Baseline Pulmonary Capillary Wedge Pressure Research Articles

HeartWare Left Ventricular Assist Device Exercise Hemodynamics With Speed Adjustment Based on Left Ventricular Filling Pressures.

Functional capacity remains limited in heart failure patients with left ventricular assist devices (LVADs) due to fixed pump speed and inability to offload the left ventricle adequately. We hypothesized that manually adjusting LVAD speed during exercise based on pulmonary capillary wedge pressures would increase total cardiac output and maximal oxygen consumption. Two participants with a HeartWare LVAD underwent an invasive ramp study at rest followed by an invasive cardiopulmonary stress test exercising in two randomized phases: fixed speed and adjusted speed. In the latter phase, speed was adjusted every 1 minute during exercise at ±20 rpm/1 mm Hg change from baseline pulmonary capillary wedge pressure. There was no difference in maximal oxygen consumption between the two phases, with a modest increase in total cardiac output during speed adjustment. Filling pressures were initially controlled during speed adjustment until speed was capped at 4,000 rpm, at which point filling pressures increased. Blood pressure was variable. The pressure across the head of the pump (ΔP) was higher with speed adjustment. Contrary to our hypothesis, LVAD speed adjustment during exercise did not improve total cardiac output and functional capacity. This variable response may be attributed to the native cardiac reserve and baroreceptor response; however, additional studies are needed.

The Atrial Flow Regulator – A Novel Treatment Strategy for Patients With HFpEF

Patients with heart failure with preserved ejection fraction (HFpEF) suffer from exertional breathlessness and reduced quality of life, related to increased left ventricular (LV) filling pressure and diastolic dysfunction. There is no effective proven medical treatment. Inter-atrial shunts have been developed to reduce filling pressure particularly with exercise, with the goal of providing symptomatic benefit. We describe the Case of a patient with HFpEF who received an atrial flow regulator (AFR), a novel implantable atrial communication device. A 76-year-old female experienced limiting exertional NYHA Class III breathlessness. Her history included paroxysmal atrial fibrillation, hypertension and hypothyroidism and the medications frusemide, amiodarone, rivaroxaban, and thyroxine. Echocardiography showed low normal LV function (ejection fraction [EF], 55%), left atrial (LA) dilatation and grade II diastolic dysfunction. Her 6-minute walk test was 315 metres, limited by breathlessness, despite optimisation of clinical congestion. Baseline pulmonary capillary wedge pressure was 12mmHg increasing to 25mmHg with exercise. Her diagnosis was of HFpEF and she was referred for an atrial communication device. Under general anaesthesia with transoephageal echo guidance, a transseptal puncture was performed and balloon dilatation undertaken. An 8mm AFR was then deployed and released without complication. The patient was discharged the following day. At follow-up she reported a significant improvement in symptoms, NYHA Class II, with an improved 6-minute walk test achieving 364 metres. We report the Case of a woman with HFpEF who experienced a significant symptomatic benefit from implantation of an AFR. This may become the treatment of choice in selected patients in the future.

Abstract 14885: E/e’ Does Not Consistently Track Left Atrial Pressure When Venous Return is Altered

Introduction: The E/e’ ratio is often used as a surrogate for left atrial pressure (LAP) despite concerns about reliability and accuracy when LAP is sequentially changed within individuals. This study tested how E/e’ tracks linearly with LAP with the aim of determining if invasive markers of diastolic function are associated with better tracking. Methods: Healthy subjects (n = 61, age 52±5 years) underwent manipulation of LAP with 2 levels of lower body negative pressure (LBNP -15 mm Hg, -30mm Hg) and 2 levels of rapid normal saline infusion (NS +15 mL/kg/min, +30 mL/kg/min) with a right heart catheter and echocardiography to define the LV end-diastolic pressure-volume relationship. E/e’ and pulmonary capillary wedge pressure (PCWP) were measured at each condition. Myocardial stiffness was calculated by the slope of the LV pressure-volume curve. LV relaxation was assessed with Tau: (Isovolumetric relaxation time/(ln(Systolic Blood Pressure x 0.9)-ln(PCWP)). R 2 of individual regressions of E/e’ and PCWP for each subject was used to determine quality of tracking across loading conditions. Results: PCWP ranged from 5 mm Hg to 20 mm Hg across loading conditions (p <0.001). As a group, E wave velocity demonstrated a consistent linear relationship with PCWP while e’ was more variable (Figure) . The mean r 2 of individual regressions was 0.50 ± 0.29 with a high coefficient of variation of 57.1%. Higher baseline PCWP, myocardial stiffness or longer LV relaxation were not associated with improved tracking (p = 0.96, p = 0.55, p = 0.62 respectively). Conclusion: This study, the largest cohort to date with experimental altered LAP, highlights the difficulty assessing E/e’: As a cohort, E/e’ tracked with PCWP moderately well, but there was significant variation on an individual level which was independent of baseline LV filling pressure, stiffness and relaxation. Caution should be used when interpreting E/e’ as LAP in healthy individuals even with abnormalities in diastolic filling.

A Clinical Prediction Model for Normalization of Pulmonary Vascular Resistance After Left Ventricular Assist Device Implantation

Background Patients with heart failure with reduced ejection fraction (HFrEF) and elevated pulmonary vascular resistance (PVR) are at risk increased for poor outcomes and may be ineligible for heart transplantation (HT). Left ventricular assist device (LVAD) therapy can lower PVR for certain patients, but it is difficult to identify these patients preoperatively. Methods Using the INTERMACS registry, we developed a clinical prediction model to predict the likelihood of PVR normalization (≤ 3 WU) or HT within 1 year of LVAD implant among patients with baseline PVR > 3 WU. Backwards stepwise selection was used to select variables from 14 candidate predictors and logistic regression was used to estimate model coefficients. Model performance was summarized using measures of discrimination (c-statistic) and calibration (Harrel's EAVG). Internal validation was performed using bootstrap resampling over 200 iterations to generate an average calibration slope, which was used to uniformly shrink all model coefficients to generate the final model. Results There were 2209 patients available for analysis. Median preoperative PVR was 4.26 WU (IQR 3.54-5.54 WU) and the median time from LVAD implant to postoperative PVR assessment was 3 months. 1596 patients (72%) experienced PVR normalization or were transplanted within 1 year. 412 (19%) patients died and 201 (9%) were alive with persistently elevated PVR at 1 year. Final model coefficients are shown in the Table. Important predictors included older age (OR 0.72 per 10 years), severe baseline mitral regurgitation (MR) (OR 2.49 vs no MR), and increased baseline pulmonary capillary wedge pressure (PCWP) (OR 1.24 per 5 mmHg increase). The model c-statistic was 0.66 and EAVG was 0.004. Conclusion Among patients with elevated PVR, preoperative patient characteristics such as severe MR and elevated PCWP are able to predict the likelihood of PVR normalization or HT within 1 year of LVAD implantation. These findings can help to inform decision making and frame patient expectations regarding anticipated improvements in pulmonary vascular disease following LVAD surgery. Future studies are needed to investigate potential management strategies to increase the likelihood of PVR normalization with LVAD support.

Increased Myocardial Stiffness in Patients With High-Risk Left Ventricular Hypertrophy: The Hallmark of Stage-B Heart Failure With Preserved Ejection Fraction.

Individuals with left ventricular hypertrophy (LVH) and elevated cardiac biomarkers in middle age are at high risk for the development of heart failure with preserved ejection fraction (HFpEF). However, it is unknown what the pathophysiological underpinnings of this high-risk state may be. We tested the hypothesis that patients with LVH and elevated cardiac biomarkers would demonstrate elevated left ventricular (LV) myocardial stiffness in comparison with healthy controls as a key marker for future HFpEF. Forty-six patients with LVH (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or troponin T [>0.6 pg/mL]) were recruited, along with 61 age- and sex-matched (by cohort) healthy controls. To define LV pressure-volume relationships, right heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion. There were significant differences in body size, blood pressure, and baseline pulmonary capillary wedge pressure between groups (eg, pulmonary capillary wedge pressure: LVH, 13.4±2.7 versus control, 11.7±1.7 mm Hg, P<0.0001). The LV was less distensible in LVH than in controls (smaller volume for the same filling pressure). When preload was expressed as transmural filling pressure (pulmonary capillary wedge pressure - right atrial pressure), LV myocardial stiffness was nearly 30% greater in LVH than in controls (LVH stiffness constant, 0.053±0.027 versus controls, 0.042±0.020, P=0.028). LV myocardial stiffness in patients with LVH and elevated biomarkers (stage-B HFpEF) is greater than in age- and sex-matched controls and thus appears to represent a transitional state from a normal healthy heart to HFpEF. Although the LV myocardial stiffness of patients with LVH is greater than that of healthy controls at this early stage, further studies are required to clarify whether interventions such as exercise training to improve LV compliance may prevent the full manifestation of the HFpEF syndrome in these high-risk individuals. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT03476785 and NCT02039154.

ANP and BNP plasma levels in patients with rheumatic mitral stenosis after percutaneous balloon mitral valvuloplasty.

IntroductionAtrial (ANP) and B-type (BNP) natriuretic peptides are hormones secreted by the heart as a response to volume expansion and pressure overload.AimTo assess the changes of ANP and BNP after percutaneous balloon mitral valvuloplasty (PBMV) and to investigate factors associated with endpoints.Material and methodsThe study included 96 patients (90.7% females, age 51.6 ±12.2 years) with rheumatic mitral valve stenosis (mitral valve area (MVA) 1.18 (1.01–1.33) cm2, mean mitral gradient (MMG) 8.2 (7.1–9.2) mm Hg, NYHA 2.09 (1.9–2.5)). Patients were followed up for 29.1 months for the search of endpoints.ResultsThe PBMV was successful in all cases. After the procedure MVA increased (1.18–1.78 cm2, p < 0.01) and pulmonary capillary wedge pressure (PCWP) decreased (29.8–21.8 mm Hg, p < 0.01). Concentration of ANP significantly rose 30 min after the PBMV (79.2 vs. 134.2 pg/ml, p = 0.012) and dropped significantly after 24 h (134.2 vs. 70.4 pg/ml, p = 0.01). Furthermore, after 36 months concentration of ANP did not differ from the baseline value (p = NS). BNP concentration at day 1 was lower than at baseline (94.5 vs. 80.2 pg/ml, p = 0.032). Moreover, during the follow-up period BNP continued to fall at all time points. In univariate analysis parameters associated with endpoint occurrence were baseline PAP (p = 0.023), baseline PCWP (p = 0.022), baseline NYHA (p = 0.041) and increase in 6-minute walk test (6MWT) (p = 0.043). In multivariate analysis the only factor associated with endpoint occurrence was baseline NYHA (HR = 1.52, 95% CI: –1.3–1.91, p = 0.022).ConclusionsPatients with MS had increased levels of both BNP and ANP. Baseline NYHA class was found to be associated with outcomes after the procedure.

Baseline Hemodynamics and Response to Contrast Media During Diagnostic Cardiac Catheterization Predict Adverse Events in Heart Failure Patients.

Contrast media administered during cardiac catheterization can affect hemodynamic variables. However, little is documented about the effects of contrast on hemodynamics in heart failure patients or the prognostic value of baseline and changes in hemodynamics for predicting subsequent adverse events. In this prospective study of 150 heart failure patients, we measured hemodynamics at baseline and after administration of iodixanol or iopamidol contrast. One-year Kaplan-Meier estimates of adverse event-free survival (death, heart failure hospitalization, and rehospitalization) were generated, grouping patients by baseline measures of pulmonary capillary wedge pressure (PCWP) and cardiac index (CI), and by changes in those measures after contrast administration. We used Cox proportional hazards modeling to assess sequentially adding baseline PCWP and change in CI to 5 validated risk models (Seattle Heart Failure Score, ESCAPE [Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness], CHARM [Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity], CORONA [Controlled Rosuvastatin Multinational Trial in Heart Failure], and MAGGIC [Meta-Analysis Global Group in Chronic Heart Failure]). Median contrast volume was 109 mL. Both contrast media caused similarly small but statistically significant changes in most hemodynamic variables. There were 39 adverse events (26.0%). Adverse event rates increased using the composite metric of baseline PCWP and change in CI (P<0.01); elevated baseline PCWP and decreased CI after contrast correlated with the poorest prognosis. Adding both baseline PCWP and change in CI to the 5 risk models universally improved their predictive value (P≤0.02). In heart failure patients, the administration of contrast causes small but significant changes in hemodynamics. Calculating baseline PCWP with change in CI after contrast predicts adverse events and increases the predictive value of existing models. Patients with elevated baseline PCWP and decreased CI after contrast merit greatest concern.

Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure.

To the Editor: Cowie et al. (Sept. 17 issue)1 report on the results of the Treatment of SleepDisordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure (SERVE-HF) trial. They found increases in all-cause and cardiovascular mortality among patients with heart failure who received adaptive servo-ventilation therapy, and the adaptive servo-ventilation group had no improvement in quality-of-life measures. These results contradict those of our Study of the Effects of Adaptive Servo-ventilation Therapy on Cardiac Function and Remodeling in Patients with Chronic Heart Failure (SAVIOR-C).2 The majority of patients who received adaptive servoventilation in our study had improvements in quality of life, and the improvement from New York Heart Association (NYHA) functional class III heart failure to class II heart failure was significant. We found that the adaptive servo-ventilation settings differed between the two studies. Cowie et al. manually increased the expiratory and inspiratory positive airway pressures from the default levels to suppress sleep apnea.1 Because the effects of positive airway pressure on cardiac output depend on the baseline pulmonary-capillary wedge pressure,3 we were concerned that excessive increases in levels of airway pressure might diminish cardiac output and induce reflex sympathetic hyperactivity in some patients with mild pulmonary congestion. For this reason, the levels of airway pressure in patients in the SAVIOR-C were maintained at or below the default levels.2,4 It would be useful to know whether high-pressure adaptive servo-ventilation settings precipitated adverse events in their patients. Yasuki Kihara, M.D., Ph.D.

Pulmonary congestion at rest and abnormal ventilation during exercise in chronic systolic heart failure.

BackgroundIn patients with chronic heart failure, abnormal ventilation at cardiopulmonary testing (expressed by minute ventilation-to-carbon dioxide production, or VE/VCO2 slope, and resting end-tidal CO2 pressure) may derive either from abnormal autonomic or chemoreflex regulation or from lung dysfunction induced by pulmonary congestion. The latter hypothesis is supported by measurement of pulmonary capillary wedge pressure, which cannot be obtained routinely but may be estimated noninvasively by measuring transthoracic conductance (thoracic fluid content 1/kΩ) with impedance cardiography.Methods and ResultsPreliminarily, in 9 patients undergoing invasive hemodynamics during cardiopulmonary testing, we demonstrated a significant relationship between VE/VCO2 slope and resting end-tidal CO2 pressure with baseline and peak pulmonary capillary wedge pressure. Later, noninvasive hemodynamic evaluation by impedance cardiography was performed before cardiopulmonary testing in 190 patients with chronic systolic heart failure and normal lung function (aged 67±3 years, 71% with ischemia, ejection fraction 32±7%, 69% with implantable cardioverter-defibrillator or cardiac resynchronization therapy). In this group, we determined the relationship between abnormal ventilation (VE/VCO2 slope and resting end-tidal CO2 pressure) and transthoracic conductance. In the whole population, thoracic fluid content values were significantly related to VE/VCO2 slope (R=0.63, P<0.0001) and to resting end-tidal CO2 pressure (R=−0.44, P<0.001).ConclusionsIn patients with chronic heart failure, abnormal ventilation during exercise may be related in part to pulmonary congestion, as detected by resting baseline impedance cardiography.

Adaptive Servo-Ventilation Has More Favorable Acute Effects on Hemodynamics Than Continuous Positive Airway Pressure in Patients With Heart Failure.

Adaptive servo-ventilation (ASV) has been attracting attention as a novel respiratory support therapy for heart failure (HF). However, the acute hemodynamic effects have not been compared between ASV and continuous positive airway pressure (CPAP) in HF patients.We studied 12 consecutive patients with stable chronic HF. Hemodynamic measurement was performed by right heart catheterization before and after CPAP 5 cmH2O, CPAP 10 cmH2O, and ASV for 15 minutes each.Heart rate, blood pressure, pulmonary capillary wedge pressure (PCWP), and stroke volume index (SVI) were not changed by any intervention. Right atrial pressure significantly increased after CPAP 10 cmH2O (3.6 ± 3.3 to 6.7 ± 1.6 mmHg, P = 0.005) and ASV (4.1 ± 2.6 to 6.8 ± 1.5 mmHg, P = 0.026). Cardiac index was significantly decreased by CPAP 10 cmH2O (2.3 ± 0.4 to 1.9 ± 0.3 L/minute/m(2), P = 0.048), but was not changed by ASV (2.3 ± 0.4 to 2.0 ± 0.3 L/ minute/m(2), P = 0.299). There was a significant positive correlation between baseline PCWP and % of baseline SVI by CPAP 10 cmH2O (r = 0.705, P < 0.001) and ASV (r = 0.750, P < 0.001). ASV and CPAP 10 cmH2O had significantly greater slopes of this correlation than CPAP 5 cmH2O, suggesting that patients with higher PCWP had a greater increase in SVI by ASV and CPAP 10 cmH2O. The relationship between baseline PCWP and % of baseline SVI by ASV was shifted upwards compared to CPAP 10 cmH2O. Furthermore, based on the results of a questionnaire, patients accepted CPAP 5 cmH2O and ASV more favorably compared to CPAP 10 cmH2O.ASV had more beneficial effects on acute hemodynamics and acceptance than CPAP in HF patients.

Abstract 9622: Baseline Hemodynamics with Cardiac Performance Response to Contrast Media During Diagnostic Cardiac Catheterization Enhances Prediction of Adverse Events in Heart Failure Patients

Background. Anticipating adverse events (death, HF rehospitalization) in heart failure patients (HF pts) could help direct care while reducing event rates and resource utilization. We hypothesized that the combination of baseline pulmonary capillary wedge pressure (PCWP) and change in measures of cardiac performance (ΔCP) following administration of contrast media during diagnostic cardiac catheterization would predict adverse events and add to the predictive value of existing models. Methods. Prospective study of 150 consecutive HF pts referred for non-emergency right and left heart catheterization using iodixanol or iopamidol contrast. Hemodynamic variables measured at baseline and following contrast included PCWP and CP (composite of cardiac output, cardiac index and stroke volume, identified from sparse principal component analysis of all hemodynamic variables). Kaplan-Meier curves were generated for 1 year followup using median baseline PCWP and ΔCP to group pts. The effect of adding these hemodynamic parameters to the predictive value of 4 validated risk models (Seattle HF Score; ESCAPE; CHARM; CORONA) was assessed using Cox proportional hazards regression model. Results. The average contrast load was 120ml. There was a graded worsening of long-term adverse events, with event rates increasing with the composite metric (Figure). Adding baseline PCWP and ΔCP to the 4 risk models significantly improved their predictive capacity (Table). Conclusions. Baseline PCWP with change in CP following administration of contrast predicts adverse events and adds to the predictive value of existing models. The calculations add no cost and can be performed in minutes.

Direct demonstration of preload dependency of myocardial flow reserve in human failing heart by15O–H2O positron emission tomography

Although myocardial flow reserve (MFR) in congestive heart failure (CHF) has been reported to be impaired, the mechanism has not been fully shown in humans. Therefore, we performed positron emission tomography to measure myocardial blood flow (MBF) in patients with CHF and compared it with hemodynamic parameters. Sixteen normal coronary patients with CHF and ten normal controls were enrolled. 15O-labeled water positron emission tomography was performed at rest and during peak hyperemia induced by adenosine triphosphate. MFR was calculated as the ratio of peak hyperemic to baseline MBF. All CHF patients underwent cardiac catheterization. Baseline MBF was similar between CHF patients and normal controls (0.73 ± 0.25 vs. 0.80 ± 0.12 mL/min/g, p = NS). Hyperemic MBF was significantly reduced in CHF patients than in controls (1.68 ± 1.09 vs. 3.21 ± 0.69 mL/min/g, p < 0.05). therefore, MFR was significantly reduced in CHF patients than in controls (2.30 ± 1.30 vs. 4.03 ± 0.90, p < 0.05). There was no significant correlation between baseline MBF and either pulmonary capillary wedge pressure or left ventricular end-diastolic pressure, while both hyperemic MBF and MFR significantly correlated with both pulmonary capillary wedge pressure (r = −0.67 and r = −0.75, respectively) and left ventricular end-diastolic pressure (r = −0.51 and r = −0.60, respectively). Despite elevated preload, MBF at rest in CHF patients was compensated to the similar level as that in controls. However, this compensation may exhaust vasodilatory reserve in the failing human heart. Thus, preload at rest is a determinant of myocardial vasodilator reserve and preload reduction may ameliorate coronary vasodilator response in CHF patients.

The Relationship of Right- and Left-Sided Filling Pressures in Patients With Heart Failure and a Preserved Ejection Fraction

Although right-sided filling pressures often mirror left-sided filling pressures in systolic heart failure, it is not known whether a similar relationship exists in heart failure with preserved ejection fraction. Eleven subjects with heart failure with preserved ejection fraction underwent right heart catheterization at rest and under loading conditions manipulated by lower body negative pressure and saline infusion. Right atrial pressure (RAP) was classified as elevated when >or=10 mm Hg and pulmonary capillary wedge pressure (PCWP) when >or=22 mm Hg. If both the RAP and the PCWP were elevated or both not elevated, they were classified as concordant; otherwise, they were classified as discordant. Correlation of RAP and PCWP was determined by a repeated measures model. Among 66 paired measurements of RAP and PCWP, 44 (67%) had a low RAP and PCWP and 8 (12%) a high RAP and PCWP, yielding a concordance rate of 79%. In a sensitivity analysis performed by varying the definition of elevated RAP (from 8 to 12 mm Hg) and PCWP (from 15 to 25 mm Hg), the mean+/-SD concordance of RAP and PCWP was 76+/-10%. The correlation coefficient of RAP and PCWP for the overall cohort was r=0.86 (P<0.0001). Right-sided filling pressures often reflect left-sided filling pressures in heart failure with preserved ejection fraction, supporting the role of estimation of jugular venous pressure to assess volume status in this condition.

Hemodynamics, diuretics, and nesiritide: a retrospective VMAC analysis.

Hypotension has been proposed as the cause of nesiritide-associated increases in serum creatinine (SCr); however, this hypothesis has not been tested. This retrospective evaluation of patients who had a pulmonary artery catheter and received nesiritide in the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial assessed hypotension, SCr elevation, concomitant therapy, and mortality. Patients were categorized by baseline pulmonary capillary wedge pressure (PCWP) and analyzed both for overall population and by diuretic dose. Compared with patients with PCWP > 23 mm Hg (n = 105), patients with PCWP < or = 23 mm Hg (n = 49) had more hypotension within 24 hours of initiating nesiritide (16% vs 7%), but neither more SCr elevation by nominal day 30 (29% vs 28%) nor higher mortality (30 days: 8.2% vs 7.7%; 6 months: 29.0% vs 29.3%). The risk of hypotension was directly related to high dose diuretics (25% vs 6%; relative risk [RR]: 4.2; 95% confidence interval [CI]: 1.10-15.82) and was not significantly increased in patients without this concomitant treatment (10% vs 7%; RR: 1.4; 95% CI: 0.34-5.93). Additionally, high dose diuretics significantly increased the risk of SCr elevation (RR: 2.6; 95% CI: 1.03-6.64) and 6 month mortality (hazard ratio: 3.6; 95% CI: 1.19-10.63) in patients with PCWP < or = 23 mm Hg. Hypotension is not the primary etiology for nesiritide-associated increases in SCr. High dose diuretics increase the risk of adverse outcomes in patients with PCWP < or = 23 mm Hg and should be reserved for patients in whom PCWPs are known to be markedly elevated.

Post coital hemoptysis

Ischemic mitral regurgitation is a complication of coronary artery disease specifically in the settings of prior myocardial infarction. It is a dynamic lesion and its severity may increase with different forms of exercise leading to flash pulmonary edema. We present the case of an 81-year-old man with ischemic mitral regurgitation who presented with long standing history of hemoptysis limited to sexual intercourse only. After a thorough negative work-up for the usual causes of hemoptysis, comprehensive right and left cardiac catheterization studies revealed marked increase in baseline mitral regurgitation and pulmonary capillary wedge pressure with isometric exercise. This case illustrates that sexual intercourse, a form of isometric exercise, can cause severe increase in ischemic mitral regurgitation and more so compared to other forms of exercise due to heightened sympathetic activity, leading to flash pulmonary edema and hemoptysis.

Comparison of lactated Ringer's, gelatine and blood resuscitation on intestinal oxygen supply and mucosal tissue oxygen tension in haemorrhagic shock

To evaluate the effects on intestinal oxygen supply, and mucosal tissue oxygen tension during haemorrhage and after fluid resuscitation with either blood (B; n=7), gelatine (G; n=8), or lactated Ringer's solution (R; n=8) in an autoperfused, innervated jejunal segment in anaesthetized pigs. To induce haemorrhagic shock, 50% of calculated blood volume was withdrawn. Systemic haemodynamics, mesenteric venous and systemic acid-base and blood gas variables, and lactate measurements were recorded. A flowmeter was used for measuring mesenteric arterial blood flow. Mucosal tissue oxygen tension (PO(2)muc), jejunal microvascular haemoglobin oxygen saturation (HbO(2)) and microvascular blood flow were measured. Measurements were performed at baseline, after haemorrhage and at four 20 min intervals after fluid resuscitation. After haemorrhage, animals were retransfused with blood, gelatine or lactated Ringer's solution until baseline pulmonary capillary wedge pressure was reached. After resuscitation, no significant differences in macrohaemodynamic parameters were observed between groups. Systemic and intestinal lactate concentration was significantly increased in animals receiving lactated Ringer's solution [5.6 (1.1) vs 3.3 (1.1) mmol litre(-1); 5.6 (1.1) vs 3.3 (1.2) mmol litre(-1)]. Oxygen supply to the intestine was impaired in animals receiving lactated Ringer's solution when compared with animals receiving blood. Blood and gelatine resuscitation resulted in higher HbO(2) than with lactated Ringer's resuscitation after haemorrhagic shock [B, 43.8 (10.4)%; G, 34.6 (9.4)%; R, 28.0 (9.3)%]. PO(2)muc was better preserved with gelatine resuscitation when compared with lactated Ringer's or blood resuscitation [20.0 (8.8) vs 13.8 (7.1) mm Hg, 15.2 (7.2) mm Hg, respectively]. Blood or gelatine infusion improves mucosal tissue oxygenation of the porcine jejunum after severe haemorrhage when compared with lactated Ringer's solution.

Oral levosimendan improves cardiac function and hemodynamics in patients with severe congestive heart failure

Levosimendan, a new calcium sensitizer, was administered orally to 10 patients with severe congestive heart failure (CHF), who had a mean baseline pulmonary capillary wedge pressure (PCWP) of 22 mm Hg and a left ventricular ejection fraction of 23%. Each patient received 3 escalating doses of 1 mg, 2 mg, and 4 mg of levosimendan within 18–24 hours in an open-label pilot study. After administration of a 1-mg dose of levosimendan, PCWP decreased by 18% (p = 0.002) and cardiac output increased by 22% (p = 0.005). Diastolic blood pressure was decreased by about 5 mm Hg. Plasma catecholamine levels were unaffected. Plasma concentrations of levosimendan were unexpectedly low after administration of the 2-mg dose, and responses were weak. This was probably due to delayed drug absorption and altered baseline hemodynamics caused by ingestion of a meal before drug intake. The 4-mg dose of levosimendan was associated with a 27% increase in cardiac output (p = 0.009). PCWP showed only a small decrease, probably a result of relatively low baseline values (carryover from previous doses). Right atrial pressure decreased substantially by 40%. Heart rate increased by only 1–8 beats/min after administration of the 1- and 4-mg doses of levosimendan. It is concluded that oral levosimendan has favorable cardiac and hemodynamic effects in patients with severe CHF, and that these effects are similar to those seen after intravenous dosing with levosimendan in this patient group.

Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance.

The cardiovascular adaptation to bed rest leads to orthostatic intolerance, characterized by an excessive fall in stroke volume (SV) in the upright position. We hypothesized that this large fall in SV is due to a change in cardiac mechanics. We measured pulmonary capillary wedge pressure (PCWP), SV, left ventricular end-diastolic volume (LVEDV), and left ventricular mass (by echocardiography) at rest, during lower-body negative pressure, and after saline infusion before and after 2 weeks of bed rest with -6 degrees head-down tilt (n=12 subjects aged 24+/-5 years). Pressure (P)-volume (V) curves were modeled exponentially by P=ae(kV)+b and logarithmically by P=-Sln[(Vm-V)/(Vm-V0)], where V0 indicates volume at P=0, and the constants k and S were used as indices of normalized chamber stiffness. Dynamic stiffness (dP/dV) was calculated at baseline LVEDV. The slope of the line relating SV to PCWP during lower-body negative pressure characterized the steepness of the Starling curve. We also measured plasma volume (with Evans blue dye) and maximal orthostatic tolerance. Bed rest led to a reduction in plasma volume (17%), baseline PCWP (18%), SV (12%), LVEDV (16%), V0 (33%), and orthostatic tolerance (24%) (all P<.05). The slope of the SV/PCWP curve increased from 4.6+/-0.4 to 8.8+/-0.9 mL/mm Hg (P<.01) owing to a parallel leftward shift in the P-V curve. Normalized chamber stiffness was unchanged, but dP/dV was reduced by 50% at baseline LVEDV, and cardiac mass tended to be reduced by 5% (P<.10). Two weeks of head-down-tilt bed rest leads to a smaller, less distensible left ventricle but a shift to a more compliant portion of the P-V curve. This results in a steeper Starling relationship, which contributes to orthostatic intolerance by causing an excessive reduction in SV during orthostasis.

BED-REST (BR) ENHANCES CALF VASODILATOR RESPONSE TO SALINE INFUSION (SI) INDUCED CENTRAL HYPERVOLEMIA 1031

Orthostatic intolerance following spaceflight or bedrest (BR) deconditioning may be due to inadequate vasoconstriction or inappropriate reflex vasodilation. The aim of this study was to test the hypothesis that the calf vasodilator response to increases in pulmonary capillary wedge pressure(PCWP) and right atrial pressure (RAP) produced by SI (100ml/min) is potentiated following BR. Eleven volunteers (age: 24±2 yrs, Wt:78±3kg, Ht:176±3cm) completed the experiments prior to (Pre) and following (Post) 2-weeks of -6° head-down tilt BR in which cardiac filling pressure (Swan-Ganz), calf blood flow (CBF, plethysmography) and mean arterial pressure (MAP, Finapres) were measured. BR significantly decreased baseline PCWP (pre vs post: 13.2 ± 1.0 vs 10.5 ± 1.1mmHg), RAP(7.9 ± 0.8 vs 6.2 ± 0.8 mmHg), CBF (2.3 ± 0.2 vs 1.7± 0.1 ml/dl/min), and increased MAP (85 ± 2 vs 91 ± 3 mmHg) and calf vascular resistance (CVR, 37 ± 4 vs 51 ± 3 PRU) calculated from the ratio (MAP-RAP)/CBF, SI with 15 or 30 ml/kg significantly increased PCWP, RAP, CBF, and decreased CVR both pre- and post-BR (seetable). MAP was not significantly changed by SI pre- or post-BR. In terms of per unit ▵PCWP or ▵RAP, ▵CVR was significantly greater in post- than pre-BR (-2.4 ± 0.0 or -3.9 ± 0.1 vs -2.0 ± 0.1 or-2.9 ± 0.2 PRU/mmHg). Conclusion: peripheral vasodilation in response to central hypervolemia appears to be augmented following BR deconditioning.

1007-17 Demonstration of Pericardial Constraint in Chronic Heart Failure

Pericardial constraint may be an important feature in chronic heart failure (CHF). We hypothesized that baseline pericardial constraint could be inferred if left ventricular end-diastolic volume (LVEDV) paradoxically increased during lower body negative pressure (LBNP), as a consequence of abolition of constraint with an increase in the left ventricular transmural and transseptal pressure gradients. 11 patients with CHF and left ventricular ejection fraction &lt;35% (age 34–82, mean 51.5 years; 8 male, 3 female) were compared with 6 healthy controls (age 31–61, mean 50.5 years; all male). Radionuclide ventriculography was performed before and during application of 30 mmHg LBNP. Left ventricular end-diastolic counts were corrected for time decay and tissue attenuation. LVEDV was then calculated with reference to an externally counted blood sample taken during each of the acquisitions. (expressed as mean ± SD): Comparing baseline with 30 mmHg LBNP, LVEDV changed by –4.5 to -26.3 ml (mean–14.2 ± 8.6 ml) in controls vs. -24.4 to +62.1 ml (mean +8.2 ± 23.5 ml) in CHF patients (p = 0.041) The % change in LVEDV with LBNP (mean ± SD) is shown in the figure. There was a linear correlation between change in LVEDV and baseline pulmonary capillary wedge pressure (b-PCWP) in CHF patients (r = 0.68; p = 0.031) Baseline pericardial constraint is demonstrated in the 4 patients with CHF in whom LVEDV increased during LBNP, a response associated with higher b-PCWP. In patients with attenuated reductions in LVEDV, abolition of baseline constraint and impaired myocardial compliance are both possible explanations.