Changes In Left Ventricular End-diastolic Pressure Research Articles

Prophylactic furosemide to prevent transfusion-associated circulatory overload: a randomized controlled study in rats

Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion related morbidity and mortality. The only treatment is empirical use of furosemide. Our aim was to investigate if furosemide can prevent TACO. A randomized controlled trial was performed using a previously validated two-hit rat model for TACO. Volume incompliance was induced (first hit) in anemic, anesthetized Lewis rats. Rats were randomized to placebo, low-dose (5 mg kg−1) or high-dose (15 mg kg−1) furosemide-administered prior to transfusion (second-hit) and divided over two doses. Primary outcome was change in left-ventricular end-diastolic pressure (∆LVEDP) pre- compared to post-transfusion. Secondary outcomes included changes in preload, afterload, contractility and systemic vascular resistance, as well as pulmonary outcomes. Furosemide treated animals had a significantly lower ∆LVEDP compared to placebo (p = 0.041), a dose–response effect was observed. ∆LVEDP in placebo was median + 8.7 mmHg (IQR 5.9–11), + 3.9 (2.8–5.6) in the low-dose and 1.9 (− 0.6 to 5.6) in the high-dose group. The effect of furosemide became apparent after 15 min. While urine output was significantly higher in furosemide treated animals (p = 0.03), there were no significant changes in preload, afterload, contractility or systemic vascular resistance. Furosemide rapidly and dose-dependently decreases the rise in hydrostatic pulmonary pressure following transfusion, essential for preventing TACO.

Instantaneous wave-free ratio and fractional flow reserve: effect of variation in left ventricular end diastolic pressure

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Among patients with intermediate coronary artery stenosis (50-90%), assessment of functional significance of the lesion by instantaneous wave free ratio (iFR)/ fractional flow reserve (FFR) is recommended in latest guidelines. Though iFR is not much affected by change in hemodynamics compared to FFR, the change in iFR vs FFR due to various hemodynamic factors need a validation. Left ventricular end-diastolic pressure (LVEDP) is one of the hemodynamic factors whose variation and effect on FFR vs iFR is largely unknown. In the present study we evaluated the association of change in LVEDP on the changing pattern of iFR/FFR which may hold a clinical significance especially with percutaneous coronary intervention in heart failure patients. Methods This was a prospective, investigator-initiated, single-center study involving 20 patients with stable coronary artery disease and at least one intermediate coronary lesion (50-90%). The enrolled patients were subjected to both iFR and FFR along with baseline LVEDP measurement. Subsequently, intravenous nitroglycerine infusion was given to reduce LVEDP and corresponding iFR and FFR were re-evaluated. The dynamic changes in iFR and FFR were studied in relation to changes in LVEDP using Pearson’s correlation analysis and linear regression analysis. Results The mean LVEDP was lowered from 16.20 ± 1.54 mmHg to 9.50 ± 1.10 mmHg, the mean iFR and FFR got changed from 0.80 ± 0.12 to 0.76 ± 0.12 mmHg and 0.75 ± 0.09 to 0.72 ± 0.09 mmHg respectively. On Pearson’s correlation analysis, LVEDP change did not show statistically significant correlation (linear relationship) with iFR (p = 0.105, r2 = 0.373) and FFR (p = 0.227, r2 = 0.283) changes across the entire range of stenosis severity and in all vessels. Linear regression analysis did not state any independent correlation between LVEDP and iFR and FFR changes in the study group (p >0.05). The % R2 value for iFR and FFR (as a coefficient of determination) of the regression equation were 13.9% and 8%, which means only these percentages of the total variance in iFR and FFR change were explained by LVEDP changes respectively. There was no serious adverse event related to the procedure. Conclusion To the best of our knowledge, this is the first study comparing the effect of changes in LVEDP on both iFR and FFR simultaneously. In our study, 1 mmHg change in LVEDP was associated with a change in FFR by 0.004 and change in iFR by 0.004 which didn’t reveal any significant association (p = 0.227 and 0.105 respectively). This helps us to put FFR at par with iFR under variable hemodynamics. So either of the variables may be used interchangeably with confidence in varied hemodynamic conditions including patients with heart failure. The correlation was non-significant across entire range of stenosis severity, irrespective of sex, age, diabetes and hypertension. This study sets platform for further research with larger number of heterogeneous patient population. Abstract Figure. Box whisker plot

Abstract 10792: Immediate Reduction in Left Ventricular End-Diastolic Pressure During Alcohol Septal Ablation in Patients with Hypertrophic Obstructive Cardiomyopathy

Introduction: Alcohol septal ablation (ASA) is an elective nonsurgical procedure proven to be effective for patients with hypertrophic obstructive cardiomyopathy (HOCM). The intraprocedural change in left ventricular end-diastolic pressure (LVEDP) is unknown. In this study we assessed the hypothesis that LVEDP decreases immediately post ablation during ASA in patients with HOCM independently of the effects of sedation and heart rate. Methods: We retrospectively identified 133 elective ASA procedures for patients with HOCM between 2015 and 2021 at our institution using an internally maintained database. Pre- and post-ablation LVEDP measurements were taken using the pressure tracing corresponding with end-expiratory R wave of the ECG tracing. LVEDP was recorded for post-“a” wave points on the pressure tracing at three distinct points during the procedure: the immediate start of the procedure (Group A), prior to alcohol injection after sedation had taken effect (Group B), and post ablation (Group C). Heart rate (HR) and left ventricular outflow tract gradient (LVOTG) were obtained from the catheterization report. Paired t-tests, ANOVA, and regression analyses were performed using SPSS Statistics. Results: The average patient age was 64 years old; mean NYHA Class 2.7; and 67% were women. There was no difference between LVEDP of Groups A and B (32mmHg, 32mmHg, p=0.92). LVEDP between Groups A and C (32mmHg, 26mmHg, respectively; p<0.001) and Groups B and C (32mmHg, 26mmHg, respectively; p<0.001) were significantly different. There was no correlation between HR and LVEDP for the groups (R2A=0.002, R2B=0.000, R2C=0.054), and similarly, no correlation between the average change in LVEDP and the change in resting or provoked LVOTG (R2=0.033, R2=0.003, respectively). Conclusions: These results support that alcohol septal ablation causes an immediate reduction in LVEDP post-ablation independent of heart rate, reduction in LVOTG, and effects of sedation. In conclusion, this instantaneous change in LVEDP may account for the immediate resolution in symptoms reported by patients with HOCM undergoing ASA.

Natural shear wave propagation speed is influenced by both changes in myocardial structural properties as well as loading conditions

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation - Flanders (FWO) Background Shear wave elastography (SWE) is a promising tool for the non-invasive assessment of myocardial stiffness. It is based on the evaluation of the propagation speed of shear waves by high frame rate echocardiography. These waves can be induced by for instance mitral valve closure (MVC) and the speed at which they travel is related to the instantaneous stiffness of the myocardium. Myocardial stiffness is defined by the local slope of the stress-strain relation and can therefore be altered by both changes in structural properties of the myocardium as well as loading conditions. Purpose The aim of this study was to investigate how changes in myocardial structural properties as well as loading conditions affect shear wave speed after MVC. Methods Until now, 8 pigs (weight: 33.6 ± 5.4 kg) were included. The following interventions were performed: 1) preload was reduced by balloon occlusion of the vena cava inferior, 2) afterload was increased by balloon occlusion of descending aorta, 3) preload was increased by intravenous administration of 500 ml of saline and 4) ischemia/reperfusion injury (I/R injury) was induced in the septal wall by balloon occlusion of the LAD for 90 min. with subsequent reperfusion for 40 min. Echocardiographic and left ventricular pressure recordings were simultaneously obtained during each intervention. Left ventricular parasternal long-axis views were acquired with an experimental high frame rate ultrasound scanner (average frame rate: 1279 ± 148 Hz). Shear waves were visualized on tissue acceleration maps by drawing an M-mode line along the interventricular septum. Shear wave propagation speed after MVC was calculated by assessing the slope of the wave pattern on the tissue acceleration map (Figure A). Results The change in left ventricular end-diastolic pressure (LVEDP) and shear wave speed after MVC between baseline and each intervention are shown in Figure B and C, respectively. Preload reduction resulted in significant lower LVEDP compared to baseline (p < 0.01), while the other loading changes did not have a significant effect. Shear wave speed after MVC significantly increased by afterload and preload increase (p < 0.01). I/R injury resulted in increased shear wave speed (p < 0.01) without significantly altering LVEDP. There was a good positive correlation between the change in LVEDP and the change in shear wave speed induced by loading changes (r = 0.76; p < 0.001) (Figure D). However, the correlation became less strong if data of I/R injury was taken into account as well (r = 0.63; p < 0.001). Conclusion Our results suggest that SWE is capable to characterize myocardial tissue properties and besides has the potential as a novel method for the estimation of left ventricular filling pressures. However, in the presence of structural changes of the myocardium, care should be taken when estimating filling pressures based on shear wave propagation speed. Abstract Figure.

Change in Left Ventricular End Diastolic Pressure (LVEDP) as apredictor of Adverse Effect in Patients undergoing Primary PCI

Background: in acute myocardial infarction (MI), decreasing compliance of the left ventricle is directly associated with prognosis. Patients and Methods: 30 patients presented with acute ST segment elevation MI Who underwent primary PCI within 12 hours of presentation. All patients were subjected to full history taking, physical examination, serial ECG, cardiac enzymes and measurement of LVEDP just before and after Primary PCI using end hole catheter. Results: post revascularization left ventricular end diastolic pressure (LVEDP) decreased. There is significant correlation between LVEDP change and left ventricular dysfunction (p value:0.014). Significant correlation between LVEDP and mortality are present. Conclusion: change in LVEDP measured just pre and post primary PCI are significantly correlated with adverse clinical outcome in patients with acute STEMI.

Preload-corrected dynamic Starling mechanism in patients with heart failure with preserved ejection fraction.

10.9 ± 3.8 vs. 11.2 ± 1.3 mmHg, P = 1.00). Transfer function analysis between diastolic pulmonary artery pressure (PAD) representing dynamic changes in LVEDP vs. SV index was applied to obtain gain and coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than in the controls, even at a similar level of LVEDP (0.46 ± 0.19 vs. 0.99 ± 0.39 ml·m-2·mmHg-1, P = 0.0018). Moreover, the power spectral density of PAD, the input variability, was greater in the HFpEF group than the controls (0.75 ± 0.38 vs. 0.28 ± 0.26 mmHg2, P = 0.01). Conversely, the power spectral density of SV index, the output variability, was not different between the groups ( P = 0.97). There was no difference in the coherence, which confirms the reliability of the linear transfer function between the two groups (0.71 ± 0.13 vs. 0.77 ± 0.19, P = 0.87). The DSM gain in HFpEF patients is impaired compared with age-matched controls even at a similar level of LVEDP, which may reflect intrinsic LV diastolic dysfunction and incompetence of ventricular-arterial coupling. NEW & NOTEWORTHY The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. Although the DSM gain is impaired in heart failure with preserved ejection fraction (HFpEF) patients, it is not clear whether this is because of higher LVEDP or left-ventricular diastolic dysfunction. The DSM gain in HFpEF patients is severely impaired, even at a similar level of LVEDP, which may reflect intrinsic left-ventricular diastolic dysfunction.

Low level exercise echocardiography helps diagnose early stage heart failure with preserved ejection fraction: a study of echocardiography versus catheterization.

Increased left ventricular end-diastolic pressure (LVEDP) with exercise is an early sign of heart failure with preserved left ventricular ejection fraction (LVEF). The abnormal exercise increase in LVEDP is nonlinear, with most change occurring at low-level exercise. Data on non-invasive approach of this condition are scarce. Our objective was assessing E/e' to estimate low level exercise LVEDP using a direct invasive measurement as the reference method. Sixty patients with LVEF>50% prospectively underwent both exercise cardiac catheterization and echocardiography. E/e' was measured at rest and during low-level exercise. Abnormal LVEDP was defined as>16mmHg. Patients with a history of coronary artery disease and/or abnormal LV morphology were classified as having apparent cardiac disease (CD). Thirty-four (57%) patients had elevated LVEDP only during exercise. Most of the change in LVEDP occurred since the first exercise level (25 W). There was a correlation between LVEDP and septal E/e' at rest and during exercise. Lateral E/e' and E/average e' ratio had worse correlations with LVEDP. In the whole population, exercise septal E/e' at 25 W had the best accuracy for abnormal exercise LVEDP, area under curve (AUC)=0.79. However, while low-level exercise septal E/e' had a high accuracy in CD patients (n=26, AUC=0.96), E/e' was not linked to LVEDP in patients without CD (n=34). Low-level exercise septal E/e' is valuable for predicting abnormal exercise LVEDP in patients with preserved LVEF and apparent CD. However, this new diagnosis approach appears not reliable in patients with normal LV morphology and without coronary artery disease. https://clinicaltrials.gov . Unique identifier: NCT01714752.

Effect of transcatheter aortic valve implantation on intraoperative left ventricular end-diastolic pressure.

Transcatheter aortic valve implantation (TAVI) for patients with aortic stenosis is a less invasive alternative to surgical aortic valve replacement. Despite this, careful anesthetic management, especially strict control of blood pressure and fluid management, is necessary. During TAVI, normalization of left ventricular afterload due to aortic balloon valvuloplasty and prosthetic valve deployment is expected to result in rapid improvement of systolic function and consequent improvement in diastolic function. However, the early effect of TAVI on left ventricular diastolic function is less clear. We hypothesized that TAVI induces a rapid decrease in left ventricular end-diastolic pressure (LVEDP) after valve deployment. This retrospective observational study included 71 patients who had undergone TAVI using the transfemoral approach with a balloon-expandable valve under general anesthesia. Intraoperative LVEDP was measured using an intracardiac catheter. The severity of residual aortic regurgitation (AR) was assessed using the Sellers criteria. The mean (SD) LVEDP was 17.8 (5.3) mmHg just before TAVI and increased significantly to 27.3 (8.2) mmHg immediately after prosthetic valve deployment (p<0.0001). The change in LVEDP was 8.7 (8.6) mmHg in patients with low residual AR (Sellers ≤1) and 11.0 (7.1) mmHg in those with high residual AR (Sellers ≥2); however, this difference was not significant. No correlation was found between the LVEDP change and intraoperative fluid balance. In conclusion, LVEDP increased significantly in the early period after valve deployment during TAVI, regardless of residual AR severity. It was suggested that the tolerability of fluid load could be reduced at that time.

Two Distinct Responses of Left Ventricular End-Diastolic Pressure to Leg-Raise Exercise in Euvolemic Patients with Exertional Dyspnea.

Background and ObjectivesFew studies have invasively assessed diastolic functional reserve and serial changes in left ventricular hemodynamics in euvolemic patients with exertional dyspnea. In this study, sequential changes in left ventricular end-diastolic pressure (LVEDP) to leg-raise exercise were measured invasively in patients with early heart failure with preserved ejection fraction (HFpEF) to determine the association between these serial changes and echocardiographic results or clinical features.Subjects and MethodsDuring their hospital stay, 181 patients with early HFpEF underwent left cardiac catheterization, coronary angiography, and transthoracic echocardiography (TTE). Leg-raise exercise was performed in two stages: during cardiac catheterization and again during TTE.ResultsCompared with the initial values, all the invasively measured LVEDP values increased significantly during the leg-raise exercise, whereas the septal e/e' ratio remained unchanged. Active leg-raise led to increased LVEDP, which caused dyspnea. The severity of symptoms correlated with the level and extent of changes in LVEDP. At the end of active leg-raise, LVEDP decreased in 40 patients (22.1%), who were younger and had significantly lower e/e' ratios. On multivariate analysis to predict the response of LVEDP to active leg-raise, age and the septal e/e' ratio remained significant predictors.ConclusionDespite having similar LVEDP values at rest, patients may respond to exercise with different LVEDP levels and clinical manifestations, depending on their diastolic capacity. The leg-raise exercise in early HFpEF can elucidate individual diastolic profiles, and the LVEDP response to the leg-raise test may serve as a useful criterion in stratifying patients with early HFpEF with respect to functional reserve.

Coronary Blood Flow in Patients With Severe Aortic Stenosis Before and After Transcatheter Aortic Valve Implantation

Patients with severe aortic stenosis and no obstructed coronary arteries are reported to have reduced coronary flow. Doppler evaluation of proximal coronary flow is feasible using transesophageal echocardiography. The present study aimed to assess the change in coronary flow in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). The left main coronary artery was visualized using transesophageal echocardiography in 90 patients undergoing TAVI using the Edwards SAPIEN valve. The peak systolic and diastolic velocities of the coronary flow and the time-velocity integral were obtained before and after TAVI using pulse-wave Doppler. Mean aortic gradients decreased from 47.1 ± 15.7 mm Hg before TAVI to 3.6 ± 2.6 mm Hg after TAVI (p <0.001). The aortic valve area increased from 0.58 ± 0.17 to 1.99 ± 0.35 cm(2) (p <0.001). The cardiac output increased from 3.4 ± 1.1 to 3.8 ± 1.0 L/min (p <0.001). Left ventricular end-diastolic pressure (LVEDP) decreased from 19.8 ± 5.4 to 17.3 ± 4.1 mm Hg (p <0.001). The following coronary flow parameters increased significantly after TAVI: peak systolic velocity 24.2 ± 9.3 to 30.5 ± 14.9 cm/s (p <0.001), peak diastolic velocity 49.8 ± 16.9 to 53.7 ± 22.3 cm/s (p = 0.04), total velocity-time integral 26.7 ± 10.5 to 29.7 ± 14.1 cm (p = 0.002), and systolic velocity-time integral 6.1 ± 3.7 to 7.7 ± 5.0 cm (p = 0.001). Diastolic time-velocity integral increased from 20.6 ± 8.7 to 22.0 ± 10.1 cm (p = 0.04). Total velocity-time integral increased >10% in 43 patients (47.2%). Pearson's correlation coefficient revealed the change in LVEDP as the best correlate of change in coronary flow (R = -0.41, p = 0.003). In conclusion, TAVI resulted in a significant increase in coronary flow. The change in coronary flow was associated mostly with a decrease in LVEDP.

Transauricular embolization of the rabbit coronary artery for experimental myocardial infarction: comparison of a minimally invasive closed-chest model with open-chest surgery

IntroductionTo date, most animal studies of myocardial ischemia have used open-chest models with direct surgical coronary artery ligation. We aimed to develop a novel, percutaneous, minimally-invasive, closed-chest model of experimental myocardial infarction (EMI) in the New Zealand White rabbit and compare it with the standard open-chest surgical model in order to minimize local and systemic side-effects of major surgery.MethodsNew Zealand White rabbits were handled in conformity with the "Guide for the Care and Use of Laboratory Animals" and underwent EMI under intravenous anesthesia. Group A underwent EMI with an open-chest method involving surgical tracheostomy, a mini median sternotomy incision and left anterior descending (LAD) coronary artery ligation with a plain suture, whereas Group B underwent EMI with a closed-chest method involving fluoroscopy-guided percutaneous transauricular intra-arterial access, superselective LAD catheterization and distal coronary embolization with a micro-coil. Electrocardiography (ECG), cardiac enzymes and transcatheter left ventricular end-diastolic pressure (LVEDP) measurements were recorded. Surviving animals were euthanized after 4 weeks and the hearts were harvested for Hematoxylin-eosin and Masson-trichrome staining.ResultsIn total, 38 subjects underwent EMI with a surgical (n = 17) or endovascular (n = 21) approach. ST-segment elevation (1.90 ± 0.71 mm) occurred sharply after surgical LAD ligation compared to progressive ST elevation (2.01 ± 0.84 mm;p = 0.68) within 15-20 min after LAD micro-coil embolization. Increase of troponin and other cardiac enzymes, abnormal ischemic Q waves and LVEDP changes were recorded in both groups without any significant differences (p > 0.05). Infarct area was similar in both models (0.86 ± 0.35 cm in the surgical group vs. 0.92 ± 0.54 cm in the percutaneous group;p = 0.68).ConclusionThe proposed model of transauricular coronary coil embolization avoids thoracotomy and major surgery and may be an equally reliable and reproducible platform for the experimental study of myocardial ischemia.

Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism

Sedentary aging leads to increased cardiovascular stiffening, which can be ameliorated by sufficient amounts of lifelong exercise training. An even more extreme form of cardiovascular stiffening can be seen in heart failure with preserved ejection fraction (HFpEF), which comprises ~40~50% of elderly patients diagnosed with congestive heart failure. There are two major interrelated hypotheses proposed to explain heart failure in these patients: 1) increased left ventricular (LV) diastolic stiffness and 2) increased arterial stiffening. The beat-to-beat dynamic Starling mechanism, which is impaired with healthy human aging, reflects the interaction between ventricular and arterial stiffness and thus may provide a link between these two mechanisms underlying HFpEF. Spectral transfer function analysis was applied between beat-to-beat changes in LV end-diastolic pressure (LVEDP; estimated from pulmonary artery diastolic pressure with a right heart catheter) and stroke volume (SV) index. The dynamic Starling mechanism (transfer function gain between LVEDP and the SV index) was impaired in HFpEF patients (n = 10) compared with healthy age-matched controls (n = 12) (HFpEF: 0.23 ± 0.10 ml·m⁻²·mmHg⁻¹ and control: 0.37 ± 0.11 ml·m⁻²·mmHg⁻¹, means ± SD, P = 0.008). There was also a markedly increased (3-fold) fluctuation of LV filling pressures (power spectral density of LVEDP) in HFpEF patients, which may predispose to pulmonary edema due to intermittent exposure to higher pulmonary capillary pressure (HFpEF: 12.2 ± 10.4 mmHg² and control: 3.8 ± 2.9 mmHg², P = 0.014). An impaired dynamic Starling mechanism, even more extreme than that observed with healthy aging, is associated with marked breath-by-breath LVEDP variability and may reflect advanced ventricular and arterial stiffness in HFpEF, possibly contributing to reduced forward output and pulmonary congestion.

Echocardiographic Predictors of Change in Left Ventricular Diastolic Pressure in Heart Failure Patients Receiving Nesiritide

To evaluate the usefulness of currently accepted echocardiographic parameters of diastolic function to assess the acute change in left ventricular end-diastolic pressure (LVEDP) following the administration of nesiritide in a heart failure population. In 25 heart failure patients (15 with systolic dysfunction, 10 with preserved ejection fraction [EF]), Doppler echocardiography, right and left heart catheterization, and invasive biventricular pressure hemodynamics were obtained at baseline and 30 minutes after nesiritide infusion. Twenty-four patients had sufficient echocardiographic images for analysis. The mean age was 60 +/- 11 years, 48% were male, 56% had coronary artery disease, and 64% had hypertension. Right ventricular systolic pressure (RVSP) had the highest correlation with LV filling pressure: pulmonary capillary wedge pressure (PCWP), pre-A wave LV, and LVEDP (r = 0.66, P = 0.0009; r = 0.63, P = 0.002; r = 0.72, P = 0.0002, respectively). Following nesiritide administration, the mean PCWP decreased from 17.1 +/- 7.8 mmHg at baseline to 9.6 +/- 6.2 mmHg (P < 0.001). Change in RVSP had the highest correlation with change in PCWP (r =-0.67, P = 0.10) and change in LVEDP (r =-0.71, P = 0.07). Echocardiographic parameters are frequently assessed in attempts to estimate left heart diastolic pressures. In heart failure patients, RVSP appears to be the best predictor of LVEDP, outperforming tissue Doppler E/E'. RVSP was found to be the best echocardiographic predictor of change in LV filling pressure with intravenous vasodilator therapy in heart failure patients. RVSP may provide a noninvasive means of assessing response to cardiac therapy.

Effect of Successful Alcohol Septal Ablation on Microvascular Function in Patients With Obstructive Hypertrophic Cardiomyopathy

We hypothesized that relief of obstruction in patients with hypertrophic cardiomyopathy (HC) by percutaneous transluminal septal myocardial ablation (PTSMA) improves microvascular dysfunction by relief of extravascular compression. Microvascular dysfunction in obstructive HC is related to extravascular compression by increased left ventricular (LV) mass and LV end-diastolic pressure. The study included 14 patients with obstructive HC (mean age 55+/-12 years, 11 men) who underwent successful PTSMA and 14 healthy volunteers (mean age 31+/-4 years, 11 men). LV hemodynamics (by Doppler echocardiography) and intramyocardial flow dynamics (by adenosine myocardial contrast echocardiography) were evaluated in healthy volunteers and before and 6 months after PTSMA in patients with HC. LV end-diastolic pressure was estimated from the ratio of transmitral early LV filling velocity to early diastolic mitral annular velocity. PTSMA reduced the invasively measured LV outflow tract gradient (119+/-35 vs 17+/-16 mm Hg, p<0.0001) and LV end-diastolic pressure (23+/-3 vs 16+/-2 mm Hg, p<0.001). Six months after PTSMA, myocardial flow reserve improved (2.73+/-0.56 vs 3.21+/-0.49, p<0.001), but did not normalize compared with healthy controls (vs 3.95+/-0.77, p<0.001). Also, septal hyperemic endo-to-epi myocardial blood flow ratio improved (0.70+/-0.11 vs 0.92+/-0.07, p<0.001). Changes in LV end-diastolic pressure, LV mass index, and LV outflow tract peak systolic gradient correlated well with changes in hyperemic perfusion (all p<0.05). In conclusion, microvascular dysfunction improves after PTSMA due to relief of extravascular compression forces.

Mechanosensitive cardiac C-fiber response to changes in left ventricular filling, coronary perfusion pressure, hemorrhage, and volume expansion in rats.

Left ventricular (LV) end-diastolic pressure (LVEDP) increase due to volume expansion (VExp) enhances mechanosensitive vagal cardiac afferent C-fiber activity (CNFA), thus decreasing renal sympathetic nerve activity (RSNA). Hypotensive hemorrhage (hHem) attenuates RSNA despite decreased LVEDP. We hypothesized that CNFA increases with any change in LVEDP. Coronary perfusion pressure (CPP), supposedly affected in both conditions, might also be a stimulus of CNFA. VExp and hHem were performed in anesthetized male Sprague-Dawley rats while blood pressure, heart rate, and RSNA were measured. Cervical vagotomy abolished RSNA response in both reflex responses. Single-unit CNFA was recorded while LVEDP was changed. Rapid changes (+/- 4, +/-6, +/-8 mmHg) were obtained by graded occlusion of the caval vein and descending aorta. Prolonged changes were obtained by VExp and hHem. Furthermore, CNFA was recorded in a modified Langendorff heart while CPP was changed (70, 100, 40 mmHg). Rapid LVEDP changes increased CNFA [caval vein occlusion: +16 +/- 3 Hz (approximately +602%); aortic occlusion: +15 +/- 3 Hz (approximately +553%); 70 units; P < 0.05]. VExp and hHem (n = 6) increased CNFA [VExp: +10 +/- 4 Hz (approximately +1,033%); hHem: +10 +/- 2 Hz (approximately +1,225%); P < 0.05]. An increase in CPP increased CNFA [+2 +/- 1 Hz (approximately +225%); P < 0.05], whereas a decrease in CPP decreased CNFA [-0.8 +/- 0.4 Hz (approximately -50%); P < 0.05]. All C fibers recorded originated from the LV. CNFA increased with any LVEDP change but changed equidirectionally with CPP. Thus neither LVEDP nor CPP fully accounts directly for afferent C-fiber and reflex sympathetic responses. The intrinsic afferent stimuli and receptive fields accounting for reflex sympathoinhibition still remain cryptic.

Biphasic changes in left ventricular end-diastolic pressure during dynamic exercise in patients with nonobstructive hypertrophic cardiomyopathy

OBJECTIVES The aim of this study was to clarify the serial changes in left ventricular (LV) end-diastolic pressure (LVEDP) during dynamic exercise in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND Although HCM is characterized by impaired resting LV diastolic function, serial changes in LVEDP during exercise have not been characterized. METHODS We simultaneously measured LV pressure and LV dimensions during symptom-limited supine bicycle exercise in 5 healthy individuals and 20 patients with HCM. Exercise thallium-201 scintigraphic studies were also performed. RESULTS The LVEDP (baseline: 12 ± 5 mm Hg) progressively increased to a maximum value at peak exercise (28 ± 8 mm Hg) in 11 patients with HCM (group I). In the remaining nine patients with HCM (group II), changes in LVEDP during exercise were biphasic, with an initial progressive increase and a subsequent gradual decline up to peak exercise (14 ± 4 mm Hg at baseline, 27 ± 5 mm Hg at the critical heart rate, 16 ± 3 mm Hg at peak exercise). Exercise-induced changes in LV dimensions and LV peak systolic pressures were similar in both groups. However, the maximum first derivative of LV pressure was greater and the LV pressure half-time was shorter in group II than in group I at a similar peak exercise heart rate. The biphasic changes in LVEDP disappeared by pretreatment with propranolol. The LV hypertrophy scores were higher in group I than in group II. Exercise thallium-201 images showed more severe perfusion defects in group I than in group II patients. CONCLUSIONS The biphasic changes in LVEDP seen during exercise may be related to improved coronary microcirculation in response to beta-adrenergic stimulation in patients with mild to moderate HCM.

Evolving changes in Doppler mitral flow velocity pattern in rats with hypertensive hypertrophy

OBJECTIVESThe aim of our study was to explore evolving changes in a mitral flow velocity pattern (MFVP) and its hemodynamic and pathological correlates in hypertensive rats in an isolated diastolic heart failure model.BACKGROUNDDevelopment of left ventricular (LV) hypertrophy and concomitant diastolic dysfunction cause heart failure in hypertensive hearts even with normal systolic function; however, associated evolving change in MFVP is still unclear.METHODSMitral flow velocity pattern was recorded every 2 weeks from 7 to 19 weeks in six hypertensive rats. Hemodynamic and pathological correlates of Doppler mitral flow indexes were examined as an additional part of the study using the hypertensive rats at the age of 13 weeks (compensatory stage, n = 7) and at 19 weeks (heart failure stage, n = 8).RESULTSInitial development of pressure overload LV hypertrophy resulted in a decrease in early diastolic filling wave (E), a reciprocal increase in the filling wave due to atrial contraction (A) and prolongation of deceleration time of E wave (relaxation abnormality pattern). These changes were associated with an increase in tau, an index of LV relaxation, but without a change in LV end-diastolic pressure. Transition to congestive heart failure caused an increase in E, a decrease in A and shortening of deceleration time. These changes were not associated with further increase in tau but with elevation of LV end-diastolic pressure, reflecting marked LV hypertrophy and myocardial fibrosis.CONCLUSIONSDevelopment of pressure overload LV hypertrophy is associated with evolving changes in MFVP from normal to relaxation abnormality pattern and, in turn, to pseudonormalized to restrictive pattern. Analysis of MFVP may be useful to follow not only functional but also constitutional changes of the myocardium in hypertensive hearts.

Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol

Background Chronic heart failure causes disturbances in ventilation and pulmonary gas transfer that participate in limiting peak exercise oxygen uptake (VO 2p ). The β-adrenergic receptor blocker carvedilol improves left ventricular (LV) function and not VO 2p . This study was aimed at investigating the pulmonary response to changes in LV performance produced by carvedilol in patients with chronic heart failure. Methods Twenty-one patients with New York Heart Association class II to III heart failure were randomly assigned (2 to 1) to carvedilol (25 mg twice daily, n = 14) or placebo (n = 7) for 6 months. Rest forced expiratory volume (FEV 1 ), vital capacity, total lung capacity, carbon monoxide diffusing capacity, its alveolar-capillary membrane component, pulmonary venous and transmitral flows (for monitoring changes in LV end-diastolic pressure), LV diastolic and systolic dimensions, stroke volume, ejection fraction, and fiber shortening velocity were measured at baseline and at 3 and 6 months. VO 2p , peak ratio of dead space to tidal volume (VD/VT p ), ventilatory equivalent for carbon dioxide production (VE/VCO 2 ), and VO 2 at anaerobic threshold (VO 2at ) were also determined. Results FEV 1 , vital capacity, total lung capacity, carbon monoxide diffusing capacity, and the alveolar-capillary membrane component were impaired in chronic heart failure compared with 14 volunteers and did not vary with treatment. Carvedilol reduced end-diastolic pressure, end-diastolic diameter, and end-systolic diameter and increased ejection fraction, stroke volume, and fiber shortening velocity without affecting VO 2p , VO 2at , VD/VT p , or VE/VCO 2 at 3 and 6 months. Placebo did not produce significant changes. Conclusions In chronic heart failure carvedilol ameliorates LV function at rest and does not significantly affect ventilation and pulmonary gas transfer or functional capacity. These results suggest that improvement in cardiac hemodynamics with carvedilol does not reverse pulmonary dysfunction. Persistent lung impairment might have some role in the failure of carvedilol to improve exercise performance. (Am Heart J 1999;138:460-7.)

Contraction-relaxation coupling and impaired left ventricular performance in coronary surgery patients.

Dependence of left ventricular (LV) relaxation on cardiac systolic load is a function of myocardial contractility. The authors hypothesized that, if a tight coupling would exist between LV contraction and relaxation, the changes in relaxation rate with an increase in cardiac systolic load would be related to the changes in LV contraction. Coronary surgery patients (n = 120) with preoperative ejection fraction >40% were included. High-fidelity LV pressure tracings (n = 120) and transgastric transesophageal echocardiographic data (n = 40) were obtained. Hearts were paced at a fixed rate of 90 beats/min. Effects on contraction were evaluated by analysis of changes in dP/dt(max) and stroke area. Effects on relaxation were assessed by analysis of R (slope of the relation between tau and end-systolic pressure). Correlations were calculated with linear regression analysis using Pearson's coefficient r. Baseline LV end-diastolic pressure was 10+/-3 mm Hg (mean +/- SD). During leg raising, systolic LV pressure increased from 93+/-9 to 107+/-11 mm Hg. The change in dP/dt(max) was variable and ranged from -181 to +254 mm Hg/s. A similar variability was observed with the changes in stroke area, which ranged from -2.0 to +5.5 cm2. Changes in dP/dt(max) and in stroke area were closely related to individual R values (r = 0.87, P<0.001; and r = 0.81, P<0.001, respectively) and to corresponding changes in LV end-diastolic pressure (r = 0.81, P< 0.001; and r = 0.74, P<0.001, respectively). A tight coupling was observed between contraction and relaxation. Leg raising identified patients who developed a load-dependent impairment of LV performance and increased load dependence of LV relaxation.

Interaction of hypoxia and aging in the heart: analysis of high energy phosphate content.

To test the hypotheses that aged myocardium has lower ATP concentration and that a greater ATP hydrolysis during hypoxia exaggerates diastolic dysfunction in aged myocardium, we used 31P NMR spectroscopy to measure ATP and phosphocreatine (PCr) contents combined with heart function at baseline and during hypoxia and reoxygenation in perfused hearts isolated from young adult (3-4 months old) and old (24-25 months old) Fisher 344 rats. At baseline, old hearts had 30% lower heart rate and prevalent supraventricular arrhythmia; they had lower PCr and creatine contents (approximately 30%) but normal ATP content. Hypoxia caused similar decreases in heart rate and rate pressure product in young and old hearts. There was a two-fold increase in left-ventricular end-diastolic pressure (LVEDP) in young adults, but, surprisingly, no change in LVEDP in old hearts. ATP decreased similarly in hearts from young and old rats, but the PCr decrease was two-fold smaller in old hearts during hypoxia. Superimposition of pacing on hypoxic old hearts caused six-fold increase in LVEDP; although utilization of PCr increased, it was still incomplete. We conclude that PCr is incompletely used to maintain ATP level during hypoxia especially in the senescent heart, and that the increase in LVEDP in old hearts cannot be explained solely by changes in indices of bioenergetics.