Abstract
Severe aortic stenosis sometimes accompanies advanced heart failure with reduced cardiac contractility (i.e. low-flow low-gradient aortic stenosis). The therapeutic strategy for the remaining heart failure following trans-catheter aortic valve implantation remains unknown. An 84-year-old man with six hospitalizations due to aortic stenosis and congestive heart failure with reduced ejection fraction was admitted to our institute. Heart failure remained following trans-catheter aortic valve implantation. Additional adaptive servo-ventilation therapy with optimal pressure setting determined by the ramp test further improved his heart failure symptoms. Combination therapy using trans-catheter aortic valve implantation and adaptive servo-ventilation might be a promising therapeutic tool to ameliorate heart failure with severe aortic stenosis.
<;Learning objective: Adaptive servo-ventilation might be a promising therapy in patients with persistent congestive heart failure following trans-catheter aortic valve implantation for severe aortic stenosis.>
Keywords: Heart failure, Non-invasive positive pressure ventilation, Hemodynamics, Case report
Introduction
Trans-catheter aortic valve implantation (TAVI) is an established therapeutic strategy for those with severe aortic stenosis who have high risks of surgical intervention, and its indication has been expanding to those with relatively lower surgical risk [1]. However, clinical outcome following TAVI is not satisfactory for those accompanying reduced cardiac function due to long-term severe aortic stenosis (i.e. low-flow low-gradient aortic stenosis), given post-procedural persistent heart failure [2].
Adaptive servo-ventilation (ASV) is a non-invasive positive pressure ventilation therapy that stabilizes respiratory pattern, reduces preload and afterload, suppresses sympathetic nerve activity, and facilitates cardiac reverse remodeling as well as improving prognosis in patients with congestive heart failure, irrespective of the existence of sleep disordered breathing [3].
In this case, we had a patient with severe aortic stenosis and reduced cardiac function whose heart failure improved by the combination therapy using TAVI and ASV.
Care report
On admission
An 84-year-old man with six previous hospitalizations due to aortic stenosis and congestive heart failure with reduced ejection fraction was admitted to our institute complaining of nocturnal dyspnea, receiving 2.5 mg of carvedilol and 30 mg of azosemide.
Blood pressure was 105/52 mmHg and heart rate was 69 bpm. The estimated glomerular filtration rate was 24.2 mL/min/1.73 m2 and plasma B-type natriuretic peptide was 798 pg/mL. Transthoracic echocardiography showed 54 mm of left ventricular end-diastolic diameter, 39% of left ventricular ejection fraction, severe mitral regurgitation, and mild tricuspid regurgitation (Fig. 1A). The peak velocity of aortic valve was 3.72 m/sec, the mean pressure gradient of aortic valve was 35.6 mmHg, and the estimated aortic valve area was 0.60 cm2.
Fig. 1.
Trans-thoracic echocardiography obtained (1) on admission, (2) after TAVI, and (3) following ASV therapy initiation.
TTE, trans-thoracic echocardiography; TAVI, trans-catheter aortic valve implantation; ASV, adaptive servo-ventilation; LVDd, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; EROA, effective regurgitant orifice area.
Trans-catheter aortic valve implantation
We initiated 2.0 mL/min/kg of intravenous infusion of dobutamine to support his hemodynamics (Fig. 2). Transthoracic echocardiography under dobutamine support showed 4.09 m/sec of peak velocity of aortic valve, 42 mmHg of mean pressure gradient of aortic valve, and 0.69 cm2 of estimated aortic valve area, which was compatible with low-flow low-gradient severe aortic stenosis. Coronary angiography showed no significant coronary artery stenosis. Heart valve team conference finally decided to perform TAVI given the results of all examinations and informed consent.
Fig. 2.
In-hospital course. The patient received ASV therapy in addition to TAVI to treat persistent congestive heart failure.
TAVI, trans-catheter aortic valve implantation; ASV, adaptive servo-ventilation; TTE, trans-thoracic echocardiography; HR, heart rate; BNP, B-type natriuretic peptide; eGFR, estimated glomerular filtration ratio; CO, cardiac output.
On day 5, trans-femoral TAVI was successfully performed using 29 mm of Sapien 3 (Edwards Lifesciences Corp., Irvine, CA, USA) without any complications. Nevertheless, his heart failure symptoms persisted probably due to the remaining moderate mitral regurgitation and reduced cardiac function (Fig. 1B). Plasma levels of B-type natriuretic peptide remained around 400 pg/mL (Fig. 2).
Adaptive servo-ventilation initiation
We decided to initiate ASV to treat his congestive symptoms refractory to the complete amelioration of aortic stenosis on day 12 and continuous medical therapy including up-titrated azosemide 60 mg/day and started 1.25 mg/day of enalapril, although he did not have any signs of sleep disordered breathing (Fig. 2). Before the initiation of ASV therapy, we performed the ASV ramp test as previously detailed [4]. In summary, we measured estimated stroke volume and cardiac output using AESCULON mini (Osypka Medical, Berlin, Germany) [5] at each expiratory positive airway pressure between 2 and 7 cmH2O (Table 1). During the ramp test, we found that the pressure setting of 3 cmH2O had the highest cardiac output of 2.82 L/min, and we initiated ASV therapy with 3 cmH2O of expiratory positive airway pressure and 3–10 cmH2O of pressure support at least 4 h per day.
Table 1.
Adaptive servo-ventilation ramp test.
| EPAP (cmH2O) | heart rate (bpm) | stroke volume (mL) | cardiac output (L/min) |
|---|---|---|---|
| none (baseline) | 66 | 40 | 2.31 |
| 2 | 63 | 42 | 2.64 |
| 3 | 64 | 42 | 2.82 |
| 4 | 64 | 41 | 2.61 |
| 5 | 64 | 42 | 2.65 |
| 6 | 65 | 41 | 2.63 |
| 7 | 64 | 41 | 2.63 |
EPAP, expiratory positive airway pressure.
Following the initiation of ASV therapy, plasma level of B-type natriuretic peptide reduced below 300 pg/mL and heart rate decreased from around 75 bpm to around 60 bpm. Trans-thoracic echocardiography on day 22 showed relatively improved cardiac contractility and mitral regurgitation (from moderate to mild; Fig. 1C). He was discharged on day 26 with continued ASV therapy.
Discussion
Low-flow low-gradient aortic stenosis and TAVI
Prognosis following TAVI is not satisfactory in patients with low-flow low-gradient aortic stenosis given their remaining reduced cardiac function [6]. However, its therapeutic strategy remains unknown.
Guideline-directed medical therapy for those with heart failure with reduced ejection fraction includes beta-blocker and renin-angiotensin-aldosterone system inhibitors as well as aldosterone antagonists if necessary. However, the implication of these medications for those following TAVI remains unknown. Furthermore, his low systolic blood pressure (around 90 mmHg) and chronic kidney disease did not allow us up-titration of these medications. Up-titration of diuretics did not ameliorate his congestive symptoms as well.
Therapeutic strategy for remaining heart failure following TAVI
An alternative strategy to ameliorate his congestion refractory to conventional diuretics might be an arginine vasopressin type-2 receptor antagonist, tolvaptan. However, his urine osmolality measured at a fasting condition was 330 mOsm/L (<350 mOsm/L), indicating non-responder, probably given the existence of chronic kidney disease that often accompanies impaired collecting duct and refractoriness to conventional diuretics [7].
Another strategy that might improve his heart failure was trans-catheter mitral valve repair using the MitraClip system (Abbott Vascular, Abbott Park, IL, USA) [8]. However, his mitral regurgitation improved from severe to moderate following TAVI, not indicating this intervention. Decrease in afterload on left ventricle by TAVI might have partially improved mitral regurgitation.
ASV for remaining heart failure following TAVI
ASV is a non-invasive positive pressure ventilation therapy that ameliorates congestive symptoms as well as short- and long-term prognosis, irrespective of the existence of sleep disordered breathing [3]. We adopted this therapy instead of aggressive up-titration of diuretics, given its neutral impact on the kidney function.
The SERVE-HF trial demonstrated that ASV therapy with relatively higher pressure settings to aggressively treat sleep disorder rather worsened prognosis compared to the control arm in systolic heart failure patients [9]. The suspected mechanism to interpret this trial is that inappropriately high-pressure setting might rather reduce the venous return that results in the low cardiac output.
We hypothesized that the pressure setting of ASV therapy should be adjusted in each individual using a ramp test, during which cardiac output is measured at each pressure setting [4]. In this patient, we found that his cardiac output was maximum at 3 cmH2O of expiratory positive airway pressure setting, instead of the default setting of 5 cmH2O. His congestive symptoms improved following the initiation of ASV therapy with an optimized pressure setting.
Of note, the clinical implication of ramp test should be validated in a larger-scale study. Also, it remains of future concern whether such a trivial difference in cardiac output during ramp test would have any clinical implications. The implication of the combination therapy using TAVI and ASV for those with low-flow low-gradient aortic stenosis should also be validated in a large-scale cohort. Our patient had moderate mitral regurgitation, which is a predictor of favorable response to ASV therapy in addition to the existence of congestion [10]. Our finding might not simply be adopted to those without mitral regurgitation. Nevertheless, many patients with low-flow low-gradient aortic stenosis would have functional mitral regurgitation.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Footnotes
Disclosure: TI receives grant support from JSPS KAKENHI: JP20K17143. Other authors have nothing to declare.
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