Summary
Background
The minute ventilation/carbon dioxide production (VE/VCO 2 ) slope and peak circulatory power, like peak oxygen consumption (VO 2 ), possess strong prognostic values in heart failure but have not been studied after ventricular resynchronization.
Aims
In this retrospective study, we evaluated the evolution of ventilatory response, effort capacity, functional status, peak circulatory power and echocardiographic variables, 6 months after cardiac resynchronization therapy (CRT).
Methods
Thirty subjects (mean age, 60 ± 12 years) underwent symptom-limited exercise testing (CPX) with ventilatory expired gas analysis before and 6 months after CRT. The VE/VCO 2 slope was measured from rest to the end of exercise. Echocardiography was performed in stable clinical and pharmacological conditions.
Results
Mean New York Heart Association (NYHA) status improved significantly from 2.9 to 1.8 ( p < 0.001). Significant improvements were seen in exercise tolerance (evaluated by peak VO 2 ; from 13.1 ± 3.1 to 15.3 ± 5.6 mL/kg/min, p = 0.02), VE/VCO 2 slope (from 44.4 ± 19.2 to 39.6 ± 13.8, p = 0.003) and maximal workload (from 74 ± 24 to 82 ± 26 W, p = 0.02). Mean peak circulatory power improved from 1663 ± 494 to 2125 ± 1014 mmHg mL/kg/min ( p = 0.009). Mean left ventricular ejection fraction increased from 25% to 29% ( p = 0.01). Mean end-systolic and end-diastolic left ventricular volumes decreased significantly from 155 to 128 mL and from 203 to 179 mL, respectively ( p < 0.05). Mean mitral regurgitation grade improved from 1.4 ± 1.0 to 1.1 ± 0.9 ( p = 0.1). No strong correlation was found between echocardiographic changes and improvement in ventilatory efficiency (VE/VCO 2 slope; all r = 0.15–0.24). Patients with narrow QRS complexes (< 130 ms) did not show significant improvement in functional or echocardiographic variables other than NYHA status.
Conclusion
Cardiac resynchronization therapy improved ventilatory and haemodynamic responses. Our results highlight the potential value of new functional variables such as ventilatory response and peak circulatory power as better markers for identifying responders to CRT.
Résumé
Background
L’étude de la réponse ventilatoire par la pente de régression linéaire de la ventilation minute et de la production de dioxyde de carbone (VE/VCO 2 ) et la mesure de la puissance circulatoire au cours d’une épreuve d’effort possède une valeur pronostique significative chez l’insuffisant cardiaque. L’évolution de la réponse ventilatoire n’a pas été étudiée après resynchronisation biventriculaire.
Objectif
L’objectif principal était d’étudier l’évolution de la réponse ventilatoire, de la puissance circulatoire au pic et des paramètres échocardiographiques après resynchronisation biventriculaire.
Méthodes et résultats
Trente patients (âge moyen : 60 ± 12 ans) ayant bénéficié d’une épreuve d’effort avec mesure des échanges gazeux ainsi que d’une échocardiographie transthoracique avant et six mois après implantation ont été inclus. La réponse ventilatoire était évaluée par la pente de régression linéaire de VE/VCO 2 en incluant l’ensemble des points du début à la fin de l’exercice. Une valeur ponctuelle de VE/VCO 2 était mesurée au pic de l’exercice. La classe New York Heart Association (NYHA) était améliorée de 2,9 à 1,8 ( p < 0,001). Le pic de VO 2 , la pente de régression de VE/VCO 2 et la charge maximale au pic de l’exercice étaient significativement améliorés après resynchronisation, de 13 ± 3 à 15 ± 5 mL/kg par minute, de 44 ± 19 à 39 ± 13 ( p = 0,02) et de 74 ± 24 à 82 ± 26 W ( p = 0,02) respectivement. La puissance circulatoire était augmentée de 1663 ± 494 à 2125 ± 1014 mmHg ml/kg par minute ( p = 0,009). La fraction d’éjection ventriculaire gauche s’est améliorée de 25 % à 29 % ( p = 0,01), ainsi que le volume télésystolique (155 à 128 mL ; p = 0,002) et télédiastolique (203 à 179 mL ; p = 0,004). L‘insuffisance mitrale était néanmoins améliorée de manière non significative (1,4 ± 1 à 1,1 ± 0,9 ; p = 0,1). Néanmoins, il n’a pas été retrouvé de corrélation significative entre l’amélioration de la réponse ventilatoire et celle des volumes ventriculaires gauches après resynchronisation (valeur de r entre 0,15 et 0,24). Enfin, les patients présentant des QRS fins (< 130 ms) ne présentaient aucune amélioration fonctionnelle objective ni échocardiographique à l’exception de la classe NYHA.
Conclusion
La resynchronisation biventriculaire améliore la réponse ventilatoire et hémodynamique. Nos résultats soulignent l’importance de l’étude de la réponse ventilatoire et de la puissance circulatoire comme marqueurs fonctionnels de réponse après resynchronisation biventriculaire.
Abbreviations
bpm
beats per minute
CP
circulatory power
CPX
symptom-limited exercise testing
CRT
cardiac resynchronization therapy
LVEF
left ventricular ejection fraction
NYHA
New York Heart Association
VCO 2
carbon dioxide production
VE
minute ventilation
VO 2
oxygen consumption
Background
CRT is one of the major treatments for patients with chronic heart failure. Current recommended definitions are QRS duration more than 120 ms, LVEF less than 35%, NYHA symptom class III/IV and an optimal heart failure medical regimen . Previous major trials have confirmed that CRT improves functional status (symptoms and NYHA symptom class), decreases acute heart failure hospitalizations and global mortality and reverses left ventricular remodelling variables .
Peak VO 2 is one of the most important independent predictors of mortality and hospitalization for patients with heart failure . This functional variable represents functional effort capacity and is improved significantly by CRT , but is influenced by non-cardiac factors (age, motivation, anaemia and obesity). Moreover, the clinical value of the relationship between the VE and VCO 2 relationship, usually expressed as the VE/VCO 2 slope, has been proved in heart failure patients, in whom it has been shown to be a significant predictor of mortality and hospitalization . The VE/VCO 2 slope seems to be a better predictor of outcome than peak VO 2 with regard to sub-maximal effort and subjective functional evaluation (6-minute walking test and quality of life score). In addition, a non-invasive haemodynamic measure of cardiac power was assessed (by the measurement of peak “CP” during CPX using the product of both peak VO 2 and systolic blood pressure) as a strong prognostic predictor in heart failure patients . However, no study has been designed to investigate ventilatory and haemodynamic responses after CRT.
Our aim was to evaluate peak VO 2 , VE/VCO 2 slope, NYHA class symptom, peak CP, peak workload, left ventricular volumes and LVEF, before and 6 months after CRT implantation, to study the ventilatory and haemodynamic response evolution and to assess improvement in functional and echocardiographic variables. We aimed to confirm the major place of the ventilatory and haemodynamic responses in the functional evaluation of heart failure patients after CRT.
Materials and methods
Inclusion criteria
Refractory heart failure patients matching the following criteria were included in the study: indication for CRT implantation according to current guidelines (QRS duration more than 120 ms, LVEF less than 35%, NYHA symptom class III/IV and optimal heart failure medical regimen); complete echocardiographic evaluation, including left ventricular volume measurements; and cardiopulmonary exercise test before and 6 months after CRT.
Echocardiographic measurement
Echocardiograms were loaded onto a computer system (Echopac, GE) and all measurements were obtained for all patients at baseline and 6 months after implantation. Echocardiograms were analysed by a single experienced sonographer. Sample loops were analysed off-line on an Echopac computer workstation to obtain end-diastolic and end-systolic left ventricular volumes using the method of discs. LVEF was calculated as follows: (end-diastolic volume − end-systolic volume)/end-diastolic volume × 100%. Mitral regurgitation was evaluated according to the European Society of Echocardiography. A second blinded evaluation was performed for 10 echocardiograms by a second sonographer. Absolute values for LVEF interobserver variability were found to be less than 5%.
Testing procedure and data collection
A symptom-limited exercise test with ventilatory expired gas analysis using a cycle ergometer with a 10 W/min protocol was performed in all patients (Medisoft). Continuous electrocardiogram measurements, manual blood pressure measurements and heart rate recordings were monitored at every stage. Data for VO 2 , VCO 2 , VE and workload were collected continuously throughout the exercise. Oxygen and carbon dioxide sensors were calibrated using gases with known oxygen, nitrogen and carbon dioxide concentrations before each test.
Ventilatory efficiency on exercise was obtained from the linear regression slope relating VE to VCO 2 from the beginning to peak exercise. Punctual VE/VCO 2 ratio at the end of exercise was also measured.
Peak CP was measured as the product of peak VO 2 and systolic blood pressure, as described by Cohen-Solal et al. .
Subgroup analysis
Responders and non-responders to CRT were characterized. The responder subgroup was defined as having an end-systolic left ventricular volume reduction more than 15% after CRT . In addition, characteristics of the patients with narrow QRS complexes (< 130 ms) were studied, included remodelling variables, mitral regurgitation grade, ventilatory response, peak CP, NYHA status and effort capacity by both peak VO 2 and maximal workload.
Statistical analysis
Paired t tests were used to compare differences between variables after CRT. All statistical tests with a p -value less than 0.05 were considered to be significant.
A Pearson r test was used to evaluate correlations between variables after CRT. All statistical tests with an r -value of more than 0.85 were considered to be highly correlated.
Results
Patients
The baseline characteristics of included patients are summarized in Table 1 . Heart failure aetiology was ischaemic in 45% and non-ischaemic in 55% of patients. Patients had severely depressed left ventricular function, with a mean LVEF of 25 ± 7%. Mean systolic blood pressure was 108 ± 18 mmHg at rest and 131 ± 21 mmHg at peak exercise. Mean heart rate was 81 ± 19 bpm at rest and 115 ± 23 bpm at peak exercise. The mean peak VO 2 value was 13 ± 3 mL/kg/min. The mean VE/VCO 2 slope and the VE/VCO 2 ratio at peak exercise were 44 ± 19 and 48 ± 9 respectively. Mean maximal workload at peak exercise and mean peak CP were 74 ± 23 W and 1663 ± 494 mmHg mL/kg/min, respectively. Mean left ventricular end-diastolic and end-systolic volumes were 203 ± 76 mL and 155 ± 65 mL, respectively. Mean mitral regurgitation grade was 1.45 ± 1.0. Most patients (93%) were in NYHA symptom class II–III and 7% were in NYHA symptom class IV. Mean QRS duration was 153 ± 38 ms.
| Baseline | 6-month follow-up | p -value | |
|---|---|---|---|
| Total patients | 30 (100) | – | – |
| Men | 23 (77) | – | – |
| Women | 7 (23) | – | – |
| Age (years) | 60 ± 12 | – | – |
| Left ventricular ejection fraction (%) | 25 ± 7 | 29 ± 7 | 0.01 |
| Aetiology | |||
| Ischaemic | 13 (45) | – | – |
| Non-ischaemic | 17 (55) | – | – |
| Systolic blood pressure at rest (mmHg) | 108 ± 18 | 107 ± 17 | 0.6 |
| Systolic blood pressure at peak (mmHg) | 131 ± 21 | 133 ± 26 | 0.6 |
| Heart rate at rest (bpm) | 81 ± 19 | 73 ± 11 | 0.05 |
| Heart rate at peak (bpm) | 115 ± 23 | 112 ± 27 | 0.5 |
| Peak VO 2 (mL/kg/min) | 13 ± 3 | 15 ± 5 | 0.02 |
| VE/VCO 2 slope | 44 ± 19 | 39 ± 13 | 0.003 |
| VE/VCO 2 ratio at peak exercise | 48 ± 9 | 42 ± 7 | < 0.001 |
| Peak CP (mmHg mL/kg/min) | 1663 ± 494 | 2125 ± 1014 | 0.009 |
| Maximal workload (W) | 74 ± 24 | 82 ± 26 | 0.02 |
| Δ NYHA: 0 | – | 4 (13.3) | – |
| Δ NYHA: 1 | – | 22 (73,4) | – |
| Δ NYHA: 2 | – | 4 (13,3) | – |
| Δ NYHA: 3 | – | 0 (0) | – |
| Left ventricular end-systolic volume (mL) | 155 ± 65 | 128 ± 55 | 0.002 |
| Left ventricular end-diastolic volume (mL) | 203 ± 76 | 179 ± 70 | 0.004 |
| Mitral regurgitation (grade) | 1.45 ± 1.0 | 1.12 ± 0.9 | 0.1 |
| QRS duration (ms) | 153 ± 38 | – | – |
| Beta-blocker | 28 (93) | – | – |
| Diuretic | 25 (83) | – | – |
| Conversion enzyme inhibitor | 27 (89) | – | – |
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