Elevated Left Ventricular Research Articles

Left ventricular diastolic function in relation to the urinary proteome: A proof-of-concept study in a general population

BackgroundIn previous studies, we identified two urinary proteomic classifiers, termed HF1 and HF2, which discriminated subclinical diastolic left ventricular (LV) dysfunction from normal. HF1 and HF2 combine information from 85 and 671 urinary peptides, mainly up- or down-regulated collagen fragments. We sought to validate these classifiers in a population study. MethodsIn 745 people randomly recruited from a Flemish population (49.8years; 51.3% women), we measured early and late diastolic peak velocities of mitral inflow (E and A) and mitral annular velocities (e' and a') by conventional and tissue Doppler echocardiography, and the urinary proteome by capillary electrophoresis coupled with mass spectrometry. ResultsIn the analyses adjusted for sex, age, body mass index, blood pressure, heart rate, LV mass index and intake of medications, we expressed effect sizes per 1-SD increment in the classifiers. HF1 was associated with 0.204cm/s lower e' peak velocity (95% confidence interval, 0.057–0.351; p=0.007) and 0.145 higher E/e' ratio (0.023–0.268; p=0.020), while HF2 was associated with a 0.174 higher E/e' ratio (0.046–0.302; p=0.008). According to published definitions, 67 (9.0%) participants had impaired LV relaxation and 96 (12.9%) had elevated LV filling pressure. The odds of impaired relaxation associated with HF1 was 1.38 (1.01–1.88; p=0.043) and that of increased LV filling pressure associated with HF2 was 1.38 (1.00–1.90; p=0.052). ConclusionsIn a general population, the urinary proteome correlated with diastolic LV dysfunction, proving its utility for early diagnosis of this condition.

Pulse pressure variation is not a valid predictor of fluid responsiveness in patients with elevated left ventricular filling pressure

PurposeThe purpose of this study was to test the hypothesis that the predictive ability of pulse pressure variation (PPV) for fluid responsiveness would be altered in patients with elevated left ventricular (LV) filling pressure. Materials and methodsAccording to the preoperative echocardiographic assessment of the ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/E′), patients undergoing surgical coronary revascularization were classified into normal (n = 34, E/E′ <8) and high (n = 34, E/E′ >15) LV filling pressure group. After anesthetic induction, PPV and hemodynamic data were measured before and after 6 mL/kg of colloid administration. Fluid responsiveness was defined as 12% or more increase in stroke volume index assessed by pulmonary artery catheter and tested by the area under the receiver operating characteristic curve (AUROC). ResultsThe AUROCs of PPV in the normal and high filling pressure group were 0.829 (95% confidence interval [CI], 0.661-0.963; P < .001) and 0.583 (95% CI, 0.402-0.749; P = .110), respectively. The AUROCs of cardiac filling pressures and right ventricular end-diastolic volume index did not show statistical significance in both groups. ConclusionsNone of the assessed preload indices including PPV were able to predict fluid responsiveness in patients with elevated LV filling pressure.

Left ventricular diastolic performance at rest is essential for exercise capacity in patients with non-complicated myocardial infarction

IntroductionIn patients with recent myocardial infarction (MI) limited exercise capacity during physical activity is an important symptom and the base for future treatment. The myocardial injury after MI leads to both systolic and diastolic left ventricular (LV) dysfunction. ObjectiveThe aim of this study was to assess the relevance of systolic and diastolic LV function for cardiopulmonary exercise capacity in patients with prior MI. MethodsSixty-five consecutive patients after first MI without signs and symptoms of heart failure, aged 52 ± 6 years, were included in the study. The following echo parameters were evaluated: LV ejection fraction (LVEF), peak early and late diastolic velocities (E, A), deceleration time of E wave (dec t E), ratio of early trans-mitral to early annular diastolic velocities (E/e′), velocity propagation of early filling (Vp), and diameters and volumes of LV and left atrium (LA). CPET variables included: oxygen uptake at peak exercise (peak VO2), oxygen pulse (VO2 HR), VE/VCO2 slope, circulatory power (CP) and recovery half time (T1/2). ResultsSignificant correlations were demonstrated between peak VO2 and E/e’ (p < 0.001), peak VO2 and dec t E (p < 0.001), VO2 HR and E/e′ (p = 0.002) and between VE/VCO2 and E/e′ (p < 0.001). Twenty patients with elevated LV filling pressure achieved significantly lower peak VO2 (1624 vs. 1932 ml, p = 0.027) VO2 HR (11.70 vs. 14.05, p = 0.011) and CP (287,073 vs. 361,719, p = 0.014). By using multivariate regression model we found that only E/e′ (p = 0.001) and dec t E (p = 0.008) significantly contributed to peak VO2. ConclusionsDiastolic dysfunction, particularly LV filling pressure, determine exercise capacity, despite differences in LV ejection fraction in patients with prior MI.

Tissue Doppler Imaging of S Wave in Mitral Valve Prolapse Syndrome

Mitral valve prolapse (MVP) syndrome refers to the combination of various symptoms and clinical findings associated with MVP (1). Mitral tissue Doppler imaging (TDI) represents the left ventricular (LV) systolic function. It is a good surrogate for diastolic function and can overcome the limitation of the mitral inflow, which is highly dependent on the left atrial (LA) volume (2). In this article, Alizadehasl A et al. (3) demonstrated that the Sm wave was prominent in the MVP group compared to the normal control group. Moreover, Em was lower and Am showed a higher tendency. An increased E/Em implies elevated LA volume and LV end-diastolic pressure. Taken together with these findings, all of the other TDI findings in this investigation consistently indicated diastolic dysfunction in the patients with the MVP syndrome. Diastolic dysfunction in the MVP syndrome is well understood by increased rigidity and a decreased ability for relaxation because of increased preload, positive sympathetic feedback, and a higher proportion of fibrin in the myocardium (4). With respect to the high Sm wave, the myocardial hypermobility appeared to be a result of increased sympathetic nervous system activity and increased blood volume due to the mitral regurgitation flow. In addition, decreased coronary blood flow and structural disarray near the MVP site resulted in a decreased response to exercise compared to that in the normal subjects. However, the major focus of this investigation is the correlation between TDI and MVP. Is there a correlation between the prolapsed site and the lateral Sm wave, or does the degree of prolapse and mitral regurgitation impact the Sm wave? According to a previous investigation, high spike systolic velocity was selectively seen on the posterolateral mitral annulus, which has low resistance compared with the anteroseptal mitral annulus interacting with the right ventricle (5). Correlation between the prolapsed site and the degree of mitral prolapse and a prominent Sm wave has never been investigated. Moreover, the clinical implication of the prominent Sm wave observed in patients with MVP has never been studied from the aspect of a further treatment strategy and prognosis. Based on the observations in this article, future investigations providing further perspectives on the issues are warranted.

Speckle strain echocardiography predicts outcome in patients with heart failure with both depressed and preserved left ventricular ejection fraction.

While speckle imaging has been shown to predict outcome in patients with heart failure (HF), it remains unclear whether speckle strain predicts outcome in patients with HF with preserved ejection fraction (HFPEF). Four hundred twenty patients with HF by Framingham criteria and either: left ventricular (LV) EF <50%, or elevated LV filling pressure by comprehensive echo Doppler study in the setting of left ventricular ejection fraction (LVEF) ≥50%, were enrolled. Speckle tracking was used to measure strain and strain rate in multiple vectors. The primary endpoint was HF hospitalization or cardiovascular death. Follow-up was completed in 380/420 patients (90%). The mean age was 55.7 ± 0.8 years, 191/380 (50%) were male, 319/380 (84%) were hypertensive, 183/380 (48%) were diabetic, and 152/380 (40%) had known coronary artery disease. At a mean follow-up of 369 ± 30 days, 107/380 patients (28%) reached the primary endpoint: 97 HF rehospitalizations and 10 cardiac deaths. The best univariate predictors of outcome were global longitudinal peak strain (GLPS) (χ(2) = 25.6, P < 0.001), mitral DT (χ(2) = 16.8, P < 0.001), LVEF (χ(2) = 16.7, P < 0.0001), longitudinal early diastolic strain (χ(2) = 8.7, P = 0.003), and circumferential peak strain (χ(2) = 7.9, P = 0.005). On multivariate analysis, GLPS (P < 0.0001), LVEF (P = 0.0002), and mitral DT (P = 0.005) were independent predictors of outcome. In the 100 HF patients with preserved LVEF, there were 17 events. Patients with GPLS ≤-15 had significantly better event-free survival than patients with GPLS >-15 (χ(2) = 4.1, P = 0.04), whereas LVEF did not predict event-free survival. Speckle strain echocardiography is an important predictor of outcome in HF patients with both depressed and preserved LVEF.

Prognostic value of left ventricular diastolic dysfunction in a general population.

BackgroundNew techniques of Tissue Doppler Imaging (TDI) enable the measurement of myocardial velocities and provide information about left ventricular (LV) diastolic function. Recent studies explored the prognostic role of TDI‐derived indexes. However, these studies considered only total mortality and did not provide information on cardiovascular mortality and morbidity. Therefore, we investigated in continuous and categorical analyses whether Doppler diastolic indexes contained any prognostic information over and beyond traditional cardiovascular risk factors in a general population.Methods and ResultsWe measured early and late diastolic peak velocities of mitral inflow (E and A) by conventional Doppler, and the mitral annular velocities (e' and a') by TDI in 793 participants (mean age 50.9 years). We calculated multivariable‐adjusted hazard ratios for conventional and TDI Doppler indexes, while accounting for family cluster and cardiovascular risk factors. Median follow‐up was 4.8 years (5th to 95th percentile, 3.0 to 5.4). With adjustments applied for covariables, e' velocity was a significant predictor of fatal and nonfatal cardiovascular (n=59; P=0.004) and cardiac events (n=40; P=0.001). TDI e' yielded a net reclassification improvement of 54.2% for cardiovascular and 64.0% for cardiac events. Hazard ratios of all cardiovascular (2.21; P=0.042) and cardiac (4.50; P=0.002) events were significantly elevated in participants with increased LV filling pressure compared with subjects with normal diastolic function.ConclusionsTDI e' velocity is a significant predictor of fatal and nonfatal cardiovascular events in a general population. Furthermore, we observed an increase in all cardiovascular events in the diastolic dysfunction group characterized by elevated LV filling pressure.

Diastolic suction in heart failure: Impact of left ventricular geometry, untwist, and flow mechanics

AimsVector flow mapping (VFM) can be used to assess intraventricular hemodynamics quantitatively. This study assessed the magnitude of the suction flow kinetic energy with VFM and investigated the relation between left ventricular (LV) function and geometry in patients with an estimated elevated LV filling pressure. Materials and methodsWe studied 24 subjects with an elevated LV filling pressure (EFP group) and 36 normal subjects (normal group). Suction was defined as flow directed toward the apex during the period from soon after systolic ejection to before mitral inflow. The flow kinetic energy index was quantified as the sum of the product of the blood mass and velocity vector and its magnitude to the peak value was measured. Key findingsSuction flow was observed in 12 (50%) EFP-group patients and 36 (100%) normal-group subjects. The magnitude of the suction kinetic energy index was significantly smaller in EFP versus normal group (2.7±3.8 vs. 5.7±4.4g/s/cm2, P<0.01). The EFP-group patients with suction had a smaller LV end-systolic volume (ESV) (P<0.01), greater ellipsoidal geometry (P<0.05) and untwisting rate (P<0.01) than the EFP-group patients without suction. A regression analysis indicated a significant linear relation between the suction kinetic energy index and LVEF (r=0.43, P=0.04), ESV (r=−0.40, P=0.05), eccentricity index (r=0.44, P=0.04), and untwisting rate (r=0.51, P=0.04). SignificanceThe magnitude of the suction flow kinetic energy index derived from VFM may allow the quantitative assessment of the suction flow, which correlates with LV systolic function, geometry, and untwisting mechanics.

Evaluation of left ventricular diastolic function with a dedicated cadmium-zinc-telluride cardiac camera: comparison with Doppler echocardiography

To evaluate the relationships between measures of left ventricular (LV) filling dynamics at cadmium-zinc-telluride (CZT) imaging and indexes of LV diastolic function at transthoracic echocardiography. Two hundred and forty-seven patients underwent myocardial perfusion imaging at rest and after stress with a low-dose CZT protocol and a baseline transthoracic echocardiography study. All patients were submitted to invasive or computed coronary angiography. The peak filling rate (PFR) and the time to PFR (TPFR) were derived from gated CZT images as measures of LV filling dynamics. LV diastolic function was also evaluated at echocardiography and the presence of significantly increased LV filling pressures determined. Increased LV filling pressures at transthoracic echocardiography were evident in 103 (42%) patients. Interestingly, independently from the presence of coronary artery disease, there was a strict correlation between the presence and severity of LV diastolic dysfunction at echocardiography and CZT-derived measures of filling dynamics, i.e., PFR (P = 0.001) and TPFR (P = 0.001). At receiving operating characteristic analysis, a composite index of reduced PFR (≤2.11 end-diastolic volume s(-1)) and increased TPFR (>234 ms) showed a sensitivity of 84% and a specificity of 67% in unmasking the presence of elevated LV filling pressures at echocardiography. CZT-derived measures of LV filling dynamics correlate with echocardiographic parameters of diastolic function and may identify the presence of increased LV filling pressures.

Association of inflammation, myocardial fibrosis and cardiac remodelling in patients with mild aortic stenosis as assessed by biomarkers and echocardiography

1. The aim of the present study was to investigate the relationships among inflammation, myocardial fibrosis and cardiac remodelling in patients with mild aortic stenosis (AS), as assessed by biomarkers and echocardiography. 2. We evaluated 32 consecutive patients with mild AS, as well as 30 age- and gender-matched healthy individuals with normal aortic valves as control subjects. 3. Baseline echocardiography showed that the left ventricular (LV) mass index (111.3 ± 26.9 vs 94.5 ± 18.2 g/m(2); P = 0.006) and left atrial (LA) volume index (LAVI 27.5 ± 9.0 vs xx.x ± 5.2 mm(3)/mm(2); P = 0.005) were significantly higher in patients with mild AS. 4. Furthermore, LA enlargement (LAVI > 33 mm(3)/mm(2); 32.4% vs 3.3%; P = 0.003) and elevated LV filling pressure (E/e' > 15; 50.0% vs 23.3%; P = 0.036) were higher in patients with mild AS. 5. In patients with mild AS, stepwise, multivariate linear regression analysis revealed that the LV end-diastolic volume index was independently associated with matrix metalloproteinase (MMP)-1 (β = 0.371; P = 0.015), that the aortic valve mean pressure gradient was independently associated with MMP-2 (β = 0.19; P = 0.019), that MMP-2 was independently associated with transforming growth factor-β (β = 0.95; P < 0.001) and interleukin (IL)-1 (β = 0.17; P = 0.019) and that IL-1 was independently associated with tissue inhibitor of matrix metalloproteinase-1 (β = 0.68; P = 0.001). 6. Myocardial fibrosis in mild AS is independently associated with three factors: LV volume overload, aortic valve pressure overload and inflammation.

Carotid Artery and Aortic Stiffness Evaluation in Aortic Stenosis

In aortic stenosis (AS), the combination of risk factors can progressively lead to an increased arterial rigidity, which can be evaluated by the carotid artery and aortic stiffness (β index). The aim of this study was to investigate the relationship between carotid and aortic β index, left ventricular (LV) function, plasma brain natriuretic peptide (BNP) level, and symptoms in patients with AS. Comprehensive echocardiography including Doppler tissue imaging of the mitral annulus was performed in 53 patients with AS (aortic valve area < 1.2 cm(2)) and preserved LV ejection fractions (≥ 50%). Carotid β index was automatically derived from ultrasound wall tracking of the right carotid artery. The mitral E/e' ratio was used to estimate LV filling pressures. Carotid β index was higher in women than in men and was significantly correlated with age (P < .0001), diastolic arterial pressure (P = .046), pulse pressure (P = .006), and systemic arterial compliance (P = .001). Interestingly, carotid β index was significantly correlated with E/e' ratio (P < .0001) and plasma BNP level (P = .011). In multivariate regression analysis, carotid β index was an independent predictor of E/e' ratio (P < .0001) and of BNP level (P = .02). Moreover, carotid β index was significantly higher in symptomatic patients (P = .009). Aortic β index was significantly correlated with carotid β index (P < .0001), E/e' ratio (P = .004), and BNP (P < .001) and was significantly higher in symptomatic patients (P = .037). In patients with moderate to severe AS and preserved LV ejection fractions, the presence of increased carotid artery and aortic stiffness, assessed using carotid and aortic β index, is independently associated with elevated LV filling pressures, BNP level, and symptoms.

Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats

BackgroundHeart failure with left ventricular (LV) hypertrophy is often associated with insulin resistance and inflammation. Recent studies have shown that dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose metabolism and inflammatory status. We therefore evaluated whether vildagliptin, a DPP4 inhibitor, prevents LV hypertrophy and improves diastolic function in isoproterenol-treated rats.MethodsMale Wistar rats received vehicle (n = 20), subcutaneous isoproterenol (2.4 mg/kg/day, n = 20) (ISO), subcutaneous isoproterenol (2.4 mg/kg/day + oral vildagliptin (30 mg/kg/day, n = 20) (ISO-VL), or vehicle + oral vildagliptin (30 mg/kg/day, n = 20) (vehicle-VL) for 7 days.ResultsBlood pressure was similar among the four groups, whereas LV hypertrophy was significantly decreased in the ISO-VL group compared with the ISO group (heart weight/body weight, vehicle: 3.2 ± 0.40, ISO: 4.43 ± 0.39, ISO-VL: 4.14 ± 0.29, vehicle-VL: 3.16 ± 0.16, p < 0.05). Cardiac catheterization revealed that vildagliptin lowered the elevated LV end-diastolic pressure observed in the ISO group, but other parameters regarding LV diastolic function such as the decreased minimum dp/dt were not ameliorated in the ISO-VL group. Histological analysis showed that vildagliptin attenuated the increased cardiomyocyte hypertrophy and perivascular fibrosis, but it did not affect angiogenesis in cardiac tissue. In the ISO-VL group, quantitative PCR showed attenuation of increased mRNA expression of tumor necrosis factor-α, interleukin-6, insulin-like growth factor-l, and restoration of decreased mRNA expression of glucose transporter type 4.ConclusionsVildagliptin may prevent LV hypertrophy caused by continuous exposure to isoproterenol in rats.

Unsuccessful treatment of accelerated hypertension and persistent hyperkinetic state in a haemodialysed patient with high-output arteriovenous fistula

The case we describe concerns a rapid progression of heart failure (HF) in a patient with hypertension crises (HC), haemodialysed (HD) with the use of a high-output arteriovenous fistula (AVF). The 48-year-old male with a body mass index of 19.27 kg/m2, renal insufficiency due to glomerulonephritis, treated with HD for two years (3 × 4.0 h/week), and with uncontrolled hypertension was admitted to the Military Institute of Medicine. On examination, reduced exercise tolerance, paroxysmal nocturnal dyspnoea and blood pressure (BP) 190/90 mm Hg were found. Laboratory tests revealed NT-pro B-type natriuretic peptide 302,009.0 pg/mL (n < 300.0). Echocardiography (ECHO) showed left ventricular (LV) hypertrophy (LV mass index [LVMI] 345.81 g/m2), enlarged LV diastolic diameter [LVDD] 7.15 cm), with slightly decreased ejection fraction (EF 49%), Doppler signs of elevated cardiac output (CO 15.05 L/min; cardiac index (CI) 8.91 L/min/m2), and pseudonormalised pattern of mitral inflow with elevated LV diastolic pressure (E/E’ 31). In ultrasonographic examination of left shoulder AVF, an aneurysmal expansion of the lumen from 5.5 mm to 35 mm (Fig. 1), and significantly increased flow up to 2,532 mL/min (Fig. 2) were detected. Cardiopulmonary recirculation rate (CPR) was 0.17. Computed tomography excluded renal artery stenosis. In polysomnography, heavy central apnoea with an apnoea/hypopnoea index of 35.4/h was found. In 48-h ambulatory BP monitoring (ABPM), BP was 162/95 mm Hg. Treatment of sleep apnoea was implemented by a continuous positive airway pressure device, but this did not improve BP control. Upon discharge from hospital, the patient was overtreated with eight hypotensive drugs. After a month, HC occurred (BP 220/120 mm Hg) associated with acute coronary syndrome without ST-segment elevation. Coronarography found non-obstructive atherosclerotic plaques. Because of the suspicion of hyperkinetic state related to a lack of BP control, AVF was narrowed by implanting a polytetrafluorethylene graft of 4 mm diameter (Fig. 3). Despite AVF flow being reduced to 1,400 mL/min, after two months another HC (BP 220/125 mm Hg) with pulmonary oedema was presented. The next HC took place three months later. Although ECHO showed features of LV hypertrophy regression (LVMI 335.62 g/m2), and significant decreases of CO (8.16 L/min) and CI (4.86 L/min/m2), a decrease of EF (40%) and an LV dilatation enlargement (LVDD 7.7 cm) were also observed. AVF flow increased up to 1,750 mL/min and significant CPR 0.21 was indicated. In 24-h ABPM, BP was 173/105 mm Hg. The hypotensive treatment used has been confirmed by experts and seems to be optimal and safe for the cardiovascular system. Probably, AVF banding was performed too late, and progression of HF and lack of BP control improvement were observed. In hyperkinetic AVF, blood flow exceeds 2,000 mL/min and CPR is over 0.2–0.3. Currently, in cases of difficulties in surgical AVF creation and the necessity of haemodialysotherapy termination as a result of a lack of vascular access, banding or closure of the AVF is a very rare event. However, in some cases, early ligation of AVF may be the only effective procedure, especially when there is rapid progression of HF.

Association between C-reactive protein level and echocardiography assessed left ventricular function in first ST-segment elevation myocardial infarction patients who underwent primary coronary intervention

BackgroundAn elevated C-reactive protein (CRP) level is associated with adverse outcomes in patients with acute myocardial infarction (AMI). Although CRP levels have been shown to be associated with left ventricular (LV) systolic function and remodeling in AMI, little is known about their relation to early LV diastolic function. MethodsWe retrospectively studied 173 consecutive patients <75 years of age with first ST-segment elevation MI (STEMI) that was treated by primary percutaneous coronary intervention (PPCI). They had presented within 24h of chest pain onset and their CRP levels were determined within 6h of hospital admission. They all underwent echocardiography within 3 days of admission and were stratified by CRP tertiles. ResultsThe cut-off points for the CRP tertiles were <2.6mg/L, 2.6–7.9mg/L, and >7.9mg/L. Patients with higher CRP levels had a significantly higher mean mitral inflow E wave velocity (68±16cm/s vs 77±19cm/s vs 76±17cm/s; p=0.02), a higher E/average e′ (8.9±1.9 vs 9.8±2.8 vs 10.4±3.2; p=0.02), and a higher systolic pulmonary artery pressure (27±6mmHg vs 30±8mmHg vs 32±10mmHg; p=0.04). Elevated CRP levels were associated with more advanced diastolic dysfunction than normal CRP levels (p=0.04). The admission CRP level was an independent predictor of average E/e′ ratio (multivariate analysis). ConclusionAdmission CRP levels are associated with echocardiographic parameters of elevated LV filling pressure in patients with STEMI treated with PPCI.

Letter to the editor: “The role of short QT interval and elevated LV end-diastolic pressure in the genesis of ventricular tachycardia and fibrillation”

to the editor: We read with great interest the article by Pizzuto and associates ([4][1]) in the American Journal of Physiology-Heart and Circulatory Physiology , entitled: “Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and

Strongyloides-Associated Left Ventricular Thrombus

Aexertional dyspnea, and a history of diarrhea. Echocardiography revealed a large intracavitary thrombus occupying the apical two thirds of the left ventricular (LV) cavity (Fig 1A) and severely elevated LV filling pressures. The mitral valve was mildly thickened, with significant subvalvular tethering. Further imaging with computed tomography and magnetic resonance imaging confirmed these findings (Fig 1B, C, D). Stool samples tested positive for Strongyloides stercoralis larvae. She was taken to the operating room with the diagnosis of endomyocardial fibrosis secondary to hypereosinophilia caused by the Strongyloides infection. Right and left ventricular apical thrombus and fibrotic tissue were identified and aggressively excised. The mitral valve was immobile because of the intense reaction and involvement of the thrombus, with the subvalvular apparatus necessitating

Insulin resistance is a major determinant of myocardial blood flow impairment in anginal patients.

In patients with chest pain, stress-induced myocardial perfusion abnormalities are often the result of depressed myocardial blood flow (MBF) reserve. We investigated the relative contribution of cardiovascular risk factors and coronary atherosclerosis to MBF abnormalities in anginal patients. We studied 167 patients with typical (n = 100) or atypical (n = 67) chest pain who underwent quantitative evaluation of MBF by PET at rest and after dipyridamole infusion, and quantitative coronary angiography (invasive or by 64-slice CT). Patients with left ventricular (LV) dysfunction (ejection fraction <45%) were excluded. Coronary atherosclerosis of ≥50% was defined as obstructive. At rest median MBF was 0.60mlmin-1g-1, and after dipyridamole infusion median MBF was 1.22mlmin-1g-1. MBF reserve was <2 in 77 of 167 patients (46%). Coronary atherosclerosis was present in 67 patients (40%), 26 with obstructive disease. In a univariate analysis several variables were associated with reduced MBF at rest, including male gender, coronary atherosclerosis and elevated LV end-diastolic diameter, and during hyperaemia, including male gender, insulin resistance (IR), smoking habit, LV ejection fraction and end-diastolic diameter. In a multivariate analysis, after adjustment for LV function and for pharmacological treatments, male gender was the only independent predictor of reduced MBF at rest (P < 0.001), while male gender (P = 0.003), IR (P = 0.033) and coronary atherosclerosis (P < 0.001) remained the only independent predictors of reduced hyperaemic MBF. IR (P = 0.043) and coronary atherosclerosis (P = 0.005) were the only predictors of depressed MBF reserve. Coronary atherosclerosis, male gender and IR showed additive effects on hyperaemic MBF. In patients with chest pain and normal LV systolic function, IR, male gender and coronary atherosclerosis are independent and additive determinants of impaired hyperaemic MBF.

Abstract 486: Increased Afterload In Sub-acute Phase Of Myocardial Infarction Exacerbates Heart Failure

Background: Hypertension (HT) increases cardiac afterload and is one of the risk factors of poor prognosis after myocardial infarction (MI). However, there is little information on how HT impacts the healing processes during sub-acute phase MI. We investigated the role of an increased afterload on left ventricular (LV) performance and remodeling shortly after MI. Methods: Anterior MIs were created in 15 Yorkshire pigs via percutaneous access. To mimic HT condition, 7 pigs (Banding, n=7) underwent surgical banding of the ascending aorta 10 days after the MI, and were compared to the remaining pigs (Control, n=8). LV remodeling and function were assessed one month after MI using 3-D echocardiography and invasive hemodynamic measurements. Results: Echocardiographic assessment at day 10 revealed no significant differences in LV ejection fraction (EF) or LV volumes. One month after MI, aortic banding increased the systemic vascular resistance index, but was not statistically significant (1658±282 dyn/s/cm5/m 2 vs 1153±658 dyn/s/cm5/m 2 , P=0.08). Banding group presented with significantly impaired LVEF (Figure, P=0.002), larger end systolic volume (Figure, P=0.045), lower cardiac index (3.1±0.9 L/min/m 2 vs 4.4±0.6 L/min/m 2 , P=0.01), and elevated LV end diastolic pressure (22.4±5.0 mmHg vs 14.4±7.5 mmHg: P=0.04, Banding vs Control, respectively). Reduced EF was associated with remote myocardial dysfunction and histological analysis revealed increased interstitial fibrosis in this area. Conclusion: Increased afterload in sub-acute phase of MI induces more severely impaired cardiac function and LV remodeling, and was associated with worse heart failure status.

Systemic Hypertension in Low-Gradient Severe Aortic Stenosis With Preserved Ejection Fraction

Low-gradient severe aortic stenosis with preserved ejection fraction is an increasingly recognized entity, and symptomatic patients may benefit from aortic valve replacement. However, systemic hypertension frequently coexists with low-gradient severe aortic stenosis, which itself may cause elevated left ventricular (LV) filling pressures with resultant symptoms of dyspnea. Symptomatic patients with hypertension (aortic systolic pressure >140 mm Hg) and low-gradient (mean gradient <40 mm Hg) severe aortic stenosis (aortic valve area <1 cm(2)) with preserved ejection fraction (ejection fraction >50%) who underwent invasive hemodynamic catheterization of the left and right sides of the heart received infusion of intravenous sodium nitroprusside to reduce blood pressure and arterial afterload. At baseline, patients had severe hypertension (aortic systolic pressure, 176±26 mm Hg), pulmonary hypertension (mean pressure, 39±12 mm Hg), elevated LV end-diastolic pressure (19±5 mm Hg), and reduced stroke volume (33±8 mL/m(2)). All measures of afterload were reduced with nitroprusside (P<0.001 for all). Nitroprusside reduced mean pulmonary artery pressure (25±10 mm Hg) and LV end-diastolic pressure (11±5 mm Hg; P<0.001 for both compared with baseline). Aortic valve area (0.86±0.11 to 1.02±0.16 cm(2); P=0.001) and mean gradient (27±5 to 29±6 mm Hg; P=0.02) increased with nitroprusside. Systemic hypertension in low-gradient severe aortic stenosis with preserved ejection fraction is associated with elevated LV filling pressures and pulmonary hypertension. Treatment of hypertension with vasodilator therapy results in a lowering of the total LV afterload, with a decrease in LV filling pressures and pulmonary artery pressures. These findings have important implications for the management of patients with low-gradient severe aortic stenosis with preserved ejection fraction and hypertension.

Left ventricular hypertrophy is associated with the risk of sudden cardiac death

Aims: The echocardiographic identification of risk markers may enhance risk stratification for the development of sudden cardiac death (SCD). However, the value of left ventricular (LV) hypertrophy in the prediction for the risk for SCD is not well known. Methods and results: Echocardiography with the assessment of LV mass was defined in a representative population-based sample of 906 men (age 42-61 years). During an average follow-up period of 20.2 years (interquartile range 18.8-21.3 years), 66 SCDs occurred. The hazard ratio (HR) for SCD was 1.10 (95% confidence interval, CI 1.06-1.15, p<0.001) for each 10 g increment in LV mass, after adjustment for age, alcohol consumption, cigarette smoking, serum low and high density lipoprotein cholesterol, systolic blood pressure, type 2 diabetes, body mass index, high sensitivity C-reactive protein, previous myocardial infarction and cardiorespiratory fitness. Men with elevated LV mass of over 253 grams (highest quartile) had a 3.24-fold (95% CI 1.52 to 6.91, p=0.002) adjusted HR for an SCD as compared to those with LV mass of less than 186 grams (lowest quartile). After additional adjustment for LV function, the relation between LV mass and SCD remained statistically significant in the highest quartile of LV mass (HR 2.72, 95% CI 1.25 to 5.96, p=0.012). The risk for SCD was increased in 175 men with an indexed LV mass of over 125 g/m2 (3.25-fold, 95% CI 1.94 to 5.43, p<0.001). The integrated discrimination index was 0.094 (p=0.0002) indicating the significant level of discrimination improvement with LV mass. Conclusion: LV mass provides an incremental predictive value for SCD beyond that of other well-known risk factors. This study provides evidence that LV hypertrophy improves risk stratification for SCD in the general male population.

Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and sudden cardiac death

Many survivors of sudden cardiac death (SCD) have normal global ventricular function and severe coronary artery disease but no evidence of symptomatic ischemia or infarction before the development of lethal ventricular arrhythmias, and the trigger for ventricular tachycardia (VT)/ventricular fibrillation (VF) remains unclear. We sought to identify the role of spontaneous ischemia and temporal hemodynamic factors preceding SCD using continuous telemetry of left ventricular (LV) pressure and the ECG for periods up to 5 mo in swine (n = 37) with hibernating myocardium who experience spontaneous VT/VF in the absence of heart failure or infarction. Hemodynamics and ST deviation at the time of VT/VF were compared with survivors with hibernating myocardium as well as sham controls. All episodes of VT/VF occurred during sympathetic activation and were initiated by single premature ventricular contractions, and the VT degenerated into VF in ∼ 30 s. ECG evidence of ischemia was infrequent and no different from those that survived. Baseline hemodynamics were no different among groups, but LV end-diastolic pressure during sympathetic activation was higher at the time of SCD (37 ± 4 vs. 26 ± 4 mmHg, P < 0.05) and the ECG demonstrated QT shortening (155 ± 4 vs. 173 ± 5 ms, P < 0.05). The week before SCD, both parameters were no different from survivors. These data indicate that there are no differences in the degree of sympathetic activation or hemodynamic stress when VT/VF develops in swine with hibernating myocardium. The transiently elevated LV end-diastolic pressure and QT shortening preceding VT/VF raises the possibility that electrocardiographically silent subendocardial ischemia and/or mechanoelectrical feedback serve as a trigger for the development of SCD in chronic ischemic heart disease.