Diastolic exercise stress testing in heart failure with preserved ejection fraction: The DEST-HF study

Aims

Pulmonary capillary wedge pressure (PAWP) ≥25 mmHg during bicycle ergometry is recommended to uncover occult heart failure with preserved ejection fraction. We hypothesized that PAWP increase would differ in available diastolic stress tests and that the margin of PAWP ≥25 mmHg would only be reliably achieved through ergometry.

Methods and results

We conducted a prospective, single-arm study in patients with an intermediate risk for heart failure with preserved ejection fraction according to the ESC HFA-PEFF score. A total of 19 patients underwent four stress test modalities in randomized order: leg raise, fluid challenge, handgrip, and bicycle ergometry. The primary outcome was the difference (Δ) between resting and exercise PAWP in each modality. Secondary outcomes were differences (Δ) in mean pulmonary artery pressure (mPAP), cardiac output (CO), as well as the ratios between mPAP and PAWP to CO. Compared to resting values, passive leg raise (Δ7.7 ± 8.0 mmHg, p = 0.030), fluid challenge (Δ9.2 ± 6.4 mmHg, p = 0.003), dynamic handgrip (Δ9.6 ± 7.5 mmHg, p = 0.002), and bicycle ergometry (Δ22.3 ± 5.0 mmHg, p < 0.001) uncovered increased PAWP during exercise. Amongst these, bicycle ergometry also demonstrated the highest ΔmPAP (27.2 ± 7.1 mmHg, p < 0.001), ΔCO (3.3 ± 2.6 L/min, p < 0.001), ΔmPAP/CO ratio (2.3 ± 2.0 mmHg/L/min, p < 0.001), and ΔPAWP/CO ratio (2.2 ± 1.4 mmHg/L/min, p < 0.001) compared to other modalities. PAWP ≥25 mmHg was only reliably achieved in bicycle ergometry (31.1 ± 3.9 mmHg). In all other modalities only 10.5% of patients achieved PAWP ≥25 mmHg (handgrip 18.4 ± 6.6 mmHg, fluid 18.1 ± 5.6 mmHg, leg raise 16.5 ± 7.0 mmHg).

Conclusions

We demonstrate that bicycle ergometry exhibits a distinct haemodynamic response with higher increase of PAWP compared to other modalities. This finding needs to be considered for valid detection of exercise PAWP ≥25 mmHg when non-bicycle tests remain inconclusive.     

Epidemiology and clinical course of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFPEF) is increasingly recognized as a major public health problem worldwide. Significant advances have been made in our understanding of the epidemiology of HFPEF over the past two decades, with the publication of numerous population‐based epidemiological studies, large heart failure registries, and randomized clinical trials. These recent studies have provided detailed characterization of larger numbers of patients with HFPEF than ever before. This review summarizes the state of current knowledge with regards to the disease burden, patient characteristics, clinical course, and outcomes of HFPEF. Despite the wealth of available data, substantive gaps in knowledge were identified. These gaps represent opportunities for further research in HFPEF, a syndrome that is clearly a rising societal burden and that is associated with substantial morbidity and mortality.     

Therapeutic interventions for heart failure with preserved ejection fraction:A summary of current evidence

Heart failure with preserved ejection fraction(HFPEF)is common and represents a major challenge in cardiovascular medicine.Most of the current treatment of HFPEF is based on morbidity benefits and symptom reduction.Various pharmacological interventions available for heart failure with reduced ejection fraction have not been supported by clinical studies for HFPEF.Addressing the specific aetiology and aggressive risk factor modification remain the mainstay in the treatment of HFPEF.We present a brief overview of the currently recommended therapeutic options with available evidence.     

沙库巴曲缬沙坦治疗射血分数保留心功能衰竭的疗效研究

目的评价同心力衰竭(心衰)治疗指南推荐的最佳治疗相比,加用沙库巴曲缬沙坦是否能够更好的改善射血分数保留心功能衰竭患者的症状及预后。方法连续入选2018年3月至2018年9月于解放军总医院第七医学中心就诊的HFpEF患者42例,其中治疗组20例,对照组22例,两组患者均给予心衰治疗指南推荐的最佳药物治疗,其中治疗组加用沙库巴曲缬沙坦100 mg,2/d。随访3月,观察患者NT-proBNP水平、纽约心功能分级及6 min步行试验改善情况,同时评估两组间主要不良心脏事件发生率。结果两组患者基线资料无统计学差异,随访3月,治疗组纽约心功能分级显著优于对照组(P<0.05);治疗组NT-proBNP水平显著低于对照组[(3311.7±781.4)pg/ml vs.(6879.6±1033.5)pg/ml,P<0.001];治疗组6 min步行试验距离显著优于对照组[(550.2±53.2)m vs.(394.2±62.8)m,P<0.001];治疗组共发生MACE事件3例,对照组共发生重点事件9例,治疗组显著优于对照组(P=0.029)。其获益主要来源于因心衰再次住院率显著减少。结论同心衰治疗指南推荐的最佳药物治疗相比,加用沙库巴曲缬沙坦能够更加有效的改善射血分数保留心衰患者的临床症状,降低NT-proBNP水平,并显著减少患者因再次心衰住院的比率。     

Role of biomarkers in cardiac structure phenotyping in heart failure with preserved ejection fraction: critical appraisal and practical use

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome characterized by cardiovascular, metabolic, and pro‐inflammatory diseases associated with advanced age and extracardiac comorbidities. All of these conditions finally lead to impairment of myocardial structure and function. The large phenotypic heterogeneity of HFpEF from pathophysiological underpinnings presents a major hurdle to HFpEF therapy. The new therapeutic approach in HFpEF should be targeted to each HF phenotype, instead of the ‘one‐size‐fits‐all’ approach, which has not been successful in clinical trials. Unless the structural and biological determinants of the failing heart are deeply understood, it will be impossible to appropriately differentiate HFpEF patients, identify subtle myocardial abnormalities, and finally reverse abnormal cardiac function. Based on evidence from endomyocardial biopsies, some of the specific cardiac structural phenotypes to be targeted in HFpEF may be represented by myocyte hypertrophy, interstitial fibrosis, myocardial inflammation associated with oxidative stress, and coronary disease. Once the diagnosis of HFpEF has been established, a potential approach could be to use a panel of biomarkers to identify the main cardiac structural HFpEF phenotypes, guiding towards more appropriate therapeutic strategies. Accordingly, the purpose of this review is to investigate the potential role of biomarkers in identifying different cardiac structural HFpEF phenotypes and to discuss the merits of a biomarker‐guided strategy in HFpEF.     

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.