Hemodynamic Assessment in Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is a reversible form of heart failure with incompletely understood pathophysiology. OBJECTIVES: This study analyzed altered cardiac hemodynamics during TTS to elucidate underlying disease mechanisms. METHODS: Left ventricular (LV) pressure-volume loops were recorded in 24 consecutive patients with TTS and a control population of 20 participants without cardiovascular diseases. RESULTS: TTS was associated with impaired LV contractility (end-systolic elastance 1.74 mm Hg/mL vs 2.35 mm Hg/mL [P = 0.024]; maximal rate of change in systolic pressure over time 1,533 mm Hg/s vs 1,763 mm Hg/s [P = 0.031]; end-systolic volume at a pressure of 150 mm Hg, 77.3 mL vs 46.4 mL [P = 0.002]); and a shortened systolic period (286 ms vs 343 ms [P < 0.001]). In response, the pressure-volume diagram was shifted rightward with significantly increased LV end-diastolic (P = 0.031) and end-systolic (P < 0.001) volumes, which preserved LV stroke volume (P = 0.370) despite a lower LV ejection fraction (P < 0.001). Diastolic function was characterized by prolonged active relaxation (relaxation constant 69.5 ms vs 45.9 ms [P < 0.001]; minimal rate of change in diastolic pressure -1,457 mm Hg/s vs -2,192 mm Hg/s [P < 0.001]), whereas diastolic stiffness (1/compliance) was not affected during TTS (end-diastolic volume at a pressure of 15 mm Hg, 96.7 mL vs 109.0 mL [P = 0.942]). Mechanical efficiency was significantly reduced in TTS (P < 0.001) considering reduced stroke work (P = 0.001), increased potential energy (P = 0.036), and a similar total pressure-volume area compared with that of control subjects (P = 0.357). CONCLUSIONS: TTS is characterized by reduced cardiac contractility, a shortened systolic period, inefficient energetics, and prolonged active relaxation but unaltered diastolic passive stiffness. These findings may suggest decreased phosphorylation of myofilament proteins, which represents a potential therapeutic target in TTS. (Optimized Characterization of Takotsubo Syndrome by Obtaining Pressure Volume Loops [OCTOPUS]; NCT03726528).

Echocardiographic assessment of embryonic and fetal mouse heart development: a focus on haemodynamics and morphology.

BACKGROUND: Heart development is a complex process, and abnormal development may result in congenital heart disease (CHD). Currently, studies on animal models mainly focus on cardiac morphology and the availability of hemodynamic data, especially of the right heart half, is limited. Here we aimed to assess the morphological and hemodynamic parameters of normal developing mouse embryos/fetuses by using a high-frequency ultrasound system. METHODS: A timed breeding program was initiated with a WT mouse line (Swiss/129Sv background). All recordings were performed transabdominally, in isoflurane sedated pregnant mice, in hearts of sequential developmental stages: 12.5, 14.5, and 17.5 days after conception (n = 105). RESULTS: Along development the heart rate increased significantly from 125 ± 9.5 to 219 ± 8.3 beats per minute. Reliable flow measurements could be performed across the developing mitral and tricuspid valves and outflow tract. M-mode measurements could be obtained of all cardiac compartments. An overall increase of cardiac systolic and diastolic function with embryonic/fetal development was observed. CONCLUSION: High-frequency echocardiography is a promising and useful imaging modality for structural and hemodynamic analysis of embryonic/fetal mouse hearts.

Left ventricular diastolic dysfunction during acute myocardial infarction: effect of mild hypothermia.

BACKGROUND: Mild hypothermia (MH) decreases infarct size and mortality in experimental reperfused myocardial infarction, but may potentiate ischaemia-induced left ventricular (LV) diastolic dysfunction. METHODS: In anaesthetized pigs (70 ± 2 kg), polystyrol microspheres (45 µm) were infused repeatedly into the left circumflex artery until cardiac power output decreased >40%. Then, pigs were assigned to normothermia (NT, 38.0°C, n=8) or MH (33.0°C, n=8, intravascular cooling) and followed for 6h (CME 6h). p<0.05 vs baseline, †p<0.05 vs NT. RESULTS: In NT, cardiac output (CO) decreased from 6.2 ± 0.3 to 3.4 ± 0.2 l/min, and heart rate increased from 89 ± 4 to 101 ± 6 bpm. LV end-diastolic volume fell from 139 ± 8 to 64 ± 4 ml, while LV ejection fraction remained constant (49 ± 1 vs 53 ± 4%). The corresponding end-diastolic pressure-volume relationship was progressively shifted leftwards, reflecting severe LV diastolic dysfunction. In MH, CO fell to a similar degree. Spontaneous bradycardia compensated for slowed LV relaxation, and the leftward shift of the end-diastolic pressure-volume relationship was less pronounced during MH. MH increased systemic vascular resistance, such that mean aortic pressure remained higher in MH vs NT (69 ± 2† vs 54 ± 4 mm Hg). Mixed venous oxygen saturation at CME 6h was higher in MH than in NT (59 ± 4† vs 42 ± 2%) due to lowered systemic oxygen demand during cooling. CONCLUSION: We conclude that (i) an acute loss of end-diastolic LV compliance is a major component of acute cardiac pump failure during experimental myocardial infarction, and that (ii) MH does not potentiate this diastolic LV failure, but stabilizes haemodynamics and improves systemic oxygen supply/demand imbalance by reducing demand.

Bramwell-Hill modeling for local aortic pulse wave velocity estimation: a validation study with velocity-encoded cardiovascular magnetic resonance and invasive pressure assessment.

BACKGROUND: The Bramwell-Hill model describes the relation between vascular wall stiffness expressed in aortic distensibility and the pulse wave velocity (PWV), which is the propagation speed of the systolic pressure wave through the aorta. The main objective of this study was to test the validity of this model locally in the aorta by using PWV-assessments based on in-plane velocity-encoded cardiovascular magnetic resonance (CMR), with invasive pressure measurements serving as the gold standard. METHODS: Seventeen patients (14 male, 3 female, mean age ± standard deviation = 57 ± 9 years) awaiting cardiac catheterization were prospectively included. During catheterization, intra-arterial pressure measurements were obtained in the aorta at multiple locations 5.8 cm apart. PWV was determined regionally over the aortic arch and locally in the proximal descending aorta. Subsequently, patients underwent a CMR examination to measure aortic PWV and aortic distention. Distensibility was determined locally from the aortic distension at the proximal descending aorta and the pulse pressure measured invasively during catheterization and non-invasively from brachial cuff-assessment. PWV was determined regionally in the aortic arch using through-plane and in-plane velocity-encoded CMR, and locally at the proximal descending aorta using in-plane velocity-encoded CMR. Validity of the Bramwell-Hill model was tested by evaluating associations between distensibility and PWV. Also, theoretical PWV was calculated from distensibility measurements and compared with pressure-assessed PWV. RESULTS: In-plane velocity-encoded CMR provides stronger correlation (p = 0.02) between CMR and pressure-assessed PWV than through-plane velocity-encoded CMR (r = 0.69 versus r = 0.26), with a non-significant mean error of 0.2 ± 1.6 m/s for in-plane versus a significant (p = 0.006) error of 1.3 ± 1.7 m/s for through-plane velocity-encoded CMR. The Bramwell-Hill model shows a significantly (p = 0.01) stronger association between distensibility and PWV for local assessment (r = 0.8) than for regional assessment (r = 0.7), both for CMR and for pressure-assessed PWV. Theoretical PWV is strongly correlated (r = 0.8) with pressure-assessed PWV, with a statistically significant (p = 0.04) mean underestimation of 0.6 ± 1.1 m/s. This theoretical PWV-estimation is more accurate when invasively-assessed pulse pressure is used instead of brachial cuff-assessment (p = 0.03). CONCLUSIONS: CMR with in-plane velocity-encoding is the optimal approach for studying Bramwell-Hill associations between local PWV and aortic distensibility. This approach enables non-invasive estimation of local pulse pressure and distensibility.

Improved aortic pulse wave velocity assessment from multislice two-directional in-plane velocity-encoded magnetic resonance imaging.

PURPOSE: To evaluate the accuracy and reproducibility of aortic pulse wave velocity (PWV) assessment by in-plane velocity-encoded magnetic resonance imaging (MRI). MATERIALS AND METHODS: In 14 patients selected for cardiac catheterization on suspicion of coronary artery disease and 15 healthy volunteers, PWV was assessed with multislice two-directional in-plane velocity-encoded MRI (PWV(i.p.)) and compared with conventionally assessed PWV from multisite one-directional through-plane velocity-encoded MRI (PWV(t.p.)). In patients, PWV was also obtained from intraarterially acquired pressure-time curves (PWV(pressure)), which is considered the gold standard reference method. In volunteers, PWV(i.p.) and PWV(t.p.) were obtained in duplicate in the same examination to test reproducibility. RESULTS: In patients, PWV(i.p.) showed stronger correlation and similar variation with PWV(pressure) than PWV(t.p.) (Pearson correlation r = 0.75 vs. r = 0.58, and coefficient of variation [COV] = 10% vs. COV = 12%, respectively). In volunteers, repeated PWV(i.p.) assessment showed stronger correlation and less variation than repeated PWV(t.p.) (proximal aorta: r = 0.97 and COV = 10% vs. r = 0.69 and COV = 17%; distal aorta: r = 0.94 and COV = 12% vs. r = 0.90 and COV = 16%; total aorta: r = 0.97 and COV = 7% vs. r = 0.90 and COV = 13%). CONCLUSION: PWV(i.p.) is an improvement over conventional PWV(t.p.) by showing higher agreement as compared to the gold standard (PWV(pressure)) and higher reproducibility for repeated MRI assessment.

Integrated assessment of diastolic and systolic ventricular function using diagnostic cardiac magnetic resonance catheterization: validation in pigs and application in a clinical pilot study.

OBJECTIVES: This study sought to develop and validate a method for the integrated analysis of systolic and diastolic ventricular function. BACKGROUND: An integrated approach to assess ventricular pump function, myocontractility (end-systolic pressure-volume relationship [ESPVR]), and diastolic compliance (end-diastolic pressure-volume relation [EDPVR]) is of high clinical value. Cardiac magnetic resonance (CMR) is well established for measuring global pump function, and catheterization-combined CMR was previously shown to accurately measure ESPVR, but not yet the EDPVR. METHODS: In 8 pigs, the CMR technique was compared with conductance catheter methods (gold standard) for measuring the EDPVR in the left and right ventricle. Measurements were performed at rest and during dobutamine administration. For CMR, the ESPVR was estimated with a single-beat approach by synchronizing invasive ventricular pressures with cine CMR-derived ventricular volumes. The EDPVR was determined during pre-load reduction from additional volume data that were obtained from real-time velocity-encoded CMR pulmonary/aortic blood flow measurements. Pre-load reduction was achieved by transient balloon occlusion of the inferior vena cava. The stiffness coefficient beta was calculated by an exponential fit from the EDPVR. After validation in the animal experiments, the EDPVR was assessed in a pilot study of 3 patients with a single ventricle using identical CMR and conductance catheter techniques. RESULTS: Bland-Altman tests showed good agreement between conductance catheter-derived and CMR-derived EDPVR. In both ventricles of the pigs, dobutamine enhanced myocontractility (p < 0.01), increased stroke volume (p < 0.01), and improved diastolic function. The latter was evidenced by shorter early relaxation (p < 0.05), a downward shift of the EDPVR, and a decreased stiffness coefficient beta (p < 0.05). In contrast, in the patients, early relaxation was inconspicuous but the EDPVR shifted left-upward and the stiffness constant remained unchanged. The observed changes in diastolic function were not significantly different when measured with conductance catheter and CMR. CONCLUSIONS: This novel CMR method provides differential information about diastolic function in conjunction with parameters of systolic contractility and global pump function.

Assessment of parallel conductance for the trans-cardiac conductance method: can we use the hypertonic saline method with pulmonary artery injections?

The trans-cardiac conductance (TCC) method provides on-line left ventricular (LV) volume signals by determining the electrical conductance of blood in the LV using central venous and epithoracic electrodes. Conductive structures outside the LV cause a 'parallel conductance' offset term (Vp) that is determined by bolus injections of hypertonic saline in the pulmonary artery (Vp(saline)). Analysis of the increased conductance signal during passage of the bolus through the LV yields Vp(saline). Since TCC signals are picked up by epithoracic electrodes, concern has been raised that hypertonic saline remaining in the lungs might lead to overestimation. The decrease in blood conductivity induced by injection of non-ionic contrast medium during a LV angiogram may also be used to determine Vp (Vp(contrast)). Since the contrast is injected directly into the LV, lung conductance should be unaltered. Thus, we compared Vp(saline) with Vp(contrast) in six anaesthetized sheep during different hemodynamic conditions. Linear regression showed that Vp(saline) = 0.99 Vp(contrast) + 2.45 ml (r2 = 0.99). Bland-Altman analysis yielded a small non-significant bias (+/-2SD) of 1.8 (+/-6.8) ml. We conclude that parallel conductance for TCC can be accurately determined with the conventional hypertonic saline method.

Perioperative assessment of left ventricular function by pressure-volume loops using the conductance catheter method.

UNLABELLED: Interpretation of perioperative measurements of cardiac function during cardiac surgery is complicated by changes in loading conditions induced by anesthesia, cardiopulmonary bypass (CPB), and the surgical procedure itself. Quantification of left ventricular (LV) function by pressure-volume relations as obtained by the conductance catheter would be advantageous because load-independent indices can be determined. Accordingly, we evaluated methodological aspects of the conductance-catheter technique and documented LV function before and after CPB in eight patients undergoing coronary artery bypass grafting. LV pressure-volume loops by transesophageal echocardiography-guided transaortic application of the conductance catheter were obtained at steady-state and during preload reduction by temporary occlusion of the inferior cava. All patients remained hemodynamically stable, and no complications occurred. Complete data were acquired within 15 min before and after CPB. Cardiac output (5.2 +/- 1.3 L/min to 6.0 +/- 1.4 L/min) and LV ejection fraction (46% +/- 17% to 48% +/- 19%) did not change, but end-diastolic pressure increased significantly after CPB (8 +/- 2 mm Hg to 16 +/- 7 mm Hg; P < 0.05). Load-independent systolic indices remained constant (end-systolic elastance: 1.31 +/- 1.20 mm Hg/mL to 1.13 +/- 0.59 mm Hg/mL). Diastolic function changed significantly after CPB, as the relaxation time constant decreased from 64 +/- 6 ms to 52 +/- 5 ms (P < 0.05) and the chamber stiffness constant increased from 0.016 +/- 0.014/mL to 0.038 +/- 0.016/mL (P < 0.05). We conclude that the conductance catheter method provides detailed data on perioperative myocardial function and may be useful for evaluating the effects of new surgical and anesthetic procedures. IMPLICATIONS: Pressure-volume loops provide on-line quantification of intrinsic systolic and diastolic myocardial function in a load-independent fashion. This study shows the feasibility of perioperative pressure-volume analysis by use of the conductance-catheter method. This method provides detailed data about the immediate effects of surgery and may be used to evaluate complex cardiac procedures.

The trans-cardiac conductance method for on-line measurement of left ventricular volume: assessment of parallel conductance offset volume.

The trans-cardiac conductance (TCC) method provides on-line left ventricular (LV) volume signals by determining the electrical conductance of blood in the LV by means of central venous and epithoracic electrodes. Conductive structures outside the LV blood pool cause a "parallel conductance" offset term (Vp) that can be determined by bolus injections of hypertonic saline in the pulmonary artery (Vp(saline)), which cause a transient increase in blood conductivity. This study in anesthetized sheep evaluates the accuracy of the saline calibration method and the variabilities of Vp between animals, between hemodynamic conditions and during the cardiac cycle. The conventional intra-cardiac conductance catheter method was used to obtain independent estimates of Vp by the zero-volume method (Vp(zero volume)). Mean baseline Vp(saline) and Vp(zerovolume) were 104 +/- 6 ml and 106 +/- 6 ml, respectively. Bland-Altman analysis showed a small nonsignificant bias (-2.5 ml) and narrow limits of agreement (4.6 ml). Vp was not significantly different between hemodynamic conditions (baseline, dobutamine, volume load, propranolol), but had a substantial interanimal variability (IAV) (38%). Average variations during the cardiac cycle were < 10% of mean Vp. We conclude that the saline method can be applied to determine Vp for TCC. IAV is substantial, so that Vp must be determined in each animal, but within-animal variability is relatively small.