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Arquivos Brasileiros de Cardiologia

Print version ISSN 0066-782X

Arq. Bras. Cardiol. vol.98 no.6 São Paulo June 2012  Epub May 29, 2012

http://dx.doi.org/10.1590/S0066-782X2012005000049 

Inferior Vena Cava collapsibility and heart failure signs and symptoms. New insights about possible links

 

 

Renato De VecchisI; Antonio CiccarelliII; Carmelina ArianoII

ICardiology Unit, Presidio Sanitario Intermedio Elena d Aosta
IINapoli; Neurorehabilitation Unit, Clinica S. Maria del Pozzo, Somma Vesuviana, Italy

Correspondência

 

 


ABSTRACT

BACKGROUND: In chronic heart failure patients (CHF), ultrasound measurement of inferior vena cava collapsibility index (IVCCI) has been proposed to yield careful assessment and grading of the hemodynamic congestion.
OBJECTIVE: The purpose of this study was to correlate the findings of physical examination with IVCCI in CHF patients.
METHODS: According to a retrospective cohort design, we analyzed 54 CHF patients with right or biventricular CHF, belonging to III NYHA class. We planned to determine whether any basal IVCCI range would be able to predict persistent or worsening clinical congestion found at the end of subsequent follow up (i.e. after 1-2 months of oral optimized therapy). For this purpose, the patients were subdivided by  three groups according to the basal IVCCI value: ≤ 15% (13 pts), 16 - 40% (21 pts) and > 40% (20 pts).Several clinical criteria of congestion were compared across the three  groups and subsequently  entered in the Cox multivariate model.
RESULTS: Multivariate predictors of  high congestion score  were jugular venous distension (HR: 13,38  95% C.I.: 2,13 - 84  p = 0,0059) and rales (HR: 11  95% C.I : 1,45 - 83,8   p = 0,0213). IVCCI ≤ 15% was always associated with high congestion score at the second visit; but IVCCI ≤ 15% failed to predict high congestion score at the second visit.
CONCLUSIONS: In CHF setting, low IVCCI did not reliably predict high congestion score. Nevertheless, the cluster with IVCCI ≤ 15% was always found associated with signs and symptoms from both right and left-sided decompensated CHF. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)

Keywords: Cardiac output, low; heart failure; vena cava,inferior/abnormalities; ventricular dysfunction, left.


 

 

Introduction

Hemodynamic congestion1 is thought to derive primarily from impaired cardiac index - with or without reduction in left ventricular ejection fraction- .This in turn generates elevation in pulmonary capillary wedge pressure (PCWP)2, in the case of left chambers isolated decompensation, or combined increase in both PCWP and  right atrial pressure, in the  case of  biventricular heart failure1. Impaired cardiac index, for left only ventricular heart failure, or the combination of impaired cardiac index plus elevated central venous pressure, in the case of right or biventricular heart failure, with or without patent fall in blood pressure, substantially reduce renal blood flow, the most important variable of kidney filtration gradient in patients presenting with congestive heart failure, thus generating neuro-hormonal stimulation and development of hydrosaline retention4-8. Hemodynamic worsening consisting in impaired cardiac index and increased filling pressures will further activate the renin-angiotensin and sympathetic nervous system, reduce nitric oxide in the endothelium, and induce inflammatory mediators, to aggravate the hypoperfusion state of the glomeruli and so to further harm the renal function9. Reduction in water and salt clearance in turn propitiates persistence of hemodynamic congestion to create   and maintain over time a condition of cardiac overload. Hemodynamic congestion contributes to the progression of HF by further activating neurohormones and by causing subendocardial ischaemia, resulting in myocardial necrosis/apoptosis and/or secondary mitral insufficiency by its effects on LV geometry (changing it from an ellipsoid to a sphere)10. In addition, elevated right atrial pressure may contribute to the cardio-renal syndrome through reduction of the perfusion gradient across the kidneys11-12.

Among the proposed methods for estimating and grading hemodynamic congestion in right or biventricular heart failure, a remarkable role is played by ultrasound evaluation of the inferior vena cava diameter (IVCD) and its collapsibility index (IVCCI)13. This technique is aimed to identify any changes in respiratory pattern of IVC indicating the presence of abnormalities in volume status (that is hemodynamic congestion or  intravascular depletion). Based on well-established knowledge, wide respiratory fluctuations of IVCCI would indicate that intravascular depletion is likely, whereas low values of this parameter would mean high probability of hemodynamic congestion. These inferences have received exhaustive confirmation by many large well-conducted studies13-20.

 

Objectives

In a number of patients with right or biventricular CHF, we have tested the possible relationships between IVCCI and some signs and symptoms of CHF. Besides, we have tried to establish whether in these CHF patients a low IVCCI value, as found at the first visit, can be assumed as a reliable predictor of subsequent clinical congestion – after a clinical follow up of one-two months - .

 

Methods

An observational  retrospective study was carried out by enrolling patients from two Centers (C.U. E. d’A. and  N.R. S.M.d P.). For enrollment in the study , documented evidence of right or bi-ventricular chronic heart failure in II- III NYHA class was required. Exclusion criteria were: patients with pace-maker or treated by cardiac resynchronization therapy; myocardial infarction within 30 days, arrhythmia-related syncope, major cardiac surgery, unstable angina, uncontrollable hypertension, cor pulmonale, advanced pulmonary disease, major neurologic disease or cerebrovascular disease, suspected renal artery stenosis, advanced renal failure (i.e. serum creatinine >2,5 mg/dl at baseline), other life-threatening disease.

Retrospective chart review was performed to analyze characteristicsof all  eligible patients. For each patient, date of birth, sex, race, and weight and heightwere noted. Comorbidities, including diabetes, dyslipidemia, nicotine abuse, hypertension , ischemic heart disease, preexisting diabetic nephropathy or  other chronic renal   disease in addition to medical treatment at the time of hospital stayalso were extracted for each patient. IVCCI was defined as the difference between maximum expiratory diameter and minimum inspiratory diameter divided by the maximum expiratory diameter . IVCCI measurements were obtained 1 to 2 cm below the level of the hepatic veins, using a two-dimensional echographic sector (Vivid 7 ultrasound machine, GE Healthcare Systems, Milwaukee, WI).The  IVC diameter recording was made on M-mode   approximately 3 cm from the right atrium with patients in a 45º recumbent position. Subcostal or subxiphoid windows were used based on available views, patient habits, presence of external impediments (e.g., drains, surgical dressings), and preference of the sonologist.

The patients were divided into three groups according to IVCCI values: IVCCI ≤ 15%(13 pts), IVCC I 16-40%(21 pts), IVCC I >40% (20 pts). Among these, first and third layers were assumed to indicate the  presence of  systemic venous congestive status  or of  likely intravascular depletion , respectively;  whereas an IVCCI in the intermediate range(0,16 to 0,40) was considered not helpful in discriminating CVP.

The following clinical criteria of  congestion were compared across  the three groups: dyspnea/orthopnea, dyspnea on exertion, jugular venous distension, peripheral edema, congestive hepatomegaly, pulmonary rales, mean weight gain ≥ 1 kg per  week through the follow up.

These signs and symptoms were chosen due  to their proven relationship with CHF syndrome. Particularly,  dyspnea at rest with orthopnea was selected as being a symptom usually associated with severe impairment in  left ventricle pump  function (in our case to be set in the context of biventricular cardiac decompensation, as right heart failure was present in all recruited cases by definite enrollment criterion ). Orthopnea was defined as any respiratory distress associated with lying down or the perceived need to use more than one pillow to avoid respiratory distress. Rales were considered owing to their well-known association with pulmonary capillary and venous hematic stagnation usually related to relatively high levels of capillary pulmonary wedge  pressure (CPWP). Dyspnea on exertion was  included in analysis as being a symptom that usually indicates lesser  cardiac impairment compared to orthopnea, generated by right-sided  as well as  by combined  biventricular  heart failure. Besides, the other four signs (jugular venous distension, peripheral edema, congestive hepatomegaly and weight gain ≥ 1 kg per  week) were evaluated in the study as markers of hydrosaline retention as usually  found in systemic  congestion from right or biventricular advanced CHF. Particularly, jugular venous distension was considered present if visualized at least 10 cm vertically above the right atrium. Weight gain was defined as ≥ 1kg mean  increase per week.

In addition, a congestion score was set up and defined retrospectively for this analysis as the sum of the seven criteria for congestion, with a possible range from 0 to 7.A score ≥ 4 was termed "high congestion score" and used as outcome variable ("end – point") in the subsequent statistical analysis. According to the customary approach applied at the two Centers, every  patient in each of the  day hospitals  underwent a careful clinical examination along with a complete echocardiography including a thorough assessment of IVC with IVCCI calculation. Subsequently, a second scheduled visit was  usually accomplished within one-two months in order to timely  establish any  appropriate  pharmacologic and dosing change to be done based on the evolving clinical picture. Should any complaint or  unexpected complication arise, the patients were recommended to bring forward the date of  the visit .

In our retrospective study, we tried to ascertain whether any association could exist between IVCCI values, as detected at the first visit, and one or more of the abovementioned signs and  symptoms of congestion, as noticed after 1-2 months of  clinical follow up. We investigated this hypothesis by using the preliminary categorization of IVCCI values by three layers (IVCCI ≤ 15% , IVCC I 16-40%, IVCC I >40%) and by considering the clinical picture after adequate  oral therapy  kept for one-two months. We also verified the possible existence of any significant association  between the cluster characterized by the lowest IVCCI (≤ 15%) at baseline and  the finding of "high congestion score", as found at the second visit after one-two months. The prescribed oral therapy usually  included ACE-inhibitors, beta-blockers and  diuretics; in addition, according to the physician’s judgment, aldosterone receptor antagonists, oral or transdermal nitrates, antiaggregant drugs, warfarin, amiodarone and digoxin were also administered if necessary. It was also established that every patient requiring intravenous diuretics or inotropes for worsening HF during follow up would have been excluded from the statistical analysis, as being considered to demonstrate treatment failure.

Statistical analysis

We used  the Statistical Package of Social Sciences (SPSS Version 14 ) and  Excel  to perform the analysis. Baseline demographics, physical examination, and laboratory findings were compared between patients  across the three IVCCI layers. The χ2 (chi square) test and the unpaired t-test were respectively applied for comparison of dichotomous or continuous variables. One-way analysis of variance (ANOVA) and Student-Newman-Keuls test for all peer comparisons ("post hoc" analysis) were used for multiple comparisons . Kruskal Wallis test was also employed for comparison of data with asymmetric distribution.

For identifying the predictors of hemodynamic  congestion, univariate and multivariate Cox proportional hazards regression analyses were used . The following variables were entered into the model as exposure variables:

IVCCI 15%
mean weight gain ≥ 1 Kg per week
edema
orthopnea
rales 
jugular venous distension  
dyspnea on exertion during optimized therapy
congestive hepatomegaly

 

Results

A total of 54 patients were retrospectively enrolled, by drawing them from the charts of all CHF patients admitted for day-hospital stay between June 2009 and June 2010 at the two Centers. This group consisted of 28 women and 26 men, with mean age of 78 ±5,5 years. Their  basal clinical and hematochemical characteristics are described in Table 1. In Table 2, the respective percentages of all of the investigated clinical signs and symptoms are listed.

Table 3 shows the results of the multivariate Cox  proportional hazards regression analysis including 8 covariates entered in the model, with  high congestion  score being used as outcome variable.

Multivariate predictors of high congestion score  were jugular venous distension (hazard ratio: 13,38  95% C.I.: 2,13 to 84  p = 0,0059) and rales (hazard ratio: 11  95% C.I : 1,45 to 83,8   p = 0,0213).

Figure 1 shows the distribution (%) of the cases (17 on the whole) of jugular venous distension (jvd) across the 3  IVCCI groups, as found at the second visit. It documents  that in the IVCCI ≤15% group, occurrence of jugular venous distension was higher  than in IVCCI=16-40% and  IVCCI>40% groups:  p (Kruskal Wallis ) <0.05 for both comparisons.

Furthermore, by considering  the relation between every category of IVCCI and the probability of developing orthopnea (figure 2), a remarkable difference emerges: actually,  the patients  with IVCCI ≤ 15%  were  burdened with a much higher risk of  being involved by orthopnea during the subsequent follow up. In addition,  low venous collapsibility  was found to entail high rate of early referral to heart failure unit, due to unscheduled re-admission for worsening  symptoms and signs of systemic and pulmonary congestion. By comparing the three classes of caval collapsibility, the most severe impairment of the clinical picture was exhibited by patients belonging to the lowest class of IVCCI values (figures 3-5) . Nevertheless, Cox multivariate proportional hazard model failed to identify IVCCI ≤ 15%  as a significant  multivariate predictor of worsening clinical congestion (Tab 3). In addition, it would be noted  that this pattern was accompanied in any case by simultaneous involvement of signs and symptoms from both left-sided and right-sided cardiac failure; on the contrary, the patients belonging to the intermediate range of caval collapsibility(IVCCI 16-40%) exhibited the highest rate of isolated systemic - but not pulmonary - congestion at the end of the prescribed follow up (30-60 days after  the first visit)(figure 5).

 

Discussion

Based on the pathophysiological concepts represented above, prognostic importance of  clinical congestion in HF patients is expected. However, clinical congestion may be the ‘tip of the iceberg’ of the hemodynamic derangements that precede symptoms21-22. For  instance, in chronic biventricular HF, even severe hemodynamic congestion rarely causes rales and/or radiographic pulmonary edema. This may be related to several adaptive pathophysiological changes such as increases in alveolar capillary membrane thickness, increased lymphatic drainage, and/or pulmonary hypertension3,21 (3,21). Thus, in the opinion of several Authors13,22, it would be very interesting and useful to explore not only clinical but also hemodynamic congestion in order to achieve  a really careful  patient assessment. In truth, this would be opportune considering that patients with even only hemodynamic congestion were shown to have poor outcomes23-25.

Ultrasound assessment of  IVC respiratory fluctuations has  been proposed from a long while as a possible  diagnostic tool for obtaining noninvasive reliable estimation of  volume status and/or right atrial pressure in CHF patients. Briefly, in spontaneously breathing subjects, intrathoracic pressure decreases during inspiration, thereby increasing venous return and inducing collapse of the IVC; inversely, during expiration, venous return decreases, so causing an increase in the diameter of the IVC26. High right atrial pressures dilate the IVC and worsen this normal IVC collapsibility. According to these observations, congestion would be indicated by relatively small  IVCCI values, while intravascular depletion would be revealed by wide fluctuations of IVC diameter, generating relatively high values of IVCCI. Therefore, small, collapsible IVCs as visualized by echocardiography represent low right atrial pressures, whereas large, non-collapsible IVCs reflect high right atrial pressures13. In the presence of marked volume overload, the respiratory cycle leads to minimal change in diameter of IVC, regardless of its absolute diameter27. This depend on the peculiar  non-linear pressure-diameter relationship of the IVC so that, above a threshold pressure (i.e., CVP >20 mmHg), no further increase in IVC diameter can be observed28.This has been confirmed by a recent study in which a IVCCI ≤ 15% was highly sensitive and specific for the diagnosis of acute decompensated heart failure, whereas the absolute diameter of the IVC in itself was non diagnostic19.

In our study, we decided to categorize IVCCI values by grouping them in three classes: ≤ 15%, 16-40 % and > 40 %.These IVCCI cut-off values were determined arbitrarily, with the intention of selecting groups with low, intermediate and high collapsibility indices.

Based on our analysis, rales and jugular venous distension were predictors of elevated score of congestion  as measured after a follow up period of 60 days.

Moreover, a low (≤ 15%) IVCCI value indicated higher  probability of presenting with elevated congestion score - that is ≥ 4 symptoms and/or signs of congestion within a range extending from 0 to 7 - compared to the other two IVCCI clusters; but , when evaluated by Cox proportional hazards regression analysis including 8 covariates, the  lowest IVCCI category  was not demonstrated to be a significant multivariate predictor of clinical congestion kept over a 60 day follow-up  on optimized oral therapy.

Furthermore, all of the patients presenting with IVCCI ≤ 15%  were found to have a clinical picture of combined right and left heart failure, this finding being presumably associated with  both high CPWP and right atrial pressure.

Study limitations

This study is limited by its retrospective nature as well as by relatively small sample size. IVC measurements were not done by a single operator, so inter-observer bias cannot be excluded. Moreover, we cannot exclude that tricuspid regurgitation affected inferior vena cava diameter, although this influence is less pronounced on IVCCI. Besides, measurement of the jugular venous pressure remains hard to be exactly performed and it also exposes to considerable risk of bias, related to high inter-observer variability expected.

In conclusion, in CHF setting both jugular venous distension and rales were useful predictors of outcome when assessed after 4 to 8 weeks of therapy to eliminate them. Low (≤ 15%)  IVCCI did not reliably predict high  congestion score as well as IVCCI classes did not reliably separate CHF patients with different congestion scores. Nevertheless, the cluster with  IVCCI ≤ 15% was always found associated with simultaneous presence of signs and symptoms from  both right and left-sided decompensated CHF.

 

Click to enlarge

 

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Correspondência:
Renato De Vecchis
P. Gaurico 21 – 80125 - Napoli, Italy
E-mail: r.de.vecchis@alice.it, carmelariano@tiscali.it

Artigo recebido em 28/08/11
Revisado recebido em 30/08/11
Aprovado em 06/02/12.

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