Reversal of severe heart failure with a continuous-flow left ventricular assist device and pharmacological therapy: a prospective study.

BACKGROUND: We have previously shown that a specific combination of drug therapy and left ventricular assist device unloading results in significant myocardial recovery, sufficient to allow pump removal, in two thirds of patients with dilated cardiomyopathy receiving a Heartmate I pulsatile device. However, this protocol has not been used with nonpulsatile devices. METHODS AND RESULTS: We report the results of a prospective study of 20 patients who received a combination of angiotensin-converting enzymes, ß-blockers, angiotensin II inhibitors, and aldosterone antagonists followed by the ß2-agonist clenbuterol and were regularly tested (echocardiograms, exercise tests, catheterizations) with the pump at low speed. Before left ventricular assist device insertion, patient age was 35.2 ± 12.6 years (16 male patients), patients were on 2.0 ± 0.9 inotropes, 7 (35) had an intra-aortic balloon pump, 2 were hemofiltered, 2 were ventilated, 3 had a prior Levitronix device, and 1 had extracorporeal membrane oxygenation. Cardiac index was 1.39 ± 0.43 L · min⁻¹ · m⁻², pulmonary capillary wedge pressure was 31.5 ± 5.7 mm Hg, and heart failure history was 3.4 ± 3.5 years. One patient was lost to follow-up and died after 240 days of support. Of the remaining 19 patients, 12 (63.2) were explanted after 286 ± 97 days. Eight had symptomatic heart failure for ≤6 months and 4 for >6 months (48 to 132 months). Before explantation, at low flow for 15 minutes, ejection fraction was 70 ± 7, left ventricular end-diastolic diameter was 48.6 ± 5.7 mm, left ventricular end-systolic diameter was 32.3 ± 5.7 mm, mV(O2) was 21.6 ± 4 mL · kg⁻¹ · min⁻¹, pulmonary capillary wedge pressure was 5.9 ± 4.6 mm Hg, and cardiac index was 3.6 ± 0.6 L · min⁻¹ · m⁻². Estimated survival without heart failure recurrence was 83.3 at 1 and 3 years. After a 430.7 ± 337.1-day follow-up, surviving explants had an ejection fraction of 58.1 ± 13.8, left ventricular end-diastolic diameter of 59.0 ± 9.3 mm, left ventricular end-systolic diameter of 42.0 ± 10.7 mm, and mV(O2) of 22.6 ± 5.3 mL · kg⁻¹ · min⁻¹. CONCLUSIONS: Reversal of end-stage heart failure secondary to nonischemic cardiomyopathy can be achieved in a substantial proportion of patients with nonpulsatile flow through the use of a combination of mechanical and pharmacological therapy.

Cardiovascular autonomic control in patients undergoing left ventricular assist device (LVAD) support and pharmacologic therapy.

OBJECTIVES: The objective of the study is to determine cardiac autonomic control in patients undergoing assessment for and/or LVAD therapy. METHODS: Heart rate variability (HRV) was measured in 17 explanted LVAD, 17 implanted LVAD and 23 NYHA III-IV classified chronic heart failure (CHF) patients and ten healthy matched controls under three conditions: supine free breathing, standing and supine controlled breathing. Five measures of HRV were assessed: mean R-R interval (mR-R), high frequency (HF) and low frequency (LF) spectral power, LF in normalised units (LFnu), and LF to HF (LF:HF) ratio. RESULTS: Repeat measures ANOVA showed significant (p < 0.05) differences in HRV between all three conditions within groups. Lower values were observed in CHF for LF(in log natural units) compared with explanted patients (-1.4 [95% CI -2.6 to -0.7], p = 0.04) and controls (-2.1 [-3.5 to -0.7], p = 0.001) and for LF:HF compared with implanted patients under paced breathing conditions (z = -2.7, p = 0.007) and controls in standing (z = -2.9, p = 0.004) and paced breathing conditions (z = -2.3, p = 0.02). However, no significant differences were seen between explanted, implanted and control groups under any condition. CONCLUSIONS: Patients implanted with an LVAD and explanted from a LVAD following myocardial recovery demonstrate a more normal dynamic response to autonomic stimuli and have a lower HRV risk profile compared to CHF patients.

Comparison of cardiac power output and exercise performance in patients with left ventricular assist devices, explanted (recovered) patients, and those with moderate to severe heart failure.

Peak cardiac power output (CPO), as a direct measurement of overall cardiac function, has been shown to be a most powerful predictor of prognosis for patients with chronic heart failure. The present study assessed CPO and exercise performance in patients implanted with a left ventricular assist device (LVAD), those explanted due to myocardial recovery, and those with moderate to severe heart failure. Hemodynamic and respiratory gas exchange measurements were undertaken at rest and at peak graded exercise. These were performed in 54 patients-20 with moderate to severe heart failure, 18 with implanted LVADs, and 16 with explanted LVADs. At rest there was a nonsignificant difference in CPO among groups (p >0.05). Peak CPO was significantly higher in the explanted LVAD than in the heart failure and implanted LVAD groups (heart failure 1.90 +/- 0.45 W, implanted LVAD 2.37 +/- 0.55 W, explanted LVAD 3.39 +/- 0.61 W, p <0.01) as was peak cardiac output (heart failure 9.1 +/- 2.1 L/min, implanted LVAD 12.4 +/- 2.2 L/min, explanted LVD 14.6 +/- 2.9 L/min, p <0.01). Peak oxygen consumption was higher in the explanted LVAD than in the heart failure and implanted LVAD groups (heart failure 15.8 +/- 4.1 ml/kg/min, implanted LVAD 19.8 +/- 5.8 ml/kg/min, explanted LVAD 28.2 +/- 5.0 ml/kg/min, p <0.05) as was anaerobic threshold (heart failure 11.2 +/- 1.9 ml/kg/min, implanted LVAD 14.7 +/- 4.9 ml/kg/min, explanted LVAD 21.4 +/- 5.0 ml/kg/min, p <0.05). In conclusion, peak CPO differentiates well during cardiac restoration using LVADs and emphasizes the benefits of this therapy. CPO has the potential to be a key physiologic marker of heart failure severity and can guide management of patients with LVAD.

The impact of acute reduction of continuous-flow left ventricular assist device support on cardiac and exercise performance.

BACKGROUND: The use of the HeartMate II continuous-flow left ventricular assist device (LVAD) improves survival, quality of life and functional capacity of patients with advanced heart failure. However, no study so far has shown the benefits of these devices for cardiac function during peak exercise. OBJECTIVE: To assess cardiac and exercise performance in patients implanted with the HeartMate II LVAD under two settings: (i) optimal device support and (ii) reduced device support. METHODS: Twelve patients implanted with a HeartMate II LVAD performed a graded cardiopulmonary exercise test with respiratory gas exchange and non-invasive (rebreathing) haemodynamic measurements. After a 4 h resting period, patients performed an additional cardiopulmonary exercise test with reduced LVAD support (pump speed was reduced from optimal 9000-9600 to 6000 revs/min). RESULTS: In response to reduced HeartMate II LVAD support, resting cardiac power output and cardiac output decreased by 21% and 13%, respectively. Also at reduced device support, peak exercise cardiac power output was 39% lower (1.40+/-0.50 vs 2.31+/-0.58 W; p<0.05), peak cardiac output 30% lower (8.6+/-2.5 vs 12.2+/-2.1 l/min; p<0.05) and mean blood pressure 13% lower (74.3+/-14.9 vs 85.4+/-15.4 vs mm Hg; p<0.05). Exercise capacity was also diminished with 23% lower peak oxygen consumption (14.1+/-5.3 vs 18.2+/-4.5 ml/kg/min; p<0.05) and an 18% shorter exercise duration (516+/-119 vs 628+/-192 s; p<0.05). CONCLUSION: It has been shown for the first time that the HeartMate II LVAD can confer both resting and peak cardiac functional benefits to patients with end-stage heart failure, thus improving exercise capacity.

Reversible loss of pre-excitation as a sign of acute cardiac rejection.

A 50-year-old woman presented with signs of mild heart failure 16 months after orthotopic heart transplantation. Cardiac biopsy revealed ISHLT Grade 2R rejection, which was treated with corticosteroids. Electrocardiograms (ECGs) after transplantation showed a pre-excitation pattern; the presenting ECG showed complete loss of pre-excitation, which returned fully within 7 days of steroid therapy. Intermittent pre-excitation had been present for 4 weeks prior to any other clinical sign of rejection. Accessory pathways can display reversible loss of function during acute cellular rejection, and this may precede other clinical signs. This rare but significant finding may have clinical relevance to other transplanted patients with pre-excitation.