Thermodilution vs estimated Fick cardiac output measurement in an elderly cohort of patients: A single-centre experience

AIMS: Patients referred to the cath-lab are an increasingly elderly population. Thermodilution (TD, gold standard) and the estimated Fick method (eFM) are interchangeably used in the clinical routine to measure cardiac output (CO). However, their correlation in an elderly cohort of cardiac patients has not been tested so far. METHODS: A single, clinically-indicated right heart catheterization was performed on each patient with CO estimated by eFM and TD in 155 consecutive patients (75.1±6.8 years, 57.7% male) between April 2015 and August 2017. Whole Body Oxygen Consumption (VO2) was assumed by applying the formulas of LaFarge (LaF), Dehmer (De) and Bergstra (Be). CO was indexed to body surface area (Cardiac Index, CI). RESULTS: CI-TD showed an overall moderate correlation to CI-eFM as assessed by LaF, De or Be (r2 = 0.53, r2 = 0.54, r2 = 0.57, all p < .001, respectively) with large limits of agreement (-0.64 to 1.09, -1.07 to 0.77, -1.38 to 0.53 l/m2/min, respectively). The mean difference of CI between methods was 0.22, -0.15 and -0.42 (all p<0.001 for difference to TD), respectively. A rate of error ≥20% occurred with the equations by LaF, De or Be in 40.6%, 26.5% and 36.1% of patients, respectively. A CI <2.2 l/m2min was present in 42.6% of patients according to TD and in 60.0%, 31.0% and in 16.1% of patients according to eFM by the formulas of LaF, De or Be. CONCLUSION: Although CI-eFM shows an overall reasonable correlation with CI-TD, the predictive value in a single patient is low. CI-eFM cannot replace CI-TD in elderly patients

Cardiac output states in patients with severe functional tricuspid regurgitation: impact on treatment success and prognosis

Aims To investigate whether there is evidence for distinct cardiac output (CO) based phenotypes in patients with chronic right heart failure associated with severe tricuspid regurgitation (TR) and to characterize their impact on TR treatment and outcome. Methods and results A total of 132 patients underwent isolated transcatheter tricuspid valve repair (TTVR) for functional TR at two centres. Patients were clustered according to k-means clustering into low [cardiac index (CI)  2.6 L/min/m2) clusters. All-cause mortality and clinical characteristics during follow-up were compared among different CO clusters. Mortality rates were highest for patients in a low (24%) and high CO state (42%, log-rank P < 0.001). High CO state patients were characterized by larger inferior vena cava diameters (P = 0.003), reduced liver function, higher incidence of ascites (P = 0.006) and markedly reduced systemic vascular resistance (P < 0.001) as compared to TTVR patients in other CO states. Despite comparable procedural success rates, the extent of changes in right atrial pressures (P = 0.01) and right ventricular dimensions (P < 0.001) per decrease in regurgitant volume following TTVR was less pronounced in high CO state patients as compared to other CO states. Successful TTVR was associated with the smallest prognostic benefit among low and high CO state patients. Conclusions Patients with chronic right heart failure and severe TR display distinct CO states. The high CO state is characterized by advanced congestive hepatopathy, a substantial decrease in peripheral vascular tone, a lack of response of central venous pressures to TR reduction, and worse prognosis. These data are relevant to the pathophysiological understanding and management of this important clinical syndrome. Graphical Abstract Proposed mechanism of hypercirculatory tricuspid regurgitation. Tricuspid regurgitation related backward failure causes liver congestion and dysfunction with portal hypertension and reduced washout of vasoactive substances. Consequent splanchnic and peripheral vasodilatation alongside with reduced renal blood flow results in renin–angiotensin–aldosterone system (RAAS) activation and sympathetic overactivation. The sympathetic drive and volume retention lead to further capacitance depletion and volume overload, eventually resulting in a high cardiac output state, with limited preload reduction and prognostic benefit following transcatheter tricuspid valve repair. The alterations in the graph should be interpreted as simultaneous interaction rather than a timeline. Continuous lines indicate findings in the present study. Dashed lines express currently accepted mechanistical considerations. AP, alkaline phosphatase; γGT, gamma-glutamyl-transferase; RA, right atrium; RV, right ventricle

Cardiac power output accurately reflects external cardiac work over a wide range of inotropic states in pigs

BACKGROUND: Cardiac power output (CPO), derived from the product of cardiac output and mean aortic pressure, is an important yet underexploited parameter for hemodynamic monitoring of critically ill patients in the intensive-care unit (ICU). The conductance catheter-derived pressure-volume loop area reflects left ventricular stroke work (LV SW). Dividing LV SW by time, a measure of LV SW min- 1 is obtained sharing the same unit as CPO (W). We aimed to validate CPO as a marker of LV SW min- 1 under various inotropic states. METHODS: We retrospectively analysed data obtained from experimental studies of the hemodynamic impact of mild hypothermia and hyperthermia on acute heart failure. Fifty-nine anaesthetized and mechanically ventilated closed-chest Landrace pigs (68 ± 1 kg) were instrumented with Swan-Ganz and LV pressure-volume catheters. Data were obtained at body temperatures of 33.0 °C, 38.0 °C and 40.5 °C; before and after: resuscitation, myocardial infarction, endotoxemia, sevoflurane-induced myocardial depression and beta-adrenergic stimulation. We plotted LVSW min- 1 against CPO by linear regression analysis, as well as against the following classical indices of LV function and work: LV ejection fraction (LV EF), rate-pressure product (RPP), triple product (TP), LV maximum pressure (LVPmax) and maximal rate of rise of LVP (LV dP/dtmax). RESULTS: CPO showed the best correlation with LV SW min- 1 (r2 = 0.89; p < 0.05) while LV EF did not correlate at all (r2 = 0.01; p = 0.259). Further parameters correlated moderately with LV SW min- 1 (LVPmax r2 = 0.47, RPP r2 = 0.67; and TP r2 = 0.54). LV dP/dtmax correlated worst with LV SW min- 1 (r2 = 0.28). CONCLUSION: CPO reflects external cardiac work over a wide range of inotropic states. These data further support the use of CPO to monitor inotropic interventions in the ICU

Influences on the Invasive Estimation of Cardiac Output with the Thermodilution and Indirect Fick-method

Introduction: Invasive measurement of cardiac output (CO) is a key hemodynamic parameter. While thermodilution (TD) is considered the method of choice, the calculation of CO based on the Fick principle is often preferred due to reduced cost and time. However, the indirect Fick method (iFM) used in clinical practice relies on an assumed oxygen consumption (VO2). Formulas to predict VO2, such as LaFarge (LaF), Dehmer (De) and Bergstra (Be), have been proposed, all of which were revealed to have limited predictive value in pediatric and adult patients compared to TD. The correlation between the iFM and TD method in an aged, realworld cohort was tested. Furthermore, variables leading to a mismatch between estimated and measured CO were investigated. Methods: A single, clinically-indicated right heart catheterization was performed on each patient with CO estimated by iFM and TD in 194 consecutive patients between April 2015 and August 2017. Six patients were excluded due to incomplete baseline data. The VO2 was assumed by applying the formulas of LaF, De and Be. Body fat estimation was performed with the formula proposed by Jackson and Pollock. Results: We included 188 consecutive patients (70±13 years, 59% male) in the current analysis. Severe tricuspid and mitral regurgitation were present in 25 and 43 patients, respectively. CO-TD exhibited an overall moderate correlation to CO-iFM as assessed by LaF, De and Be formulas with large limits of agreement (-1.22 to 1.62, -2.31 to 1.65, -2.80 to 1.17 l/m², respectively). The mean difference of the CO between methods was 0.40, -0.24 and -0.81 (all p<0.001 for difference to TD), respectively. A rate of error ≥20% occurred with the equations by LaF, De and Be in 32%, 29% and 51% of patients, respectively. TD-method as compared to iFM with LaF formula underestimated CO in patients with severe tricuspid regurgitation (p=0.022) but not when iFM was calculated based on the De (p=0.229) or Be (p=0.418) formula. Body fat estimation (29%± 12%) was performed in a subgroup of patients (n=149). Mitral regurgitation, body fat as well as cardiac rhythm disturbances did not affect the correlation between TD- and iFM. Conclusion: Although CO-eFM exhibits an overall reasonable correlation with CO-TD, the predictive value in a single patient is low. CO-eFM cannot replace CO-TD in elderly patients. Common variables leading to a mismatch between the estimated and the measured CO, such as morbid obesity did not lead to a significant difference in this cohort.Einführung: Die Bestimmung des Herzzeitvolumens (HZV) stellt eine zentrale hämodynamische Messgröße dar. Das HZV wird üblicherweise mittels ThermodilutionsMethode (TD) oder der Methode nach Fick gemessen. Die Fick-Methode benötigt zur Berechnung des HZV den Sauerstoffverbrauch (VO2). In der klinischen Praxis wird der VO2 häufig nicht gemessen, sondern anhand einer von drei empirischen Formeln nach LaFarge (Lf), Dehmer (De) oder Bergstra (Bg) geschätzt. Diese Formeln wurden jedoch vornehmlich an pädiatrischen Kohorten untersucht. Daher wird in der vorliegenden Arbeit die Korrelation dieser Methoden in einer gealterten kardiologischen Population untersucht und zusätzlich werden Variablen untersucht die potenziell zu einer Verschlechterung der Korrelation führen. Methoden: Zwischen April 2015 und August 2017 wurden bei 194 Patienten mit der klinischen Indikation zur Rechtsherzkatheteruntersuchung Messungen des HZV mittels TD- und indirekter Fick-Methode vorgenommen. Sechs Patienten wurden aufgrund von fehlenden Daten aus der Analyse ausgeschlossen. Der VO2 wurde anhand der Formeln von Lf, De und Bg berechnet. Der Körperfettanteil wurde mittels der Formel nach Jackson und Pollock berechnet. Ergebnisse: 188 Patienten (70 ± 13, 59 % männlich) wurden in die vorliegende Analyse eingeschlossen. Eine hochgradige Trikuspidal- bzw. Mitralklappeninsuffizienz lag bei 25 (13 %) bzw. 43 Patienten (23 %) vor. Es gab eine moderate Korrelation der TD-Methode und der indirekten Fick-Methode (iFM) berechnet nach den Formeln von Lf, De und Be mit einem großen Übereinstimmungsbereich in den Analysen der Bland-Altman-Graphiken (-1.22 bis 1.62 [Lf], -2.31 bis 1.65 [De] und -2.80 bis 1.17 l/m² [Be]). Der mittlere Unterschied zwischen dem HZV der TD-Methode und der iFM war 0.40 (Lf), -0.24 (De) und -0.81 l/min (Be) (alle p < 0.001). Ein Unterschied zwischen dem HZV nach TD-Methode und iFM von ≥20 % wurde bei 32 % (Lf), 29 % (De) und 51 % (Bg) der Patienten beobachtet. Die TD-Methode zeigte niedrigere HZV-Werte im Vergleich zur iFM Lf (p = 0.022), nicht jedoch nach der Formel von De (p = 0.229) oder Be (p = 0.418), bei Patienten mit hochgradiger Trikuspidalklappeninsuffizienz. Körperfettmessungen (Körperfettanteil 29% ± 12 %) erfolgten in einer Subgruppe von 149 Patienten. Es konnte kein relevanter Einfluss von Mitraklappeninsuffizienzen, dem Körperfettanteil und dem Herzrhythmus auf die Diskrepanz zwischen TD- und iFM beobachtet werden. Zusammenfassung: Die TD-Methode und iFM zeigen eine moderate Korrelation, jedoch mit großen individuellen Unterschieden. Die iFM kann die Messung des HZV in älteren kardiologischen Patienten nicht ersetzen. Übliche Variablen, die wie eine morbide Adipositas zu einer Fehleinschätzung des HZV führen sollten, zeigten keinen Effekt in der vorliegenden Arbeit

Treatment response to spironolactone in patients with heart failure with preserved ejection fraction: a machine learning-based analysis of two randomized controlled trialsResearch in context

Summary: Background: Whether there is a subset of patients with heart failure with preserved ejection fraction (HFpEF) that benefit from spironolactone therapy is unclear. We applied a machine learning approach to identify responders and non-responders to spironolactone among patients with HFpEF in two large randomized clinical trials. Methods: Using a reiterative cluster allocating permutation approach, patients from the derivation cohort (Aldo-DHF) were identified according to their treatment response to spironolactone with respect to improvement in E/e’. Heterogenous features of response (‘responders’ and ‘non-responders’) were characterized by an extreme gradient boosting (XGBoost) algorithm. XGBoost was used to predict treatment response in the validation cohort (TOPCAT). The primary endpoint of the validation cohort was a combined endpoint of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Patients with missing variables for the XGboost model were excluded from the validation analysis. Findings: Out of 422 patients from the derivation cohort, reiterative cluster allocating permutation identified 159 patients (38%) as spironolactone responders, in whom E/e’ significantly improved (p = 0.005). Within the validation cohort (n = 525) spironolactone treatment significantly reduced the occurrence of the primary outcome among responders (n = 185, p log rank = 0.008), but not among patients in the non-responder group (n = 340, p log rank = 0.52). Interpretation: Machine learning approaches might aid in identifying HFpEF patients who are likely to show a favorable therapeutic response to spironolactone. Funding: See Acknowledgements section at the end of the manuscript

Twenty‐Four‐Month Blood Pressure Results After Renal Denervation Using Endovascular Ultrasound

BACKGROUND Renal denervation has proven its efficacy to lower blood pressure in comparison to sham treatment in recent randomized clinical trials. Although there is a large body of evidence for the durability and safety of radiofrequency‐based renal denervation, there are a paucity of data for endovascular ultrasound–based renal denervation (uRDN). We aimed to assess the long‐term efficacy and safety of uRDN in a single‐center cohort of patients. METHODS AND RESULTS Data from 2 previous studies on uRDN were pooled. Ambulatory 24‐hour blood pressure measurements were taken before as well as 3, 6, 12, and 24 months after treatment with uRDN. A total of 130 patients (mean age 63±9 years, 24% women) underwent uRDN. After 3, 6, 12, and 24 months, systolic mean 24‐hour ambulatory blood pressure values were reduced by 10±12, 10±14, 8±15, and 10±15 mm Hg, respectively, when compared with baseline (P<0.001). Corresponding diastolic values were reduced by 6±8, 6±8, 5±9, and 6±9 mm Hg, respectively (P<0.001). Periprocedural adverse events occurred in 16 patients, and all recovered without sequelae. CONCLUSIONS In this single‐center study, uRDN effectively lowered blood pressure up to 24 months after treatment

Trends in thrombolytic treatment and outcomes of acute pulmonary embolism in Germany

Pulmonary embolism (PE) is the third most common cardiovascular cause of death; systemic thrombolysis is potentially lifesaving treatment in patients presenting with haemodynamic instability instability. We investigated trends in the use of systemic thrombolysis and the outcome of patients with with acute PE.We analysed data on the characteristics, comorbidities, treatment, and in-hospital outcome outcome of 885 806 PE patients in Germany between 2005 and 2015. Incidence of acute PE was 99/100 000 population/year and increased from 85/100 000 in 2005 to 109/100 000 in 2015 [β 0.32 (0.26–0.38), P < 0.001]. During the same period, in-hospital case fatality rates decreased from 20.4% to 13.9% [β −0.51 (−0.52 to −0.49), P < 0.001]. The overall proportion of patients treated with with systemic thrombolysis increased from 3.1% in 2005 to 4.4% in 2015 [β 0.28 (0.25–0.31), P <  0.001]. Thrombolysis was associated with lower in-hospital mortality rates in patients with haemodynamic haemodynamic instability, both in those with shock not necessitating cardiopulmonary resuscitation (CPR) or mechanical ventilation [odds ratio (OR) 0.42 (0.37–0.48), P < 0.001], and in those who underwent underwent CPR [OR 0.92 (0.87–0.97), P = 0.002]. This association was independent from age, sex, and comorbidities comorbidities. However, systemic thrombolysis was administered to only 23.1% of haemodynamically unstable unstable patients.Although the proportion of PE patients treated with systemic thrombolysis increased increased slightly in Germany between 2005 and 2015, only the minority of haemodynamically unstable patients patients currently receive this treatment. In the nationwide inpatient cohort, thrombolytic therapy was associated with reduced in-hospital mortality rates in PE patients with shock, and also in those those who underwent CPR

Changes in left atrial function in patients undergoing cardioversion for atrial fibrillation: relevance of left atrial strain in heart failure

Background!#!Left atrial (LA) reservoir strain provides prognostic information in patients with and without heart failure (HF), but might be altered by atrial fibrillation (AF). The aim of the current study was to investigate changes of LA deformation in patients undergoing cardioversion (CV) for first-time diagnosis of AF.!##!Methods and results!#!We performed 3D-echocardiography and strain analysis before CV (Baseline), after 25 ± 10 days (FU-1) and after 190 ± 20 days (FU-2). LA volumes, reservoir, conduit and active function were measured. In total, 51 patients were included of whom 35 were in SR at FU-1 (12 HF and preserved ejection fraction (HFpEF)), while 16 had ongoing recurrence of AF (9 HFpEF). LA maximum volume was unaffected by cardioversion (Baseline vs. FU-2: 41 ± 11 vs 40 ± 10 ml/m!##!Conclusion!#!Reestablished SR improves LA reservoir strain by restoring LA active strain. Despite prolonged atrial stunning following CV, preserved SR might be of hemodynamic and prognostic benefit in HFpEF

Evaluation of phosphodiesterase 9A as a novel biomarker in heart failure with preserved ejection fraction

Abstract Aims Murine models implicate phosphodiesterase 9A (PDE9A) as a nitric oxide‐independent regulator of cyclic guanosine monophosphate and promising novel therapeutic target in heart failure (HF) with preserved ejection fraction (HFpEF). This study describes PDE9A expression in endomyocardial biopsies (EMBs) and peripheral blood mononuclear cells (PBMNCs) from patients with different HF phenotypes. Methods and results Endomyocardial biopsies and PBMNCs were obtained from patients with HFpEF (n = 24), HF with reduced ejection fraction (n = 22), and inflammatory cardiomyopathy (n = 24) and patients without HF (n = 7). PDE9A expression was increased in EMBs and PBMNCs from patients with HFpEF as compared with other HF phenotypes or subjects without HF. Endomyocardial PDE9A expression in HFpEF correlated with the inflammatory cell count in EMBs, but not with cardiac fibrosis or left ventricular diastolic wall stress. PDE9A expression in PBMNCs was increased in HFpEF patients with higher high‐sensitivity C‐reactive protein levels and in response to pro‐inflammatory stimulation. As a validation cohort, 719 patients with HFpEF and 1106 subjects without HF were identified from the LIFE‐Heart study. PDE9A expression in PBMNCs was obtained from array data and displayed an age‐dependent distribution. PDE9A levels were elevated and conferred increased risk for HFpEF in middle‐aged subjects, but not in elderly HFpEF patients. Following age adjustment, lower PDE9A expression in PBMNCs was associated with worse survival in patients with HFpEF (log‐rank test P‐value <0.001). Conclusion Expression profiling indicates an up‐regulation of endomyocardial PDE9A in different HF phenotypes with the most robust increase in EMBs and PBMNCs from patients with HFpEF. An exclusive risk effect of PDE9A expression on HFpEF in middle‐aged patients and an unexpected association with survival calls for further studies to better characterize the role of PDE9A as a treatment target

Cardiac output states in patients with severe functional tricuspid regurgitation: impact on treatment success and prognosis

Aims To investigate whether there is evidence for distinct cardiac output (CO) based phenotypes in patients with chronic right heart failure associated with severe tricuspid regurgitation (TR) and to characterize their impact on TR treatment and outcome. Methods and results A total of 132 patients underwent isolated transcatheter tricuspid valve repair (TTVR) for functional TR at two centres. Patients were clustered according to k-means clustering into low [cardiac index (CI)  2.6 L/min/m2) clusters. All-cause mortality and clinical characteristics during follow-up were compared among different CO clusters. Mortality rates were highest for patients in a low (24%) and high CO state (42%, log-rank P < 0.001). High CO state patients were characterized by larger inferior vena cava diameters (P = 0.003), reduced liver function, higher incidence of ascites (P = 0.006) and markedly reduced systemic vascular resistance (P < 0.001) as compared to TTVR patients in other CO states. Despite comparable procedural success rates, the extent of changes in right atrial pressures (P = 0.01) and right ventricular dimensions (P < 0.001) per decrease in regurgitant volume following TTVR was less pronounced in high CO state patients as compared to other CO states. Successful TTVR was associated with the smallest prognostic benefit among low and high CO state patients. Conclusions Patients with chronic right heart failure and severe TR display distinct CO states. The high CO state is characterized by advanced congestive hepatopathy, a substantial decrease in peripheral vascular tone, a lack of response of central venous pressures to TR reduction, and worse prognosis. These data are relevant to the pathophysiological understanding and management of this important clinical syndrome. Graphical Abstract Proposed mechanism of hypercirculatory tricuspid regurgitation. Tricuspid regurgitation related backward failure causes liver congestion and dysfunction with portal hypertension and reduced washout of vasoactive substances. Consequent splanchnic and peripheral vasodilatation alongside with reduced renal blood flow results in renin–angiotensin–aldosterone system (RAAS) activation and sympathetic overactivation. The sympathetic drive and volume retention lead to further capacitance depletion and volume overload, eventually resulting in a high cardiac output state, with limited preload reduction and prognostic benefit following transcatheter tricuspid valve repair. The alterations in the graph should be interpreted as simultaneous interaction rather than a timeline. Continuous lines indicate findings in the present study. Dashed lines express currently accepted mechanistical considerations. AP, alkaline phosphatase; γGT, gamma-glutamyl-transferase; RA, right atrium; RV, right ventricle