Israel Belenkie

Suppression of Central Sleep Apnea by Continuous Positive Airway Pressure and Transplant-Free Survival in Heart Failure A Post Hoc Analysis of the Canadian Continuous Positive Airway Pressure for Patients With Central Sleep Apnea and Heart Failure Trial (CANPAP)

Background— In the main analysis of the Canadian Continuous Positive Airway Pressure (CPAP) for Patients with Central Sleep Apnea (CSA) and Heart Failure Trial (CANPAP), CPAP had no effect on heart transplant–free survival; however, CPAP only reduced the mean apnea-hypopnea index to 19 events per hour of sleep, which remained above the trial inclusion threshold of 15. This stratified analysis of CANPAP tested the hypothesis that suppression of CSA below this threshold by CPAP would improve left ventricular ejection fraction and heart transplant–free survival. Methods and Results— Of the 258 heart failure patients with CSA in CANPAP, 110 of the 130 randomized to the control group and 100 of the 128 randomized to CPAP had sleep studies 3 months later. CPAP patients were divided post hoc into those whose apnea-hypopnea index was or was not reduced below 15 at this time (CPAP-CSA suppressed, n=57, and CPAP-CSA unsuppressed, n=43, respectively). Their changes in left ventricular ejection fraction and heart transplant–free survival were compared with those in the control group. Despite similar CPAP pressure and hours of use in the 2 groups, CPAP-CSA–suppressed subjects experienced a greater increase in left ventricular ejection fraction at 3 months (P=0.001) and significantly better transplant-free survival (hazard ratio [95% confidence interval] 0.371 [0.142 to 0.967], P=0.043) than control subjects, whereas the CPAP-CSA–unsuppressed group did not (for left ventricular ejection fraction, P=0.984, and for transplant-free survival, hazard ratio 1.463 [95% confidence interval 0.751 to 2.850], P=0.260). Conclusions— These results suggest that in heart failure patients, CPAP might improve both left ventricular ejection fraction and heart transplant–free survival if CSA is suppressed soon after its initiation.

Diastolic ventricular interaction in chronic heart failure

BACKGROUND Diastolic ventricular interaction describes a situation in which the volume of one ventricle is directly influenced by the volume of the other ventricle. Such interaction is normally negligible, but it is accentuated in circumstances associated with pulmonary hypertension and volume overload. When this interaction occurs, acute volume unloading results in a reduction in right ventricular end-diastolic volume, as expected, but left ventricular end-diastolic volume paradoxically increases. Since chronic heart failure is a volume-overloaded state associated with pulmonary hypertension, we hypothesised that this interaction may be clinically important in patients with heart failure. METHODS A radionuclide technique incorporating cardiac scintigraphy was used to measure the effect of acute volume unloading, achieved by 30 mm Hg lower-body suction, on right and left ventricular end-diastolic volumes in 21 patients with chronic heart failure and 12 healthy individuals (controls). FINDINGS In nine heart-failure patients, there was a paradoxical increase in left ventricular end-diastolic volume in association with an expected decrease in right ventricular end-diastolic volume during lower-body suction. This response was not seen in the control group. The mean change in left ventricular end-diastolic volume differed significantly between the heart-failure patients and controls (6 [SD 19] vs -19 [12] mL, p = 0.0003). However, the change in right ventricular end-diastolic volume was similar in the two groups (-18 [11] vs -20 [8]%. p = 0.70). Patients who increased left ventricular end-diastolic volume during lower-body suction had higher resting pulmonary arterial and pulmonary capillary wedge pressures than the remaining heart-failure patients. INTERPRETATION The response of nine patients in our study suggests diastolic ventricular interaction, which we believe could be common in patients with chronic heart failure. This finding is relevant to their management, since it emphasises the importance of venodilator therapy. The relation between stroke volume and left ventricular end-diastolic volume, by the Frank-Starting law of the heart, may explain why some patients with chronic heart failure paradoxically increase stroke volume when pulmonary capillary wedge pressure is lowered with vasodilators.

Exercise Capacity in Hypertrophic Cardiomyopathy Role of Stroke Volume Limitation, Heart Rate, and Diastolic Filling Characteristics

BACKGROUND We previously showed that exercise capacity in patients with hypertrophic cardiomyopathy (HCM) is related to peak exercise cardiac output. Cardiac output augmentation during exercise is normally dependent on heart rate (HR) response and stroke volume (SV) augmentation by increased left ventricular end-diastolic volume and/or increased contractility. We hypothesized that in contrast to normal subjects, peak exercise capacity in patients with HCM is determined by the diastolic filling characteristics of the left ventricle during exercise, which would in turn determine the degree to which SV is augmented, and that HR is a relatively unimportant determinant of peak exercise capacity. METHODS AND RESULTS Twenty-three patients with HCM underwent invasive hemodynamic evaluation and measurement of maximal oxygen consumption (VO2max) during erect treadmill exercise to assess the relative importance of changes in HR and SV in determining exercise capacity. Hemodynamic responses to erect and supine exercise were compared in 10 of these patients. In a separate group of 46 patients with HCM, the relation between VO2max and exercise diastolic filling indexes was assessed. Peak HR during erect exercise was 92 +/- 8% of predicted maximum. VO2max was 29.0 +/- 6.4 mL.kg-1.min-1 and was related significantly to peak exercise cardiac index and SV index (r = .71, P < .001 and r = .66, P = .001, respectively) but not to peak HR, HR deficit, or resting or peak pulmonary capillary wedge pressure. Peak cardiac output during erect exercise was not related to peak HR (r = .13, P = NS). When erect and supine exercise were compared, peak HR was lower in the supine position (153.3 +/- 19.9 beats per minute supine versus 172.0 +/- 17.6 beats per minute erect, P = .003), but peak exercise cardiac index was similar (7.9 +/- 2.6 L.min-1.m-2 supine versus 7.5 +/- 2.8 L.min-1.m-2 erect). Pulmonary capillary wedge pressure was higher at rest in the supine versus erect position (15.3 +/- 5.2 versus 8.1 +/- 6.1 mm Hg) but was not significantly higher at peak exercise in the supine versus erect position (28.5 +/- 8 versus 22.4 +/- 11.6 mm Hg erect, P = NS). In the separate group of 46 patients with HCM, VO2max was significantly inversely related to time to peak filling at peak exercise (r = -.60, P < .0001) but did not correlate with time to peak filling at rest, resting ejection fraction, peak filling rate, or peak exercise peak filling rate. CONCLUSIONS SV is the major determinant of peak exercise capacity in the erect position in patients with hypertrophic cardiomyopathy. This in turn is determined by the exercise left ventricular diastolic filling characteristics. HR augmentation does not appear to be a major determinant of peak cardiac output in the erect position.

Left ventricular wall thickness and regional systolic function in patients with hypertrophic cardiomyopathy. A three-dimensional tagged magnetic resonance imaging study.

BackgroundRegional performance of the hypertrophied left ventricle (LV) in hypertrophic cardiomyopathy (HCM) is still incompletely characterized with studies variably reporting that the hypertrophied myocardium is hypokinetic, akinetic, or has normal function. Different imaging modalities (M-mode or two-dimensional echocardiography) and methods of analysis (fixed or floating frame of reference for wall motion analysis) yield different results. We assessed regional function in terms of systolic wall thickening and shortening and related these parameters to end-diastolic thickness using tagged magnetic resonance imaging and the three-dimensional volume-element approach. Methods and ResultsIn 17 patients with HCM and 6 healthy volunteers, four parallel short-axis images with 12 radial tags and two mutually orthogonal long-axis images with four parallel tags were obtained at end diastole and end systole. After the LV endocardial and epicardial borders were traced, three-dimensional volume elements were constructed by connecting two matched planar segments in two adjacent short-axis image planes, accounting for translation, twist, and long-axis short-ening. A total of 72 such volume elements encompassed the entire LV. From each of these elements, end-diastolic thick-ness and systolic function (fractional thickening and circum-ferential shortening) were calculated. The average end-dia-stolic thickness was 15.8±4.2 mm in patients with HCM, which was significantly greater than that in healthy subjects (8.6±2.1 mm, P<.001). Fractional thickening was significantly less in patients with HCM than in healthy subjects (0.31±0.22 versus 0.56±0.23, P<.001). There was a highly significant inverse correlation between fractional thickening and end-diastolic thickness that was independent of the type of hypertrophy or age group. Similar inverse relations were observed between circumferential shortening and end-diastolic wall thickness. ConclusionsThe myocardium in patients with HCM is heterogeneously thickened and the fractional thickening and circumferential shortening of the abnormally thickened myocardium are reduced compared with healthy subjects. The decrease in fractional thickening and shortening is inversely related to the local thickness.

Effects of volume loading during experimental acute pulmonary embolism.

Volume loading is used to treat hemodynamically compromised patients with acute pulmonary embolism despite data to suggest that volume loading after embolism might cause a leftward shift of the ventricular septum with a subsequent decrease in left ventricular (LV) end-diastolic volume and stroke work. We studied 10 closed-chest, anesthetized, and ventilated dogs to assess the effects of volume loading after pulmonary embolism caused by autologous clot. LV, right ventricular, and right atrial pressures as well as LV anteroposterior, septum-to-right ventricular, and septum-to-LV free wall diameters (sonomicrometry) were measured. Pericardial pressure was measured with flat, liquid-containing balloons. The effects of volume loading were assessed before embolism, after one episode of embolization, and after repeated embolizations. The LV area index (as a reflection of LV volume) increased during volume loading before embolism (2,870 +/- 430 to 3,080 +/- 520 mm2; p less than 0.05), did not change significantly during infusion of fluid after one embolization (2,850 +/- 470 to 2,860 +/- 500 mm2; p = NS), and decreased significantly during volume expansion after repeated embolizations (2,760 +/- 440 to 2,660 +/- 420 mm2; p less than 0.01). An index of LV stroke work increased (188 +/- 85 to 260 +/- 101 mm Hg x mm2; p less than 0.05), did not change significantly (188 +/- 39 to 203 +/- 52 mm Hg x mm2; p = NS), and decreased markedly (133 +/- 64 to 45 +/- 27 mm Hg x mm2; p less than 0.001) before embolism, after one embolization, and after repeated embolizations, respectively. The decrease in LV area index during volume loading after repeated embolizations was associated with an increase in septum-to-right ventricular free wall diameter (31 +/- 8 to 34 +/- 8 mm; p = 0.001) and a decrease in the septum-to-LV free wall diameter (44 +/- 5 to 42 +/- 5 mm; p less than 0.001), whereas the LV anteroposterior diameter did not change (62 +/- 5 to 63 +/- 5 mm; p = NS). This is compatible with a leftward septal shift being partially responsible for the decrease in LV end-diastolic volume; such a shift would be expected with the observed decrease in transseptal end-diastolic pressure gradient (-3 +/- 2 to -5 +/- 2 mm Hg; p = 0.001). In addition, after repeated embolizations, LV transmural pressure decreased in response to the volume load reflecting a marked increase in pericardial pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Ventricular interaction during experimental acute pulmonary embolism.

Although stroke volume may decrease markedly after acute pulmonary embolism, left ventricular end-diastolic pressure (LVEDP) usually changes very little, which suggests that compliance or contractility or both are reduced. To test the hypothesis that the altered LV function during pulmonary embolism is primarily due to reduced preload mediated by increased pericardial constraint, hemodynamics and chamber dimensions (measured by sonomicrometry) were assessed in seven anesthetized dogs during control volume loading, after pulmonary embolism (with autologous blood clot), and after repeated pulmonary embolism in the volume-loaded state. The correlation between LVEDP and an index of LVED volume (LVED area index) throughout a wide range of LVEDP before and after embolism was poor (mean r = 0.42; range, 0-0.82). However, the correlation between transmural LVEDP (LVEDP-directly measured pericardial pressure) and LVED area index (mean r = 0.78; range, 0.61-0.94) was significantly higher (p = 0.03). Similarly, an index of stroke work (LV area stroke work) correlated less well (p less than 0.01) with LVEDP (mean r = 0.43; range, 0.07-0.77) than with transmural LVEDP (mean r = 0.82; range, 0.68-0.92). LV area stroke work also correlated well with the LV area index (mean r = 0.84; range, 0.70-0.95). These data indicate that neither compliance nor contractility is substantially altered during acute pulmonary embolism. The altered LV performance is due to reduced LV preload as reflected by a decrease in transmural LVEDP. This study also demonstrates that LVEDP is a poor index of LV preload during pulmonary embolism, whereas transmural LVEDP accurately reflects LVED dimensions.

Effects of aortic constriction during experimental acute right ventricular pressure loading. Further insights into diastolic and systolic ventricular interaction.

BACKGROUND Acute right ventricular (RV) hypertension may result in hemodynamic collapse. The associated reduction in left ventricular (LV) end-diastolic volume is thought to result from reduced RV output (secondary to RV ischemia) and adverse direct ventricular interaction. Aortic constriction improves cardiac function in these circumstances; this has been attributed to a reversal of the RV ischemia caused by an increased coronary perfusion pressure. We hypothesized that altered ventricular interaction, potentially via altered septal mechanics, may also contribute to the beneficial effects of aortic constriction. METHODS AND RESULTS We instrumented nine dogs with ultrasonic dimension crystals to measure RV segment length, septum-to-RV free wall and septum-to-LV free wall diameters, and LV anterioposterior diameter. Catheter-tipped manometers were used to measure LV and RV pressures. Pericardial pressure was measured with flat, liquid-containing balloon transducers. Inflatable cuff constrictors were placed on the pulmonary artery (PA) and aorta, and a flow probe was placed on the PA. The right coronary artery (RCA) was perfused independently by a roller pump calibrated for flow. During moderate PA constriction, while RCA pressure was maintained at control level, RCA flow did not change significantly (15.8 +/- 6.2 to 16.9 +/- 11.5 mL/min) and was similar during severe PA constriction (18.6 +/- 9.8 mL/min). During severe PA constriction, RV stroke volume decreased from a control value of 10.3 +/- 4.9 to 2.3 +/- 1.4 mL/beat (P < .05). When aortic constriction was added while RCA pressure was maintained at control level, there was an increase in RV stroke volume to 4.5 +/- 2.0 mL/beat (P < .05) with no associated change in RCA flow (17.8 +/- 9.5 mL/min). However, pressure-dimension loops clearly demonstrated changes in diastolic and systolic ventricular interaction; with aortic constriction, there was a large increase in the transeptal pressure gradient associated with a rightward septal shift. During either isolated severe PA constriction or simultaneous severe PA and aortic constriction, RCA flow was increased until RCA pressure was approximately equal to that in the aorta. This produced an increase in RCA flow of 50% (P < .05); however, this increase in coronary flow was ineffective in improving any measure of RV function. CONCLUSIONS In this model of acute RV hypertension, aortic constriction improves cardiac function, at least in part, by altering ventricular interaction independent of changes in RCA flow. Changes in RCA flow do not appear to have a significant impact on cardiac function in this model in which coronary artery pressure was maintained at normal or increased levels.

Ventricular interaction: from bench to bedside

Decreased right ventricle (RV) output results in decreased left ventricle end-diastolic volume (LVEDV) and output by series interaction. Direct ventricular interaction may also have a major effect on LV function. Thus, decreased LVEDV caused by reduced RV output may be further reduced by a leftward septal shift and pericardial constraint. This has been shown to be true in acute and chronic pulmonary hypertension and is now also apparent in severe congestive heart failure. The use of intracavitary LV end-diastolic pressure (LVEDP) to assess LVEDV is inappropriate if pressure surrounding the LV is increased: the surrounding pressure should be subtracted from LVEDP to calculate the effective distending (transmural) pressure which governs preload. If the surrounding pressure increases more than LVEDP, transmural LVEDP and LVEDV will decrease despite the increased LVEDP. Thus, the use of filling pressure to reflect changes in LVEDV has led to erroneous conclusions regarding changes in myocardial compliance and contractility. It is now clear that volume loading may reduce LVEDV and stroke work in pulmonary embolism, chronic lung disease and severe congestive heart failure despite increased LVEDP. The decreased stroke work is a result of reduced LV preload, not decreased contractility as would be suggested if filling pressure is used to reflect preload.

The importance of pericardial constraint in experimental pulmonary embolism and volume loading

To clarify the magnitude of the contribution of pericardial constraint to the hemodynamic deterioration that is observed during acute pulmonary embolism, hemodynamics and chamber dimensions (sonomicrometry) were measured during pulmonary embolization and subsequent volume loading in six anesthetized and instrumented open-chest, open-pericardium dogs. Embolization markedly increased peak right ventricular systolic pressure (38 +/- 5 mm Hg before embolism to 64 +/- 12 mm Hg after repeated embolization, p less than 0.05). However, right ventricular stroke volume decreased by only an insignificant amount (17 +/- 7 ml to 15 +/- 6 ml, p = not significant). Indices of left ventricular end-diastolic volume (left ventricular area = anteroposterior x septum-to-left ventricle free wall diameters) and stroke work (stroke work = area of the left ventricular pressure-area loop) were also similar before and after repeated embolization. Volume loading after repeated embolization resulted in increased right ventricular stroke volume (15 +/- 6 ml to 20 +/- 4 ml, p = 0.06), left ventricular area (3320 +/- 600 mm2 to 3470 +/- 580 mm2, p less than 0.05) and stroke work (261 +/- 158 mm Hg to 425 +/- 170 mm Hg x mm2, p less than 0.05). These results are in marked contrast to those in a previously reported study in a closed-chest and closed-pericardium model in which there was a decrease in left ventricular preload and systolic function after similar embolization-induced right ventricular pressure loading. Moreover, there was a further decrease in these parameters as a result of volume loading after embolism in the closed pericardium experiments. In conclusion, pericardial constraint contributes to hemodynamic deterioration during both acute right ventricular pressure loading and subsequent volume loading. The hemodynamic response to both interventions in the intact animal is determined not only by the degree of right ventricular dysfunction but also by the degree of direct ventricular interaction.

Transit-time flow predicts outcomes in coronary artery bypass graft patients: a series of 1000 consecutive arterial grafts §

OBJECTIVE This study was undertaken to evaluate transit-time flow (TTF) as a tool to detect technical errors in arterial bypass grafts intra-operatively and predict outcomes. METHODS TTFs three parameters, pulsatility index (PI, index of resistance), flow (cc min(-1)) and diastolic filling (DF, proportion of diastole with coronary flow), were measured in 990/1000 (99%) of arterial grafts in 336 consecutive patients, prospectively enrolled in a database. Grafts were revised when TTF findings supported the otherwise suspected graft malfunction. If no other signs/suspicion of graft malfunction existed (normal electrocardiogram (EKG), stable haemodynamics and unchanged ventricular function on trans-oesophageal echocardiography (TEE)), and the PI was >5, grafts were not revised. Major adverse cardiac events (MACEs: recurrent angina, perioperative myocardial infarction, postoperative angioplasty, re-operation and/or perioperative death) were related to TTF measurements. RESULTS The average number of grafts per patient was 3.02, of which 99% were arterial. Satisfactory grafts were achieved in 916/990 (93%) of the grafts, with flows from 34 to 61 cc min(-1), PI < or =5 and DF of 62-85%. Fourteen conduits, 20 grafts (2%) suspected to be problematic, were revised. Patients were divided into two groups: 277 (82%) with at least one graft with PI < or =5 and 59 (18%) with a PI >5. MACE occurred in 25 (7.4%) patients--15/277 patients with a PI < or =5 (5.4%) and 10/59 with a PI >5 (17%, p=0.005). Mortality following non-emergent surgery was significantly higher in patients with a PI >5 (5/54, 9%) than in patients with a PI < or =5 (5/250, 2%, p=0.02). Flow and DF were not predictive of outcomes. CONCLUSION A high PI predicts technically inadequate arterial grafts during surgery--even if all other intra-operative assessments indicate good grafts; it also predicts outcomes, particularly mortality.