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.

Tracking Early Systolic Motion for Assessing Acute Response to Cardiac Resynchronization Therapy in Real Time.

An abnormal systolic motion is frequently observed in patients with left bundle branch block (LBBB), and it has been proposed as a predictor of response to cardiac resynchronization therapy (CRT). Our goal was to investigate if this motion can be monitored with miniaturized sensors feasible for clinical use to identify response to CRT in real time. Motion sensors were attached to the septum and the left ventricular (LV) lateral wall of eighteen anesthetized dogs. Recordings were performed during baseline, after induction of LBBB, and during biventricular pacing. The abnormal contraction pattern in LBBB was quantified by the septal flash index (SFI) equal to the early systolic shortening of the LV septal-to-lateral wall diameter divided by the maximum shortening achieved during ejection. In baseline, with normal electrical activation, there was limited early-systolic shortening and SFI was low (9 ± 8%). After induction of LBBB, this shortening and the SFI significantly increased (88 ± 34%, p < 0.001). Subsequently, CRT reduced it approximately back to baseline values (13 ± 13%, p < 0.001 vs. LBBB). The study showed the feasibility of using miniaturized sensors for continuous monitoring of the abnormal systolic motion of the LV in LBBB and how such sensors can be used to assess response to pacing in real time to guide CRT implantation.

Determinants of left atrial reservoir and pump strain and use of atrial strain for evaluation of left ventricular filling pressure.

AIMS: The aim of this study is to investigate determinants of left atrial (LA) reservoir and pump strain and if these parameters may serve as non-invasive markers of left ventricular (LV) filling pressure. METHODS AND RESULTS: In a multicentre study of 322 patients with cardiovascular disease of different aetiologies, LA strain and other echocardiographic parameters were compared with invasively measured LV filling pressure. The strongest determinants of LA reservoir and pump strain were LV global longitudinal strain (GLS) (r-values 0.64 and 0.51, respectively) and LV filling pressure (r-values -0.52 and -0.57, respectively). Left atrial volume was another independent, but weaker determinant of both LA strains. For both LA strains, association with LV filling pressure was strongest in patients with reduced LV ejection fraction. Left atrial reservoir strain <18% and LA pump strain <8% predicted elevated LV filling pressure better (P < 0.05) than LA volume and conventional Doppler parameters. Accuracy to identify elevated LV filling pressure was 75% for LA reservoir strain alone and 72% for pump strain alone. When combined with conventional parameters, accuracy was 82% for both LA strains. In patients with normal LV systolic function by GLS, LA pump strain >14% identified normal LV filling pressure with 92% accuracy. CONCLUSION: Left atrial reservoir and pump strain are determined predominantly by LV GLS and filling pressure. Accuracy of LA strains to identify elevated LV filling pressure was best in patients with reduced LV systolic function. High values of LA pump strain, however, identified normal LV filling pressure with good accuracy in patients with normal systolic function.

Diastolic Stress Test: Invasive and Noninvasive Testing.

Diastolic dysfunction is a key factor in the pathogenesis of heart failure. Around 50% of cases of heart failure, the hemodynamic correlate of which is increased left ventricular filling pressure, are caused by diastolic dysfunction in the setting of apparently normal systolic function. Due to its high prevalence, diastolic dysfunction is often recognized as an incidental finding. Many patients have Doppler echocardiographic evidence of impaired diastolic function but do not have any symptoms of heart failure at rest. In many of these patients, symptoms of diastolic dysfunction occur only during exercise, as left ventricular filling pressure is normal at rest, but increases with exercise. This implies that filling pressures should also be measured during exercise. The diastolic stress test refers to the evaluation of diastolic function, either invasively or noninvasively, during exercise. This review focuses on the clinical need for diastolic stress testing, both invasively and noninvasively.

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.

Mechanism of Abnormal Septal Motion in Left Bundle Branch Block: Role of Left Ventricular Wall Interactions and Myocardial Scar.

OBJECTIVES: This study sought to investigate how regional left ventricular (LV) function modifies septal motion in left bundle branch block (LBBB). BACKGROUND: In LBBB, the interventricular septum often has marked pre-ejection shortening, followed by immediate relengthening (rebound stretch). This motion, often referred to as septal flash, is associated with positive response to cardiac resynchronization therapy (CRT). METHODS: In 10 anesthetized dogs, we induced LBBB by radiofrequency ablation and occluded the circumflex (CX) (n = 10) and left anterior descending (LAD) (n = 6) coronary arteries, respectively. Myocardial dimensions were measured by sonomicrometry and myocardial work by pressure-segment length analysis. In 40 heart failure patients with LBBB, including 20 with post-infarct scar and 20 with nonischemic cardiomyopathy, myocardial strain was measured by speckle-tracking echocardiography and myocardial work by pressure-strain analysis. Scar was assessed by cardiac magnetic resonance imaging with late gadolinium enhancement. RESULTS: During LBBB, each animal showed typical septal flash with pre-ejection shortening and rebound stretch, followed by reduced septal systolic shortening (p < 0.01). CX occlusion caused LV lateral wall dysfunction and abolished septal flash due to loss of rebound stretch (p < 0.0001). Furthermore, CX occlusion restored septal systolic shortening to a similar level as before induction of LBBB and substantially improved septal work (p < 0.001). LAD occlusion, however, accentuated septal flash by increasing rebound stretch (p < 0.05). Consistent with the experimental findings, septal flash was absent in patients with LV lateral wall scar due to lack of rebound stretch (p < 0.001), and septal systolic shortening and septal work far exceeded values in nonischemic cardiomyopathy (p < 0.0001). Septal flash was present in most patients with anteroseptal scar. CONCLUSIONS: LV lateral wall dysfunction and scar abolished septal flash and markedly improved septal function in LBBB. Therefore, function and scar in the LV lateral wall should be taken into account when septal motion is used to evaluate dyssynchrony.

Mean Right Atrial Pressure for Estimation of Left Ventricular Filling Pressure in Patients with Normal Left Ventricular Ejection Fraction: Invasive and Noninvasive Validation.

BACKGROUND: There is a paucity of data on the utility of right atrial pressure (RAP) for estimating pulmonary capillary wedge pressure (PCWP) in patients with normal ejection fraction (EF), including patients with heart failure with preserved EF. METHODS: Mean RAP was compared with PCWP in 129 patients (mean age, 61 ± 11 years; 45% men) with exertional dyspnea enrolled in a multicenter study. Measurements included left ventricular volumes, EF, and mitral inflow velocities. RESULTS: Mean PCWP was 14 ± 7 mm Hg, and mean RAP was 8 ± 5 mm Hg. A significant relation was present between mean RAP and mean PCWP (r2 = 0.5, P < .001). RAP > 8 mm Hg had 76% sensitivity and 86% specificity in detecting mean PCWP > 12 mm Hg. In 101 patients with inconclusive mitral filling pattern (defined according to American Society of Echocardiography/European Association of Cardiovascular Imaging 2016 diastolic function recommendations), RAP by catheterization had sensitivity of 73% and specificity of 91%. In a subset of 59 patients with echocardiographic assessment of mean RAP, RAP by echocardiography had sensitivity of 76% and specificity of 89%. CONCLUSIONS: Mean RAP provides useful information about mean PCWP in many patients with normal left ventricular EF. There is good sensitivity and excellent specificity when combining invasive or noninvasive RAP and mitral velocities to determine if PCWP is elevated.

Estimating Left Ventricular Filling Pressure by Echocardiography.

BACKGROUND: The diagnosis of heart failure may be challenging because symptoms are rather nonspecific. Elevated left ventricular (LV) filling pressure may be used to confirm the diagnosis, but cardiac catheterization is often not practical. Echocardiographic indexes are therefore used as markers of filling pressure. OBJECTIVES: This study investigated the feasibility and accuracy of comprehensive echocardiography in identifying patients with elevated LV filling pressure. METHODS: We conducted a multicenter study of 450 patients with a wide spectrum of cardiac diseases referred for cardiac catheterization. Left atrial volume index, in combination with flow velocities and tissue Doppler velocities, was used to estimate LV filling pressure. Invasively measured pressure was used as the gold standard. RESULTS: Mean left ventricular ejection fraction (LVEF) was 47%, with 209 patients having an LVEF <50%. Invasive measurements showed elevated LV filling pressure in 58% of patients. Clinical assessment had an accuracy of 72% in identifying patients with elevated filling pressure, whereas echocardiography had an accuracy of 87% (p < 0.001 vs. clinical assessment). The combination of clinical and echocardiographic assessment was incremental, with a net reclassification improvement of 1.5 versus clinical assessment (p < 0.001). CONCLUSIONS: Echocardiographic assessment of LV filling pressure is feasible and accurate. When combined with clinical data, it leads to a more accurate diagnosis, regardless of LVEF.