ResultsMean follow-up time was 18 (1–36) months, 47 patients (18.9%) died or underwent cardiac assist implantation. Pi max correlated weakly with BMI ( r = 0.19), peakVO2 ( r = 0.15), and FEV1 ( r = 0.34, all p. Both the clinical picture and the prognosis of patients with congestive heart failure (CHF) are characterized by impaired exercise tolerance and dyspnoea, and the impact of respiratory muscle dysfunction on these symptoms has been evaluated since the early 1990s ,.
( 500 ml or 20% of the predicted FEV1) that is not clearly associated with any clinical adverse event. Unstable asthma can lead to abnormal volumes. Volunteer tests or a test transfer, whenever possible. A series of tests on a healthy volunteer (likely a co-worker at the facility) can be collected and submitted to the core lab. Patients with PAP may suffer from progressive dyspnea and cough, which may be accompanied by exacerbated hypoxia. Its course is variable, ranging from progressive deterioration to spontaneous improvement (2). Radiographic analysis of the disease revealed ground-glass opacities with.
These studies proved that weakness of respiratory muscles expressed as maximum inspiratory pressure Pi max is not only a predictor of worse outcome in patients with CHF but also an independent risk factor for cardiovascular events in an elderly normal population. Several factors may contribute to this respiratory muscle weakness, among which are at cellular level a metabolic impairment and structural abnormalities of myocytes , , and at tissue level an altered blood flow and switch from type I into type II fibers. Recent studies found structural tissue changes in the diaphragm of heart failure rats, with degradation of sarcomer and mitochondria and expansion of intermyofibrillar spaces. At level of the entire organism, these processes result in general loss of skeletal muscle which impairs chemo- and baroreflex control independently from the peripheral chemoreceptors.
This dysfunction of feedback may limit exercise and aggravate dyspnoea, as it was outlined in the “muscle hypothesis of CHF”. Recently, a close relation between inspiratory muscle strength and pulmonary hypertension has been described in patients with left and right ventricular dysfunction.But regardless of these cellular and functional explanations, the relation between respiratory muscle dysfunction and impaired exercise capacity is loose, and joining co-factors have to be assumed. So far, there are data of only one prospective study that proved the prognostic significance of maximum mouth occlusion pressure Pi max and peak oxygen uptake peakVO 2 , but excluded explicitly patients with weight loss and cachexia.
In extension of these findings, we hypothesized that just this presence or absence of wasting would determinate respiratory muscle weakness, and that the patients’ prognosis is mainly depending on cachexia and the respiratory muscle is rather subordinated in this catabolic process. To prove this hypothesis, we analysed the data of a large study on CHF patients and pulmonary hypertension that has been published in part before. In contrast to this former study, we included only patients with known BMI and documented weight measures within the last 6 months. Our assumptions were (a) a close relation between body mass index BMI and Pi max and (b) a prognostic significance of this relation with regard to prognostic factors (e.g. LVEF, peakVO 2, serum sodium, and cardiac index) in CHF patients. 2.1 Study populationWe enrolled 249 consecutive patients (11.2% female) with mild to severe congestive left heart failure at the outpatient transplantation centre of the German Heart Institute Berlin.
The original study contained 292 patients, and only the subjects with complete tests on respiratory muscle function and documented course of body weight were included in this analysis. The median age was 54.2 years interquartile range (IQR) 11.8 years, range 20–66 years, and the aetiology of heart failure (defined as LVEF 6% in the last year ( n = 10 patients, 4.0%), with two of these patients matching both criteria of cachexia.Since patients were included in the study between 1998 and 2002, medical therapy with beta blockade (64.3%) and aldosteron inhibition (20.5%) was not yet ubiquitary in CHF patients, whereas ACE inhibitors/angiotensin receptor blockers (95.6%), diuretics (92.4%), and oral anticoagulation (78.7%) were widely used.
Concomitant conditions that could influence respiratory muscles were diabetes mellitus (20.1%), chronic renal failure (18.5%), previous sternotomy (17.3%), implanted cardioverter/defibrillator (19.7%), and chronic obstructive pulmonary disease (COPD, 8.8%). The QRS duration was prolonged to 120 ms in 155 patients (62.2%), thus again representing the state-of-the-art before introduction of cardiac resynchronisation therapy. The baseline clinical and functional characteristics of the patients are presented in Table. In addition to the parameters explained below, we applied the characteristical parameters of right heart catheterization: mean pulmonary artery pressure (PAPm), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and cardiac index (CI). The data collection and analysis were approved by the local ethics committee and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Body mass index BMI (kg/m 2)26.3 ± 3.9Cachectic by BMI. If not stated as number and percent, values indicate mean ± standard deviation. Higher anthropometric measures (height, weight, and BMI) were formally correlated with respiratory muscle strength Pi max (cf.
To BMI r = 0.19, cf. To weight r = 0.29, cf. To height 0.25, all p ≤ 0.003, see Fig. A division of patients in quintiles proved an increase in Pi max from low BMI (1st quintile BMI 29.4 kg/m 2 and Pi max = 7.4 ± 2.9 kPa, ANOVA p = 0.03, Fig. Pi max of cachectic patients, i.e. Quintiles of BMI. ANOVA p = 0.03.
Boxes indicate mean and 75th percentile, error bars indicate 90 th percentile. Absolute values see below time axisPi max correlated with most parameters of pulmonary function, such as VC ( r = 0.36), FEV1 ( r = 0.34), TLCO VA ( r = 0.2; all p ≤ 0.002). There was no correlation of Pi max with any of cardiac parameters (blood pressure, heart rate, PAPm, PCWP, cardiac index, LVEF, LVEDd, all r resp. Ρ 0.1).Pi max was significantly lower in females (3.9 ± 1.7 kPa) than in males (6.6 ± 2.7 kPa; p 0.1). Similarly, there was no difference between cachectic and non-cachectic patients regarding P0.1 0.22 (0.08) vs. 0.18 (0.07) kPa and P0.1/Pi max 4% (1.4%) vs.
3% (1.1%); all p 0.3.The ventilatory drive P0.1 depended on pulmonary pressure (PAPm ρ = 0.2; p = 0.002). A higher ratio P0.1/Pi max correlated with lower respiratory efficiency (VE/VCO 2 slope, ρ = 0.16, p = 0.015) and a higher exhaustion of the breathing reserve peakVE/MVV ( ρ = 0.26; p 0.12). Ventilatory drive was higher in females P0.1 = 0.24 (0.29) vs.
0.18 (0.15) kPa; p = 0.21, and the respiratory pump was more utilized P0.1/Pi max 6% (1.6%) vs. 2.8% (1.1%); p. The median time of follow-up was 18.8 months with a range from 1 to 36 months. During this time, 38 (15.3%) patients died, 9 (3.6%) underwent urgent implantation of a cardiac assist device, and 22 patients (8.8%) were heart transplanted.
Patients with heart transplantation were statistically treated as survivors up to the date of transplantation and censored. Fatal events and assist implantations (in the following: “death/assist”) sum up to 47 patients (18.9%), according to a 1-year event rate of 16.7%. Compared to survivors, patients in the death/assist group had a lower weight, BMI, diastolic blood pressure, FEV1, TLCO VA, peakVO 2, eGFR, and higher uric acid and VE/VCO 2 slope. Both groups did not differ in age, haemodynamic parameters except LVEF, peakVE/MVV, sodium, haemoglobin, and all parameters of respiratory muscle function and ventilatory drive (see Table ).
The aetiology of heart failure (dilative cardiomyopathy, coronary or valvular heart disease) did not influence outcome ( χ 2 = 0.04; p = 0.8), as well as the concomitant diseases diabetes mellitus ( χ 2 = 3.4; p = 0.06), renal failure ( χ 2 = 1.7; p = 0.2), and previous sternotomy ( χ 2 = 3.7; p = 0.053), whereas only COPD ( χ 2 = 4.5; p = 0.03) was linked to a higher event rate. Kaplan–Meier survival curves allowed the best prognostic stratification according to body mass index. The lowest quintile (BMI 14 ml/min/kg (Log rank χ 2 = 3.8; p = 0.05). 4Kaplan–Meier survival curves of the total study population subdivided by cachectic and non-cachectic patients. The symbols indicate circle cachectic plus sign non-cachectic. The difference in survival was significant (log-rank χ 2 = 9.4, df = 1, p = 0.002). There were 249, 222, 205, and 112 patients at risk at days 0, 200, 400, and 600 3.4 Univariate analysis of survivalNeither Pi max hazard ratio (HR) 0.98; confidence interval (CI) 0.88–1.08 nor P0.1 HR 0.52 (CI 0.06–4.6) predicted survival in the univariate Cox regression analysis.
In order to evaluate possible confounding effects, we extended this analysis to all factors associated to Pi max. The parameters correlating to respiratory muscle strength Pi max and predicting survival were, in order of declining hazard ratio, BMI HR 0.87 (CI 0.8–0.95), peakVO 2 HR 0.93 (0.87–0.99), body mass HR 0.97 (0.95–0.99), FEV1 HR 0.98 (0.96–0.99), eGFR HR 0.98 (0.97–0.99), and TLCO VA HR 0.98 (0.96–0.99).
In a multivariate analysis including four factors, only BMI remained an independent prognostic parameter (HR 0.9; CI 0.82–0.98; p = 0.017), whereas peakVO 2 (HR 0.95), FEV1 (HR 0.99), and TLCO VA (HR 0.98) lost significance (all p 0.1). Similarly, a reduction to three factors revealed always BMI as the only independent factor, and weight was eliminated in every analysis that included BMI. 4 Discussion.
Our data show that neither the respiratory muscle strength (Pi max) nor the ventilatory drive (P0.1) is an independent predictor of survival in the presented CHF patients. Worse outcome is mainly associated with a low BMI, respectively with the development of cachexia, and with low peakVO 2.
Formally, the BMI correlates weakly with Pi max and is apart from gender and lung volume the only determinate of Pi max, but this relation between body mass and Pi max is too weak to confirm our hypothesis that respiratory muscle weakness could depend on the presence or absence of wasting.As expected, there is a linear relation between BMI and Pi max over the whole range of body size from underweight to adiposity. However, this relation is quite frail, and one would expect a more pronounced drop in Pi max if BMI falls below a critical value, e.g.