Heart failure with preserved ejection fraction: insights from a single-center registry

Herzinsuffizienz mit erhaltener Linksventrikelfunktion (HFpEF) ist ein weltweit wachsendes Gesundheitsproblem, welches 50% aller Herzinsuffizienz PatientInnen betrifft. Dieses Erkrankungsbild ist mit einer hohen Morbiditäts- und Mortalitätsrate, sowie einer noch immer steigenden Prävalenz assoziiert. Viele PatientInnen entwickeln eine Pulmonale Hypertension, die den Verlauf der Erkrankung zusätzlich erschweren kann. Bis dato konnte noch keine Evidenz-basierte Therapie, die über eine Diuretika Therapie beziehungsweise dem Management von Komorbiditäten hinausläuft gefunden werden, um die Prognose der PatientInnen zu verbessern. Dies liegt vor allem an der komplexen Pathophysiologie die dieser Erkrankung zugrunde liegt. Unser Ziel war die Initiierung des ersten österreichischen HFpEF Patientenregisters um diese Patientenpopulation umfassend zu untersuchen. Patienten mit HFpEF wurden in unser prospektives Register eingeschlossen, wobei die Diagnose gemäß den aktuellen Richtlinien erfolgte und mittels Rechtsherzkatheter Untersuchung bestätigt wurde. Die Baseline Untersuchungen umfassten ein Herzultraschall, ein Elektrokardiogram, ein 6-minuten Gehtest mit Borg Dyspnoe Score Erhebung, eine Routinelaboruntersuchung und bei einem Teil der PatientInnen eine Herzmuskelbiopsie. Halbjährlich fanden Folgevisiten, beziehungsweise Telefonvisiten statt. Kardiale Hospitalisierung sowie Herztod wurden als primärer Endpunkt definiert. Im Zeitraum zwischen 2010 und 2015, wurden insgesamt 174 ältere, vor allem weibliche HFpEF PatientInnen eingeschlossen. PatientInnen waren charakterisiert durch ein fortgeschrittenes Krankheitsstadium mit einer hohen Rate an Komorbiditäten, einer hohen PH Prävalenz und stark eingeschränkter Leistungsfähigkeit. Ein vermindertes Leistungspotenzial stand im Zusammenhang mit einer vermehrten Anreichung von Extrazellulär Matrix im Herzen und anderen kardialen als auch nicht-kardialen Parametern. Eine zusätzliche PH verschlechterte die Prognose der PatientInnen, mit dem schlechtesten Event-freien Überleben in der Gruppe der PatientInnen mit zusätzlich präkapillärer Komponente. Chronische Hypoxie kann die Entstehung einer Lungengefäßerkrankung in diesen Patienten triggern. Unsere Daten bestätigen die allgemeine Ansicht, dass HFpEF ein komplexes Syndrom mit multifaktoriellen Ursachen darstellt. Therapeutische Maßnahmen sollten daher ihren Fokus vermehrt auf die systemische Behandlung dieser Patienten ausrichten.Heart failure (HF) with preserved ejection fraction (HFpEF) represents more than 50% of HF cases and is recognized as a major and growing public health problem worldwide. HFpEF is associated with markedly increased morbidity and mortality with a still rising prevalence. Some patients develop pulmonary hypertension (PH) that further complicates disease process. To date, no evidence-based therapy, beyond diuretics and conventional treatments for comorbidities, has been proven in pivotal clinical trials to improve outcome in this population. This is mainly due to the pathophysiological heterogeneity that exists within the broad spectrum of HFpEF. Our goal was to start the first HFpEF registry in Austria, to comprehensively characterize this patient population. Patients with HFpEF diagnosed according to current guidelines and confirmed by right heart catheter were enrolled in our prospective, single-center registry. Baseline evaluations consisted of transthoracic echocardiography, 12-lead electrocardiogram, a six-minute walking distance with Borg dyspnea score, a routine laboratory analysis of blood samples and myocardial biopsy in a subset of patients. In roughly six month-intervals follow-up visits or telephone calls in case of immobility were performed. The primary study endpoint was a combined one consisting of hospitalization for HF or death due to cardiac reason. Between 2010 and 2015, 174 elderly, predominantly female patients with HFpEF were included. Patients in our cohort were characterized by an advanced disease state with a high rate of comorbidities, a high prevalence of PH and severely impaired exercise capacity. The limited exercise performance was related to a high deposition of extracellular matrix in the myocardium and several other cardiac and non-cardiac parameters. The presence of PH was associated with adverse outcome, with the worst event-free survival observed in a subgroup of patients with pre-and postcapillary PH. Hypoxemia was found to primarily trigger pulmonary vascular remodeling in these patients. Our data reflect the multi-organ involvement of this disease and confirms the concept that HFpEF is a complex heterogeneous syndrome. Therefore, our study may also have therapeutic implications shifting focus from cardiac factors to more systemic treatments.Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMedizinische Universität Wien, Dissertation, 2016OeBB(VLID)171574

Gender-related differences in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) affects more women than men, suggesting gender to play a major role in disease evolution. However, studies investigating gender differences in HFpEF are limited. In the present study we aimed to describe gender differences in a well-characterized HFpEF cohort. Consecutive HFpEF patients underwent invasive hemodynamic assessment, cardiac magnetic resonance imaging and exercise testing. Study endpoints were: cardiac death, a combined endpoint of HF hospitalization or cardiac death and all-cause death. 260 HFpEF patients were prospectively enrolled. Men were more compromised with regard to exercise capacity and had significantly more co-morbidities. Men had more pronounced pulmonary vascular disease with higher diastolic pressure gradients and a lower right ventricular EF. During follow-up, 9.2% experienced cardiac death, 33.5% the combined endpoint and 17.3% all-cause death. Male gender was independently associated with cardiac death, but neither with the combined endpoint nor with all-cause mortality. We detected clear gender differences in HFpEF patients. Cardiac death was more common among men, but not all-cause death. While men are more prone to develop a right heart phenotype and die from HFpEF, women are more likely to die with HFpEF.(VLID)463742

Wiener klinische Wochenschrift / Extracellular volume quantification by cardiac magnetic resonance imaging without hematocrit sampling : Ready for prime time?

Background Myocardial tissue characterization by cardiovascular magnetic resonance (CMR) T1 mapping currently receives increasing interest as a diagnostic tool in various disease settings. The T1-mapping technique allows non-invasive estimation of myocardial extracellular volume (ECV) using T1-times before and after gadolinium administration; however, for calculation of the myocardial ECV the hematocrit is needed, which limits its utility in routine application. Recently, the alternative use of the blood pool T1-time instead of the hematocrit has been described. Methods The results of CMR T1 mapping data of 513 consecutive patients were analyzed for this study. Blood for hematocrit measurement was drawn when placing the i. v. line for contrast agent administration. Data from the first 200 consecutive patients (derivation cohort) were used to establish a regression formula allowing synthetic hematocrit calculation, which was then validated in the following 313 patients (validation cohort). Synthetic ECV was calculated using synthetic hematocrit, and was compared with conventionally derived ECV. Results Among the entire cohort of 513 patients (mean age 57.4 17.5 years old, 49.1% female) conventionally measured hematocrit was 39.9 4.7% and native blood pool T1-time was 1570.6 117.8 ms. Hematocrit and relaxivity of blood (R1 = 1/blood pool T1 time) were significantly correlated (r = 0.533, r2 = 0.284, p < 0.001). By linear regression analysis, the following formula was developed from the derivation cohort: synthetic hematocrit = 628.5 R1 0.002. Synthetic and conventional hematocrit as well as ECV showed significant correlation in the validation (r = 0.533, r2 = 0.284, p < 0.001 and r = 0.943, r2 = 0.889, p < 0.001, respectively) as well as the overall cohort (r = 0.552, r2 = 0.305, p < 0.001 and r = 0.957, r2 = 0,916, p < 0.001). By Bland Altman analysis, good agreement between conventional and synthetic ECV was found in the validation cohort (mean difference: 0.007%, limits of agreement: 4.32 and 4.33%, respectively). Conclusion Synthetic ECV using native blood pool T1-times to calculate the hematocrit, is feasible and leads to almost identical results in comparison with the conventional method. It may allow fully automatic ECV-mapping and thus enable broader use of ECV by CMR T1 mapping in clinical practice.(VLID)357823

PLOS ONE / Presence of isolated tricuspid regurgitation should prompt the suspicion of heart failure with preserved ejection fraction

Background Diastolic dysfunction of the left ventricle is common but frequently under-diagnosed. Particularly in advanced stages affected patients may present with significant functional tricuspid regurgitation (TR) as the most prominent sign on echocardiography. The underlying left ventricular pathology may eventually be missed and symptoms of heart failure are attributed to TR, with respective therapeutic consequences. The aim of the present study was to determine prevalence and mechanisms underlying TR evolution in heart failure with preserved ejection fraction (HFpEF). Methods and results Consecutive HFpEF patients were enrolled in this prospective, observational study. Confirmatory diagnostic tests including echocardiography and invasive hemodynamic assessments were performed. Of the 175 patients registered between 2010 and 2014, 51% had significant (moderate or severe) TR without structural abnormalities of the tricuspid valve. Significant hemodynamic differences between patients with and without relevant TR were encountered. These included elevated pulmonary vascular resistance (p = 0.038), reduced pulmonary arterial compliance (PAC, p = 0.005), and elevated left ventricular filling pressures (p = 0.039) in the TR group. Multivariable binary logistic regression analysis revealed diastolic pulmonary artery pressure (p = 0.029) and PAC (p = 0.048) as independent determinants of TR. Patients were followed for 18.114.1 months, during which 32% had a cardiac event. While TR was associated with outcome in the univariable analysis, it failed to predict event-free survival in the multivariable model. Conclusions The presence of isolated functional TR should prompt the suspicion of HFpEF. Our data show that significant TR is a marker of advanced HFpEF but neither an isolated entity nor independently associated with event-free survival.(VLID)486885

PLOS One / Outcome in Heart Failure with Preserved Ejection Fraction : The Role of Myocardial Structure and Right Ventricular Performance

Background Heart failure with preserved ejection fraction (HFpEF) is recognized as a major cause of cardiovascular morbidity and mortality. Thus, a profound understanding of the pathophysiologic changes in HFpEF is needed to identify risk factors and potential treatment targets in this specific patient population. Therefore, we aimed to comprehensively assess the impact of left- and right-ventricular function and hemodynamics on long-term mortality and morbidity in order to improve risk prediction in patients with HFpEF. Methods and Results We prospectively included 142 consecutive patients with HFpEF into our observational, non-interventional registry. Echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic assessments including myocardial biopsy were performed at baseline. We detected significant correlations between left ventricular extracellular matrix and left ventricular end-diastolic diameter (r = -0.64;p = 0.03) and stroke volume (r = -0.53;p = 0.04). Hospitalization for heart failure and/or cardiac death was observed over a median follow up of 10 months. The strongest risk factors were reduced right ventricular function (adj. HR 6.62;95%CI 3.12- 14.02;p<0.001), systolic pulmonary arterial pressure (adj. HR per 1-SD 1.55;95%CI 1.15- 2.09;p = 0.004) and the pulmonary artery wedge pressure (adj. HR per 1-SD 1.51;95%CI 1.092.08; p = 0.012). The area under the ROC curve for right ventricular function was 0.63, for systolic pulmonary arterial pressure 0.75, and for pulmonary artery wedge pressure 0.68. Conclusion The current study emphasizes the importance of right ventricular function and pulmonary pressures on outcome in patients with HFpEF providing pathophysiological insights into the hemodynamic changes in HFpEF.(VLID)492124

Journal of Cardiovascular Magnetic Resonance / Pulmonary artery to aorta ratio for the detection of pulmonary hypertension : cardiovascular magnetic resonance and invasive hemodynamics in heart failure with preserved ejection fraction

Background Previous work indicates that dilatation of the pulmonary artery (PA) itself or in relation to the ascending aorta (PA:Ao ratio) predicts pulmonary hypertension (PH). Whether these results also apply for heart failure with preserved ejection fraction (HFpEF) is unknown. In the present study we evaluated the diagnostic and prognostic power of PA diameter and PA:Ao ratio on top of right ventricular (RV) size, function, and septomarginal trabeculation (SMT) thickness by cardiovascular magnetic resonance (CMR) in HFpEF. Methods and Results 159 consecutive HFpEF patients were prospectively enrolled. Of these, 111 underwent CMR and invasive hemodynamic evaluation. By invasive assessment 64 % of patients suffered from moderate/severe PH (mean pulmonary artery pressure (mPAP) 30 mmHg). Significant differences between groups with and without moderate/severe PH were observed with respect to PA diameter (30.9 5.1 mm versus 26 5.1 mm, p < 0.001), PA:Ao ratio (0.93 0.16 versus 0.78 0.14, p < 0.001), and SMT diameter (4.6 1.5 mm versus 3.8 1.2 mm; p = 0.008). The strongest correlation with mPAP was found for PA:Ao ratio (r = 0.421, p < 0.001). By ROC analysis the best cut-off for the detection of moderate/severe PH was found for a PA:Ao ratio of 0.83. Patients were followed for 22.0 14.9 months. By Kaplan Meier analysis event-free survival was significantly worse in patients with a PA:Ao ratio 0.83 (log rank, p = 0.004). By multivariable Cox-regression analysis PA:Ao ratio was independently associated with event-free survival (p = 0.003). Conclusion PA:Ao ratio is an easily measureable noninvasive indicator for the presence and severity of PH in HFpEF, and it is related with outcome.(VLID)486713

Baseline imaging characteristics in HFpEF patients, stratified by tricuspid regurgitation severity.

<p>Baseline imaging characteristics in HFpEF patients, stratified by tricuspid regurgitation severity.</p