Clinical Investigation
Hydrogen- and Methane-Based Breath Testing and Outcomes in Patients With Heart Failure

https://doi.org/10.1016/j.cardfail.2018.10.004Get rights and content

Highlights

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    Breath tests are easy and noninvasive methods for identifying small intestinal microbiota overgrowth. These tools could be a potential method for quantifying the contribution of intestinal bacteria in the pathophysiology of heart failure (HF).

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    This study is the first to show that small intestinal bacterial overgrowth, assessed by exhaled concentrations of hydrogen and methane after a lactulose test, is highly prevalent in patients with HF.

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    In this cohort, exhaled concentration of hydrogen was positive and independently associated with higher risk of the composite of all-cause death/admissions and with recurrent hospitalizations.

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    Patients with higher exhaled hydrogen concentration after a lactulose test may identify a subgroup of patients with greater contribution of gut microbiota in the pathophysiology of HF that would benefit from specific treatments such as modification of microbiota composition, modulation of the immune response, or even intensifying HF drug therapy.

ABSTRACT

Background

Recent evidence endorses gut microbiota dysregulation in the pathophysiology of heart failure (HF). Small intestinal bacterial overgrowth (SIBO) might be present in HF and associated with poor clinical outcomes. Lactulose breath testing is a simple noninvasive test that has been advocated as a reliable indicator of SIBO. In patients with HF, we aimed to evaluate the association with clinical outcomes of the exhaled hydrogen (H2) and methane (CH4) concentrations through the lactulose breath test.

Methods and Results

We included 102 patients with HF in which lactulose SIBO breath tests were assessed. Cumulative gas was quantified by the area under the receiver operating characteristic curve of CH4 (AUC-CH4) and H2 (AUC-H2). Clinical end points included the composite of all-cause death with either all-cause or HF hospitalizations, recurrent all-cause hospitalizations, and recurrent HF hospitalizations. Medians (interquartile ranges) of AUC-H2 and AUC-CH4 were 1290 U (520-2430) and 985 U (450-2120), respectively. In multivariable analysis, AUC-H2 (per 1000 U) was associated with all-cause death/all-cause hospitalization (hazard ratio [HR] 1.21, 95% CI 1.04–1.40; P = .012), all-cause death/HF hospitalization (HR 1.20, 95% CI 1.03–1.40; P = .021), and an increase in the rate of recurrent all-cause (incidence rate ratio [IRR] 1.31, 95% CI 1.14–1.51; P < .001) and HF (IRR 1.41, 95% CI 1.15–1.72; P = .001) hospitalizations. AUC-CH4 was not associated with any of these end points.

Conclusions

AUC-H2, a safe and noninvasive method for SIBO estimation, is associated with higher risk of long-term adverse clinical events in patients with HF. In contrast, AUC-CH4 did not show any prognostic value.

Section snippets

Study Population

This was a prospective single-center study that enrolled 107 ambulatory patients recruited from March 15, 2015, to February 2, 2016. The inclusion criteria were: (1) HF diagnosis according to the current clinical practice recommendations,11 (2) at least 1 previous episode of acute decompensated HF, (3) signs of fluid overload, and (4) New York Heart Association functional class II–IV. Exclusion criteria were: (1) treatment with corticosteroids, antibiotics, or fiber supplements at screening,

Baseline Characteristics for the Entire Population

The median (IQR) age of the study population was 75 (70–78) years and 71.6% were male. The proportions of patients with reduced (<40%), preserved (≥50%), and midrange (41%–49%) LVEF were 44.2%, 42.1%, and 13.7%, respectively. Medians (IQRs) of AUC-H2 and AUC-CH4 were 1290 (520-2430) U and 985 (450-2120) U, respectively. Ischemia was the most frequent etiology (42.2%), and 71.6% of patients were recently discharged (within previous 30 days) from an acute decompensated HF episode. All

Discussion

To the best of our knowledge, this study is the first to show that exhaled H2 after lactulose breath testing, a surrogate of SIBO, was related to higher risk of adverse events, including the composite of death/all-cause hospitalizations and recurrent hospitalizations. In contrast, exhaled CH4 had no effect on either of those end points. We think that these findings add indirect evidence about the role of gut microbiota, and probably SIBO, in the pathophysiology of HF.

Conclusion

In a cohort of patient with advanced HF, exhaled H2 concentration after lactulose breath test—a surrogate of SIBO—was positively associated with surrogates of inflammatory activity, clinical status, and a higher risk of the death and hospitalizations.

Disclosures

None.

Acknowledgement

Vicente Navarro MD, grupo MiBioPath, Universidad Catlica San Antonio de Murcia.

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    Funding: This work was supported in part by grants from CIBER CV (16/11/00420 and 16/11/00403) and FEDER, Instituto Carlos III (FI12/00467 and PIE15/00013).

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