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One Heart, Two Lungs Together Forever

University of Ferrara, and, Fondazione Salvatore Maugeri IRCCS, Cardiovascular Pathophysiology Centre Gussago, Italy

Cardiovascular diseases represent the leading cause of death worldwide and chronic heart failure (CHF), the final common pathway of heart diseases, is the most important morbidity/mortality factor in Western countries. Chronic respiratory diseases, and, in particular, chronic obstructive pulmonary disease (COPD), also account for a large proportion of human illness and are responsible for 7% of all the deaths due to chronic diseases (1). The impact of heart and pulmonary chronic diseases on health is therefore huge, and, given the relative frequency of the two diseases, the possibility that they are associated in the same patient is high.

Studies investigating the interrelation of CHF and chronic pulmonary disease are few and the epidemiologic data on their association are fragmentary. This is even more surprising if we consider that heart and pulmonary diseases have, in general, several common risk factors, most notably smoking. Concerns arise from the fact that disease-specific guidelines often do not address the issue of comorbidity (2, 3). The long-term benefit and harm associated with the combination of drugs prescribed in adherence to disease-specific guidelines for patients with coexisting illnesses may not be clear: this can be particularly critical in some subsets of patients, such as the elderly (3).

The article by Abroug and colleagues in this issue of the Journal (pp. 990–996) addresses the importance of cardiac comorbidity in the setting of severe acute exacerbation of COPD (AECOPD) (4). The article provides valuable clinical implications. We particularly wish to emphasize the following aspects:

1. The authors report a high relative frequency of left-ventricular dysfunction in the specific setting of AECOPD; the fact that more than 40% of the selected patients suffered cardiac comorbidity emphasizes the considerations expressed above and brings up new pathophysiologic questions and scenarios. This figure needs to be verified in larger cohorts, but it fills a gap in our knowledge. Only recently, a cross-sectional epidemiologic study reported that unrecognized heart failure in elderly patients with stable COPD is about 20%; the prevalence of heart failure in patients with COPD (stable or during exacerbation) is therefore several times higher than in the population at large (5).
   
2. With this study, the authors validate the diagnostic performance of measuring natriuretic peptides in the setting of acute dyspnea due to a final diagnosis of AECOPD. The patient population is different from that included in the Breathing Not Properly (BNP) multinational trial (6) and other previous studies, which constituted the state-of-the-art of knowledge in the field (7, 8). Notably, Abroug and colleagues (4) in their article suggest a cut-off threshold for ruling out left-ventricular dysfunction, which seems higher than the values for patients with acute dyspnea or for patients evaluated in emergency departments (8)
   
3. The results obtained imply that routine measurement of natriuretic peptides in the setting of AECOPD, even if in the presence of less severe respiratory insufficiency, may be useful to identify patients who may benefit from further cardiologic assessment.
   
4. Troponin T assessment is neither sensitive nor specific enough for recognition of left-ventricular dysfunction in the specific setting of AECOPD. Nevertheless, tropinin T is a more reliable marker of myocardial ischemic damage than clinically defined cardiac overload. The authors have found that Troponin T is elevated to a greater extent in the group of patients with AECOPD and left-heart dysfunction. This may also suggest the hypothesis that myocardial ischemia—for example, precipitated by hypoxia—may have occurred. Indeed, this possibility needs to be investigated in prospective studies, but it is likely that this subgroup of patients may benefit from further investigation to exclude coronary artery disease.
   

There are also some aspects of the study that require additional critical analysis. In particular, as mentioned by the authors, the standard for diagnosis of heart failure (adjudicated by a panel of physicians based only on diagnostic information, and not on previously validated parameters, such as the Framingham, Boston or NHANES scores) is indeed subjective and potentially biased. However, although imperfect, this standard can be considered the best presently available and consistent with the clinical aim of the study. Another possible limitation arises from the fact that heart catheterization was performed only in patients with weaning problems and with strong clinical and echocardiographic indications of left-ventricular dysfunction, a potential source of verification bias.

The article by Abroug and colleagues (4) represents an important starting point for future mechanistic studies. Two major fields warrant priority of investigation: First, it is crucial to understand the key pathophysiologic features of heart and lung comorbidity and the determinants that influence illness progression in the presence of both diseases. The other field that needs further investigation is related to the potential implications of heart and lung comorbidity in terms of treatment. In this regard, a recent study, based on retrospective cohorts of patients, suggests that statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers exert a dual-protective role at cardiac and pulmonary levels, not only reducing cardiac events but also COPD hospitalization and mortality regardless of the cardiovascular risk profile and concomitant use of steroids (9). These suggestive data need confirmation in prospective clinical trials, but they open new perspectives on the interplay between heart and lung disease.

FOOTNOTES

Conflict of Interest Statement: C.C. received 3,150 from Servier for serving as a consultant on multicenter clinical trials (2006); he received 4,750 from Merck, Sharpe & Dohme for serving as a consultant (2006); he has participated as a speaker in scientific meetings or courses organized and financed by various pharmaceutical companies (Servier, Merck, Sharpe & Dohme, Stroder, AstraZeneca). R.F. received grants from Servier ( 1,500/yr in 2004–2006), Guidant ( 1,500/yr in 2004–2006), AstraZeneca ( 3,000/yr in 2004–2006) for serving as a consultant on multicenter clinical trials; he has participated as a speaker in scientific meetings or courses organized and financed by various pharmaceutical companies (Servier, Merck, Sharpe & Dohme, Stroder, AstraZeneca).

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