( P)-volume ( V) relation, and E(A) is arterial elastance. Mechanical efficiency was determined as the ratio of SW to a total P-V area (PVA). Before CHF, E(ES) and E(A) increased similarly with increased heart rate to 180 min(-1). Thus, E(ES)/ E(A) remained unaltered (0.96 +/- 0.08 vs 0.94 +/- 0.35), and SW/PVA was unchanged (0.62 +/- 0.03 vs 0.59 +/- 0.06). Compared with the results prior to CHF and after CHF the resting E(ES) was decreased, thus both E(ES)/ E(A) (0.58 +/- 0.09) and SW/PVA (0.48 +/- 0.06) were less ( P << 0.05) than baseline. After CHF, an increase in HR to 180 min(-1) increased E(A) but not E(ES), thus E(ES)/ E(A) fell to 0.44 +/- 0.06 ( P << 0.05) and SW/PVA fell to 0.41 +/- 0.05 ( P << 0.05). Under normal conditions, LV-arterial coupling remains optimal during increases in HR. After CHF, tachycardia exacerbates the suboptimal baseline LV-arterial coupling, reducing the efficiency of producing SW.

Animals↗

PubMed2002

Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure.

CONTEXT: Many older patients with symptoms of congestive heart failure have a preserved left ventricular ejection fraction (LVEF). However, the pathophysiology of this disorder, presumptively termed diastolic heart failure (DHF), is not well characterized and it is unknown whether it represents true heart failure. OBJECTIVE: To assess the 4 key pathophysiological domains that characterize classic heart failure by systematically performing measurements in older patients with presumed DHF and comparing these results with those from age-matched healthy volunteers and patients with classic systolic heart failure (SHF). DESIGN AND SETTING: Observational clinical investigation conducted in 1998 in a general community and teaching hospital in Winston-Salem, NC. PARTICIPANTS: A total of 147 subjects aged at least 60 years. Fifty-nine had isolated DHF defined as clinically presumed heart failure, LVEF of at least 50%, and no evidence of significant coronary, valvular, or pulmonary disease. Sixty had typical SHF (LVEF < or =35%). Twenty-eight were age-matched healthy volunteer controls. MAIN OUTCOME MEASURES: Left ventricular structure and function, exercise capacity, neuroendocrine function, and quality of life. RESULTS: By echocardiography, mean (SE) LVEF was 60% (2%) in patients with DHF vs 31% (2%) in those with SHF and 54% (2%) in controls. Mean (SE) LV mass-volume ratio was markedly increased in patients with DHF (2.12 [0.14] g/mL) vs those with SHF (1.22 [0.14] g/mL) (P<.001) and vs controls (1.49 [0.17] g/mL) (P =.002). Peak oxygen consumption by expired gas analysis during cycle ergometry was similar in the DHF and SHF groups (14.2 [0.5] and 13.1 [0.5] mL/kg per minute, respectively; P =.40) and in both was markedly reduced compared with healthy controls (19.9 [0.7] mL/kg per minute) (P =.001 for both). Ventilatory anaerobic threshold was similar in the DHF and SHF groups (9.1 [0.3] and 8.7 [0.3] mL/kg per minute, respectively; P<.001) and in both was reduced compared with healthy controls (11.5 [0.4] mL/kg per minute) (P<.001). Norepinephrine levels were similar in the DHF (306 [64] pg/mL) and SHF (287 [62] pg/mL) groups (P =.56) and in both were markedly increased vs healthy controls (169 [80] pg/mL) (P =.007 and.03, respectively). Brain natriuretic peptide was substantially increased in both the DHF (56 [30] pg/mL) and the SHF (154 [28] pg/mL) groups compared with healthy controls (3 [38] pg/mL) (P =.02 and.001, respectively). Quality-of-life decrement score as assessed by the Minnesota Living with Heart Failure Questionnaire was substantially increased from the benchmark score of 10 in both groups (SHF: 43.8 [3.9]; DHF: 24.8 [4.4]). CONCLUSION: Patients with isolated DHF have similar though not as severe pathophysiologic characteristics compared with patients with typical SHF, including severely reduced exercise capacity, neuroendocrine activation, and impaired quality of life.

Aged↗

PubMed2002

Vascular closure devices in patients treated with anticoagulation and IIb/IIIa receptor inhibitors during percutaneous revascularization.

OBJECTIVES: The study assessed clinical outcomes of closure device use following percutaneous coronary revascularization using current standards of anticoagulation and antiplatelet therapy. BACKGROUND: Evaluation of the outcomes of patients by use of vascular closure devices during coronary interventions employing current standards of anticoagulation and glycoprotein (GP) IIb/IIIa inhibitor therapy is limited. METHODS: We evaluated outcomes of 4,525 consecutive patients who underwent percutaneous coronary intervention between July 1997 and April 2000. All patients received anticoagulation with heparin and GP IIb/IIIa inhibitor therapy with abciximab. The closure method was manual in 1,824 patients, Angioseal in 524 patients and Perclose in 2,177 patients. Procedural and hospital vascular outcomes were evaluated. RESULTS: Closure device success was 97.1% Angioseal and 94.1% Perclose (p < 0.05). Minor vascular complications occurred in 1.8% of manual patients, 1.1% of Angioseal patients and 1.2% of Perclose patients (p = NS); major complications occurred in 1.3% of manual patients, 1.1% of Angioseal patients and 1.0% of Perclose patients (p = NS). Multivariate logistic regression identified only closure device failure as an independent predictor of a vascular complication. In patients with successful closure with a device, minor complications (0.8% vs. 1.8%, p < 0.05) and any complication (1.5% vs. 2.5%, p < 0.05) were reduced compared to manual compression. CONCLUSIONS: Arterial closure following coronary interventions using anticoagulation and GP IIb/IIIa inhibitor therapy can be safely and effectively performed, with vascular complication rates similar to or lower than with manual pressure. Additionally, vascular complication rates using GP IIb/IIIa inhibitor therapy regardless of the method of arterial closure are equivalent to or lower than previously published rates of vascular complications.

Abciximab↗

PubMed2002

Current treatment and future directions in heart failure.

Recent research in the pathophysiology of congestive heart failure has focused on the blockade of neurohormonal systems. Large clinical trials have clearly demonstrated morbidity and mortality benefits of angiotensin-converting-enzyme inhibitors and beta blockers. Indeed, all patients with heart failure should be treated with these agents unless there is a specific contraindication otherwise. Despite this treatment, however, mortality from heart failure remains high. Current investigation is now focused on other pathophysiological mechanisms and the interruption of these pathways.

Adrenergic beta-Antagonists↗

PubMed2002

Can left ventricular diastolic stiffness be measured noninvasively?

BACKGROUND: A noninvasive estimation of left ventricular (LV) diastolic chamber stiffness (K(LV)) is still a challenge. Experimental data suggests that K(lv) can be obtained by using Doppler mitral flow deceleration time (DT) as the only variable: K(lv) = (70/[DT-20])(2) mm Hg/mL. We assessed the accuracy of this noninvasive estimate of K(lv) by comparing it with invasive measurement of K(lv) in intact patients with a wide range of LV size and function under varying loading conditions. METHODS: Twenty-five patients (age 54 +/- 12 years) with ischemic heart disease (n = 19) or primary LV dysfunction (n = 6), with a wide range of DT (79-324 ms) and ejection fraction (8%-57%), underwent simultaneous assessment of LV pressure by micromanometer and volume by 2-dimensional (2D) echocardiography-guided Doppler mitral flow velocity (where volume = mitral flow velocity integral x annular area) calibrated to 2D echocardiography stroke volume. Invasive K(lv) [delta pressure (from minimum to end-diastolic)/delta volume (during the same time interval)] was obtained at baseline and in 23 patients after LV unloading by prostaglandin E(1) (30-60 ng/kg/min) (n = 12), nitroglycerin (0.2 mg) (n = 9) or magnesium (1 g) (n = 2). Noninvasive K(lv) was estimated according to the above formula. RESULTS: In this set of patients with normal mitral annular area (3.9 +/- 1.1 cm(2)/m(2)), multivariate analysis showed that DT is inversely related to K(lv) (P <.001) but not to left atrial chamber stiffness, LV volume, relaxation time constant, mitral valve opening pressure, or area. The relation between noninvasively calculated and directly measured K(lv) was close to the line of identity under all conditions, (y = 0.93x + 0.05, r = 0.67, n = 48, P <.001), although with a wide standard error of the estimate (0.26 mm Hg/mL). CONCLUSION: We conclude that K(lv) can be calculated +/- 0.5 mm Hg/mL from noninvasively measured DT in patients.

Adult↗

PubMedDate not supplied

Therapy for diastolic heart failure.

There is little objective to guide the therapy of patients with diastolic heart failure. Because of the similarities of pathophysiology abnormalities in diastolic and systolic heart failure, it is a reasonable inference to suggest that the proven therapy for systolic heart failure may also be of benefit in patients with diastolic heart failure. Treatment of underlying or exacerbating conditions in diastolic heart failure, such as hypertension, left ventricular hypertrophy, ischemia, diabetes, anemia, obesity and pulmonary disease is an important means of managing diastolic heart failure. Control of systolic blood pressure is effective in improving and preventing the development of diastolic heart failure. Treatment of diastolic heart failure is most effective when it is associated with hypertension. Production of systolic arterial pressure acutely reduces pulmonary congestion, ischemia, and chronically may lead to regression of left ventricular hypertrophy. Patients with diastolic heart failure in the absence of hypertension are very difficult to treat.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Contribution of systolic and diastolic abnormalities to heart failure with a normal and a reduced ejection fraction.

Heart failure (HF) has traditionally been divided into HF with a reduced ejection fraction (EF; systolic HF) and HF with a normal EF (diastolic HF). Both groups have reductions in exercise tolerance, neurohumoral activation, and abnormal left ventricular (LV) filling dynamics and impaired relaxation. Although the normal EF indicates that pump performance is adequately compensated, some of the patients with HF and a normal EF have reduced longitudinal systolic velocity indicating cardiac muscular contractile dysfunction. Regardless of EF, the severity of HF and its prognosis and degree of exercise intolerance are closely related to the degree of diastolic filling abnormalities. Patients with HF and a reduced EF have ventricular dilatation and elongated myocytes, whereas patients with HF and a normal EF do not. Thus, patients with HF have diastolic abnormalities regardless of EF and many patients with HF and a normal EF have contractile abnormalities despite preserved systolic pump performance. Heart failure with a normal EF and a reduced EF differs in the systolic LV pump performance and the type of remodeling. The mechanism of the differing remodeling responses is not known, but aging, sex differences, and diabetes may contribute.

Cardiac Output, Low↗