Predictors of heart failure and all-cause mortality in asymptomatic patients with moderate and severe aortic regurgitation.

BACKGROUND: Class I indications for aortic valve replacement (AVR) for severe chronic aortic regurgitation (AR) include AR attributable symptoms or left ventricular (LV) ejection fraction <50%. As noninvasive estimates of elevated LV filling pressures (LVFP's) have been noted to predict heart failure (HF) readmission and all-cause mortality (ACM) in HF patients, we hypothesize that elevated LVFP's may also be independent predictors of HF and ACM in chronic AR. METHODS: We developed a single center patient database of moderate or greater AR diagnoses between 2003 and 2008 and followed each patient through January 2013. We included patients with >30 days follow-up with interpretable Doppler-echocardiograms. We recorded demographic variables, EuroScore II, incident HF and ACM, and Doppler-echo variables of LV size, systolic and diastolic function. RESULTS: Patients with severe AR (105 patients) and moderate AR (201 patients) had similar EuroScore II values and similar incident HF and ACM. For the 180 patients who developed HF, effective arterial elastance (aHR = 1.70 (1.01-2.83), p = .041), LV end-diastolic dimension (aHR = 1.83, (1.11-3.03), p = .0176), E/e' (aHR = 3.04, (1.83-5.05), p < .0001), eccentric hypertrophy (EH) (aHR = 2.39, (1.62-5.12), p = .0004), and tricuspid regurgitation (TR) velocity (aHR = 5.75, (3.70-10.36), p < .0001) were independent predictors. For the 118 patients with ACM, EH (aHR = 1.73, (1.02-3.28), p = .0414), systolic blood pressure (aHR = .58, (.33-.95), p = .0301), left atrial volume index (aHR = 1.82, (1.06-3.06), p = .0293), E/e' (aHR = 1.83, (1.07-3.08), p = .0280), and TR velocity (aHR = 4.14, (2.22-6.49), p < .0001) were independent predictors. CONCLUSIONS: Elevated TR velocity and EH were strong markers of HF and ACM in patients with asymptomatic severe AR and in moderate AR.

Diastolic function grading by American Society of Echocardiography guidelines and prediction of heart failure readmission and all-cause mortality in a community-based cohort.

BACKGROUND: Diastolic function (DF) guidelines have been simplified but lack extensive outcome data. Using a rural university heart failure (HF) database, we assessed whether DF grading could predict HF, HF readmission, and all-cause mortality (ACM). METHODS: In this single-center retrospective study that included 613 patients in sinus rhythm hospitalized for HF (HF with preserved-254 patients, with mid-range-216 patients, and reduced ejection fraction-143 patients), we recorded demographics, Doppler-echo, Framingham HF score, laboratories, HF readmission, and ACM with follow-up to 2167 days. RESULTS: Diastolic dysfunction (Ddys) parameters (left atrial volume index [LAVI] > 34 ml/m2 , tricuspid regurgitation [TR] velocity > 2.8 m/sec, and E/e' > 14) had moderate sensitivity (46.2%-65.0%) for predicting HF among all phenotypes combined with DF grading having moderate predictability and additive to a clinical composite for HF prediction (AUC = .677, P < 0.0001; difference = .043, P < 0.001) for combined phenotypes. Ddys parameters and Ddys severity (2016 ASE criteria: grade II and III) were significantly associated with HF readmission for decompensated HF within 60-2167 days of follow-up (LAVI > 34 ml/m2 : HR 1.56 [1.26-2.19]; E/e' > 14: HR 1.44 [1.21-1.99]; TR > 2.8 m/sec: H1.43 [1.19-1.88]; LV Dys grade II: HR 2.12 [1.42-2.96]; LV Ddys grade III: HR 2.39 [1.57-4.82]). CONCLUSION: The findings of this study highlight the clinical and prognostic relevance of determining the severity of LV Ddys in patients with HF with regard to HF verification and HF readmission.

The relation of left ventricular geometry to left ventricular outflow tract shape and stroke volume index calculations.

BACKGROUND: Stroke volume (SV) and aortic valve area calculations require the left ventricular (LV) outflow tract (LVOT) or aortic annular area calculations that involve squaring the respective diameters. Area calculation errors became evident with transcatheter aortic valve replacement where areas were underestimated due to an elliptical annulus. We hypothesized that LVOT and annular shape are more elliptical in patients with greater relative LV wall thickness (RWT) leading to underestimation of SV index using 2D Doppler echocardiography. METHODS: We studied 203 consecutive patients referred to an outpatient noninvasive laboratory for Doppler echocardiograms which included acceptable 3-dimensional images. 3-dimensional assessment of the LVOT at 3-5 mm from the valve insertion, at the site of valve insertion, and at the sinus of Valsalva (SOV) was performed with assessment of the minor axis (MN), major axis (MJ), and areas at mid-systole. SV index was calculated from LVOT and annular diameters obtained from 2-dimensional echo and from 3-dimensional LVOT areas. RESULTS: An inverse relation of RWT with MN/MJ at mid-systole for the LVOT (r = 0.5812, P < 0.0001) and annulus (r = 0.6865, P < 0.0001) was noted. LVOT and annulus areas were similar among groups at mid-systole. SV index calculated from 2D LVOT dimensions was significantly smaller than using 3D LVOT areas (35.6 ± 8.9 vs 53.6 ± 16.1 mL, P < 0.0001). CONCLUSION: There is an inverse relation between MN/MJ and RWT at the LVOT and aortic annulus despite the LVOT and annular areas being similar across most geometries resulting in SV index underestimation calculated using LVOT diameters vs 3D LVOT areas.

The Effect of Glycemic Control on Left Ventricular Function in Clinical and Experimental Diabetes.

Background: Glycemic control in diabetes mellitus (DM) has not improved cardiovascular outcomes with normal left ventricular (LV) function. We assessed the effect on LV dysfunction using a canine model of LV dysfunction and DM, and in patients with DM and LV dysfunction. Methods: Chronic LV dysfunction was produced by coronary microsphere embolization in 34 canines (15-25 kg). Following 8 weeks of stabilization, DM was induced in 24 canines and randomized to good or poor glycemic control for 3 months. Ten canines without DM were controls. Hemodynamic and Doppler echocardiographic data were obtained prior to and following pressure loading. We reviewed the Doppler-echocardiography at baseline and follow-up in 207 patients with DM with reduced ejection fraction (EF; median follow-up = 612 days) and 60 age- and sex-matched non-DM patients with normal EF. Laboratory results, medications, and incident adverse events from medical records were obtained. Results: EF = 43.8% ± 11.2% for all canines at 8 weeks. Canines with poor glycemic control (hemoglobin [Hb]A1c = 8.05% ± 3.02%) demonstrated reduced LV mass and rate-corrected velocity of circumferential fiber shortening, compared to those with LV dysfunction (1.36 ± 0.73 vs 0.88 ± 0.13 circumference per second, P < 0.01). Good glycemic control (HbA1c = 3.88% ± 0.89%) demonstrated similar LV parameters, compared to controls (HbA1c = 2.99% ± 0.44%). EF was similar among groups. Patients with vs without DM were followed for up to 3 years. Patients with DM and poor glycemic control had reduced EF, lower rate-corrected velocity of circumferential fiber shortening = 0.93 ± 0.26 vs 1.11 ± 0.26, P < 0.001), and greater incidence of heart failure. Conclusions: Poor glycemic control had an adverse effect on preexisting LV dysfunction experimentally and in patients with type 2 diabetes.

Contexte: Chez les personnes atteintes de diabète sucré (DS), la maîtrise glycémique n'a pas amélioré les résultats cardiovasculaires en présence d'une fonction ventriculaire gauche (VG) normale. Nous avons évalué l'effet d'une dysfonction VG au moyen d'un modèle canin de dysfonction VG et de DS, ainsi que chez des patients atteints de ces deux troubles. Méthodologie: Une dysfonction VG chronique a été produite chez 34 chiens (pesant de 15 à 25 kg) au moyen d'une embolisation coronarienne par microsphères. Après huit semaines de stabilisation, un DS a été provoqué chez 24 chiens, qui ont été répartis aléatoirement pour faire l'objet d'une bonne ou d'une mauvaise maîtrise glycémique pendant trois mois. Les 10 chiens sans DS ont servi de témoins. Des données hémodynamiques et échocardiographiques (Doppler) ont été obtenues avant et après la mise en charge. Nous avons aussi étudié l'échocardiogramme Doppler, au départ et lors du suivi, de 207 patients atteints de DS et présentant une fraction d'éjection (FE) réduite (suivi médian de 612 jours) et de 60 patients non atteints de DS qui ont été appariés en fonction de l'âge et du sexe et dont la FE était normale. Enfin, nous avons obtenu leurs dossiers médicaux : résultats des épreuves de laboratoire, listes de médicaments et manifestations indésirables découvertes fortuitement. Résultats: La FE était de 43,8 % ± 11,2 % pour l'ensemble des chiens après huit semaines. Chez les chiens dont la maîtrise glycémique était mauvaise (hémoglobine [Hb]A1c = 8,05 % ± 3,02 %), la masse VG et la vitesse de raccourcissement circonférentiel des fibres myocardiques corrigée en fonction de la fréquence cardiaque (VCFc) étaient toutes deux réduites comparativement à celles observées chez les chiens présentant une dysfonction VG (1,36 ± 0,73 vs 0,88 ± 0,13 circonférence par seconde [circ/s], p < 0,01). Chez les chiens avec une bonne maîtrise glycémique (HbA1c = 3,88 % ± 0,89 %), les paramètres VG étaient semblables à ceux observés chez les témoins (HbA1c = 2,99 % ± 0,44 %). La FE était également similaire dans tous les groupes. Les patients atteints de DS ont été suivis et comparés à des patients non atteints de DS pendant une durée allant jusqu'à trois ans. Les patients qui étaient atteints de DS et dont la glycémie était mal maîtrisée présentaient une FE réduite, une diminution de la VCFc (0,93 ± 0,26 vs 1,11 ± 0,26; p < 0,001) et une incidence accrue de cas d'insuffisance cardiaque. Conclusions: Une mauvaise maîtrise glycémique a eu un effet indésirable sur une dysfonction VG préexistante, tant dans le modèle animal que chez les patients atteints de diabète de type 2.

Adverse Outcomes with Eccentric Hypertrophy in a Community Based University Cohort with Aortic Stenosis.

OBJECTIVE: Aortic stenosis (AS) patients with eccentric hypertrophy (Ecc-LVH) have increased left ventricular (LV) size and possibly reduced ejection fraction (EF). However, previous studies suggest worse outcomes with concentric remodeling and hypertrophy. We hypothesized that Ecc-LVH pattern in AS patients will also be associated with greater heart failure (HF) and all-cause mortality (ACM). METHODS: We queried the electronic medical record from a community-based university practice for all AS patients. We included patients with >60 days follow-up and interpretable Doppler echocardiograms. We recorded demographics, Doppler-echo parameters, laboratories, HF readmission and ACM with follow-up to 2083 days. There were 329 patients divided into 4 groups based on the presence of LV hypertrophy (LVH) and relative wall thickness (RWT) by echocardiography. Ecc-LVH had RWT<0.43 and LVH. RESULTS: Patients with severe AS were older, had greater coronary disease prevalence, lower hemoglobin, greater LV mass index, more abnormal diastolic function, greater HF and ACM. Multivariate Cox proportional analysis revealed that valvulo-arterial impedance (p=0.017) and Ecc-LVH (p=0.033) were HF predictors. Brain natriuretic peptide>100 pg/ml (p<0.001) and Ecc-LVH (p=0.019) were ACM predictors. ACM was increased in Ecc-LVH patients with both moderate (HR=3.67-8.18 vs other geometries, p=0.007-0.0007) and severe AS (HR=3.94-9.48 vs normal and concentric remodeling, p=0.0002). In patients with HF, Ecc-LVH was associated with greater HF in moderate AS vs normal geometry (HR=3.28, p=0.0135) and concentric remodeling (HR=2.66, p=0.0472). CONCLUSIONS: Patients with AS and Ecc-LVH have greater ACM than other LV geometries with both moderate and severe AS and greater HF in moderate AS.

Clinical Characteristics, Comorbidities and Prognosis in Patients With Heart Failure With Mid-Range Ejection Fraction.

BACKGROUND: Patients with left ventricular ejection fractions between 40% and 49% either discovered de novo, having declined from ≥50%, or improved from <40% have been described as heart failure (HF) with mid-range ejection fraction (HFmrEF). Though clinical signs and symptoms are similar to other phenotypes, possible prognostic differences and therapeutic responses reinforce the need for further understanding of patients' characteristics especially in a rural community based population. The purpose of this study is to evaluate the clinical characteristics, comorbidities and prognosis of a rural patient population with HFmrEF. MATERIALS AND METHODS: We queried the electronic medical record from a community based university practice for all patients with a HF diagnosis. We included only those patients with >3 months follow-up and interpretable Doppler echocardiograms. We recorded demographic, Doppler-echo, and outcome variables (up to 2,083 days). RESULTS: There were 633 HF patients: 42.4% with preserved ejection fraction (HFpEF, EF ≥50%), 36.4% with HFmrEF, and 21.0% with reduced ejection fraction (HFrEF, EF <40%). HFmrEF patients were older, had greater coronary disease prevalence, lower systolic blood pressure, elevated brain natriuretic peptide, lower hemoglobin, and higher creatinine than HFpEF. All-cause mortality was intermediate between HFrEF and HFpEF but was not significantly different. Landmark analysis revealed a trend toward greater second readmission in HFmrEF as compared to HFpEF (hazard ratio: 1.43 [0.96-2.14],P = 0.0767). CONCLUSIONS: Rural patients with HFmrEF without an ambulatory HF clinic represent a higher percentage of HF patients than previously reported with greater coronary disease prevalence with comparable readmission rates and nonsignificantly different all-cause mortality.

Indexing peak rapid filling velocity to both relaxation and filling volume to estimate left ventricular filling pressures.

AIMS: The peak transmitral velocity/peak mitral annular velocity (E/e') ratio has been used as a left ventricular (LV) filling pressure (LVFP) correlate. However, the E/e' and its changes with haemodynamic alterations have not always correlated with changes in LVFP's. We hypothesized that indexing E/e' to a measure of LV filling volume may enhance the correlation with LVFP and LVFP changes. METHODS AND RESULTS: We summarized previously obtained haemodynamic and Doppler echo data in 137 dogs with coronary microsphere embolization induced-chronic LV dysfunction prior to and following haemodynamic induced alterations in LVFP's. E/e' values were obtained as E*tau where tau is the inverse logarithmic LV pressure decay. E*tau was indexed to LV filling volume by dividing by the diastolic time velocity integral (DVI) and correlated with LV mean diastolic pressure (LVmDP). Similarly, the relationship of E/e' and E/e'/DVI to LV pre A wave pressure was evaluated in 84 patients by invasive haemodynamics and Doppler echo. Combining data from all interventions, LVmDP correlated with E*tau (r = 0.408) but more strongly with E*tau/DVI (r = 0.667, z = 3.03, P = 0.0008). The change in LVmDP correlated with the change in E*tau/DVI (r = 0.742) more strongly than E*Tau (r = 0.187, Z = 4.01, P < 0.0001). In the patient cohort, E/e' was modestly correlated with LV pre A wave pressure (r = 0.301) but more strongly correlated with E/e'/DVI (r = 0.636, z = 2.36, P = 0.0161). CONCLUSION: Indexing E to both LV relaxation and filling volume results in a more robust relation with LVFP's and with LVFP changes.

Comparison of the effect of pressure loading on left ventricular size, systolic and diastolic function in canines with left ventricular dysfunction with preserved and reduced ejection fraction.

BACKGROUND: Decompensated heart failure may present with severe hypertension in patients with preserved (PreEF) or reduced left ventricular (LV) ejection fraction (RedEF) and is clinically indistinguishable. Previously, we demonstrated that arterial pressure elevation increases LV filling pressures in a canine model of chronic LV dysfunction with PreEF or RedEF. It is not clear whether any differences in hemodynamics, LV volume or performance, or diastolic function can be demonstrated between canines with PreEF or RedEF in response to arterial pressure elevation. We hypothesized that the LV systolic, diastolic, and hemodynamic response to pressure loading would be similar in RedEF or PreEF. METHODS: We studied 25 dogs with chronic LV dysfunction due to coronary microsphere embolization with RedEF (35 +/- 4%) and 20 dogs with PreEF (50 +/- 3%). Arterial pressure was increased with methoxamine infusion and hemodynamics and echo-Doppler parameters of LV size, function, transaortic and transmitral pulsed Doppler prior to and with methoxamine infusion was obtained. RESULTS: Though LV filling pressures were similar at baseline, LV size was larger (p < 0.01) and ejection fraction lower in dogs with RedEF (p < 0.001). With methoxamine, there were similar increases in LV size, LV pressures, and index of myocardial performance with the ejection fraction reduced similarly. Diastolic parameters demonstrated similar tau increases, E/A reduction, and diastolic filling shortening in RedEF and PreEF dogs. A similar extent of isovolumic contraction and relaxation times and index of myocardial performance prolongation occurred with pressure loading. CONCLUSION: Pressure loading in a canine model of LV dysfunction with PreEF and RedEF resulted in similar degrees of LV dilatation, increased filling pressures, and increased index of myocardial performance.

Effect of changes in contractility on the index of myocardial performance in the dysfunctional left ventricle.

BACKGROUND: The index of myocardial performance has prognostic power in patients with cardiomyopathy and following myocardial infarction. As the index of myocardial performance has been shown to be preload and afterload dependent, the effect of altering contractility on IMP and its components with left ventricular dysfunction has been incompletely delineated. METHODS: Chronic left ventricular dysfunction was induced in 10 canines using coronary microsphere embolization. Each dog was instrumented and imaged with 2D echo and Doppler. At the same atrially paced rate, contractility was increased with a dobutamine infusion and then following 4 weeks of oral digoxin. RESULTS: With chronic left ventricular dysfunction, a reduced left ventricular ejection fraction (42 +/- 3%, p < 0.001) and increased index of myocardial performance (0.58 +/- 0.17, p < 0.01) due to isovolumic contraction time lengthening and shortened left ventricular ejection time were noted. Dobutamine increased ejection fraction (p < 0.001), reduced left ventricular end diastolic pressure (p < 0.01), and reduced the index of myocardial performance (0.33 +/- 0.17, p < 0.001) due to isovolumic contraction time, isovolumic relaxation time, and left ventricular ejection time shortening. Digoxin increased ejection fraction (p < 0.05), reduced left ventricular end diastolic pressure (p < 0.05), and reduced the index of myocardial performance (0.42 +/- 0.13, p < 0.01) due to isovolumic contraction time shortening (p < 0.001). Both dobutamine and digoxin lengthened the diastolic filling period (p < 0.01). CONCLUSION: Increased inotropy with digoxin and dobutamine reduced the index of myocardial performance in dogs with left ventricular dysfunction. Shortened isovolumic contraction time, increased diastolic filling period, and reduced left ventricular end diastolic pressure with digoxin may provide insight into its efficacy in heart failure.

The index of myocardial performance and aortic regurgitation: the influence of a volume overload lesion.

OBJECTIVE: The index of myocardial performance (IMP) is a global cardiac function index with prognostic utility in patients with myocardial infarction and dilated cardiomyopathy but is preload dependent. We hypothesized that a volume overload lesion prolonging LV ejection time (LVET) may reduce IMP despite LV dysfunction (LVD). METHODS: The study groups consisted of 35 normals, 26 with LV dysfunction, and 60 with aortic regurgitation (AR): 40 with ejection fraction (EF) >50% (AR+Normal EF) and 20 with ejection fraction > or = 50% (AR+Reduced EF). We evaluated consecutive patients in each group with technically adequate 2D and Doppler echocardiography. RESULTS: When compared to normal subjects (0.357+/-0.122), IMP was increased with LVD (0.604+/-0.278 p<0.001) but was similar in AR+Normal EF patients due to isovolumic relaxation time (IRT) and LVET prolongation. The IMP was lower in AR+Reduced EF group (0.346+/-0.172, p<0.001) as compared to the LVD group due to a prolonged LVET and a reduced IRT and isovolumic contraction time (ICT). CONCLUSIONS: The IMP in AR+Normal EF patients was similar to normals due to IRT and LVET prolongation. The IMP was reduced in AR+Reduced EF patients compared to LVD patients due to IRT and ICT shortening and LVET prolongation. The index of myocardial performance in AR patients should be applied with caution.

Adverse Cardiac Events and the Impaired Relaxation Left Ventricular Filling Pattern.

BACKGROUND: Increasing diastolic dysfunction (DD) grade is associated with increased heart failure (HF). Patients with preserved ejection fractions and grade 1 DD may have left atrial dilatation, e' < 8 cm/sec, increased left ventricular (LV) mass, or variable E/e' ratios. The aim of this study was to test the hypothesis that LV hypertrophy or E/e' ratio > 8 may be associated with a greater incidence of HF. METHODS: Two hundred twelve patients with grade 1 DD and ejection fractions > 50% were retrospectively studied. Group 1 comprised 108 patients with E/A ratios < 0.8, without LV hypertrophy, e' < 8 cm/sec, and E/e' ratios < 8. Group 2 comprised 104 patients with LV hypertrophy or E/e' ratios > 8. Patients with incident HF and valvular or coronary disease were excluded. Using two-dimensional Doppler echocardiography, LV and left atrial volumes and transmitral spectral and tissue Doppler were analyzed. Medical records were examined for laboratory data, HF admissions, and all-cause mortality from 2004 to 2012. RESULTS: Despite similar ejection fractions, patients in group 2 had greater LV and left atrial volumes, LV mass index values, and E/e' ratios (P < .01 for all). HF incidence was greater in group 2 (30 vs 4, P < .001). Combined HF or all-cause mortality was greater in group 2 (46 vs 14, P < .001). Multivariate analysis revealed that HF was associated with E/e' ratio (P < .0001), systolic blood pressure (P = .0123), and LV mass index (P = .042). Combined HF or all-cause mortality was associated with E/e' ratio (P < .0001), LV mass index (P = .009), and lower calcium channel blocker use (P = .0011). CONCLUSIONS: HF alone or HF and all-cause mortality were increased in patients with grade 1 DD in the presence of LV hypertrophy or elevated LV filling pressures.

Aortic Dissection in a Healthy Male Athlete: A Unique Case with Comprehensive Literature Review.

A young otherwise healthy 27-year-old male who has been using anabolic steroids for a long time developed Type I aortic dissection associated with heavy weightlifting. The patient did not have a recent history of trauma to the chest, no history of hypertension, and no illicit drug use. He presented with severe chest pain radiating to back and syncopal event with exertion. Initial vitals were significant for blood pressure of 80/50 mmHg, pulse of 80 beats per minute, respirations of 24 per minute, and oxygen saturation of 92% on room air. Physical exam was significant for elevated jugular venous pressure, muffled heart sounds, and cold extremities with diminished pulses in upper and absent pulses in lower extremities. Bedside echocardiogram showed aortic root dilatation and cardiac tamponade. STAT computed tomography (CT) scan of chest revealed dissection of ascending aorta. Cardiothoracic surgery was consulted and patient underwent successful repair of ascending aorta. Hemodynamic stress of weightlifting can predispose to aortic dissection. Aortic dissection is a rare but often catastrophic condition if not diagnosed and managed acutely. Although rare, aortic dissection needs to be in the differential when a young weightlifter presents with chest pain as a delay in diagnosis may be fatal.

Fractional flow reserve using computed tomography for assessing coronary artery disease: a meta-analysis.

AIMS: Noninvasive fractional flow reserve (FFR) measurement with computed tomography (FFRCT) is a newly described method for assessing functional significance of coronary disease. The objective of this meta-analysis is to determine the diagnostic performance of FFRCT in the assessment of hemodynamically significant coronary artery stenosis. METHODS: PubMed and the Cochrane Center Register of Controlled Trials were searched from January 2000 through February 2015. Six original studies were found comparing FFRCT to invasive FFR in evaluating hemodynamic significance of coronary lesions (1354 vessels; 812 patients). Lesions were considered hemodynamically significant if invasive FFR was 0.80 or less. FFRCT used the same cutoff as invasive FFR to be considered as a positive test. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were calculated. RESULTS: One-third of the lesions (n = 443) were hemodynamically significant. The pooled per-vessel analysis showed that the sensitivity, specificity, negative and positive likelihood ratios, and diagnostic odds ratio of FFRCT to diagnose hemodynamically significant coronary disease were 0.84 [95% confidence interval (CI): 0.80-0.87], 0.76 (95% CI: 0.73-0.79), 0.22 (95% CI: 0.17-0.29), 3.48 (95% CI: 2.21-5.47), and 16.82 (95% CI: 8.20-34.49), respectively. CONCLUSION: The results of this meta-analysis demonstrate that FFRCT results correlate closely with invasive coronary angiography and FFR measurement. It is a feasible noninvasive method to assess hemodynamic significance of coronary lesions in patients with stable coronary artery disease.

Index of myocardial performance is afterload dependent in the normal and abnormal left ventricle.

BACKGROUND: The index of myocardial performance (IMP) has been used as a prognostic systolic-diastolic index for patients with dilated cardiomyopathy and postmyocardial infarction. To date, systematic evaluation of afterload alteration (arterial pressure) on IMP has not been performed with normal or reduced left ventricular (LV) function. METHODS: We studied 15 mongrel dogs at baseline, after the induction of acute ischemic LV dysfunction, and with chronic LV dysfunction. Each dog was atrially paced, and the arterial pressure was reduced with nitroprusside (NTP) (>10 mm Hg) and increased with methoxamine (Methox) (>30 mm Hg) in random order. Hemodynamics and transmitral and transaortic pulsed Doppler were obtained. RESULTS: With normal LV function, there were no changes in IMP with NTP. Methox reduced IMP (0.51 +/- 0.12-0.45 +/- 0.12, P < .05) as a result of a shortened isovolumic contraction time (ICT). With acute LV dysfunction, IMP declined with NTP (0.74 +/- 0.19-0.65 +/- 0.17, P < .01) because of a shortened ICT and isovolumic relaxation time. Methox prolonged IMP (0.73 +/- 0.16-0.83 +/- 0.21, P < .05). With chronic LV dysfunction, NTP resulted in a reduced IMP (0.75 +/- 0.27-0.57 +/- 0.27, P < .01) as a result of a reduced ICT and isovolumic relaxation time and a prolonged LV ejection time associated with an increased LV ejection fraction. Methox increased IMP (0.72 +/- 0.26-1.31 +/- 0.43, P < .001) because of an increased ICT and isovolumic relaxation time and a reduced LV ejection time associated with a reduced LV ejection fraction. Forward stepwise regression indicated that both LV systolic pressure ( P = .0006) and LV ejection fraction ( P = .0222) were independent predictors of IMP. CONCLUSION: IMP is afterload dependent in the normal LV. IMP is afterload dependent with acute and chronic LV dysfunction by influencing the isovolumic indices and LV ejection time in opposite directions. Further systematic evaluation of IMP is needed if this index is to be useful as a prognostic indicator.

Effect of heart rate and preload on index of myocardial performance in the normal and abnormal left ventricle.

BACKGROUND: The index of myocardial performance (IMP) has been used as a prognostic systolic-diastolic index for patients with dilated cardiomyopathy and postmyocardial infarction. To date, systematic evaluation of the effect of heart rate and preload alteration on IMP has not been performed with normal or reduced left ventricular (LV) function. METHODS: We studied 14 mongrel dogs at baseline, after the induction of acute ischemic LV dysfunction, and with chronic LV dysfunction. Heart rate was altered by atrial pacing 10 and 20 beats above baseline, and volume loading was accomplished with 10 mL/kg of saline at a paced rate. Hemodynamics, and transmitral and transaortic pulsed Doppler, were obtained. RESULTS: With normal LV function, there were no changes in IMP with pacing. With acute LV dysfunction, IMP was also unchanged with pacing, although both LV ejection time (ET) (192 +/- 23 vs 208 +/- 25 milliseconds, P < .05) and isovolumic contraction time (58 +/- 25 vs 72 +/- 31 milliseconds, P < .05) declined. With chronic LV dysfunction, IMP was unchanged although LV ET declined (188 +/- 15 vs 204 +/- 18 milliseconds, P < .01). Volume loading did not alter the IMP with normal LV function although LV ET increased (208 +/- 25 vs 220 +/- 20 milliseconds, P < .001). With acute LV dysfunction, IMP decreased (0.66 +/- 0.11 vs 0.82 +/- 0.20, P < .05) because of a decrease in isovolumic relaxation time (63 +/- 33 vs 76 +/- 38 milliseconds, P < .05). With chronic LV dysfunction, IMP also declined with volume loading (0.59 +/- 0.29 vs 0.73 +/- 0.28, P < .01) because of an increase in LV ET (224 +/- 30 vs 198 +/- 22 milliseconds, P < .0001). CONCLUSION: Heart rate incrementation does not change IMP. However, volume loading reduces IMP primarily as a result of LV ET lengthening with chronic LV dysfunction. Further systematic evaluation of IMP is needed if this index is to be useful as a prognostic indicator.

Reduced Longitudinal Function in Chronic Aortic Regurgitation.

BACKGROUND: Chronic aortic regurgitation (AR) patients demonstrate left ventricular (LV) remodeling with increased LV mass and volume but may have a preserved LV ejection fraction (EF). We hypothesize that in chronic AR, global longitudinal systolic and diastolic function will be reduced despite a preserved LV EF. METHODS: We studied with Doppler echocardiography 27 normal subjects, 87 patients with chronic AR with a LV EF > 50% (AR + PEF), 66 patients with an EF < 50% [AR + reduced LV ejection fraction (REF)] and 82 patients with hypertensive heart disease. LV volume, transmitral spectral and tissue Doppler were obtained. Myocardial velocities and their timing and longitudinal strain of the proximal and mid wall of each of the 3 apical views were obtained. RESULTS: As compared to normals, global longitudinal strain was reduced in AR + PEF (13.8 ± 4.0%) and AR + REF (11.4 ± 4.7%) vs. normals (18.4 ± 3.6%, both p < 0.001). As an additional comparison group for AR + PEF, global longitudinal strain was reduced as compared to patients with hypertensive heart disease (p = 0.032). The average peak diastolic annular velocity (e') was decreased in AR + PEF (6.9 ± 3.3 cm/s vs. 13.4 ± 2.6 cm/s, p < 0.001) and AR + REF (4.8 ± 2.1 cm/s, p < 0.001). Peak rapid filling velocity/e' (E/e') was increased in both AR + PEF (14.4 ± 6.2 vs. 6.2 ± 1.3, p < 0.001) and AR + REF (18.8 ± 6.4, p < 0.001 vs. normals). Independent correlates of global longitudinal strain (r = 0.6416, p < 0.001) included EF (p < 0.0001), E/e' (p < 0.0001), and tricuspid regurgitation velocity (p = 0.0176). CONCLUSION: With chronic AR, there is impaired longitudinal function despite preserved EF. Moreover, global longitudinal strain was well correlated with noninvasive estimated LV filling pressures and pulmonary systolic arterial pressures.

Treatment of heart failure in patients with diabetes mellitus.

Patients with diabetes mellitus have an increased morbidity and mortality from cardiovascular disease. Both coronary artery disease and congestive heart failure (CHF) are largely responsible for the increased cardiovascular adverse events in patients with diabetes. This review discusses the pathophysiology of CHF, the mechanisms of left ventricular (LV) dysfunction and the neurohormonal mechanisms involved in both LV dysfunction and CHF. Diabetes with and without hypertension is an important cause of LV dysfunction and CHF. Diabetes may be responsible for the metabolic and ultrastructural causes of LV dysfunction, while hypertension may be responsible for the marked fibrotic changes that are found. Experimental induction of diabetes in animals has shed light on the biochemical and ultrastructural changes seen. The role of insulin to reverse both metabolic and structural changes is reviewed both from experimental data and with the limited amount of clinical data available. The therapy of CHF in patients with diabetes is similar to that of patients without diabetes, with therapy directed toward the use of beta-blockers and angiotensin converting enzyme (ACE) inhibitors. As the morbidity and mortality are higher in patients with diabetes, several studies have pointed out the importance of this subgroup where the opportunity to make a significant clinical impact exists. A significant opportunity exists to reduce morbidity and mortality with beta-blockers and ACE inhibitors when ischaemia and CHF are both present. However, studies in patients diabetes have been limited to post hoc subgroup analyses and rarely as predefined subgroups. Clinical trials involving patients with diabetes with and without hypertension and LV dysfunction are clearly needed in the future to adequately address the needs of this high risk subgroup.

Genesis of the restrictive filling pattern: pericardial constraint or myocardial restraint.

BACKGROUND: Restrictive filling pattern has been predictive of heart failure in patients with cardiomyopathy and after myocardial infarction, and is similar to the filling pattern in constrictive pericarditis and amyloid heart disease. The purpose of this study was to determine the role of both myocardial restraint and pericardial constraint in a chronic left ventricular dysfunction model with restrictive filling. METHODS: After instrumentation, a flat balloon containing a high-fidelity pressure catheter was inserted through a pericardial incision in 12 dogs with chronic left ventricular dysfunction. Intracardiac volume (ICV) was manipulated by inferior venal caval balloon occlusion and volume loading while hemodynamics, echo-assessed chamber size, and transmitral Doppler were obtained at the same atrial paced rate with an intact pericardium and after pericardiectomy. RESULTS: With an intact pericardium, deceleration time increased with reduced ICV (130 +/- 35 vs 153 +/- 47 milliseconds, P <.05) and shortened with increased ICV (107 +/- 45 milliseconds, P <.05). The filling fraction at one-third of diastole decreased with reduced ICV (45.6 +/- 29.3 vs 24.2 +/- 15.8%, P <.01) and increased with increased ICV (60.1 +/- 14.8%, P <.05). Deceleration time could be predicted from intrapericardial pressure, the transmural left ventricular chamber stiffness constant, and filling fraction at one-third of diastole. After pericardiectomy, deceleration time also shortened with increased ICV (141 +/- 26 vs 112 +/- 38 milliseconds, P <.01). However, filling fraction at one-third of diastole was markedly reduced at paced baseline (19.9 +/- 14.4%, P <.01) and with increased ICV (15.5 +/- 11.8%, P <.001) as compared with an intact pericardium. CONCLUSIONS: Pericardial constraint and myocardial restraint play a role in restrictive filling pattern. Pericardial constraint becomes evident with redistribution of diastolic filling to later in diastole after pericardiectomy.