A Systematic Approach to the Evaluation of the Coronary Microcirculation Using Bolus Thermodilution: CATH CMD.

Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD.

Cardiogenic Shock Intravascular Cooling Trial (CHILL-SHOCK).

BACKGROUND: Cardiogenic shock (CS) is complicated by high mortality rates. Targeted temperature control (TTC) has been proposed as an adjunct therapy in CS. This study aims to examine the safety of TTC in patients presenting with CS. METHODS AND RESULTS: In this open-label, randomized controlled pilot trial, 20 patients with hemodynamic criteria for CS were assigned to standard of care plus TTC vs standard of care alone. The primary outcome was a composite safety outcome, including well-described complications of TTC. Secondary outcomes included mortality at 90 days, invasive hemodynamic and echocardiographic parameters, electrocardiographic measurements, and inotrope dosing. There were no significant differences in the composite analysis of prespecified safety outcomes (3 events in the TTC group vs 0 events in the control group; P = 0.24). Patients randomized to TTC demonstrated a statistically significant increase in cardiac index and cardiac power index compared to the control group at 48-96 hours after randomization (3.6 [3.1, 3.9] L/min/m2 vs 2.6 [2.5, 3.15] L/min/m2; P = 0.029 and 0.61 [0.55, 0.7] W/m2 vs 0.53 [0.435, 0.565] W/m2; P = 0.029, respectively). CONCLUSION: TTC may be a safe adjunct therapy for patients presenting with CS and may yield improvement in specific hemodynamic parameters.

Recurrent ST-elevation myocardial infarction: a case report of a rare complication of caseous mitral annular calcification.

BACKGROUND: Caseous mitral annular calcification (MAC) is an under-diagnosed division of calcific mitral valve disease that has recently been reported to have increased propensity for embolic disease. Early recognition of this entity as a cause of embolic disease can lead to prevention of occlusive vascular disease and long-standing complications. CASE SUMMARY: We present the case of a patient with end-stage renal disease who presented for evaluation of chest pain and was found to have ST-segment myocardial infarction. Despite thrombectomy and stenting, he had multiple recurrent events, and imaging evaluation demonstrated caseous MAC with mobile components. He was taken for surgical replacement of the mitral valve, with pathology confirming diagnosis. DISCUSSION: Caseous MAC may represent an increased risk of embolic disease. Better understanding of this pathology and it's propensity for embolic disease will be important to best determine treatment plans and timing of operative intervention.

Concomitant Lower-Extremity Deep Vein Thrombosis in Patients With Pulmonary Embolism Undergoing Catheter-Directed Therapy.

BACKGROUND: Deep vein thrombosis (DVT) is often seen in patients with acute pulmonary embolism (PE). Risk stratification of PE patients is useful in predicting mortality risk and hospital course. However, rates or predictors of DVT or proximal DVT (popliteal, femoral, common femoral, or iliac thrombosis) have not been studied in the highest-risk patients who receive catheter-directed therapy (CDT) for their PE. A single-center retrospective analysis of patients referred for CDT for confirmed PE was conducted to evaluate rates and predictors of DVT or proximal DVT and the impact on short-term outcomes. In 137 consecutive patients undergoing CDT for PE with available lower-extremity ultrasound, the rates of DVT and proximal DVT in PE patients receiving CDT were 76.6% and 65.0%, respectively. Rates of DVT (P=.68) and proximal DVT (P=.72) did not differ between high-risk or non-high risk PE patients. The only significant factor associated with presence of concomitant DVT was previous DVT (P=.045). The presence of a concomitant DVT or proximal DVT was not associated with an increase in all-cause mortality or hospitalization at 30 days or 1 year compared with an absence of concomitant DVT or proximal DVT. The results of this study suggest that patients with PE clinically requiring CDT have high rates of concomitant DVT and proximal DVT, prior DVT predicts concomitant DVT, and the presence of DVT is not associated with additional risk in this already high-risk population of patients.

A composite metric for predicting benefit from spironolactone in heart failure with preserved ejection fraction.

AIMS: The TOPCAT trial showed no benefit for spironolactone in heart failure patients with preserved ejection fraction (HFpEF). Post-hoc, spironolactone helped participants from the Americas, but not Eastern Europe. Determining which patients with HFpEF could respond like TOPCAT's responders should help guide their care. We aimed to develop a TOPCAT Trial Score (TS) as a composite metric to identify such patients. METHODS AND RESULTS: From the TOPCAT individual-level data, we calculated a TS of age, body mass index, systolic blood pressure, heart rate, creatinine, potassium, glucose, left ventricular ejection fraction, and left atrial volume for each participant as a weighted distance in multidimensional space from the theoretical perfectly average Americas participant. Logistic regression was used to measure TS and spironolactone as predictors of TOPCAT's primary outcome. The relationship between TS and the H2 FPEF score was also determined in TOPCAT and a registry cohort of real-world patients in the U.S. with HFpEF. A bimodal distribution of TS separated American (n = 1766) and Eastern European (n = 1,677) participants. Those with lower TS showed no significant response to spironolactone. Spironolactone's benefit rose with rising TS [ßinteraction  = -0.28 (P < 0.01)]. Significantly more American participants had benefit from spironolactone based on higher TS (> 1.14), in addition to higher likelihood of HFpEF based on higher H2 FPEF scores (≥3). The cohort of real-world patients with HFpEF had even higher TS than American TOPCAT participants. CONCLUSIONS: Patients with HFpEF can be quantified by the TS to capture the likelihood of benefit from spironolactone.

Left Ventricular Pressure Ratio Predicts In-Hospital Outcomes in Hospitalized Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Given the risk of hemodynamic compromise in heart failure with reduced ejection fraction (HFrEF) patients undergoing left heart catheterization (LHC), there is a need for a simple parameter that can predict clinical outcomes. We hypothesize that left ventricular pressure ratio (LVPR), calculated as left ventricle systolic/left ventricle end-diastolic pressure, is a strong predictor of hemodynamic collapse in these patients. METHODS: Retrospective analysis of consecutive hospitalized HFrEF patients undergoing combined LHC and right heart catheterization (RHC) at a single institution from 2015-2017 was performed. LVPR was compared with standard RHC hemodynamic variables. The primary outcome was in-hospital escalation of therapy, defined as ≥40 mm Hg drop in systolic blood pressure (SBP), SBP ≤90 mm Hg for ≥15 minutes, start or escalation of vasoactive medications, cardiopulmonary resuscitation, or in-hospital death. Receiver-operating characteristic (ROC) analysis and Kaplan-Meier survival analysis were performed for prediction of the primary outcome. RESULTS: A total of 176 patients were included in this study. ROC analysis determined an optimal cut-off value of ≤3.96, which correlated with an area under the curve (AUC) of 0.65 (sensitivity, 45.9%; specificity, 83.2%; correctly classified, 64.9%). AUC was similar to other variables obtained using RHC. In-hospital survival free of escalation of therapy was lower in the low LVPR group vs the high LVPR group (0% vs 33%, respectively; P<.01). CONCLUSION: LVPR is an easily measured index obtained during LHC that can risk stratify hospitalized patients with HFrEF at the time of LHC.

Aortic Pulsatility Index: A Novel Hemodynamic Variable for Evaluation of Decompensated Heart Failure.

BACKGROUND: Right heart catheterization for invasive hemodynamics has shown only modest correlation with clinical outcomes. We designed a novel hemodynamic variable that incorporates ventricular output and filling pressure. We anticipated that the aortic pulsatility index (API) would correlate with clinical outcomes in patients with heart failure. METHODS AND RESULTS: We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (February 2013 to November 2019). The API was calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure. The primary outcome was freedom from advanced therapies, defined as the need for inotropes, temporary mechanical circulatory support, a left ventricular assist device, or orthotopic heart transplantation, or death at 30 days. A total of 224 patient encounters, age 57 years (48-66 years; 34% women; 31% ischemic cardiomyopathy) were included. In univariable analysis, lower baseline API was significantly associated with progression to advanced therapies or death at 30-days (odds ratio 0.43, 95% confidence interval 0.30-0.61; P < .001) compared with those on continued medical management. Receiver operator characteristic analysis specified an optimal cutpoint of 1.45 for API. A Kaplan-Meier analysis indicated an association of API with the primary outcome (79% for API ≥ 1.45 vs 48% for API < 1.45). In multivariable analysis, higher API was strongly associated with freedom from advanced therapies or death (odds ratio 0.38, 95% confidence interval 0.22-0.65, P ≤ .001), even when adjusted for baseline characteristics and routine right heart catheterization measurements. CONCLUSIONS: The API is a novel invasive hemodynamic measurement that is associated independently with freedom from advanced therapies or death at 30-day follow-up.

Aortic pulsatility index predicts clinical outcomes in heart failure: a sub-analysis of the ESCAPE trial.

AIMS: Aortic pulsatility index (API), calculated as (systolic-diastolic blood pressure)/pulmonary capillary wedge pressure (PCWP), is a novel haemodynamic measurement representing both cardiac filling pressures and contractility. We hypothesized that API would better predict clinical outcomes than traditional haemodynamic metrics of cardiac function. METHODS AND RESULTS: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial individual-level data were used. Routine haemodynamic measurements, including Fick cardiac index (CI), and the advanced haemodynamic metrics of API, cardiac power output (CPO), and pulmonary artery pulsatility index (PAPI) were calculated after final haemodynamic-monitored optimization. The primary outcome was a composite endpoint of death or need for orthotopic heart transplant (OHT) or left ventricular assist device (LVAD) at 6 months. A total of 433 participants were enrolled in the ESCAPE trial of which 145 had final haemodynamic data. Final API measurements predicted the primary outcome, OR 0.47 (95% CI 0.32-0.70, P < 0.001), while CI, CPO, and PAPI did not. Receiver operator characteristic analyses of final advanced haemodynamic measurements indicated API best predicted the primary outcome with a cutoff of 2.9 (sensitivity 76.2%, specificity 55.3%, correctly classified 61.4%, area-under-the-curve 0.71), compared with CPO, CI, and PAPI. Kaplan-Meier analyses indicated API ≥ 2.9 was associated with greater freedom from the primary outcome (83.5%), compared with API < 2.9 (58.4%), P = 0.001. While PAPI was also significantly associated, CI and CPO were not. CONCLUSIONS: The novel haemodynamic measurement API better predicted clinical outcomes in the ESCAPE trial when compared with traditional invasive haemodynamic metrics of cardiac function.

Two-year follow-up of bioresorbable vascular scaffolds in severe infra-popliteal arterial disease.

OBJECTIVES: To assess the safety, efficacy, and durability of the Absorb bioresorbable vascular scaffold in predominantly complex, infra-popliteal lesions for the management of chronic limb ischemia at two-year clinical follow-up. Bioresorbable vascular scaffold are biodegradable scaffolds that provide short-term vascular support before undergoing intravascular degradation. A recent trial reported excellent 36-month vessel patency rates in simple infrapopliteal arterial lesions treated with Absorb bioresorbable vascular scaffold. METHODS: This single-center, retrospective study evaluated the use of the Absorb bioresorbable vascular scaffold (everolimus impregnated poly-L-lactic scaffold) in patients with infra-popliteal peripheral arterial disease (PAD) with respect to safety (thrombosis and TIMI bleeding), technical success, and freedom from clinically driven target vessel failure at 24 months. RESULTS: 31 patients (51.6% male) with a median age of 67 years with predominantly advanced infra-popliteal disease were treated with 49 bioresorbable vascular scaffold in 41 vessels. The mean stenosis was 94% (80-100), with 49% of lesions being chronic thrombotic occlusions. No scaffold thrombosis or peri-procedural bleeding was observed. Procedural success was achieved in all patients; 93.5% of patients experienced freedom from clinically driven target vessel failure at 24 months, driven by one revascularization and one amputation. Primary patency was 96.7% at 12 months and 87.1% at 24 months. All patients were alive at 12 and 24 months. CONCLUSIONS: At 24 months, our study found that patients with predominantly advanced infra-popliteal PAD who were treated with Absorb bioresorbable vascular scaffold reported improved clinical status and a low and durable rate of clinically driven target vessel failure extending out to 24 months.

Impact of Loop Diuretic Use on Outcomes Following Transcatheter Aortic Valve Implantation.

The use of LDT may signify significant hemodynamic changes and left ventricular remodeling in severe aortic stenosis (AS). Therefore, we sought to determine whether loop diuretic therapy (LDT) is associated with adverse outcomes following transcatheter aortic valve implantation (TAVI) in patients with severe symptomatic AS. Subjects undergoing TAVI at a single institution from June 2008 to December 2017 were analyzed. LDT doses were normalized to oral furosemide daily equivalents. All outcomes were adjudicated using VARC2 criteria. Descriptive statistics, multivariate logistic regression, and propensity score matching were used. Of the 804 subjects studied, 48.3% were on pre-TAVI LDT with a mean dose of 51.1 mg furosemide dose-equivalents. Subjects on LDT were higher risk, frail patients with more co-morbidities including chronic kidney disease, coronary artery disease requiring prior bypass grafting, peripheral arterial disease, atrial fibrillation or flutter, and diabetes with more severe heart failure symptoms. Those on LDT also had worse left ventricular systolic function, lower transvalvular gradients, and markers of adverse left ventricular remodeling, including increased left ventricular mass index and higher rates of concentric and eccentric hypertrophy. On propensity-score matching, death within one year post-TAVI was borderline significantly higher in the pre-LDT as compared with no-LDT group (16.9% vs 10.4 %, p = 0.068). In conclusion, use of pre-TAVI LDT for severe symptomatic AS is associated with a trend towards worse 1-year mortality and is a marker of high-risk, frail individuals with advanced left ventricular remodeling.

Targeting Rho-associated coiled-coil forming protein kinase (ROCK) in cardiovascular fibrosis and stiffening.

Introduction: Pathological cardiac fibrosis, through excessive extracellular matrix protein deposition from fibroblasts and pro-fibrotic immune responses and vascular stiffening is associated with most forms of cardiovascular disease. Pathological cardiac fibrosis and stiffening can lead to heart failure and arrythmias and vascular stiffening may lead to hypertension. ROCK, a serine/threonine kinase downstream of the Rho-family of GTPases, may regulate many pro-fibrotic and pro-stiffening signaling pathways in numerous cell types.Areas covered: This article outlines the molecular mechanisms by which ROCK in fibroblasts, T helper cells, endothelial cells, vascular smooth muscle cells, and macrophages mediate fibrosis and stiffening. We speculate on how ROCK could be targeted to inhibit cardiovascular fibrosis and stiffening.Expert opinion: Critical gaps in knowledge must be addressed if ROCK inhibitors are to be used in the clinic. Numerous studies indicate that each ROCK isoform may play differential roles in regulating fibrosis and may have opposing roles in specific tissues. Future work needs to highlight the isoform- and tissue-specific contributions of ROCK in fibrosis, and how isoform-specific ROCK inhibitors in murine models and in clinical trials affect the pathophysiology of cardiac fibrosis and stiffening. This could progress knowledge regarding new treatments for heart failure, arrythmias and hypertension and the repair processes after myocardial infarction.

Use of Prospective Radiobrachial Angiography in Transradial Cardiac Catheterization and Intervention.

OBJECTIVES: This study examined the utility of prospective radiobrachial angiography (pRBA) in transradial coronary angiography and intervention as a method for reducing procedural complications. BACKGROUND: A growing body of evidence has supported the transradial approach (TRA) as superior to the transfemoral approach (TFA) due to advantages such as reduced bleeding and improved outcomes in high-risk patients. However, TRA has a higher failure rate than TFA, and has seen slow rates of adoption among United States operators. METHODS: This was a retrospective, single center, case-control analysis of coronary angiography procedures, performed by two experienced operators at the University of Chicago Medical Center between October 28, 2015 and July 21, 2017. Operator 1 began using pRBA during the study, whereas Operator 2 used pRBA in all TRA procedures. There were 567 patients stratified into three groups based on operator and pRBA use. Comparisons of procedural outcomes for Operator 1 before and after adoption of pRBA, and of outcomes between Operator 1 and Operator 2 were made. RESULTS: Use of pRBA was associated with reduced overall procedural complication rates (2.5% versus 10.4%, p = 0.004), driven primarily by reflexive radiobrachial angiography (rRBA) after resistance or pain was encountered (8.6% versus 0.0%, p = 0.0001) for Operator 1. A slight reduction in contrast associated with pRBA for Operator 1 was noted, but no difference in procedural time, radiation dose, or additional equipment used across groups was found. No significant difference in adverse procedural outcomes between the pRBA groups of Operator 1 and Operator 2 were observed. In patients with radiobrachial variants in anatomy, use of pRBA was associated with shorter times to cross anatomic lesions, shorter procedure times, reduced use of extra catheters, and less perforations and crossovers compared to patients requiring rRBA. Lack of pRBA was associated with higher procedural complications (hazard ratio 1.08, 95% CI, 1.03-1.13, p = 0.004). CONCLUSION: pRBA may be a useful tool for mitigating procedural complications, reducing time needed to cross difficult radiobrachial anatomy, and reducing the need to utilize additional equipment in TRA. pRBA may offer operators a tool to improve outcomes and increase adoption of this approach.

Urgent Open Atrial Transcatheter Mitral Valve Replacement as Bailout for Planned Surgery.

Hybrid transcatheter mitral valve replacement (TMVR) has shown great promise for patients with severe mitral annular calcification. However, there have been limited reports of its use as a bailout for planned surgical MVR. Here, we present a bailout TMVR with an excellent patient outcome. (Level of Difficulty: Advanced.).

Single arm retrospective study of bioresorbable vascular scaffolds to treat patients with severe infrapopliteal arterial disease.

OBJECTIVES: To assess the safety and efficacy of the Absorb bioresorbable vascular scaffold (BVS) in complex, infrapopliteal lesions for the management of chronic limb ischemia. BACKGROUND: The interventional management of infrapopliteal PAD remains challenging due to high restenosis rates with metallic drug-eluting stents and balloon angioplasty. Metallic stents are associated with impaired vessel vasomotor tone, remodeling, autoregulation, and long-term inflammation. BVSs are biodegradable scaffolds that provide short-term vascular support before degrading to allow restoration of vasomotor tone and endothelial function. A recent trial reported excellent 12-month vessel patency rates in simple infrapopliteal arterial lesions treated with Absorb BVS. METHODS: This single-center, retrospective study evaluated the use of the Absorb BVS (everolimus impregnated poly-L-lactic scaffold) in patients with infrapopliteal PAD with respect to safety (thrombosis and TIMI bleeding), technical success, and clinically driven target vessel failure (CD-TVF) at 12 months. RESULTS: Thirty-one patients (51.6% male) with a median age of 67 years with advanced infrapopliteal disease were treated with 49 BVS in 41 vessels. The mean stenosis was 94% (80-100), with 49% of lesions being CTOs. No scaffold thrombosis or periprocedural bleeding was observed. Procedural success was achieved in all patients. Freedom from CD-TVF was 95.1% at 12 months driven by one revascularization and one amputation. Primary patency was 96.7% at 12 months. All patients were alive at 12 months, and 96.8% of patients improved their Rutherford-Becker classification. CONCLUSIONS: At 12 months, our study found that patients with advanced infrapopliteal PAD who were treated with Absorb BVS reported improved clinical status and a low rate of CD-TVF.

Monocyte and macrophage subtypes as paired cell biomarkers for coronary artery disease.

NEW FINDINGS: What is the central question of this study? Are circulating monocyte markers correlated with their derived macrophage polarization patterns and coronary artery disease severity? What is the main finding and its importance? There was an inverse relationship between circulating CD16+ monocytes (high) and M2 macrophages (low) that marked coronary disease severity, and the differences in polarization of macrophages were seen despite a week of cell culture ex vivo. This study highlights the importance, and potential prognostic implications, of circulating monocyte and descendant macrophage phenotypes in coronary artery disease. ABSTRACT: Monocytes and macrophages are central to atherosclerosis, but how they combine to mark progression of human coronary artery disease (CAD) is unclear. We tested whether patients' monocyte subtypes paired with their derived macrophage profiles were correlated with extent of CAD. Peripheral blood was collected from 40 patients undergoing cardiac catheterization, and patients were categorized as having no significant CAD, single vessel disease or multivessel disease according to the number of affected coronary arteries. Mononuclear cells were measured for the monocyte markers CD14 and CD16 by flow cytometry, and separate monocytes were cultured into macrophages over 7 days and measured for the polarization markers CD86 and CD206. At baseline, patients with a greater CAD burden were older, with higher rates of statin, ß-blocker and antiplatelet drug use, whereas other characteristics were similar across the spectrum of coronary disease. CD16+ (both intermediate and non-classical) monocytes were elevated in patients with single vessel and multivessel disease compared with those without significant CAD (P < 0.05), whereas regulatory M2 macrophages (CD206+ ) were decreased in patients with single vessel and multivessel disease (P < 0.001). An inverse relationship between paired CD16+ monocytes and M2 macrophages marked CAD severity. On multivariable linear regression, CAD severity was associated, along with age and traditional cardiovascular risk factors, with CD16+ monocytes (directly) and M2 macrophages (inversely). Circulating monocytes may influence downstream polarization of lesional macrophages, and these measures of monocyte and macrophage subtypes hold potential as biomarkers in CAD.

Percutaneous Transapical Left Ventricular Access to Treat Paravalvular Leak and Ventricular Septal Defect.

BACKGROUND: Surgical transapical (TA) access is an established technique for structural heart (SH) procedures, but is associated with considerable morbidity. Percutaneous TA puncture provides direct access for SH procedures and may overcome the disadvantages of surgical access. This study sought to evaluate the safety of percutaneous TA left ventricular access for SH interventions. METHODS: We performed a retrospective analysis at a university hospital. Thirteen percutaneous TA procedures were performed on consecutive patients between January 2013 and July 2017 to provide LV access for transcatheter therapies. All procedures were performed under general anesthesia with three-dimensional transesophageal echocardiography guidance. RESULTS: All TA punctures were successful. Delivery sheath sizes ranged from 5 Fr to 7 Fr. Eleven of the 13 TA sites were closed with a device. Total median procedural and fluoroscopy times were 106 minutes (interquartile range, 39-117 minutes) and 26.5 minutes (interquartile range, 8.3-43.8 minutes), respectively. The planned procedure was completed successfully in all cases. One access-site complication occurred, involving embolism of a duct occluder into the pleural space and extravasation from the apical puncture site. Hemostasis of the apex site was achieved immediately with placement of three vascular plugs from a femoral approach. Two patients died prior to discharge and neither death was related to a procedural complication. There were no significant pericardial effusions. CONCLUSION: Percutaneous TA access can be achieved safely in most cases to provide access for transcatheter procedures with short procedure times. Device closure of the TA access site is reliable, with a low complication rate and no procedure-related mortality.

Advanced Hybrid Complete Revascularization with TECAB and Impella-Assisted PCI of CTO.

An 80-year-old man was referred for multi-vessel coronary artery disease with baseline SYNTAX score of 45 after evaluation for persistent stable angina. He underwent complete hybrid revascularization combining total endoscopic coronary artery bypass utilizing bilateral internal mammary arteries (IMA) with sequential LIMA to left anterior descending artery and diagonal arteries, and RIMA to obtuse marginal after Impella-assisted chronic total occlusion percutaneous coronary intervention of the right coronary artery. This represents a successful case of advanced hybrid coronary revascularization.

Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association.

Cardiorenal syndrome encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in 1 organ may induce acute or chronic dysfunction in the other organ. It represents the confluence of heart-kidney interactions across several interfaces. These include the hemodynamic cross-talk between the failing heart and the response of the kidneys and vice versa, as well as alterations in neurohormonal markers and inflammatory molecular signatures characteristic of its clinical phenotypes. The mission of this scientific statement is to describe the epidemiology and pathogenesis of cardiorenal syndrome in the context of the continuously evolving nature of its clinicopathological description over the past decade. It also describes diagnostic and therapeutic strategies applicable to cardiorenal syndrome, summarizes cardiac-kidney interactions in special populations such as patients with diabetes mellitus and kidney transplant recipients, and emphasizes the role of palliative care in patients with cardiorenal syndrome. Finally, it outlines the need for a cardiorenal education track that will guide future cardiorenal trials and integrate the clinical and research needs of this important field in the future.