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

Guideline-directed medical therapy assessment in heart failure patients undergoing percutaneous mitral valve repair

Aims: Achieving optimized guideline-directed medical therapy (GDMT) is recommended prior to transcatheter mitral valve edge-to-edge repair (M-TEER) for secondary mitral regurgitation (SMR). We aimed to propose and validate an easy-to-use score for assessing the quality of GDMT in patients with heart failure with reduced ejection fraction (HFrEF) undergoing M-TEER. Methods and results: Among the 1641 EuroSMR patients enrolled in the EuroSMR Registry who underwent M-TEER, a total of 1072 patients [median age 74, interquartile range (IQR) 67–79 years, 29% female] had complete data on GDMT and a left ventricular ejection fraction ≤ 40% and were included in the current study. We proposed a GDMT score that considers the dosage levels of three medication classes (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists), with a maximum score of 12 points indicating optimal GDMT. The primary outcome was all-cause mortality. The median GDMT score was 4 points (IQR 3–6). All three domains of the scoring system were associated with all-cause mortality (P < 0.05 for all). The overall GDMT score was associated with all-cause mortality (hazard ratio 0.90, 95% confidence interval 0.86–0.95 for each 1-point increase in the GDMT score). This association remained significant after adjusting for renal function and co-morbidities. Conclusions: This study demonstrates the utility of a simple GDMT scoring system for assessing the adequacy of GDMT in HFrEF patients with relevant SMR undergoing M-TEER. The GDMT score has potential applications in guiding the design of future clinical trials and aiding clinical decision-making processes

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

A cardiologist’s guide to machine learning in cardiovascular disease prognosis prediction

Abstract A modern-day physician is faced with a vast abundance of clinical and scientific data, by far surpassing the capabilities of the human mind. Until the last decade, advances in data availability have not been accompanied by analytical approaches. The advent of machine learning (ML) algorithms might improve the interpretation of complex data and should help to translate the near endless amount of data into clinical decision-making. ML has become part of our everyday practice and might even further change modern-day medicine. It is important to acknowledge the role of ML in prognosis prediction of cardiovascular disease. The present review aims on preparing the modern physician and researcher for the challenges that ML might bring, explaining basic concepts but also caveats that might arise when using these methods. Further, a brief overview of current established classical and emerging concepts of ML disease prediction in the fields of omics, imaging and basic science is presented

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

In vivo application and validation of a novel noninvasive method to estimate the end-systolic elastance

Accurate assessment of the left ventricular (LV) systolic function is indispensable in the clinic. However, estimation of a precise index of cardiac contractility, i.e., the end-systolic elastance (E-es), is invasive and cannot be established as clinical routine. The aim of this work was to present and validate a methodology that allows for the estimation of E-es from simple and readily available noninvasive measurements. The method is based on a validated model of the cardiovascular system and noninvasive data from arm-cuff pressure and routine echocardiography to render the model patient-specific. Briefly, the algorithm first uses the measured aortic flow as model input and optimizes the properties of the arterial system model to achieve correct prediction of the patient's peripheral pressure. In a second step, the personalized arterial system is coupled with the cardiac model (time-varying elastance model) and the LV systolic properties, including E-es, are tuned to predict accurately the aortic flow waveform. The algorithm was validated against invasive measurements of E-es (multiple pressure-volume loop analysis) taken from n = 10 patients with heart failure with preserved ejection fraction and n = 9 patients without heart failure. Invasive measurements of E-es (median = 2.4 mmHg/mL, range = [1.0, 5.0] mmHg/mL) agreed well with method predictions (normalized root mean square error = 9%, rho = 0.89, bias = -0.1 mmHg/mL, and limits of agreement = [-0.9, 0.6] mmHg/mL). This is a promising first step toward the development of a valuable tool that can be used by clinicians to assess systolic performance of the LV in the critically ill. NEW & NOTEWORTHY In this study, we present a novel model-based method to estimate the left ventricular (LV) end-systolic elastance (E-es) according to measurement of the patient's arm-cuff pressure and a routine echocardiography examination. The proposed method was validated in vivo against invasive multiple-loop measurements of E-es, achieving high correlation and low bias. This tool could be most valuable for clinicians to assess the cardiovascular health of critically ill patients