Alterations in Left Atrial Structure, Phasic Function and Atrioventricular Coupling Impact Cardiac Performance in Heart Failure with Preserved Ejection Fraction

The 18th Annual Scientific Meeting



HFSA

S71

Cardiovascular Physiology II 179 WITHDRAWN

progressively increased over 5365 days (minimum517 days; maximum574 days) until the stimulation target was reached. Mean electrode impedance decreased 16% during TP (from 24676164 U to 20726130 U, p!0.001). VNS parameters were systematically adjusted during TP and significantly accelerated adaptation of TZB from 0.360.12 mA/week to 0.8460.04 mA/week (p!0.025). There were no deviceor stimulation-related adverse events or chronic side effects. Holter analysis showed no increase in ectopic activity, heart block, or other cardiac abnormalities. Conclusions: Chronic low-intensity, natural frequency ART is well tolerated and elicits no side effects while reflex adaptation occurs during the titration period. These findings have important implications for the clinical application of ART in human subjects, and may provide a means to minimize the duration of titration and maximize therapy delivery.

181 Pulmonary Arterial Capacitance and Pulmonary Vascular Resistance are Inversely Related and May Predict Mortality in Critically Ill Mechanically Ventilated Surgical Patients Muddassir Mehmood, Ronald J. Markert, Mukul S. Chandra, Mary C. McCarthy, Kathryn M. Tchorz; Wright State University, Dayton, OH Background: Pulmonary arterial capacitance (PAC, the ratio of stroke volume over pulmonary pulse pressure) (mL/mmHg), a recently proposed determinant of right ventricular afterload, has been shown to be a better predictor of mortality than pulmonary vascular resistance (PVR) (Wood Units) in pulmonary arterial hypertension. In healthy individuals and in patients with pulmonary artery hypertension, PVR and PAC are inversely related. This relationship and the prognostic value of PAC have not been investigated in mechanically ventilated critically ill surgical patients. Objectives: To determine the relationship between serial PAC and PVR and to compare PAC and PVR among survivors and non-survivors in critically ill mechanically ventilated surgical patients during the first 48 hours of admission to the surgical ICU. Methods: We prospectively studied 32 critically ill and/or injured mechanical ventilated adult surgical patients admitted to a Level I Trauma Center. Invasive hemodynamics were transduced from pulmonary artery catheter every 12 hrs for 48 hours. Spearman’s rank correlation was used to assess the relationship, and repeated measures analysis of variance was used to compare survivors and non-survivors on PAC and PVR. Results: Patients (n532), mean age 49620 years, 69% male were included. Of the 27 trauma patients, mean Injury Severity Score 24610, seven expired. All 5 emergency general surgery patients survived. Serial PAC showed strong inverse correlation with PVR (r 5 -0.74, -0.62, -0.78, -0.72, and -0.68, p !0.001). The differences in PAC and PVR amongst survivors and non-survivors at 0, 12 and 36 hours were not statistically significant. However at 48-hrs non-survivors had significantly lower PAC (3.161.5 vs 5.461.7, p 5 0.007) and higher PVR (4.161.8 vs 1.860.9, p 5 0.001) compared to survivors. Conclusion: The strong inverse relationship of PAC and PVR is maintained in mechanically ventilated critically ill trauma and surgical patients. The prognostic value of PAC and PVR may have important implications for management during first 48hrs of resuscitation.

180 Autonomic Regulation Therapy Titration Methodology Accelerates Adaptation to Low-Intensity Vagus Nerve Stimulation Imad Libbus1, Badri Amurthur1, Bruce H. KenKnight1, Inder S. Anand2; 1 Cyberonics, Houston, TX; 2VA Medical Center and University of Minnesota, Minneapolis, MN Background: Recent studies have demonstrated that autonomic regulation therapy (ART) via chronic open-loop, intermittent vagus nerve stimulation (VNS) may have cardioprotective effects in animals and humans with heart failure and cardiac arrhythmias. When ART is first activated, VNS intensity is constrained by a central expiratory reflex that triggers mild coughing that coincides with VNS. In response to chronic, continuously-cyclic VNS, reflex adaptation occurs, and the tolerance zone boundary (TZB) increases over several weeks. Improved understanding of TZB adaptation is critically important to avoid exposing patients to intolerable side effects that could otherwise limit VNS therapy delivery. Methods: Normal canines (n512) were randomized 1:1 to left or right-sided cervical VNS system implant. After 2 weeks of post-surgical recovery, cyclic (14 s-ON, 66 s-OFF) ART was progressively adjusted to a natural pulse frequency of 10 Hz, pulse width of 250 msec, and pulse amplitude of 2.5 mA (right side) or 3.0 mA (left side) over a 10-week titration period (TP). Holter monitoring (24 hr) was performed every 4 weeks to assess heart rate and rhythm. To accelerate VNS tolerance during TP, pulse width was reduced (to 130 ms), duty cycle was increased (to 14 s-ON, 30 s-OFF), and frequency was adjusted. Results: All animals were titrated to the VNS target intensity, and no chronic side effects or arrhythmias were observed. During TP, the TZB

182 Alterations in Left Atrial Structure, Phasic Function and Atrioventricular Coupling Impact Cardiac Performance in Heart Failure with Preserved Ejection Fraction Rosita Zakeri, Hiroyuki Takahama, Philip A. Araoz, Hon-Chi Lee, Margaret M. Redfield; Mayo Clinic, Rochester, MN Introduction: In heart failure with preserved ejection fraction (HFpEF), left atrial (LA) enlargement ostensibly compensates for chronically elevated left ventricular (LV) filling pressures. However, LA pathophysiology has not been characterized in HFpEF. Diminished LA compliance and emptying function, analogous to LV remodelling in HFpEF, may effectively limit atrial contribution to LV filling and worsen filling pressures, despite LA enlargement. Hypothesis: We sought to define LA structural remodelling and phasic function in HFpEF and test the hypothesis that maladaptive atrioventricular coupling compromises cardiac performance, as assessed by LV stroke volume (SV). Methods: HFpEF was modelled by induced hypertension (bilateral renal wrap) and exogenous aldosterone administration in elderly dogs (n59). After 8 weeks, LA and LV structure, function, and invasively assessed pressure-volume relationships (PVR, open-chest) were compared to sham-operated young dogs (n513). Results: HFpEF dogs displayed increased LA volume (magnetic resonance imaging), LA cellular hypertrophy, and increased LA mass. Active emptying fraction was higher and the proportional contribution of LA reservoir and active function to LVSV was greater than in controls. Atrioventricular coupling was assessed by the quotient of LV (ELV) and LA (ELA) end-systolic PVR. At matched heart rate and LA pressure, ELA was steeper in HFpEF than control (2.760.9 vs 1.560.6mmHg/ mL, p50.01) but atrioventricular mismatch occurred due to a disproportionate rise

S72 Journal of Cardiac Failure Vol. 20 No. 8S August 2014 in ELV (HFpEF 1.360.4 vs sham 0.860.4, p!0.05). Higher ELV/ELA correlated with increased LA volume and lower LVSV. The LA end-reservoir PVR was also steeper in HFpEF (0.1660.08 vs 0.0860.04, p50.01) suggesting reduced LA compliance. Net atrioventricular compliance (Cn), calculated from mean LA and LV compliance, was significantly lower in HFpEF, and explained greater variance in LVSV (^r250.72, p!0.01) than mean LV compliance alone (^r250.38, p!0.01). There was no correlation between LA volume and Cn. Conclusion: These data indicate that HFpEF pathophysiology includes LA hypertrophy, reduced LA compliance and, despite enhanced LA contractile function, impaired atrioventricular coupling. The contribution of LA active function and LA-LV interaction to cardiac performance in this model suggests that operant atrioventricular synchrony is beneficial in HFpEF.

183 Pulmonary Arterial Pressure Patterns During Recovery From Incremental Exercise Reflect Right Ventricular-Pulmonary Vascular Reserve Aaron S. Eisman, Paul P. Pappagianopoulos, Stacyann S. Hough, Laurie A. Farrell, Ashley E. Dress, Gregory D. Lewis; Massachusetts General Hospital, Boston, MA Background: Acquisition of hemodynamic (HD) measurements during maximum incremental exercise testing can be highly informative but poses several challenges, including the need to account for patient motion, simultaneous additional data collection, and prediction of when peak exercise is anticipated to occur. We hypothesized that mean pulmonary arterial pressure (mPAP) patterns during recovery (i.e. slow recovery and persistent elevation vs. baseline) would be closely related to abnormal pulmonary vascular (RV-PV) reserve during exercise. Methods and Results: 76 consecutive patients referred to the Massachusetts General Hospital for maximum incremental cardiopulmonary exercise testing (CPET) with invasive HD monitoring (age 5861.7, 53% male, BMI 2860.6, LVEF 6362%; mean6SEM) to evaluate dyspnea on exertion were studied. mPAP was measured continuously with a Swan Ganz catheter and analyzed every 20 sec during exercise and recovery. CO was measured by the Fick method every minute during exercise. Resting and peak exercise mPAP were 1760.7 and 3661.2 mmHg, respectively. 55 patients were determined to have a normal and 21 to have abnormal pressure flow responses defined as exhibiting a #3:1 and a O3:1 ratio of change in mPAP to change in cardiac output (DPQ) during exercise. We observed a mPAP recovery pattern characterized by a steep decline for w2 min followed by a plateau from 2-4 min (Figure). At 2 min post exercise, mPAP in patients with normal DPQ decreased by 39% to within 4.060.4 mmHg of baseline, while patients with high DPQ decreased by 31%, and remained 10.161.3 mmHg above baseline (p!0.01 for both between group comparisons). Between 2 and 4 min of recovery, the high DPQ group maintained a mean elevation in mPAP above baseline that was more than 2.4X that of the normal DPQ group. In regression models adjusted for age and sex, at 2 min into recovery, both %DmPAP from peak and DmPAP above baseline were significantly related to indicators of RVPV reserve, such as peak exercise pulmonary vascular resistance, RVEF, and PaO2 (p!0.05 for all). Conclusions: Through detailed characterization of PAP measurements during incremental exercise and recovery we defined rapid descent and plateau phases of PAP recovery. These findings may inform the interpretation of invasive and non-invasive (i.e. echocardiographic) assessments of pulmonary vascular responses to exercise during a period that is conducive to performing HD measurements. A slow initial descent in mPAP and persistent mPAP elevation above baseline were closely associated with impaired RV-PV performance during exercise.

184 Hemodynamic Basis for Exercise Intolerance in Right Heart Failure Due to Tricuspid Regurgitation Mads J. Andersen, Barry A. Borlaug; Mayo Clinic, Rochester, MN Introduction: Tricuspid regurgitation (TR) is associated with symptoms of exertional fatigue and dyspnea, but the hemodynamic basis for functional limitation in TR is not well understood. Elevated pulmonary capillary wedge pressure (PCWP) is often assumed to indicate primary left heart failure, but may be observed with right heart congestion owing to pericardial restraint. Methods and Results: 15 patients with normal LVEF and grade $3 TR (10 women, age 7667) underwent invasive supine exercise testing with expired gas analysis and were compared to 13 age and sex-matched controls. At rest, TR patients had lower cardiac output (CO) (3.961.4 vs 5.161.9 L/min; p50.08), increased right atrial pressure (RAP) (1265 vs 461 mmHg; p!0.0001) and higher PCWP (1865 vs 963 mmHg; p!0.0001). However, left ventricular transmural pressure (LVTMP5PCWP-RAP), which better reflects LV preload independent of right heart and pericardial restraint, was similar in TR and controls (663 vs 462 mmHg, p50.11). With exercise, TR patients displayed lower CO (6.361.5 vs 10.363.3 L/min; p50.001) and VO2 (7.462.6 vs 11.164.2 ml/min/kg; p50.01), with less increase in CO relative to VO2 (Figure 1). TR patients displayed higher PCWP with exercise (Figure 2), but this was solely due to right atrial hypertension (2668 vs 863 mmHg, p!0.0001), as LVTMP fell with exercise, suggesting inadequate left heart filling despite high PCWP (Figure 3). Conclusion: Impaired exercise capacity in patients with severe TR is the result of reduced CO reserve relative to metabolic needs, coupled with elevated biventricular filling pressures. Left heart pressures are elevated with exercise in patients with TR, despite low LV preload, secondary to right heart congestion and poor right ventricular output.

Figure 1.

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