Cardiorenal syndrome is a clinical manifestation of the bidirectional interaction between the heart and kidney diseases. Over the last years, in patients with cardiovascular diseases, several biomarkers have been studied in order to better assess renal function as well as to identify patients prone to experiencing chronic or acute worsening of renal function. The aim of this review is to focus on the possible clinical usefulness of the most recent biomarkers in the setting of cardiorenal syndrome.

The renal resistance index (RRI) has been demonstrated to be a useful parameter that can detect patients at a high risk of worsening of renal function (WRF). This study was designed to evaluate the role of the RRI in predicting WRF mediated by the intravascular administration of contrast media. We enrolled patients who were referred for coronary angiography. Renal arterial echo-color Doppler was performed to calculate the RRI. WRF was defined as an increase of > 0.3 mg/dL and at least 25% of the baseline value in creatinine concentration 24–48 h after coronary angiography. Among the 148 patients enrolled in this study, 18 (12%) had WRF. In the multivariate logistic analysis, the RRI was independently associated with WRF (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.09–1.36; p = 0.001). After angiography, the RRI significantly increased in both patients with and without WRF. In the receiver operating characteristic curve analyses for WRF, the RRI at baseline and after angiography showed similar accuracy, and the best cutoff value for predicting WRF was 70%. In patients undergoing coronary angiography, the RRI is independently associated with WRF, probably because it provides more accurate information about cardiorenal pathophysiological factors and reflects kidney hemodynamic status and flow reserve.

Over the past years, a number of studies have demonstrated the relevance of strain assessed by two-dimensional speckle tracking echocardiography (STE) in evaluating ventricular function. The aim of this study was to analyze changes in left (LV) and right ventricular (RV) longitudinal strain associated with variations of heart rate (HR) in participants with and without chronic heart failure (CHF). We enrolled 45 patients, 38 of these diagnosed with CHF and carrying an implantable cardioverter defibrillator, and seven patients with pacemakers and without CHF. The frequency of atrial stimulation was increased to 90 beats/min and an echocardiogram was performed at each increase of 10 beats/min. Global LV and RV longitudinal strain (LVGLS and RVGLS, respectively) and RV free wall longitudinal strain (RVfwLS) were calculated at each HR. When analyzed as continuous variables, significant reductions in LVGLS were detected at higher HRs, whereas improvements in both RVGLS and RVfwLS were observed. Patients with a worsening of LVGLS (76% overall) were more likely to present lower baseline LV function. Only a few patients (18% for RVGLS and 16% for RVfwLS) exhibited HR-related deteriorations of RV strain measures, which was associated with lower levels of baseline RV function and higher pulmonary systolic pressures. Finally, 21 (47%) and 25 (56%) participants responded with improvements in RVGLS and RVfwLS, respectively. Our findings revealed heterogeneous RV and LV responses to increases in HR. These findings might ultimately be used to optimize cardiac functionality in patients diagnosed with CHF.

Brain natriuretic peptide (BNP) and its inactive N-terminal fragment, NT-proBNP, are serum biomarkers with key roles in the management of heart failure (HF). An increase in the serum levels of these peptides is closely associated with the pathophysiological mechanisms underlying HF such as the presence of structural and functional cardiac abnormalities, myocardial stretch associated with a high filling pressure and neuro-hormonal activation. As BNP and NT-proBNP measurements are possible, several studies have investigated their clinical utility in the diagnosis, prognostic stratification, monitoring and guiding therapy of patients with HF. BNP and NT-proBNP have also been used as criteria for enrollment in randomized trials evaluating the efficacy of new therapeutic strategies for HF. Nevertheless, the use of natriuretic peptides is still limited in clinical practice due to the controversial aspect of their use in different clinical settings. The purpose of this review is to discuss the main issues associated with using BNP and NT-proBNP serum levels in the management of patients with HF under current clinical and therapeutic scenarios.

Background The two–dimensional speckle tracking analysis (2D–ST) is a new useful tool in order to evaluate both atrial and ventricular function. Aim of the study. To evaluate the accuracy of the 2D–ST measures reflecting atrial and ventricular function in predicting the outcome among outpatients affected by chronic heart failure (CHF). Methods We enrolled 212 outpatients (age 64±13 years, 77% males, mean left ventricular ejection fraction, LVEF, 38±11%, NYHA class 2.4±0.5) affected by CHF in conventional therapy (sacubitril/valsartan or ACE–inhibitors or Angiotensin II receptor blockers in 85%, beta–blockers in 94%, mineralcorticoid receptor antagonists in 74%, diuretics in 72%, SGLT2 inhibitors in 20%). All patients underwent a medical visit, an ECG and an echocardiographic examination. The following 2D–ST parameters reflecting atrial and ventricular function were analyzed: global longitudinal left ventricular strain (LV–GLS, mean –11.4±3.9%), global longitudinal right ventricular strain (RV–GLS, mean –15.2±5.2%), free wall right ventricular longitudinal strain (RV–fwLS, mean –20.2±5.8%); left atrial reservoir (LAr, mean 19±10.8%), conduit (LAcd, mean –10.–8±6.8) and contraction (LAct, mean –8.1±8.2). Moreover, the early diastolic peak at pulsed Doppler (E) and at the level of septal (e’s) and lateral (e’l) mitral annulus by Tissue Doppler Imaging (TDI) were also evaluated. Then the ratio between E and e’s (E/es, mean 13.9±6.4) and between E and the mean of e’s and e’l (E/em, mean 11.1±5.4) were also calculated. Finally, the ratio between LAr and E/es (LAr/Ees, mean 1.98±1.65) and E/em (LAr/Eem, mean 2.51±1.95) were computed. During follow–up the progression of heart failure, defined as heart failure hospitalization or cardiovascular death, were evaluated. Results During a mean follow–up of 13±6, 32 patients experienced death (13) and/or hospitalization (25) for heart failure worsening. The table shows the relationship among echocardiographic variables and outcome At Cox univariate regression analysis and the relative C–index. LAR/Ees showed the greater accuracy (C–index) in predicting heart failure progression. Conclusions 2D–ST is an echocardiographic approach able to more accurately assess both left ventricular and atrial function. In our series, among the 2D–ST parameters, the ratio between LAr and E/es is characterized by the greater accuracy in predicting heart failure progression.

Worsening of renal function (WRF) is frequently observed after cardiac surgery and it is associated with both short– and long–term worse outcome. Among the pathophysiological conditions favoring the occurrence of WRF, the abnormalities in renal blood flow could play a key role. The aim of this study was to evaluate the changes in renal resistance index (RRI), a parameter reflecting renal parenchymal and hemodynamic parameters, after cardiac surgery. Methods Thirty–one patients were enrolled (age 65±12 years, 29% males, mean left ventricular ejection fraction 55±5%, mean creatinine serum levels 0.89±0.18 mg/dl, mean eGFR 89±28 ml/min*1.73 m2). All patients underwent cardiac surgery. Before cardiac surgery, after 3 days and before discharge, RRI was evaluated according to Peurcelot’s formula by renal interlobular arteries pulsed Doppler. Worsening of renal function was defined as an increase in serum creatinine of > 0.3 mg/dl associated with a change > 25% or the need of renal replacement therapy due to severe acute kidney injury. Results As shown in the table 1, after cardiac surgery a significant increase in RRI was observed at 3 days after cardiac surgery but not before discharge. The significant increase in RRI was observed both in patients with and without WRF. However, in patients with WRF significant higher values of RRI were observed before as well as after cardiac surgery. Conclusions Among patients undergoing cardiac surgery a significant increase in RRI values is observed after surgery. Among patients with WRF a significant greater values of RRI are observed before as well as cardiac surgery thus suggesting that a critical increase in renal resistance could play a role in the cardiorenal syndrome worsening.

Renal resistance index (RRI) is a parameter which is easily evaluable by the echo Doppler technique and which has been demonstrated to predict worsening of renal function (WRF) in patients affected by chronic heart failure as well as among those undergoing coronary angiography. The aim of this study was designed to evaluate the role of the RRI in predicting WRF after cardiac surgery. Methods Thirty–one patients were enrolled. Their clinical characteristics are shown in Table 1. All patients underwent cardiac surgery. Before surgery, RRI was evaluated according to Peurcelot’s formula by renal interlobular arteries pulsed Doppler. WRF was defined as an increase in serum creatinine of > 0.3 mg/dl associated with a change > 25% or the need of renal replacement therapy due to severe acute kidney injury. Results Among the patients in 12 WRF occurred, in 10 a worsening of creatinine serum levels and in 2 a severe AKI requiring RRT were observed. As shown in Table 1, RRI and the presence of peripheral artery disease were the only parameters which were significantly different among patients with and without WRF, whereas no difference in GFR values was observed. Baseline RRI showed a significant AUC of 0.74 (95% CI, 0.55–0.93) whereas baseline GFR of 0.52 (95% CI, 0.28–0.75) was not significant. Conclusions Among patients with WRF after cardiac surgery an increased RRI but not a different baseline GFR is observed. This parameter could allow a more accurate stratification of the risk of cardiorenal syndrome worsening among patients candidated to cardiac surgery.

Background and aim of the study. Left atrium (LA) is poorly understood in many pathological conditions and it is often considered a passive bystander of these pathophysiologic alterations. In the setting of impaired heart rate related LV response, the LA function could play a relevant role. The relevance of LA has been also recently demonstrated by studies which have evaluated its function by using new echocardiographic techniques such as two–dimensional speckle tracking evaluation (2D–STE). The aim of this study was to evaluate the relationship between changes in LV and LA function, assessed by 2D–STE, in response to the increase of heart rate (HR) in a group of patients carrying a pacemaker (PM) or an implantable cardioverter defibrillator (ICD). Methods We enrolled 45 patients. Among them, 38 were evaluated with LA strain. 31 patients were affected by CHF, among whom 18 with implanted cardioverter defibrillator (ICD), 13 with ICD and cardiac resynchronization therapy (ICD–CRT) and 7 without CHF who had a PM implanted. All were in clinically stable conditions for at least 30 days and in conventional medical therapy. Starting from basal values, HR was increased by 10 beats/min programming the implantable devices at higher atrial stimulation frequencies to max 90 beats/min. At each HR, echocardiography was performed and for left atrium the strain of reservoir (LAr), strain of conduit (LAcd) and contraction (LAct) were calculated (figure 1). Changes in left ventricle global longitudinal strain (LVGLS) were also calculated. Results The LAr shows a significant reduction from baseline at a heart rate of 90 bpm in conjunction with a significant change in the LAcd. No variation in LAct was observed at the various frequencies. Among the 38 patients, 29 showed a worsening of LVGLS and 9 no worsening with increasing heart rate. We demonstrated a close relationship between LV and LA function assessed by longitudinal strain measures (figure 2). A significant decrease in LAr was observed in patients with worsening LV–GLS that was not evident in patients with no or improvement. Conclusions Our study demonstrates that, in chronic HF outpatients, HR increase has different and heterogeneous effects on the LA function, assessed by STI and this response is more frequent among patients with LV systolic dysfunction. These results could be useful for guiding the optimal heart rate responsiveness of the implanted devices.