Patients with COPD can have sustained (patients with chronic respiratory failure), or intermittent hypoxia (during exercise, exacerbations, or during sleep). Hypoxia can cause abnormalities in ventricular relaxation and contraction due to changes in the myocyte cell metabolism.19 It can also affect the pathogenesis of atherosclerosis by various mechanisms, including increased vascular and systemic inflammation, elevated C-reactive protein and increased oxidative stress.20,21 Furthermore, it can induce hemodynamic stress by increasing the heart rate and activating the sympathetic nervous system.22,23 Finally, hypoxia is involved in pulmonary vascular remodeling that increases pulmonary vascular resistance, which may negatively affect LV diastolic filling by the phenomenon of ventricular interdependence, described below.

Coronary artery disease (CAD) or atherosclerosis is the end result of the accumulation of atheroma plaques on the walls of the coronary arteries. Numerous epidemiological studies have shown that COPD patients have a high risk of developing CAD, with its inherent complications (ischemic heart disease, stroke, sudden death), and that this risk increases during exacerbations.24–26 Some studies have found this association to be independent of smoking and other confounding factors, such as age. Sub-clinical atherosclerosis (the “early” phase of CAD) has also been described in smokers with airflow limitation and in emphysema patients.27,28

The etiology of CAD and COPD is complex and multifactorial, since they share common etiological factors apart from smoking (release of endothelial microparticles, changes in hemostasis and oxidative stress, among others).29–31

The precise prevalence of CAD in COPD is not known; estimates published to date vary widely (4.7%–60%).32 Nevertheless, data from population studies indicate that it could be high.33–35

Other evidence that highlights the close relationship between CAD and COPD is the role of the latter as an independent factor for poor progress and mortality following coronary revascularisation.36–38 COPD, together with 5 other major clinical variables including age, sex and LV ejection fraction (LVEF), is a predictor of mortality 4 years after revascularization in the SYNTAX score II (an angiographic grading tool to determine the complexity of CAD that helps clinicians decide the optimum revascularization method in patients with complex CAD).39

CAD can affect myocardial relaxation by decreasing arterial distensibility, and increasing central arterial pressure and LV afterload,40 while subclinical atherosclerosis has been negatively associated with diastolic dysfunction parameters due to altered coronary reserve.29

Right ventricular function and pulmonary hypertension (PH), usually only mild to moderate, are common in COPD. Both pulmonary vascular changes and pathological changes in the RV have been found even in early stages of the disease.7,41 Ventricular interdependence describes the phenomenon in which both RV pressure and volume overload cause the interventricular septum to shift toward the LV, modifying its geometry (“D-shape”). The pathophysiological mechanisms involved are summarized in Fig. 1. Dilatation of the RV also increases the constrictive effect of the pericardium, all of which can result in a reduction in the distensibility and filling of the LV.42 This mechanism may explain why a preserved ejection fraction can be observed in the LV, despite a sub-optimal filling phase.

Fig. 1.

Figure summarizing the pathophysiological mechanisms involved and their effects on the left ventricle in COPD. CF: cardiac frequency; FEV1: forced expiratory volume in the first second; IC/TLC: ratio between the inspiratory capacity and total lung capacity; PH: pulmonary hypertension; RV: right ventricle; RVol: residual volume.

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Thanks to recent advances and the widespread availability of imaging techniques, the effect of emphysema and hyperinflation on LV dysfunction (LVD) is now understood in greater detail. Ten years ago, Jörgensen et al.43–45 hypothesized that hyperinflated lungs and high intrinsic positive end-expiratory pressure will decrease intrathoracic blood volume and ventricular preload, resulting in “hypovolemic diastole”. The authors showed through various studies that patients with severe emphysema had various functional and hemodynamic alterations, such as a decrease in the end-systolic and end-diastolic volumes of the LV, lower cardiac index and lower stroke volume index compared to a control group, and that furthermore, these parameters could improve after volume reduction surgery.47

In this respect, Watz et al.,11 in an echocardiographic study of 138 patients with COPD of varying severity, observed that pulmonary hyperinflation (measured by the inspiratory capacity/total lung capacity [IC/TLC] ratio) was more strongly correlated with the decreased size of the heart chambers and impaired LV diastolic filling pattern than with airflow obstruction or the carbon monoxide diffusing capacity.

Barr et al.10 provided solid evidence of the effect of emphysema on ventricular filling in the MESA study, an extensive population study in patients without CVRF. Emphysema detected by computed tomography (CT) and airflow obstruction were linearly and inversely correlated with the reduction in LV end-diastolic volume, systolic volume and cardiac output measured by magnetic resonance imaging (MRI). These associations were of greater magnitude among the active smokers than among former and never-smokers. These findings indicate that even in the early stages of COPD, the systolic volume and size of the LV are affected.46 In 2 MESA sub-studies, Smith et al.47 described an association between 2 pulmonary hyperinflation parameters (residual volume and the residual volume/TLC ratio) with a larger LV mass in 119 patients with COPD, while another study by the same group showed that the percentage of emphysema was inversely correlated with the diameter of the pulmonary veins,48 which were narrower in COPD patients (GOLD I–III) than in controls, although the difference was not statistically significant (P=.06). This structural alteration may also be detrimental to LV filling.

As shown above, ventriculography and autopsy studies in patients with chronic bronchitis and emphysema show LV hypertrophy (LVH) and increased ventricular mass.18 In addition to the study by Smith et al.,47 which describes an association between pulmonary hyperinflation and LV mass independent of other CVRF, Anderson et al.,49 using echocardiography, reported a prevalence of LVH of 21.4% in men and 43.2% in women with normoxemic COPD and no underlying PH; the LV mass was significantly larger than that of controls. These findings indicate an independent effect of COPD on LVH that is not related with PH. The authors suggested sympathetic activation as the possible mechanism, mainly through the renin–angiotensin–aldosterone system.

LVH is a pivotal factor in cardiovascular events, and preventive treatment has been shown to reduce cardiovascular morbidity and mortality to a large extent.50 LVH is considered an arrhythmogenic factor and can result in the eventual onset of ventricular dysfunction (both diastolic and systolic), and atrial fibrillation (AF) and dilatation. Moreover, LVH reduces the coronary reserve, increasing the risk of ischemic heart disease.51 Controlling ventricular remodeling as far as possible has thus become one of the therapeutic targets in the management of chronic diseases in which LVH is prevalent, such as diabetes mellitus and chronic renal failure.

During diastole, the LV receives blood from the left atrium, which is subsequently ejected into the systemic circulation. In simple terms, the efficiency of LV filling can be measured as the ability to receive a large volume of blood at rapid filling rate but under low pressures.52 Consequently, various physiological parameters interact in LV diastole, principally relaxation, ventricular distensibility and atrial contraction (Table 2). Among the most common causes of diastolic dysfunction are PH, senility and CAD.

Various studies in COPD patients describe a high rate of LV diastolic dysfunction (LVDD) compared to age-matched controls, even in those without CVRF.53–70 Its prevalence also varies considerably, reaching 90% in COPD patients with severe airflow limitation.68 The most frequently described pattern is slow relaxation, which is characterized by a reduced E wave (due to a decrease in the relaxation velocity of the myocardial fibers) and an increased A (atrial contraction) wave with an E:A ratio <1.40 This impaired ventricular filling can be a major complication in patients with AF, a very prevalent arrhythmia in COPD, due to both loss of atrial systole and shortening of the filling period.59

Several authors attributed this impairment to the phenomenon of ventricular interdependence. Funk et al.,59 however, described LVDD in COPD patients without PH, demonstrating that its development may be due to the interaction of other mechanisms, as described above.

Impaired ventricular filling has been negatively associated with exercise tolerance assessed using the 6-min walk test,11,68 and with a reduction in physical activity.71

Bhattacharyya et al.65 conducted a study to determine whether LVDD could be secondary to ischemic lesions that were not detected by conventional studies (electrocardiogram and echocardiography). They included patients with COPD GOLD III and IV with no risk factors for developing LVDD (HT, diabetes mellitus, history of ischemic heart disease or hypothyroidism). Patients diagnosed with LVDD by echocardiography were examined using myocardial perfusion single-photon emission computed tomography imaging. Reversible perfusion defects were found in 7 of the 14 patients studied (50%). On the basis of these findings, the authors hypothesized that ischemic heart disease in these patients could also be a cause of LVDD. Further studies are required with a larger patient sample to confirm these results.

Left ventricular systolic dysfunction (LVSD) is defined as an LVEF <50%.72 The reported prevalence of LVSD in patients with stable COPD varies widely, and is related to the exclusion of CVRF in different series (0%–16% in COPD patients without CVRF).73 The frequency of this abnormality ranges from 8% to 25% in non-selected patients.62,63,66,67

Analysis of ventricular deformation or strain and the ventricular deformation rate or strain rate are the new parameters that quantitatively assess the segmental contractility of the LV, irrespective of a normal LVEF. This can be done using tissue Doppler imaging, and more recently, using two-dimensional ultrasound speckle tracking. Sabit et al.61 found that these parameters were significantly reduced compared to controls in a series of 36 patients with COPD. Schoos et al.,70 meanwhile, reported that these parameters were predictors of mortality by multivariate analysis in a series of 90 patients with COPD of varying severity.

LVD (systolic and diastolic) was described as a predictor of survival in a cohort of COPD patients undergoing vascular surgery who were followed up for 2 years.62 Macchia et al.66 found higher mortality in COPD patients with this abnormality compared non-LVD patients, although this difference did not reach statistical significance.

Heart failure (HF) may not be suspected in patients with COPD, since the signs and symptoms are common and overlap in both diseases. The prevalence of HF in patients with COPD in different series ranges from 7.1% to 31.3%.4,32–35,62,74

There are 2 patterns of HF, one involving preserved systolic function (HFpEF), more associated with HT, advanced age and extracardiac diseases, and the other involving a reduced ejection fraction (HFrEF), more related with ischemic heart disease.

Rutten et al.75 reported a prevalence of HF of 20.5% in a cohort of patients with stable COPD. During a 4-year follow-up period, mortality among patients diagnosed with HF was higher, regardless of other factors such as age, sex, history of ischemic heart disease or HT.76 Although there is little information in this respect, the prognosis in COPD patients with HF appears to be independent of LVEF.77

Conversely, COPD is a common comorbidity in patients with HF, and has been described in up to one third of this population.78 Comorbid COPD has been shown to worsen the prognosis in HF, and COPD exacerbation is known to cause or precipitate acute HF.72 In a study comparing the impact of different comorbidities on prognosis in 2843 patients diagnosed with HFpEF and 6599 with HFrEF, COPD was the only comorbidity that acted as an independent variable of mortality for both groups.79 It is remarkable that, despite the importance of COPD as a comorbidity in HF, the latest HF guidelines do not include spirometry among the complementary tests recommended in the management of this entity.