Phenotyping heart failure by echocardiography: imaging of ventricular function and haemodynamics at rest and exercise.

Traditionally, congestive heart failure (HF) was phenotyped by echocardiography or other imaging techniques according to left ventricular (LV) ejection fraction (LVEF). The more recent echocardiographic modality speckle tracking strain is complementary to LVEF, as it is more sensitive to diagnose mild systolic dysfunction. Furthermore, when LV systolic dysfunction is associated with a small, hypertrophic ventricle, EF is often normal or supernormal, whereas LV global longitudinal strain can reveal reduced contractility. In addition, segmental strain patterns may be used to identify specific cardiomyopathies, which in some cases can be treated with patient-specific medicine. In HF with preserved EF (HFpEF), a diagnostic hallmark is elevated LV filling pressure, which can be diagnosed with good accuracy by applying a set of echocardiographic parameters. Patients with HFpEF often have normal filling pressure at rest, and a non-invasive or invasive diastolic stress test may be used to identify abnormal elevation of filling pressure during exercise. The novel parameter LV work index, which incorporates afterload, is a promising tool for quantification of LV contractile function and efficiency. Another novel modality is shear wave imaging for diagnosing stiff ventricles, but clinical utility remains to be determined. In conclusion, echocardiographic imaging of cardiac function should include LV strain as a supplementary method to LVEF. Echocardiographic parameters can identify elevated LV filling pressure with good accuracy and may be applied in the diagnostic workup of patients suspected of HFpEF.

Mechanical Effects on Right Ventricular Function From Left Bundle Branch Block and Cardiac Resynchronization Therapy.

OBJECTIVES: The purpose of this study was to investigate how LBBB and CRT modify RV free wall function by direct ventricular interaction. BACKGROUND: Right ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function. METHODS: In 24 patients with LBBB with nonischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers. RESULTS: Patients with LBBB demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall, which pushed the septum toward the RV. CRT reduced abnormal septal motion and increased RV free wall work because there was less inefficient shortening against low pressure. CONCLUSIONS: LBBB reduces workload on the RV free wall because of abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185).

Left bundle branch block increases left ventricular diastolic pressure during tachycardia due to incomplete relaxation.

We investigated whether tachycardia in left bundle branch block (LBBB) decreases left ventricular (LV) diastolic distensibility and increases diastolic pressures due to incomplete relaxation, and if cardiac resynchronization therapy (CRT) modifies this response. Thirteen canines were studied at baseline heart rate (120 beats/min) and atrial paced tachycardia (180 beats/min) before and after induction of LBBB and during CRT. LV and left atrial pressures (LAP) were measured by micromanometers and dimensions by sonomicrometry. The time constant τ of exponential pressure decay and degree of incomplete relaxation at mitral valve opening (MVO) and end diastole (ED) based on extrapolation of the exponential decay were assessed. Changes in LV diastolic distensibility were investigated using the LV transmural pressure-volume (PV) relation. LBBB caused prolongation of τ (P < 0.03) and increased the degree of incomplete relaxation during tachycardia at MVO (P < 0.001) and ED (P = 0.08) compared with normal electrical activation. This was associated with decreased diastolic distensibility seen as upward shift of the PV relation at MVO by 18.4 ± 7.0 versus 12.0 ± 5.0 mmHg, at ED by 9.8 ± 2.3 versus 4.7 ± 2.3 mmHg, and increased mean LAP to 11.4 ± 2.7 versus 8.5 ± 2.6 mmHg, all P < 0.006. CRT shifted the LV diastolic PV relation downwards during tachycardia, reducing LAP and LV diastolic pressures (P < 0.03). Tachycardia in LBBB reduced LV diastolic distensibility and increased LV diastolic pressures due to incomplete relaxation, whereas CRT normalized these effects. Clinical studies are needed to determine whether a similar mechanism contributes to dyspnea and exercise intolerance in LBBB and if effects of CRT are heart rate dependent.NEW & NOTEWORTHY Compared with normal electrical conduction, tachycardia in left bundle branch block resulted in incomplete relaxation during filling, particularly of the late activated left ventricular lateral wall. This further resulted in reduced left ventricular diastolic distensibility and elevated diastolic pressures and thus amplified the benefits of cardiac resynchronization therapy in this setting.

Afterload Hypersensitivity in Patients With Left Bundle Branch Block.

OBJECTIVES: This study sought to investigate the hypothesis that patients with left bundle branch block (LBBB) are hypersensitive to elevated afterload. BACKGROUND: Epidemiological data suggest that LBBB can provoke heart failure in patients with hypertension. METHODS: In 11 asymptomatic patients with isolated LBBB and 11 age-matched control subjects, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured by echocardiography. Systolic arterial pressure was increased by combining pneumatic extremity constrictors and handgrip exercise. To obtain more insight into mechanisms of afterload response, 8 anesthetized dogs with left ventricular (LV) micromanometer and dimension crystals were studied during acutely induced LBBB and aortic constriction. Regional myocardial work was assessed by LV pressure-dimension analysis. RESULTS: Consistent with normal afterload dependency, elevation of systolic arterial pressure by 38 ± 12 mm Hg moderately reduced LVEF from 60 ± 4% to 54 ± 6% (p < 0.01) in control subjects. In LBBB patients, however, a similar blood pressure increase caused substantially larger reduction in LVEF (p < 0.01), from 56 ± 6% to 42 ± 7% (p < 0.01). There were similar findings for GLS. In the dog model, aortic constriction abolished septal shortening (p < 0.02), and septal work decreased to negative values (p < 0.01). Therefore, during elevated systolic pressure, the septum made no contribution to global LV work, as indicated by net negative work, and instead absorbed energy from work done by the LV lateral wall. CONCLUSIONS: Moderate elevation of arterial pressure caused marked reductions in LVEF and GLS in patients with LBBB. This reflects a cardiodepressive effect of elevated afterload in the dyssynchronous ventricle and was attributed to loss of septal function.

Left ventricular end-systolic volume is a more sensitive marker of acute response to cardiac resynchronization therapy than contractility indices: insights from an experimental study.

AIMS: There are conflicting data and no consensus on how to measure acute response to cardiac resynchronization therapy (CRT). This study investigates, which contractility indices are best markers of acute CRT response. METHODS AND RESULTS: In eight anaesthetized dogs with left bundle branch block, we measured left ventricular (LV) pressure by micromanometer and end-diastolic volume (EDV) and end-systolic volume (ESV) by sonomicrometry. Systolic function was measured as LV ejection fraction (EF), peak rate of LV pressure rise (LV dP/dtmax) and as a gold standard of contractility, LV end-systolic elastance (Ees), and volume axis intercept (V0) calculated from end-systolic pressure-volume relations (ESPVR). Responses to CRT were compared with inotropic stimulation by dobutamine. Both CRT and dobutamine caused reduction in ESV (P < 0.01) and increase in LV dP/dtmax (P < 0.05). Both interventions shifted the ESPVR upwards indicating increased contractility, but CRT which reduced V0 (P < 0.01), caused no change in Ees. Dobutamine markedly increased Ees, which is the typical response to inotropic stimulation. Preload (EDV) was decreased (P < 0.01) by CRT, and there was no change in EF. When adjusting for the reduction in preload, CRT increased EF (P = 0.02) and caused a more marked increase in LV dP/dtmax (P < 0.01). CONCLUSION: Increased contractility by CRT could not be identified by Ees, which is a widely used reference method for contractility. Furthermore, reduction in preload by CRT attenuated improvement in contractility indices such as EF and LV dP/dtmax. These results suggest that changes in LV volume may be more sensitive markers of acute CRT response than conventional contractility indices.

Dysfunction of the systemic right ventricle after atrial switch: physiological implications of altered septal geometry and load.

Atrial switch operation in patients with transposition of the great arteries (TGA) leads to leftward shift and changes the geometry of the interventricular septum. By including the implications of regional work and septal curvature, this study investigates if changes in septal function and geometry contribute to reduced function of the systemic right ventricle (RV) in adult TGA patients. Regional myocardial work estimation has been possible by applying a recently developed method for noninvasive work calculation based on echocardiography. In 14 TGA patients (32 ± 6 yr, means ± SD) and 14 healthy controls, systemic ventricular systolic strains were measured by speckle tracking echocardiography and regional work was calculated by pressure-strain analysis. In TGA patients, septal longitudinal strain was reduced to -14 ± 2 vs. -20 ± 2% in controls ( P < 0.01) and septal work was reduced from 2,046 ± 318 to 1,146 ± 260 mmHg·% ( P < 0.01). Septal circumferential strain measured in a subgroup of patients was reduced to -11 ± 3 vs. -27 ± 3% in controls ( P < 0.01), and a reduction of septal work (540 ± 273 vs. 2,663 ± 459 mmHg·%) was seen ( P < 0.01). These reductions were in part attributed to elevated afterload due to increased radius of curvature of the leftward shifted septum. To conclude, in this mechanistic study we demonstrate that septal dysfunction contributes to failure of the systemic RV after atrial switch in TGA patients. This is potentially a long-term response to increased afterload due to a flatter septum and suggests that medical therapy that counteracts septal flattening may improve function of the systemic RV. NEW & NOTEWORTHY We have demonstrated that transposition of the great arteries patients with systemic right ventricles (RVs) have reduced function of the interventricular septum (IVS). Since the IVS is constructed to eject into the systemic circulation, it may seem unexpected that it does not maintain function when being part of the systemic RV. By applying the principles of regional work, wall tension, and geometry, we have identified unfavorable working conditions for the IVS when the RV adapts to systemic pressures.

Non-invasive myocardial work index identifies acute coronary occlusion in patients with non-ST-segment elevation-acute coronary syndrome.

AIMS: Acute coronary artery occlusion (ACO) occurs in ∼30% of patients with non-ST-segment elevation-acute coronary syndrome (NSTE-ACS). We investigated the ability of a regional non-invasive myocardial work index (MWI) to identify ACO. METHODS AND RESULTS: Segmental strain analysis was performed before coronary angiography in 126 patients with NSTE-ACS. Left ventricular (LV) pressure was estimated non-invasively using a standard waveform fitted to valvular events and scaled to systolic blood pressure. MWI was calculated as the area of the LV pressure-strain loop. Empirical cut-off values were set to identify segmental systolic dysfunction for MWI (<1700 mmHg %) and strain (more than -14%). The number of dysfunctional segments was used in ROC analysis to identify ACO. The presence of ≥4 adjacent dysfunctional segments assessed by MWI was significantly better than both global strain and ejection fraction at detecting the occurrence of ACO (P < 0.05). Regional MWI had a higher sensitivity (81 vs. 78%) and especially specificity (82 vs. 65%) compared with regional strain. Logistic regression demonstrated that elevated systolic blood pressure significantly decreased the probability of actual ACO in a patient with an area of impaired regional strain. CONCLUSION: The presence of a region of reduced MWI in patients with NSTE-ACS identified patients with ACO and was superior to all other parameters. The regional MWI was able to account for the influence of systolic blood pressure on regional contraction. We therefore propose that MWI may serve as an important clinical tool for selecting patients in need of prompt invasive treatment.

Cardiac responses to left ventricular pacing in hearts with normal electrical conduction: beneficial effect of improved filling is counteracted by dyssynchrony.

Cardiac resynchronization therapy (CRT) has been proposed in heart failure patients with narrow QRS, but the mechanism of a potential beneficial effect is unknown. The present study investigated the hypothesis that left ventricular (LV) pacing increases LV end-diastolic volume (LVEDV) by allowing the LV to start filling before the right ventricle (RV) during narrow QRS in an experimental model. LV and biventricular pacing were studied in six anesthetized dogs before and after the induction of LV failure. Function was evaluated by pressures and dimensions, and dyssynchrony was evaluated by electromyograms and deformation. In the nonfailing heart, LV pacing gave the LV a head start in filling relative to the RV (P < 0.05) and increased LVEDV (P < 0.05). The response was similar during LV failure when RV diastolic pressure was elevated. The pacing-induced increase in LVEDV was attributed to a rightward shift of the septum (P < 0.01) due to an increased left-to-right transseptal pressure gradient (P < 0.05). LV pacing, however, also induced dyssynchrony (P < 0.05) and therefore reduced LV stroke work (P < 0.05) during baseline, and similar results were seen in failing hearts. Biventricular pacing did not change LVEDV, but systolic function was impaired. This effect was less marked than with LV pacing. In conclusion, pacing of the LV lateral wall increased LVEDV by displacing the septum rightward, suggesting a mechanism for a favorable effect of CRT in narrow QRS. The pacing, however, induced dyssynchrony and therefore reduced LV systolic function. These observations suggest that detrimental effects should be considered when applying CRT in patients with narrow QRS.