Yong K. Cho

Transition From Chronic Compensated to Acute Decompensated Heart Failure Pathophysiological Insights Obtained From Continuous Monitoring of Intracardiac Pressures

Background— Approximately half of all patients with chronic heart failure (HF) have a decreased ejection fraction (EF) (systolic HF [SHF]); the other half have HF with a normal EF (diastolic HF [DHF]). However, the underlying pathophysiological differences between DHF and SHF patients are incompletely defined. The purpose of this study was to use echocardiographic and implantable hemodynamic monitor data to examine the pathophysiology of chronic compensated and acute decompensated HF in SHF versus DHF patients. Methods and Results— Patients were divided into 2 subgroups: 204 had EF <50% (SHF) and 70 had EF ≥50% (DHF). DHF patients had EF of 58±8%, end-diastolic dimension of 50±10 mm, estimated resting pulmonary artery diastolic pressure (ePAD) of 16±9 mm Hg, and diastolic distensibility index (ratio of ePAD to end-diastolic volume) of 0.11±0.06 mm Hg/mL. In contrast, SHF patients had EF of 24±10%, end-diastolic dimension of 68±11 mm, ePAD of 18±7 mm Hg, and diastolic distensibility index of 0.06±0.04 mm Hg/mL (P<0.05 versus DHF for all variables except ePAD). In SHF and DHF patients who developed acute decompensated HF, these events were associated with a significant increase in ePAD, from 17±7 to 22±7 mm Hg (P<0.05) in DHF and from 21±9 to 24±8 mm Hg (P<0.05) in SHF. As a group, patients who did not have acute decompensated HF events had no significant changes in ePAD. Conclusions— Significant structural and functional differences were found between patients with SHF and those with DHF; however, elevated diastolic pressures play a pivotal role in the underlying pathophysiology of chronic compensated and acute decompensated HF in both SHF and DHF.

Application of Implantable Hemodynamic Monitoring in the Management of Patients With Diastolic Heart Failure : A Subgroup Analysis of the COMPASS-HF Trial

BACKGROUND Nearly half of all patients with chronic heart failure (HF) have a normal ejection fraction (EF), and abnormal diastolic function (ie, diastolic heart failure [DHF]). However, appropriate management of DHF patients remains a difficult and uncertain challenge. METHODS AND RESULTS The Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial was designed to evaluate whether an implantable hemodynamic monitor (IHM) was safe and effective in reducing the number of heart failure-related events (HFRE) in patients with chronic HF. The current study presents data on a prespecified and planned subgroup analysis from the COMPASS-HF trial: 70 patients with an EF > or =50% (ie, DHF). As such, this represents a subgroup analysis of the COMPASS-HF Trial. DHF patients were randomized to IHM-guided care (treatment) vs. standard care (control) for 6 months. All 70 patients received optimal medical therapy, but the hemodynamic information from the IHM was used to guide patient management only in the treatment group. The HFRE rate in DHF patients randomized to treatment was 0.58 events/6 months compared with DHF patients randomized to control, which was 0.73 events/6 months; this represented a 20% nonsignificant reduction in the overall HFRE rate in the treatment group (95% CI = -46, 56, P = .66). There was a 29% nonsignificant reduction in the relative risk of a HF hospitalization in the DHF patients randomized to treatment compared with DHF patients randomized to control (95% CI = -69, 70, P = .43). CONCLUSIONS The IHM was shown to be safe and was associated with a very low system-related and procedure-related complication rate in DHF patients. However, in this subgroup analysis limited to 70 DHF patients, the addition IHM-guided care did not significantly lower the rate of HFR events. The results of this subgroup analysis in DHF patients, for whom there are currently no proven, effective management strategies, will be used to design future studies defining the effects of IHM-guided care in patients with DHF.

Effects of Exercise on Left Ventricular Systolic and Diastolic Properties in Patients With Heart Failure and a Preserved Ejection Fraction Versus Heart Failure and a Reduced Ejection Fraction

Background—The purpose of the current study was to define exercise-induced changes in indices of left ventricular (LV) systolic and diastolic properties in patients with chronic heart failure (HF), compare these changes in patients with HF and a reduced ejection fraction (EF) versus HF and a preserved EF, and compare the hemodynamic responses to activities of daily living with symptom-limited upright exercise. Methods and Results—Subjects with HF and a preserved EF (n=8) and subjects with HF and a reduced EF (n=5) underwent symptom-limited Naughton protocol treadmill exercise tests. Implantable hemodynamic monitor data and echocardiographic data were obtained before exercise and at peak exercise. Implantable hemodynamic monitor data were obtained during activities of daily living during a 24-hour time period. In patients with HF and a reduced EF, limited exercise time (639±164 seconds) was associated with a marked rise in right ventricular systolic, diastolic, and estimated pulmonary artery diastolic (ePAD) pressures and an increase in LV end diastolic volume (EDV). LV systolic properties, namely EF, end systolic elastance, stroke work, and preload recruitable stroke work, all decreased. The ePAD/EDV ratio increased; to a large extent, this was dependent on an increase in EDV. By contrast, in HF and a preserved EF, limited exercise time (411±128 seconds) and the marked rise in right ventricular systolic, diastolic, and ePAD pressures were associated with no change in LV EDV. LV systolic properties increased or were unchanged; ePAD/EDV ratio increased during exercise, but the increase was independent of a change in EDV. The ranges of right ventricular systolic, diastolic, and ePAD pressures during activities of daily living were higher than the ranges of these values during the exercise stress test. Conclusions—Although exercise limitations were similar between HF and a reduced EF and HF and a preserved EF, there were significant differences in exercise-induced changes in LV systolic and diastolic properties. These differences likely reflect the different pathophysiologies of these clinical syndromes of HF.

Hemodynamic Factors Associated With Acute Decompensated Heart Failure: Part 1—Insights into Pathophysiology

BACKGROUND The purpose of this study was to determine which pressure-based hemodynamic factor was most closely associated with the transition from chronic compensated to acute decompensated heart failure. METHODS AND RESULTS Intracardiac pressures were retrospectively examined in 274 heart failure patients using an implantable hemodynamic monitor. The relationship between the development of a heart failure-related event (HFRE) and 3 pressure variables were analyzed: peak estimated pulmonary artery diastolic pressure (ePAD) at the time of an HFRE, change in ePAD from baseline to peak pressure, and the product of ePAD pressure and time (P×T) calculated as the area under the pressure-versus-time curve from baseline to peak pressure. Patients without an HFRE served as control subjects. Peak ePAD and change in ePAD were not closely associated with the development of an HFRE. In patients with an HFRE, P×T was 221 ± 130 mm Hg·days with only 4% of the P×T values <60 mm Hg·days. In contrast, in patients without an HFRE, the P×T was 5 ± 23 with only 4% of the P×T values >60 mm Hg·days. CONCLUSIONS The product of small increases in pressure that occur over an extended period of time (P×T) is the pressure-based hemodynamic factor most closely associated with the transition to acute decompensated heart failure.

277 DEVELOPING A CANINE MODEL TO TEST ELECTROACUPUNCTURE TREATMENT OF HYPERTENSION

Introduction: : Hypertension causes cardiovascular mortality and morbidity. Recent studies of electroacupuncture (EA) have demonstrated benefits in rodent models of hypertension, but EA has not been proven in larger animal models and human trials report mixed results. Methods: A canine model of hypertension was developed using the Goldblatt 1K1C method, removing one kidney and clipping the renal artery (RA) on the remaining kidney to reduce flow up to 80%. Implantable hemodynamic monitors were implanted to record acute and chronic arterial blood pressure (BP). EA was delivered at the ST-36 by an external stimulator or an implanted lead/stimulator. Continuous ambulatory BP was recorded before, during, and after EA stimulus to determine effects on BP. Results: Three of 8 dogs studied had complications from the 1K1C procedure and 1 dog removed from the study due to aggressive behaviour. Four dogs were followed for the duration of the study. Two had increases in BP in the first 2-4 weeks which returned to near baseline; it was subsequently confirmed that both clips had dislodged from the RA. The remaining 2 dogs had sustained increases in BP with the IK1C procedure. Acute and chronic EA cycling over time produced no sustained changes in BP. Conclusions: In the canine 1K1C model, significant RA occlusion is required to develop hypertension but too much risks the animals survival. Effective EA for hypertension in dogs requires a) use of alternate acupoints b) better identification of ST-36 and/or c) more effective stimulation methods than achieved in this study.

Use of paravascular admittance waveforms to monitor relative change in arterial blood pressure

Non-invasive methods to monitor ambulatory blood pressure often have limitations that can affect measurement accuracy and patient adherence [1]. Minimally invasive measurement of a relative blood pressure surrogate with an implantable device may provide a useful chronic diagnostic and monitoring tool. We assessed a technique that uses electrocardiogram and paravascular admittance waveform morphology analysis to one, measure a time duration (vascular tone index, VTI in milliseconds) change from the electrocardiogram R-wave to admittance waveform peak and two, measure the admittance waveform minimum, maximum and magnitude as indicators of change in arterial compliance/distensibility or pulse pressure secondary to change in afterload. Methods: Five anesthetized domestic pigs (32 ± 4.2 kg) were used to study the effects of phenylephrine (1-5 ug/kg/min) on femoral artery pressure and admittance waveform morphology measured with a quadrapolar electrode array catheter placed next to the femoral artery to assess the relative change in arterial compliance due to change in peripheral vascular tone. Results: Statistical difference was observed (p < 0.05) comparing baseline VTI to phenylephrine VTI (246 ± .05 ms to 320 ± .07 ms) and baseline admittance waveform maximum to phenylephrine admittance waveform maximum (0.0148 ± .002 siemens to 0.0151 ± .002 siemens). Conclusion: Chronic minimally invasive admittance measurement techniques that monitor relative change in blood pressure may be suitable for implantable devices to detect progression of cardiovascular disease such as hypertension.