Heart Failure (HF) is a complex clinical syndrome which results from structural or functional impairment of ventricular filling or ejection of blood, which in turn leads to the cardinal clinical symptoms of dyspnea and fatigue and signs of HF, namely edema and rales[1]. Heart failure affects more than 64 million people worldwide[2].

HF by definition begins with a “failing heart,” its pathology extends far beyond this site to affect multiple organ systems. Perhaps the most underappreciated victim of HF pathology is the respiratory system. The heart and lungs are intimately linked.

Airway abnormalities in heart failure may range from mild restriction to mixed obstructive restrictive pattern and coexisting COPD [3]. In HF with reduced ejection fraction (HFrEF), the backward transmission of elevated left-sided filling pressure leads to pulmonary congestion. As left ventricular filling pressure increases, interstitial edema develops, causing reductions of lung volume and DLCO, while FEV1/FVC remains normal. Thus, FVC and DLCO may decline with even moderate congestion, whereas an obstructive-like pattern (low FEV1/FVC) may emerge in decompensated HF due to bronchial wall edema[4].

Hence, although pulmonary function testing (PFT) may provide useful additional information for the management of patients with chronic HF, this is currently under-used.

Wasserman et al.  showed in a large multicenter study that, at rest, forced expiratory volume in the first second and vital capacity are either normal or proportionately reduced in heart failure[5]. Agostoni et al. demonstrated that pulmonary function at rest is usually normal in patients with moderate heart failure, while a restrictive lung disease is observed in 50% of patients with severe heart failure [6]. In a study conducted by Dalsgaard M et al. the prevalence of airflow obstruction in chronic heart failure was found to be 39%[7].

In previous studies conducted so far either air flow obstruction or restriction was evaluated in chronic heart failure patients. None of the previous studies evaluated both obstructive and restrictive and mixed type of respiratory abnormalities in patients of chronic heart failure. None of the study has been done in similar settings in the Indian context.

Our study was conducted to evaluate the different types of respiratory abnormalities in patients of chronic heart failure in Indian context. Furthermore we also evaluated relationship between respiratory abnormalities and LVEF and functional status of patients.

This cross-sectional study was conducted in 100 patients from the Cardiology OPD & Heart failure Clinic of ABVIMS and Dr. RML Hospital, New Delhi from September 2022 to December 2023.

Inclusion criteria were age > 18 years and LVEF < 40%.Exclusion criteria were no hospitalisation for decompensated heart failure in last 6 months,Class IV NYHA patients,chronic kidney disease stage 4 and 5,pregnancy and preexiting chronic  lung disease on treatment.

Detailed history and clinical examination were done. Data of demographic characteristics, comorbidities,body mass index, smoking status and functional capacity assessed by New York Heart Association (NYHA) functional classification were done for all patients.

All patient undergone routine blood tests, X-ray chest, electrocardiogram and 2D Echocardiography.

The transthoracic echocardiographic study was conducted according to the recommendations from the American Society of Echocardiography. LV ejection fraction was calculated from the LV end-diastolic volume and end-systolic volume estimates by biplane Simpson method.

Pulmonary function test was performed using spirometry according to the American Thoracic Society standards.After a 5-minute rest in a seated position, spirometric parameters were measured.The predicted values were calculated using validated spirometric prediction equations, and  FVC, and forced expiratory volume in the first second (FEV1) are presented as the percentage of their relevant predicted values. The ventilatory abnormalities were further categorized into 3 types: obstructive type is defined as FEV1/FVC <70% and FVC ≥80% of the predicted value; restrictive type is defined as FEV1/FVC ≥70% and FVC <80% of the predicted value; mixed type is  defined as FEV1/FVC <70% and FVC <80% of the predicted value.The severity of respiratory abnormality was graded as per American Thoracic Society Grades for Severity of a Pulmonary Function Test Abnormality[8].

Statistical Analysis

Descriptive statistics were reported in the form of means/standard deviations and medians/IQRs for continuous variables and frequencies and percentages for categorical variables. Group comparisons for continuously distributed data were performed using an independent student "t" test when comparing two groups. If data was found to be non-normally distributed, appropriate non-parametric test in the form of Wilcoxon Test was used. Three or more group comparisons done with ANOVA(parametric) or Kruskal Wallis test(non-parametric).

Chi-squared test was used for group comparisons for categorical data. If the expected frequency in the contingency tables was found to be <5 for >25% of the cells, Fisher's exact test was used instead.

Linear correlation between two continuous variables was examined using Pearson's correlation (if data were normally distributed) and Spearman's correlation (for non-normally distributed data).All the reported p-values are two-sided and p-values <0.05 were considered to indicate statistical significance. SPSS v28 (IBM Corp.) was used for data analysis.

A total of 164 patients with heart failure were screened for eligibility.  Among those, 64 patients were excluded from the study since 34 patients were having acute decompensation, 15 patients were in CKD stage 4 or 5 and 15 patients had prior respiratory abnormalities. Study was conducted in 100 patients.

Amongst the study population, 65% were males and 35% were females.The mean age of study population was 52.55 (±12.7; S.D) years. Mean age of female was 51.23 (±12.63; S.D).Mean age of male was 53.26 (±12.78; S.D). Patients were divided into 3 groups: NYHA I,II and III as per their symptom of  dyspnoea, palpitation or fatigue. Number of patients in NYHA Class I, II and III were 19, 54 and 27 respectively. NYHA Class IV was excluded from the study.

Baseline Characteristics: Baseline characteristics of various NYHA groups were well matched. However, the decompensation  frequency of heart failure was low in NYHA I & II{NYHA I:0(0-1)/yr, NYHA II:0(0-1)/yr} as compared to NYHA III {NYHA III:1(0-1)/yr,}.There was significant difference in decompensation frequency between NYHA I & III(p:0.004) and NYHA II & III (p:0.037).No difference in decompensation frequency between NYHA I and NYHA II(p:0.46)

Blood urea level in NYHA I was 27.37 mg/dl(±4.32),NYHA II 29.15 mg/dl(±5.35) and in NYHA III 33 mg/dl(±5.60).There was significant difference in blood urea levels between NYHA I and III (p:0.004) and between NYHA II and III( p:0.037).No statistical significant difference exist in blood urea level between NYHA I and II(p:0.46). Patients in NYHA III received significantly higher dose of furosemide or equivalent dose of other diuretics as compared to NYHA II and NYHA I (p:<0.001).All patients received Beta blocker and mineralocorticoid receptor antagonist(MRA).

Table 1: Baseline Characteristics

Echocardiography and ECG Parameters: The mean LVEF in NYHA I,II and III was found to be 34.87(±4.02), 33.16(±3.63) and 30.95(±2.94) % respectively(p:0.005). Overall LVEF was 32.89(±3.75)%.Higher grade of LVDD was seen in NYHA III and II(p:0.028)

Table 2: Echocardiography & ECG Parameters

Spirometry: Spirometry revealed 42(42%) patients with no respiratory abnormality,42(42%) with restrictive pattern,6(6%) with obstructive pattern and 10(10%) with mixed pattern.So,respiratory abnormality was detected in 58(58%) patients of stable chronic heart failure.  

Figure 1:Distribution of respiratory abnormalties

The pattern of respiratory abnormalities i.e normal,restrictive,obstructive and mixed patterns were grouped in NYHA functional classes. NYHA class III had more obstructive and mixed pattern as compared to NYHA I & II(p: <0.001).Furthermore NYHA III had more severe respiratory abnormalities than NYHA I & II (p<0.001)

Table 3:Distribution of pattern of respiratory abnormalities

Table 4:Severity of respiratory abnormality as per NYHA classes

Table 5: FEV1 & FVC across NYHA classes

 Correlation of LVEF with spirometric parameters: Correlational study was conducted between LVEF and respiratory parameters in the form of FEV1,FVC and FEV1/FVC.There was positive and significant correlation between LVEF and FEV1(Pearson’s coefficient-0.253,p:0.01).There was also positive and significant correlation between LVEF and FVC((Pearson’s coefficient-0.209,p:0.03).No statistically significant correlation was found between LVEF and FEV1/FVC(Pearson’s coefficient-0.186,p:0.063)

Simple linear regression analysis showed significant slope for FEV1 and FVC against LVEF with p value of 0.019 and 0.036 respectively.

Y(FEV1) = 0.9389*(LVEF) + 42.05

Y(FVC) = 0.6610*(LVEF) + 56.75

Figure 2: Simple linear regression analysis for FEV1 and FVC against LVEF

Heart failure is a major global burden in terms of hospitalization, morbidity, readmission, and mortality. Population studies have consistently shown that impaired lung function is an independent predictor of both of all-cause and cardiovascular mortality and is associated with reduced systolic and diastolic cardiac function[9].

Even in patients admitted to hospital because of HF, impaired lung function is an independent predictor of mortality. Olson et al. have shown that spirometry and DLCO significantly predicted mortality in patients with stable HF of more than 1 year duration[10].

We conducted this cross sectional study to study the extent and pattern of respiratory abnormalities in stable chronic heart failure patients and to find correlation between respiratory abnormalities and LVEF and functional status of patients.

Patients were divided in 3 groups as per NYHA classification:NYHA I,II and III.NYHA IV was excluded from the study.Number of patients in NYHA I were 19(19%),NYHA II 54(54%) and NYHA III 27(27%).In the study conducted by Dalsgaard et al.,75% patients were in NYHA I-II and 25% in NYHA III-IV[7].   In the study performed by Brenner et al,21.4% of patients in were in NYHA III/IV[11]. So,the proportion of patients with severe functional impairment is similar in our study as compared to previous studies.

The blood urea level was significantly higher in NYHA III and II as compared to NYHA I(p:0.003).This could be explained by higher dose of loop diuretics used in NYHA III class of patients as compared to NYHA II or I. This may also be result of chronic cardio renal syndrome. The decompensation frequency of heart failure was more in NYHA III as compared to NYHA I and II(p:0.016). It suggests that patients with poor EF have more chances of decompensation and re-hospitalization as compared to same population with relatively better LVEF.

Mean Left Ventricular Ejection Fraction(LVEF) was 32.89(±3.75)% which is comparable to study by Dalsgaard  et al[7] with mean EF 31±9% and study by Plesner et al with mean EF of 30±9.6%[12]. Left Ventricular Diastolic Dysfunction (LVDD) was detected in 94% patients.There were significantly higher percentage of patients with grade 2(22.2%) and 3(7.4%) LVDD in NYHA class III patients as compared to NYHA I or II(p:0.028).This may be attributed to lower LVEF in NYHA class III as compared to NYHA class II/I which causes pooling of blood and reduced compliance of left ventricle.It may also result from adverse effect of remodelling on left ventricle resulting in increased stiffness.

Most of the patients in our study were in sinus rhythm (96%).Atrial fibrillation was detected in 4(4%) patients.This is in contrast to the study conducted by Brenner S et al. where atrial fibrillation was seen in 21.5% patients[11]. RBBB/LBBB/IVCD was seen in 15% patients in our study. In the study by Lam CS et al.  LBBB was found in 13.9% in overall study group with 11.9% in Northeast Asia group, 20.3% in South Asia and 11.3% in Southeast Asia population[13].

Pulmonary function test revealed abnormality in 58(58%) patients.Among these 58 patients ,42 (42%) patients had restrictive pattern,6(%) patients had obstructive pattern and 10(10%) had mixed pattern. In the study done by Dalsgaard et al.[7],respiratory abnormality was detected in 60% patients which is similar to the result obtained in our study(58%).However,there were 38% with obstructive pattern and 22% with restrictive pattern in the study conducted by Dalsgaard et al. as compared to 6% obstructive pattern in our study.Lesser percentage of obstructive pattern may be due to the fact that pre-existing respiratory illness like COPD were excluded in our study.

In the study done by Plesner et al. ,obstructive pattern was found in 39% patients and restrictive pattern in 22.5% patients[12].In another study by Naum C et al respiratory abnormality was detected in 44(78.5%) patients.Of these 30 patients (53.6%) patients had restrictive defect and 14 patients(25%) had obstructive defect[14]. In the study conducted by  Agostoni et al. in 2006 on 136 patients of CHF in NYHA I-III,restrictive pattern was found in 58 patients(42.6%)[6].

So, the extent of respiratory abnormality detected in our study is similar to previous study with lesser proportion of obstructive lung disease.

It was observed that 78% of patients in NYHA I were normal,restriction occurred in 15.7% and obstruction in 5.2%.In NYHA II,50% patients were normal.There is greater percentage of restrictive impairment in NYHA II(46.3%) as compared to NYHA I (15.7%).Further it was also observed that there is greater percentage of obstructive(11.1%) and mixed (37.1%) abnormalities in NYHA III as compared to NYHA II where there is no mixed pattern and obstructive pattern was seen in 3.7%.(p:<0.001).This shows that as LVEF falls and functional class worsens,respiratory abnormality increases.Also as  functional class worsens,the respiratory pattern shifts from normal to restrictive and with further worsening mixed and obstructive pattern appears.

It was observed that severe respiratory impairment (48.1%) occurred more in NYHA III as compared to NYHA I or NYHA II. This shows that severity of respiratory abnormality correlates with NYHA functional class. The % predicted FEV1 and FVC decreased significantly as functional NYHA class worsens. This further corroborates that severity of respiratory abnormality worsens with progression of NYHA functional class.

There was positive and significant correlation between LVEF and FEV1 & FVC. The correlational study has shown that as the LVEF decreases, the respiratory impairment becomes more severe.

Limitations

Our study has several limitations. First patients with pre-existing lung disorders were excluded from the study. This was done to negate the effect of drug treatment on pulmonary function test. This may have led to lesser proportion of obstructive abnormality in our study.

Mixed respiratory abnormality requires total lung capacity for confirmation which was not done in our study.

A direct temporal relationship between reduced LVEF and severity of respiratory abnormality could not be established as the study was not done to evaluate the effect of drug treatment on improvement of LVEF and subsequent improvement in respiratory function.

Respiratory abnormalities are common in patients with stable chronic heart failure.In our study 58% subjects had respiratory abnormalities.Forty two percentage patients had restrictive pattern,6% had obstructive pattern and 10% patients had mixed pattern of respiratory abnormality.So,both restrictive and obstructive patterns of respiratoty abnormalities are common in stable chronic heart failure.

As functional class of dyspnea progresses,the severity of respiratory abnormality worsens.Also the respiratory pattern shifts from normal to restrictive and further to obstructive and mixed pattern with progression of NYHA class.There exists positive correlation between LVEF and FEV1 and FVC signifying that as LVEF decreases ,respiratory impairment becomes more severe.

Mixed pattern of respiratory abnormality could be either due to presence of COPD along with heart failure or it may be due to congestive airway obstruction.The two conditions could be differentiated by evaluation of lung hyperinflation by body plethysmography which confirms the diagnosis of COPD.Also if on treatment of heart failure there is improvement in airway obstruction,then it is most likely congestive airway obstruction.

It has important clinical implication as erroneous bronchodilator therapy in congestive airway obstruction may worsen heart failure. Therefore, a valid diagnosis of COPD in systolic heart failure demands serial PFT under stable conditions with special attention to hyperinflation.

Further studies need to be conducted to evaluate the effect of drug treatment on pulmonary function abnormalities seen in patients of heart failure.This would also help to study the impact of drug treatment in reducing mortality in patients with heart failure and respiratory abnormality.

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