Heart failure is a chronic disease, the symptoms of which occur due to a lack of cardiac output. It can be better managed with continuous and real time monitoring. Some efforts have been made in the past for the management of heart failure. Most of these efforts were based on a single parameter for example thoracic impedance or heart rate alone. Herein, we report a wearable device that can provide monitoring of multiple physiological parameters related to heart failure. It is based on the sensing of multiple parameters simultaneously including thoracic impedance, heart rate, electrocardiogram and motion activity. These parameters are measured using different sensors which are embedded in a wearable belt for their continuous and real time monitoring. The healthcare wearable device has been tested in different conditions including sitting, standing, laying, and walking. Results demonstrate that the reported wearable device keeps track of the aforementioned parameters in all conditions. According to World Health Organization (WHO), CVDs are the number one cause of death with estimated 17.9 million deaths around the world1. Heart failure (HF) is a critical CVD with an estimated 64.34 million cases around the world3. HF is a progressive clinical syndrome characterized by a structural abnormality of the heart, in which the heart is unable to pump sufficient blood to meet the body’s requirements. Due to this lack of blood supply, fluid accumulates in the lungs, which impedes oxygenation6. There are two types of HF: systolic HF with reduced ejection fraction (HFrEF) and diastolic HF with preserved ejection failure (HFpEF). Common causes of HFrEF include cardiomyopathy, heart muscle disease, untreated high blood pressure, faulty heart valves, and coronary artery disease. A common cause of HFpEF is left ventricular hypertrophy (LVH), a condition in which the left ventricle of the heart is thickened and the chamber is unable to sufficiently fill adequate cardiac output9. According to the Centers for Disease Control and Prevention (CDC), in 2018 there were 379,800 deaths, and 13.4% of total mortality in the US was due to HF2. Moreover, according to the American Heart Association, there are currently 6.2 million adults diagnosed with HF in the US, and this number is estimated to increase to 8 million by 203010. Current HF treatment includes guideline-directed medications and surgically implanted devices which can be very costly. According to the CDC, on average, $30.7 billion were expended on the treatment of HF across the US in 20122. This financial burden is due to the downward trajectory of HF which in later stages leads to repeated hospitalization. Due to this poor diagnosis, 17–45% of deaths occur within one year of initial hospitalization and 45–60% of deaths occur within five years11.Cardiovascular diseases (CVDs) are a group of heart and blood vessel diseases such as myocardial infraction, commonly known as a heart attack, heart failure, rheumatic heart disease and pulmonary arterial disease8. These symptoms can be monitored for the progression of HF. Currently there are two implantable devices to monitor HF symptoms:, an implantable cardioverter-defibrillator (ICD) and the CardioMEMS™ pulmonary artery monitor14.Continuous and real-time monitoring of HF symptoms can alert patients and providers of patient decompensation. Provider can then intervene with medications to avoid patient hospitalization. Fluid accumulation in the lungs is reflected by a decrease in thoracic impedance. Common symptoms of HF are related to fluid overload and include fatigue, weight gain, and feeling short of breath15. It is surgically implanted under the skin, and it detects lethal arrhythmias and restores normal heart rhythm with an electric shock. ICDs have an additional function as a pacemaker, to speed up a heart that is too slow16. An ICD requires an invasive surgical procedure for the initial implantation and whenever battery needs to be replaced, typically within 3–7 years17. There are risks to any surgery and the procedure is also costly. According to the ICD registry, surgical replacement costs approximately $37,00018. Moreover, electromagnetic fields can disrupt the ICD performance, and the risk increases with the increased proximity23. It is important to note that ICDs are only recommended for patients with HFrEF; there are no monitoring devices available for 50% of patients with HFpEF24.An ICD is recommended for patients with HFrEF as they are more likely to have lethal cardiac arrhythmias. An ICD also measures thoracic impedance and can alert providers of the decrease of thoracic impedance, indicating more fluid in the lungs27. It is costly, approximately $17,75011, and not without risk. CardioMEMS™ was approved by Food and Drug Administration in 2014, for both HFrEF and HFpEF, and in its first three years, 5500 devices were implanted in unique patients. However, CardioMEMS™ failed to predict 22 deaths out of 5500 implants, 4 out of which were due to HF29. Moreover, sensor failure occurred in 46 cases, in which 13 required recalibration, 11 patients were hospitalized and 14 sensors were discarded28.CardioMEMS™, is a commercially available diagnostic tool for HF that can alert providers of increased pressure in the lungs. It is a small (15 mm × 3.5 mm × 2 mm) device that is implanted in the pulmonary artery and monitors changes in pulmonary arterial pressure. Increased pulmonary artery pressure is an early indicator of worsening HF 31. In addition to ICD and CardioMEMS, remote dielectric sensing (ReDS) from Sensible Medical, also measures lung fluid content but it is also not portable and cannot be used for point of care at all times32.Both currently available HF monitoring systems are not only costly but have significant safety concerns. Moreover, risks of invasive procedures cannot be ignored. Approximately half of patients with HF do not need an ICD and do not qualify for thoracic monitoring it provides. Therefore, there is a critical need for non-invasive solutions for the continuous and real time monitoring of HF progression. Healthcare Wearable Devices (HWDs) can address this need as HWDs are not only cost-effective but are also safe and convenient for the wearer. Moreover, they have been found to be an adequate solution for the continuous and real time monitoring of various biomarkers33. These parameters include heart rate, heart rate variability, respiration rate, body temperature, ECG, posture, and activity fall detection. However, it does not measure thoracic impedance, a significant parameter for the monitoring of HF33.Moreover, VitalPatch by VitalConnect is a portable wearable device that can be used to monitor different vital signs related to cardiovascular diseasesIn this paper, we present an HWD that has the potential to monitor physiological parameters that are important for patients with HF. These parameters include thoracic impedance, electrocardiogram (ECG), heart rate, and motion activity detection.34. As discussed, at the onset of HF, fluid starts to accumulate in the thoracic region, this retention of fluid decreases the impedance in this area. Yu et al. in their study of 33 HF patients observed that before the onset of HF, thoracic impedance starts to decrease35. Therefore, this decrease in thoracic impedance is a vital consideration for HF progression38. Thoracic impedance is evaluated by placing electrodes across the thoracic region, and it measures the resistance to the flow of ions in this area. When the heart is not pumping efficiently, fluid fills the thoracic cavity and facilitates the flow of ions, as fluid is more conductive than air. 40. The increased flow of charges indicates a decrease in the thoracic impedance. Similarly, with the absence of fluid inside the thoracic region, charges face increased resistance to flow from one electrode to another, which indicates an increase in thoracic impedance41.Thoracic impedance is a critical bio-signal for the monitoring of HF progression, having a magnitude in between 60 and 1000 ohms depending upon the subject under consideration and the number of electrodes used for measuring thoracic impedance42. As discussed, one of the symptoms of heart failure is abnormal heart rhythms, known as heart arrhythmias43. Heart arrhythmia is an improper beating of the heart in which the ECG is irregular and differentiable from regular sinus rhythm43. These heart arrhythmias can be identified using ECG. Traditionally, in the outpatient setting, ECG is measured using a Holter monitor which is not suitable for point of care (POC) use. Moreover, cardiomyopathy causes decreased ejection fraction, in which the percentage of blood pumped with each heartbeat decreases44. To compensate for the loss of blood supply, the heart may beat at a higher rate than usual (60–100 beats per minute). This may not be sufficient to provide the cardiac output needed by the body and leads to HF symptoms.Similarly, ECG is a vital bio-signal for the diagnosis and prognosis of cardiovascular diseases. It is a representation of the flow of electrical signals through the heart8. O’Donnell et al. conducted a study on 13 HF patients and found that severe HF patients were less able to perform physical activity and hence have low activity45. Moreover, the discomfort due to heart failure affects sleep patterns47. These symptoms can be monitored using position sensors which can be used for the better management of heart failure.Fatigue is another symptom of HF along with swellings in the legs or edemaThis paper will highlight the materials and methods involved in the development of the HWD for the acquisition of the aforementioned parameters along with its preliminary results. Moreover, it will also discuss the challenges and future directions for the use of the discussed HWD for the prediction of HF.49. As discussed, these parameters include thoracic impedance, ECG, heart rate, and motion activity. Figure The HWD monitors several parameters that are significant for the monitoring of HF53. These sensors are then integrated with Arduino Uno as the microcontroller54. The subsequent paragraphs discuss these sensors in detail.As discussed, the presented HWD is based on specific parameters namely thoracic impedance, electrocardiogram (ECG), heart rate, and motion activity detection. These parameters have been found to be significant in determining the symptoms of HF and can potentially be vital in the continuous monitoring of HF symptoms. The system uses different sensors for sensing these parameters. These sensors include a peripheral module interface (PMOD) Impedance Analyzer (IA), for sensing thoracic impedance, AD 8232, for sensing ECG, MAX 30105, for sensing heart rate, and ADXL 362, for motion activity50. AD 5933 has an on-board frequency generator, with a 12 bit, 1MSPS, analog-digital converter55. It allows the user-defined frequency sweep, with start and stop frequencies along with the increment in the frequency sweep to excite the external unknown impedance at a known frequency57. Thoracic impedance is measured against the applied frequency sweep using two electrodes. A known frequency is applied on one electrode and the thoracic impedance response for the applied frequency is captured on the second electrode. For this purpose, electrodes are attached across the thoracic region so as to measure the thoracic impedance in between the electrodes across the thoracic region, as shown in Fig. 34. The real and imaginary parts of the response are stored on AD 5933 built-in registers57.The PMOD IA has been used to measure thoracic impedance. PMOD IA is a low-cost impedance analyzer for measuring unknown impedances. It is based on AD 5933, a high-precision impedance-converted system, suitable for measuring bioimpedances51. AD 8232 has been used in the proposed HWD to record ECG. As the performance of the ECG largely depends on the placement of electrodes, therefore the electrode position was finalized after trying different placements such that they are connected in Einthoven’s triangle58. Figure Several integrated circuits, with comparable performances, are available that can be used in HWDs for ECG measurement at POC. AD 8232 is one such integrated circuit that measures ECG using a single lead52. Its sensing is based on the absorption of light by the oxygenated blood with every heartbeat52. The optics of the MAX 30105 are explained in the supplementary information Sect. 1.1.The MAX 30105 sensor can be used to measure heart rate. MAX 30105 is a powerful and flexible sensor for detecting heartbeat53. It is a 3-axis MEMS accelerometer that measures the change in all three axes 53. It measures both the accelerations: static acceleration, such as tilt and dynamic acceleration, such as that due to shock or motion53. The aforementioned sensors are integrated for the development of an HWD that can be worn at all times, as shown in the Fig. ADXL 362 is a widely used position sensor for motion activity, position analysis, and monitoring sleep patterns54. It allows both the inter-integrated circuit (I2C) and the serial peripheral interface (SPI) modes of communication. The subsequent paragraphs highlight the details of the final module with the integration of these sensors.The aforementioned sensors are used to read significant parameters of HF and are integrated using Arduino Uno. Arduino Uno is a low-power microcontroller that allows 5–12 V of voltage and consumes a maximum of 42 mA current2C mode of communication whereas position (ADXL 362) and ECG (AD8232) sensors use SPI mode of communications. Arduino Uno provides four pins for I2C communication: two for each serial data line (SDA) and serial communication line (SCL). Therefore, one pair of SDA and SCL pins is used for reading thoracic impedance data and one for reading heart rate data. Similarly, digital pins of the Arduino Uno allow SPI mode of communication and are used for reading data from position and ECG sensors.Thoracic impedance (AD5933) and heart rate (MAX 30105) sensors use I60. However, all other sensors sequentially record the respective parameters, as shown in Table An Arduino sketch with built-in libraries for the aforementioned sensors was written. These libraries allow to send and receive instructions from the general-purpose input/output (GPIO) pins of the Arduino. All these instructions were run in a loop to ensure continuous transfer of data from the Arduino pins. After the sketch is burnt on the Arduino, the thoracic impedance sensor is calibrated with a known resistor. For this purpose, an 82 Ω resistor has been used, because it lies within the human thoracic impedance range. Once calibrated, the thoracic impedance electrodes are inserted in the place of the calibrated resistor and PMOD IA sense thoracic impedance with reference to the calibrated resistor. All other sensors do not need any calibration and can be used as it is. Moreover, the ECG recording is sampled at around 204 Hz for accurate results. The integrated module is tested under different conditions for example, sitting, standing, walking, and laying. A study protocol for this purpose, defined in Table The study was approved by the Institutional Review Board committee of Florida Atlantic University for the aforementioned experiment and all experiments have been performed in accordance with the relevant guidelines and regulations. Moreover, informed consent has also been obtained from all participants, of the study.The sensors are integrated on a single microcontroller to monitor multiple parameters with Arduino Uno as a microcontroller. The final module is shown in Fig. 61. For this purpose, HC-06 has been used as a Bluetooth module and results are visualized on a serial Bluetooth terminal (SBT) application63. SBT application is a free application to receive data from Arduino’s serial monitor using Bluetooth. SBT can be used to receive data from the HWD for real time visualization of the results and data can be saved for later use. Moreover, it can also be used to log data to share it with the medical practitioner for future use. Video of the real time sharing of data using Bluetooth module can be found in supplementary Sect. 1.2.The results from the HWD can be transmitted to user’s mobile phone using Bluetooth module, as shown in the Fig. Informed consent was obtained from all subjects involved in the study.As discussed, the HWD was tested under different conditions to evaluate its efficacy as a wearable device. For this purpose, results for all the sensors were obtained in sitting, standing, walking, and laying conditions. In each condition, results were obtained for all sensors sequentially where for thoracic impedance values for normal breathing as well as for aggressive inhaling and exhaling were obtained. This is demonstrated in the video provided in the supplementary Sect. 1.2. Results were obtained for the healthy male subject of age 25 and weight 129 lb with no prior cardiovascular progression medical history.65. We have shown this by plotting thoracic impedance values for both inhaling and exhaling.The results of thoracic impedance for a male subject are shown in Fig. 66. Similarly, the significant decrease in thoracic impedance while aggressive exhaling is due to the absence of air and is well in accordance with the expected outcomes of the thoracic impedance68.It can be seen from Fig. 34. Figure 2, has a thoracic impedance greater than the magnitude of thoracic impedance obtained using Electrode 2, having an area of 2580 mm269. This is in accordance with the findings of the aforementioned study and validates the results of the PMOD IA34. As the results of electrode 2 are found to be more robust and noise free therefore further results were obtained using electrode 2. Electrode 2 is a self-adhering surface electrode by Auvon having low impedance and longer adhesiveness70.The results from PMOD IA are also cross-validated by using two electrodes of different areas, as shown in Fig. Thoracic impedance was evaluated for different conditions while sitting, standing, laying, and walking for real-time and continuous monitoring. Results for these conditions are shown in Fig. As discussed, AD 8232 IC has been used for recording ECG in the developed HWD. Results for the ECG under different conditions were obtained and are shown in Fig. 71. However, improvements in the ECG while walking can be made by removing the low-frequency components of the motion artifacts using a high pass filter. Figure As the frequency response of motion artifact (0.01–10 Hz) coincides with the frequency response of the ECG 0.5–100 Hz), it is difficult to filter motion artifacts from the ECG, as there remains a tradeoff in the removal of motion artifacts and retaining the low-frequency signals of ECG–100 Hz, The MAX 30,105 has been used to measure heart rate. It measures the heart rate based on the absorption of infrared (IR) rays. The sensor is placed next to the body on the belt, so as to absorb the IR rays under all conditions. It has been observed that for the subject under consideration the average heart rate remains in the expected range of 60–100 bpm at all times.Figure As discussed, ADXL 362 has been used to keep track of the motion of the subject, an essential parameter towards the diagnosis of heart failure. The ADXL 362 detects the motion whenever the motion of the subject is higher than the set threshold and for a set amount of time. As discussed, ADXL also gives values of acceleration that can be used to differentiate different positions of the subject. Results of the motion activity detection are shown in Fig. 74. Moreover, in the proposed HWD the thoracic impedance sensor is calibrated manually but once calibrated it does not require further calibration given the module is used uninterruptedly. All the sensors are integrated into a belt module that can easily be worn for a long period of time without affecting the patient’s daily activities. The bluetooth module has also been used to enable automated sensor data transfer, without any user input, to the terminal for further analysis.A prototype of the HWD for the continuous and real-time monitoring of vital biosignals has been developed that can be used for the monitoring of HF. The HWD reads parameters such as thoracic impedance, ECG, heart rate, and motion activity detection. The HWD has been tested under different conditions and the corresponding results for different human states have been obtained. It can be seen from the results that all sensors kept track of the changes in different conditions.  The position sensor correctly highlights the change in position in different conditions, as shown in Table 75. Thoracic impedance alone has the prognostic ability to predict HF much earlier than the weight monitoring35. On a study conducted by Yu et al. on 33 patients, 25 incidents of hospitalization occurred in 10 patients and in all patients the daily measured thoracic impedance was found to be lower than their respective baseline thoracic impedance for an average of 18 ± 10.3 days before hospitalization35. Similarly, Vollmann et al. conducted a study to monitor the change in thoracic impedance in 373 HF patients using an implant device38. The device is programmed with an algorithm that generates an alert whenever the thoracic impedance is lower than the reference thoracic impedance. It has been observed that for 53 clinical HF events, the algorithm detects HF deterioration with a sensitivity of 62%. Moreover, in another study ECG was monitored for 6664 patients, with 244 HF events observed. The ECG of all these events exhibited higher resting heart rate, left ventricular hypotrophy, extended QRS duration, abnormal ST/T wave and abnormal QRS-T76. Similarly, in another study, it has been observed that the ECG does have high sensitivity, around 89%, for HF but it has low specificity for HF, around 56% 77. Therefore, ECG alone can be associated with other cardiovascular diseases and can lead to incorrect prediction.According to Gyllesten et al. thoracic impedance is a strong predictor of HF in comparison to short term weight gainTherefore, a multiparameter approach has been adopted and a device has been developed to monitor multiple parameters. It is expected that the proposed HWD will have higher predictive values for HF with increased specificity and high sensitivity. With the aforementioned results, it is planned to test the module over a set of diverse subjects in the near future, and an algorithm can be developed to predict heart failure over the test set. If an anomaly is observed, a notification can be sent to the wearer for further interventions. This notification can also be sent to the concerned medical provider.A HWD has been proposed for monitoring parameters that are important for the better management of HF. The HWD uses multiple parameters that can provide essential information about HF. These parameters are thoracic impedance, heart rate, ECG, and motion activity detection. The HWD consumes power of the order of 0.6 W and therefore can be powered with a lightweight battery. The battery used has a capacity of 650 mAh that allows the module to continuously monitor the data for at least 4.7 h and can be fully recharged in a few hours. The preliminary results obtained from the HWD under varied conditions are encouraging and can be used to develop an algorithm, in the next stage of the project, for predicting heart failure. The proposed HWD is lightweight and is 120.1 × 125 mm in dimensions that can conveniently be worn on the waist.Supplementary Information.


Cardiovascular disease is underreported in donkeys, possibly related to their limited athletic posture and frequent poor performance-related examinations. Reports on treatments for cardiovascular disease are anecdotal in donkey. Normal echocardiographic parameters have been reported in healthy donkeys. The aim of the present study was to establish the reference values and repeatability for Pulsed Wave Doppler echocardiographic variables of the mitral valve, aortic valve and myocardial performance. Two-dimensional Color flow mapping and spectral Doppler modes were performed. For the mitral valve, the mean velocity, pressure gradient and duration of E-wave were 57.7 ± 12.5 cm/s, 1.4 ± 0.7 mmHg and 0.4 ± 0.13 s, respectively. The results of the present study provide the reference values of PW echocardiographic parameters measurements in normal adult donkeys. Such reference values are helpful, especially when confronted with clinical cases with cardiovascular disorders.2, 66 ± 17 ms, 2.8 ± 1.4, 0.9 ± 0.03 and 19.1 ± 5.7 cm, respectively. For the aortic valve, the mean velocity was 64.9 ± 10.4 cm/s, pressure gradient was 1.8 ± 0.4 mmHg, pulsatility index was 1.4 ± 0.3, resistance index was 0.9 ± 0.02, VTI was 25.02 ± 6.2 cm, systolic/diastolic was 19 ± 4.7 and heart rate was 95.7 ± 28.9 per minute. For Myocardial Performance Index (LV)–Tei Index, the mean ejection, isovolumic relaxation, isovolumic contraction time and myocardial performance index were 0.24 ± 0.01, 0.14 ± 0.01, 0.14 ± 0.02 and 1.2 ± 0.1 s, respectively. The results of the present study provide the reference values of PW echocardiographic parameter measurements in normal adult donkeys. Such reference values are helpful, especially when confronted with clinical cases with cardiovascular disorders.In the present study, thirty clinically healthy donkeys were used to establish the reference values and repeatability for Pulsed Wave Doppler echocardiographic variables of the mitral valve, aortic valve and myocardial performance. 2-dimensional Color flow mapping and spectral Doppler modes were performed. For the mitral valve, the mean velocity, pressure gradient and duration of E-wave were 57.7 ± 12.5 cm/s, 1.4 ± 0.7 mmHg and 0.4 ± 0.13 s, respectively. The velocity, pressure gradient and duration of the A-wave were 32.3 ± 9.1 cm/s, 0.3 ± 0.04 mmHg and 0.3 ± 0.1 s, respectively. The mitral valve area, pressure half time, pulsatility index (PI), resistance index (RI) and velocity time integral (VTI) were 1.8 ± 0.5 cm Nowadays, donkeys are of high interest, both for clinicians and owners, due to their inner working abilities and as companion animals. Thus, in recent years, people’s awareness of the well-being and care of these animals has continued to increase, and the demand for professional veterinary services has increased. According to reports, there are many differences between donkeys and horses. Therefore, clinical data, treatment and diagnostic protocols from horse to donkey may lead to misdiagnosis and unnecessary or inadequate treatment . It was Pulsed wave (PW) Doppler uses short ultrasound bursts, which are transmitted to a point (designated as “sample volume”) distant from the transducer . PW DoppIn humans and horses, the velocity time integral (VTI) is a hemodynamic echocardiographic parameter measured from the Doppler spectrum across the valves through the left ventricular outflow tract (LVOT) . The areIn horses, the pressure gradient, which was calculated using a simplified Bernoulli equation, is applied to insufficient valves, ventricular and atrial septal defects, and intracardiac pressure determination . The preTill now, echocardiographic parameters, including pulsatility index (PI), resistance index (RI) and myocardial performance index (MPI), which are used in human studies to evaluate the cardiac performance, was not recorded in horses with cardiac disorders ,23. PI aData regarding reference values of Doppler echocardiographic parameters in healthy donkeys are scarce. Consequently, the current study was conducted to determine the reference values and repeatability for PW Doppler echocardiographic variables of the mitral valve, aortic valve and myocardial performance in normal donkeys.Equus asinus) were used for this study. The age of the donkeys was 5 to 9 years (7.2 ± 1.43), and their body weight was 100 to 220 Kg (172 ± 40.49). None of the donkeys had cardiovascular disorders nor any evidence of other systemic diseases based on clinical examination. All donkeys were free from significant valvular regurgitation using Doppler echocardiography. All donkeys under investigation were housed in straw-bedded boxes in the animal house of the veterinary teaching hospital, Faculty of Veterinary Medicine, Mansoura University. All donkeys were fed twice per day with 1.5 kg hay/100 kg B.W. and 1.5 kg concentrate with ad libitum water access at least two weeks before the trials. This study was carried out at the Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt. The study was approved by the Animal welfare and Ethics Committee, Faculty of Veterinary Medicine, Mansoura University .Thirty clinically healthy donkeys , the sample volume was placed at the tips of the mitral valve leaflets. The isovolumic contraction time (ICT) interval was measured from the end to the onset of mitral inflow. Meanwhile, the isovolumic relaxation time (IRT) interval was measured at the time between the onset and the end of LV outflow when the sample volume was placed below the aortic valve. The myocardial performance index was later calculated from the equation (ICT + IRT)/ET .Each donkey was examined via echocardiography three times at one-week intervals by the same observer. Each day, 3 PW echocardiographic measurements with a variance <5% were recorded on 3 non-consecutive cardiac cycles. Measurements with a variance >5% were discarded. Thus, by the end of the study, there were 9 PW echocardiographic measurements for each donkey.p < 0.05 were considered significant. All statistical procedures were performed with a commercially available software program .Statistical analysis followed the American Society for Veterinary Clinical Pathology (ASVCP) reference interval guidelines. Specifically, a histogram was used to illustrate the reference values. The data of PW echocardiography were checked for normality by the Kolmogorov–Smirnov normality test. The result revealed normally distributed data. The summary statistics and the frequency distribution  of the PW echocardiographic measurements for the mitral and aortic valve in all donkeys were reported. The reproducibility of the PW echocardiographic measurements was assessed by calculation of the intra-assay and interassay coefficient of variation (CVs). For each of the 3 days that data were collected, the intra-assay CV was calculated by dividing the SD of the measurements for that day by the mean of the measurements for that day. For each donkey, the interassay CV was calculated for each of the 3 measurements  of PW echocardiographic measurements obtained on each data collection day by dividing the SD for that particular measurement by the mean for that particular measurement. To assess the variation in the intra-assay CV among days and the interassay CV% among reads, repeated measures ANOVA was performed. Mauchly’s sphericity test was used to detect the significant variations. When there was a significant result, one-way ANOVA with post-hoc Duncan multiple comparison tests were used to detect the specific variations. For all analyses, values of Equus asinus) were summarized —Tei Index evaluated by PW Doppler echocardiography in healthy donkeys (mmarized .Equus asinus) were summarized —Tei Index evaluated by PW Doppler echocardiography in healthy donkeys (mmarized .The intra-assay and interassay coefficient of variation (CVs) of the mitral valve in healthy donkeys using PW Doppler echocardiography were summarized .The intra-assay and interassay CVs of the aortic valve in healthy donkeys using PW Doppler echocardiography were summarized .The intra-assay and interassay CVs of myocardial Performance Index (LV)–Tei Index in healthy donkeys using PW Doppler echocardiography were summarized .PW Doppler is used in combination with the 2D image to assess flow velocities within discrete regions of the heart and great vessels, which are used to evaluate the cardiac performance . In the PW Doppler evaluates the mitral velocity, which provides intuition into the dynamics of LV filling and helps to evaluate the diastolic function . FurtherThe ventricular filling results from isovolumic relaxation, ventricular compliance, filling pressures from the left atrium to left ventricle, pericardial restraint, ventricular interaction and atrial function, and it may be influenced by afterload and contractility . ConsequThe pressure gradient of the E-wave is higher than the A-wave of the mitral inflow during filling of the left ventricle in healthy donkeys. In equine, the pressure gradient is a reflection of normal intra-cardiac pressure and pathological increased pressure . The preIn the current study, the velocity of the aortic outflow is 64.9 ± 10.4 during the first third of systole in healthy donkeys. The aortic flow pattern is found in normal thoroughbred and thoroughbred cross horses (0.937 ± 0.094) , in normThe flow velocity of aortic flow is affected by heart rate. A faster heart rate will increase peak and mean velocity . The vel2, and the PHT equals 135 ± 93.9 ms in healthy donkeys. However, in humans, the MVA is found to be 4.0–6.0, and the PHT is 40–70 ms [In the current study, the MVA equals 2.4 ± 1.5 cm40–70 ms .The Doppler study can be used to calculate pressure half-time (PHT), which is defined as the time required for the pressure gradient across an obstruction to decrease to half of its maximal value. Thus, PHT increases as the severity of stenosis increases.Overestimation of the MVA occurs when PHT is shortened by concomitant significant aortic insufficiency, decreased ventricular compliance and atrial septal defect . PHT is In patients with aortic regurgitation, the Doppler velocity becomes significantly shorter <250 ms because of the rapid increase in left ventricular diastolic pressure and decrease in aortic pressure. Furthermore, it may be affected by severe diastolic dysfunction with marked elevation of left ventricular diastolic pressure without severe aortic regurgitation .In the current study, PI was 1.4 ± 0.4, RI was 0.9 ± 0.03 for the mitral valve, the PI was 1.4 ± 0.3 and RI was 0.9 ± 0.02 for the aortic valve in healthy donkeys. Normal values for the PI and RI are 1.36–1.56 and 0.6–0.8, respectively.PI is equal to the difference between the peak systolic velocity and the minimum diastolic velocity divided by the mean velocity during the cardiac cycle. The value of PI decreases with distance from the heart . The twoIn the current study, the VTI is 19.1 ± 5.7 cm for mitral inflow and equals 25.02 ± 6.2 for aortic outflow in healthy donkeys. The VTI is found to be 25.369 ± 3.209 cm in normal horses for aortic flow , 0.146 ±In the present study, Myocardial Performance Index (LV)–Tei Index was 1.7 ± 0.7, isovolumic contraction time was 0.3 ± 0.1, isovolumic relaxation time was 0.3 ± 0.1, and ejection time was 0.4 ± 0.1. The MPI was found to be 0.52 ± 0.12 in dog  and in hThe Myocardial Performance Index (LV)–Tei Index is independent of heart rate, arterial blood pressure, ventricular geometry, atrioventricular valve regurgitation, loading condition as afterload and preload, and can be used to evaluate the function of both the LV and the RV . The MyoResults of the present study provided an initial reference for PW (PW) Doppler echocardiographic variables of the mitral valve, aortic valve and myocardial performance in donkeys, which will be beneficial for clinicians who perform cardiac examinations in these animals. The intra-assay and interassay CVs for the mitral valve, aortic valve measurements and myocardial performance indicated that the technique is a feasible and precise method for determining cardiac measurements and functions in donkeys.


The treatment of dilated cardiomyopathy (DCM) has recently been greatly improved, especially with the widespread use of sacubitril/valsartan (ARNI) combination therapy. We know that ARNI-like drugs can significantly improve the symptoms of heart failure with reducing ejection fraction. However, clinical studies evaluating the safety and efficacy of ARNI in DCM-associated arrhythmia are limited, and whether individuals with arrhythmia would benefit from ARNI remains controversial. In this case, we report a patient with complete left bundle branch block (CLBBB) associated with DCM whose CLBBB returned to normal after treatment with ARNI.A 38-year-old man was admitted to the hospital for 20 days for idiopathic paroxysmal dyspnea. He presented with exacerbated dyspnea symptoms at night, accompanied by cough and sputum.Physical examination revealed a grade 4/6 systolic murmur could be heard in the apical area of the heart and mild edema was present in both lower limbs. Laboratory examination found that the B-type natriuretic peptide was significantly increased. Echocardiography indicated left atrial internal diameter, right ventricular internal diameter, and left ventricular diastolic diameter were enlarged and ejection fraction was significantly decreased. Besides, the pulsation of the wall was diffusely attenuated. Electrocardiogram was suggestive of tachycardia and CLBBB. A diagnosis of DCM with CLBBB was considered based on a comprehensive evaluation of the physical examination, laboratory examination, echocardiography and electrocardiogram.The patient was treated with ARNI at a dose of 50 mg (twice a day) at first, gradually increasing to the target dose  in the following 9 months as shown in Table After treatment with ARNI during the 9-month follow-up, the patient’s symptoms improved, and CLBBB returned to normal.Clinical studies evaluating the safety and efficacy of ARNI in DCM-associated arrhythmia are limited, and whether individuals with arrhythmia would benefit from ARNI remains controversial. This report will help to instruct the clinical treatment of DCM patients with CLBBB and the potential application of ARNI. DCM is a common cause of heart failure (HF), arrhythmia, and sudden death. Inhibiting activation of the sympathetic nervous system, suppressing the renin–angiotensin–aldosterone system (RAAS), and improving imbalances of the natriuretic peptide system are important strategies for delaying the progression of DCM. Based on this mechanism, sacubitril/valsartan (ARNI) improves HF by reducing ejection fraction (EF). Drugs such as angiotensin receptor-1 enkephalin inhibitors can delay and reverse ventricular remodeling, and furthermore, it can reduce hospitalization and mortality of HF. However, clinical studies evaluating the safety and efficacy of ARNI in DCM-associated arrhythmia are limited, and whether individuals with arrhythmia would benefit from ARNI remains controversial. Due to DCM-associated degeneration and fibrosis of the conduction system, poor ventricular remodeling, and ischemia, complete left bundle branch block (CLBBB) can occur in DCM patients. This article reports a case of DCM with severe HF and CLBBB. After treatment with ARNI during the 9-month follow-up, the patient’s symptoms improved, and CLBBB returned to normal. This report will help to instruct the clinical treatment of DCM patients with CLBBB and the potential application of ARNI.Dilated cardiomyopathy (DCM) is a heterogeneous form of cardiomyopathy characterized by left ventricular or biventricular enlargement with systolic dysfunction.The patient, a 38-year-old man, was admitted to the hospital for 20 days for idiopathic paroxysmal dyspnea. He presented with exacerbated dyspnea symptoms at night, accompanied by cough and sputum, with no accompanying abdominal pain. The patient did not receive any treatment. The patient was previously physically fit.Clinical signs on admission: temperature 36.5°C, pulse 78 beats/min, respiration 16 breaths/min, blood pressure 111/63 mm Hg, clear consciousness, and cooperative examination. The patient’s skin and sclera were not jaundiced, and he had a regular heart rhythm, but a grade 4/6 systolic murmur could be heard in the apical area of the heart and mild edema was present in both lower limbs.9/L (3.50–9.50 × 109/L), platelets 355 × 109 L (125–350 × 109/L), and creatinine 98.9 µm (57–97 µm). Coronary angiography did not indicate coronary stenosis or collateral circulation.The patient’s electrocardiogram  at first, gradually increasing to the target dose  in the following 9 months, along with metoprolol 25 mg (once a day [qd]), diuretics 20 mg (qd), aldosterone 20 mg (qd). The patient’s cardiac ultrasound ECG was rechecked 1, 2, 4, and 8 months after initiating treatment. ECG was still CLBBB at month 1 postdischarge Fig. . FurtherDCM is characterized by LV dilatation and contractile dysfunction in the absence of abnormal loading conditions or severe coronary artery disease. The most common presenting symptoms are related to congestive HF, but can also include circulatory collapse, arrhythmias, and thromboembolic events. The progression and prognosis of DCM are primarily influenced by the degree of LV dilatation.,5 We found that LBBB induction caused decreased left ventricular EF (LVEF), increased LVDD and wall mass, and decreased reduced septal perfusion. These findings suggested that LBB-related electromechanical dyssynchrony could play an important role in progression of DCM.LBBB is an independent predictor of adverse events and outcomes in DCM, which include sudden cardiac death, mortality due to HF, and myocardial infarction. There is a large potential electrical gradient between the fibrotic and normal myocardium, resulting in significant heterogeneity in excitability and conduction in different parts of the myocardium. This heterogeneity in conductivity causes uncoordinated cardiac contraction and arrhythmias. In addition, enlargement of the heart causes excessive elongation and potential rupture of the conduction system, resulting in delayed and blocked conductivity.The cellular pathology DCM is characterized by cardiomyocyte hypertrophy and degeneration, myocardial interstitial fibrosis, ventricular cavity dilation, and thinning of the ventricular wall with fibrous scar formation.,8 CRT can reverse left ventricular dyssynchrony in a process referred to as left ventricular reverse remodeling (LVRR).,10 In combination with appropriate pharmacologic interventions, CRT improves survival, reduces hospital admissions, and induces reverse left ventricular remodeling in appropriately selected patients. However, the use of CRT is limited due to its high cost and relatively high failure rate of 30%. Therefore, optimized treatment plans such as ARNI are of great significance in patients with DCM and CLBBB.Therefore, the conventional treatment for DCM patients with CLBBB is cardiac resynchronization therapy (CRT), also known as biventricular pacing. In addition to modulating the RAASes sympathetic tone through its diuretic effects.,12 However, the potential antiarrhythmic effects of ARNI have not been elucidated.ARNI is an angiotensin receptor-enkephalinase inhibitor and is used in HF patients with reduced EF based on the results of the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial trial. Currently available experimental studies do not support a direct antiarrhythmic effect. A large-scale real-world clinical trial demonstrated that ARNI attenuated electrical and structural remodeling in the context of atrial fibrillation (AF), possibly by inhibiting T-cell activation and calcium-regulated phosphatase, subsequently attenuating AF. Therefore, for HF patients with AF, ARNI may reduce the occurrence of AF by reversing electrical and structural remodeling of the heart. ARNI likely improves HF symptoms by simultaneously modulating the RAAS and sympathetic nervous system. HF patients with AF may benefit more from simultaneous treatment with AF therapies and ARNI.We postulated that the ability of ARNI to reverse pathological myocardial remodeling could indirectly decrease ventricular arrhythmias by improving uneven and slow conduction associated with remodeling. LVRR is a complex process involving remodeling of the LV and many other cardiac structures, as observed in our follow-up. LVRR is considered to be an important prognostic tool in the treatment of DCM.–15 However, many studies of LVRR are ongoing, including the optimal timing of LVRR quantification and the background of individual genetics.,14 LVRR is estimated to occur in up to 40% of patients with DCM, suggesting that DCM is not necessarily an irreversible progressive myocardial disease. This implies that LVRR is a significant therapeutic target for DCM.In the present case study, the patient’s CLBBB disappeared, which is extremely rare. We suggest that this could be due to 2 possible mechanisms. First, as lesions develop, the right bundle branch could develop the same degree of conduction block or delay. If this is the case, the patient will evolve from CLBBB to atrioventricular block type I. Second, DCM-triggering factors could be improved by ARNI. For example, if myocardial ischemia is improved, ventricular remodeling would be controlled, and the ventricle would decrease in size. These events, or a combination thereof, could cause CLBBB to intermittently return to normal. In this case, CLBBB resolution was concomitant with improved symptoms, decreased LVDD, and improved LVEF. The patient did not present with prolonged PR interval. Given these findings, we suggest that the second possibility, wherein ARNI alleviates DCM triggers, is more likely. Therefore, we hypothesize that ARNI could suppress pathological ventricular remodeling or even LVRR in DCM. LVRR is defined as reduced LVDD and improved LVEF.Despite novelty and potential clinical relevance of this study, its limitations should be acknowledged to avoid its overinterpretation. During treatment of the patient, cardiac magnetic resonance imaging was performed too late to develop a strong baseline. The patient was also not advised to undergo cardiac magnetic resonance imaging during subsequent follow-up, so we were unable to obtain more intuitive imaging data to evaluate the improvement of cardiac fibrosis. This deficiency will be addressed in future follow-up studies.In summary, the present case demonstrated that ARNI could improve DCM prognosis, reverse ventricular remodeling, improve uneven electrical conduction, and improve CLBBB. Future clinical studies will evaluate the further application of ARNI in cardiac arrhythmias.The authors would like to thank the patient and her family for granting us their permission to publish this case report.Conceptualization: Meng-Ling Peng.Data collection and curation: Meng-Ling Peng, Yu Fu, Ying Zhang.Methodology: Yu Fu, Ying Zhang, Chu-Wen Wu.Writing – original draft: Meng-Ling Peng, Yu Fu, Chu-Wen Wu.Writing – review & editing: Meng-Ling Peng, Hang Ren, Shan-Shan Zhou.


Methamphetamine abuse is a serious public health concern and causes various life-threatening disorders including pulmonary arterial hypertension (PAH). Herein, we present the first case report describing the anesthetic management of a patient with methamphetamine-associated PAH (M-A PAH) undergoing laparoscopic cholecystectomy.A 34-year-old female with M-A PAH suffered from deterioration of right ventricular (RV) heart failure due to recurrent cholecystitis and was scheduled for laparoscopic cholecystectomy. Preoperative assessment of PA pressure showed 82/32  mmHg, and transthoracic echocardiology revealed a slight reduction of RV function. General anesthesia was induced and maintained by thiopental, remifentanil, sevoflurane, and rocuronium. PA pressure gradually increased after peritoneal insufflation; therefore, we administered dobutamine and nitroglycerin to decrease pulmonary vascular resistance (PVR). The patient emerged from anesthesia smoothly.Avoiding increased PVR by appropriate anesthesia and medical hemodynamic support is an important consideration for patients with M-A PAH. Methamphetamine is a highly addictive drug, which releases neurotransmitters, such as serotonin, norepinephrine, and dopamine, in the brain, resulting in psychokinetic change . ChronicA 34-year-old woman  suffered from recurrent cholecystitis and was scheduled to undergo laparoscopic cholecystectomy under general anesthesia. She had PAH that was induced by abuse of various drugs, particularly methamphetamine. She had long-term, repeated exposure to methamphetamine and toluene from 17 to 28 years old. When she was 31 years old, she developed whole-body edema and dyspnea and was diagnosed with right ventricular (RV) heart failure due to M-A PAH based on sufficient exposure to methamphetamine and exclusion of other common cases of PAH. Pulmonary vascular resistance (PVR) decreased after the administration of epoprostenol (prostaglandin I2); however, alveolar hemorrhage induced by high pulmonary perfusion occurred. She developed hemoptysis and respiratory failure, which required mechanical ventilation. At that point, we observed tolerance to the sedative effect of propofol.5, respectively, with a normal cardiac index of 3.6 L/min/m2. She was receiving multiple PAH-specific medicines, including macitentan 10 mg, tadalafil 40 mg, selexipag 3.2 mg, and sildenafil citrate 60 mg, and several benzodiazepines and antidepressants for the treatment of sleep impairment. Her activated partial thromboplastin clotting time was 47.1 s. The cardiologist and anesthesiologist assessed that her intraoperative risk was very high in accordance with previous reports showing higher mean PAP as a risk factor for increased mortality [Preoperative assessment of pulmonary arterial catheterization revealed that pulmonary arterial pressure (PAP) and PVR were 82/32  mmHg and 460 dynes･s/cm2O, and ventilation rate of 12/min. The BIS value was between 47 and 60 during the operation. As shown in Fig. 2 was set around 35 mmHg to decrease PVR. Intraoperative TEE demonstrated RV dilation without significant change after peritoneal insufflation. Cholecystectomy was uneventfully performed, followed by the replacement of the tracheal tube with the i-gel  and discontinuation of anesthesia.On arrival in the operating room, we used the standard monitors, including a pulse oximeter, electrocardiograph, capnometer, and bispectral index (BIS) monitor, and monitored the artery blood pressure via a radial artery. In addition, we placed a pulmonary arterial catheter and performed transesophageal echocardiography (TEE) after induction of anesthesia and intubation. Anesthesia was induced with thiopental, rocuronium, and remifentanil and maintained by sevoflurane, remifentanil, fentanyl, and rocuronium. After intubation, we performed a transverse abdominal plane block for postoperative pain control. The ventilation settings were a tidal volume of 5 ml/kg (450 ml), positive end-expiratory pressure of 5 cmHWhen all procedures had been performed, anesthesia was discontinued. The patient was extubated after confirming smooth emergence. The patient was transferred to an intensive care unit, and the mean PAP was around 40 mmHg during the intensive care unit stay. Three days after the operation, she was discharged without complication.We experienced the anesthetic management of the case with M-A PAH who underwent laparoscopic cholecystectomy. Although the 2018 World Symposium on Pulmonary Hypertension categorized methamphetamine use as a definite cause of PAH , anestheEvidence supporting the association between methamphetamine and PAH has been accumulated. A previous study demonstrated that rates of prior methamphetamine use in patients with idiopathic PAH were 8–10 times higher compared with other forms of PAH ; thus, tAnesthetic management of patients with M-A PAH needs to be performed more carefully than of those with idiopathic PAH patients, because M-A PAH patients show higher right atrial pressure, lower cardiac index and excise tolerance, and more dysfunctional RV than patients with idiopathic PAH . FurtherWe monitored PAP using a pulmonary artery catheter, although its intraoperative use remains controversial . We consPatients with long-term exposure to methamphetamine have high risks during the intraoperative period due to PAH. We successfully anesthetized a patient with M-A PAH by monitoring RV function and avoided increased pulmonary arterial resistance with appropriate anesthesia and medical hemodynamic support.


Ventricular assist device implantation presents a possible bridge to heart transplantation for patients with failing Fontan physiology. However, evidence regarding outcome and possible pitfalls associated with the Fontan circulation is still insufficient. We describe the course of a 13-year-old male, who was born with hypoplastic left heart syndrome and underwent HeartMate III implantation due to refractory failure of the systemic right ventricle. The establishment of a Fontan circulation is essential to facilitate early survival of patients with functionally univentricular hearts but remains a palliative procedure nonetheless. Patients will eventually experience Fontan failure either due to reduced transpulmonary blood flow with or without increased pulmonary vascular resistance, resulting in reduced preload or failure (systolic or diastolic) of the systemic ventricle itself . Improve2. Surgical access was impaired due to extensive adhesions from previous procedures. ECLS was switched to cardiopulmonary bypass via the femoral vessels. The HM III was placed in the systemic—anatomically—right ventricle. Therefore, the sewing ring was enhanced with four layers of pledgets . Echocardiography and magnetic resonance imaging revealed a high-grade tricuspid valve regurgitation due to severe annular dilation (60 mm) and a markedly reduced systemic ventricle ejection fraction of 36%. His last heart catheterization showed a mean pulmonary artery pressure of 16 mmHg, and a transpulmonary gradient of 4 mmHg with increased right ventricular end diastolic pressure of 12 mmHg, so elevated pulmonary vascular resistance was ruled out. There was no more significant collateral blood flow to the lungs at that time. He deteriorated and was admitted to our center in cardiogenic shock with hypotension and lactate acidosis peripheral veno-arterial extracorporeal life support (ECLS) was established using the femoral vessels. Tricuspid valve replacement (33 mm perimount) was performed on the 3rd day of ECLS support, which was continued postoperatively. Renal and hepatic functions were preserved while on ECLS support, but ECLS-weaning attempts were repeatedly unsuccessful. The decision was made to implant a HeartMate III (HM III) on the 9th day of ECLS treatment. The child was 45 kg and 165 cm which resulted in a body surface area of 1.43 mpledgets , 2 to repledgets , 4. The ®  remain the only options for pediatric durable support. We opted for the HM III as size was not an issue in our patient (body surface area 1.4 m2) and we aimed for hospital discharge during the expected long waiting time for heart transplantation. Additionally, intracorporeal flow devices are associated with the highest survival rates and fewer adverse events due to the lower thrombogenicity (Over the last two decades, durable mechanical circulatory support advanced to a solid second-line treatment after heart transplantation for pediatric patients suffering from end-stage heart failure. With growing experience in the pediatric community, improving survival data and decline in adverse events, patients with failing Fontan circulation are increasingly considered suitable for VAD implantation –4, 6. Wigenicity . NumerouThe original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.MH, SM, JP, and JH wrote the first draft of the manuscript. All authors contributed to data analysis and data curation, contributed to manuscript revision, read, and approved the submitted version.


Cardiac conduction system pacing provides physiological ventricular activation by directly stimulating the conduction system. This review describes the two types of conduction system pacing: His bundle pacing (HBP) and left bundle area pacing (LBAP). The most significant advantage of HB pacing is that it can provide a regular, narrow QRS; however, the disadvantages are challenging implantation and a high risk of re-intervention due to lead dislodgement and the development of high pacing threshold. LBAP provides optimum physiological activation of the left ventricle by engaging the left bundle/fascicular fibers. LBAP is more physiological than traditional RV apical pacing and could be an attractive alternative to conventional cardiac resynchronization therapy (CRT). The advantages of LBAP are a relatively more straightforward implantation technique than HBP, better lead stability and pacing thresholds. HBP and LBAP are more physiological than right ventricular pacing and may be used instead of conventional pacemakers. Both HBP and LBBP are being investigated as alternatives to conventional CRT. Conventional cardiac resynchronization therapy (CRT) is an essential part of treating selected patients with HFrEF and ventricular dyssynchrony due to wide QRS. However, conventional CRT requires implantation of an extra lead in the coronary sinus, which sometimes may be challenging and less feasible due to unsuitable anatomy, phrenic nerve stimulation, and unacceptably high local thresholds. Moreover, the left ventricular epicardial stimulation may not entirely resolve the electrical dyssynchrony , 2. EpicThese challenges with conventional CRT led to the development of a new concept of pacing—the conduction system pacing (namely His bundle pacing (HBP) and left bundle area pacing (LBAP)), which can also be alternatives to conventional right ventricular pacing in selected patients.The His bundle (HB) is a thin structure penetrating the central fibrous body of the heart and has two main anatomical variants. The type I HB, present in 46.7% of subjects, when the AV bundle is covered by a thin layer of myocardial fibers and runs along the lower border of the membranous septum. Conversely, the type II HB runs within the muscular part of the interventricular septum below the pars membranacea , 3. BothLBB’s anatomical features determine the feasibility of LBBP as a potential physiological pacing modality. In contrast to HBP, LBBP that is determined by the capture of the LBB and distal conduction system tissues has a much wider target zone for area pacing that is likely to be beyond the site of the block in distal HB . In contImplementing physiological pacing techniques directly activating the conduction system has been and continues to be a crucial issue in managing cardiac conduction disease. Hence, electrophysiological challenges arose as development progressed. Nearly 5 decades ago Narula et al. reported that the pacing impulse to ventricular activation time (PI-R) during the procedure was the same as the H-V time during normal sinus rhythm . SubsequSince 2006, several reports which described the use of HBP in clinical practice have been published . These rHowever, due to significant procedural limitations and technical complexities of HBP associated with the risk of causing distal conduction block, high capture threshold, and low sensed R wave amplitude Fig. , researcHis bundle pacing (HBP) has arisen as a novel and alternative method for cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and left bundle branch block (LBBB). The main reason for implementing effective ventricular resynchronization and more physiological activation is the obvious improvement in cardiac function. This method can also significantly reduce QRS duration and restore normal intrinsic activation patterns in patients with ventricular conduction delays, as demonstrated by Ali et al. .Thus, for the first time, the concept of longitudinal dissociation with the fibers within the His bundle committed to the left bundle with asynchronous conduction resulting in an LBBB pattern was described. The study showed that localized lesions within the His bundle induced LBBB. Meanwhile, stimulation of the HB proximal to the intra-His lesion could lead to ventricular depolarization. HB stimulation at a site distal to the lesion, in turn, resulted in narrow QRS complexes due to synchronous impulse conduction to LBB and RBB. These fundamental concepts confirmed the feasibility of HBP, including in advanced His to ventricular electrogram interval (HV) disease stages .The pacing lead is placed distal to the site of BBB fibers within the HB are ordered in strands predestined for the LBB or RBB. The position of a pacing lead can reverse conduction delays within the HB .The connection between source and sink: the block is overcome with sufficient stimulus for activation of distal dormant tissue based on the source-sink connection during pacing versus intrinsic impulse propagation .Retrograde activation: the activation of the His-Purkinje system happens through the capture of an upper septal branch that permits onward antegrade activation beyond a block site .In some cases, the factors like the higher lead revision rate or pacing thresholds can prevent HBP from reversing LBB. Concerning the mechanisms for HBP narrowing or reversing BBB, there are the following:In a prospective crossover study, Catanzariti et al. proved that during direct HBP, physiologic distribution of myocardial blood flow was preserved more in comparison with right ventricular apical pacing . In anotIn a more recent study, where the effects of HBP in patients with LV systolic dysfunction, first-degree atrioventricular block (AVB), and either RBBB or narrow QRS complex were evaluated, it was proved that temporary HBP did not lead to an increase in QRS duration (in comparison with temporary biventricular pacing) . A randoSeveral prospective randomized studies proved the effects of BVP in reducing mortality rates and heart failure hospitalization, improving quality of life, and increased exercise capacity. However, the CRT non-response is up to 30% in all CRT candidates . In patiA multicenter study by Ali et al. evaluated the feasibility and outcomes of the LBBAP method in CRT-eligible patients or those who underwent unsuccessful CRT. In this cohort study, all patients had NYHA class II to IV, baseline LVEF ≤ 50%, and indications for ventricular pacing and/or CRT. Based on the results, LBBAP was associated with reduced paced QRS duration, improving clinical and echocardiographic outcomes. Hence, LBBAP can be a feasible, safe, and potentially an alternative option for CRT ; howeverIn a randomized crossover study, Gasparini et al. demonstrated no significant difference in clinical and echocardiographic improvements while applying HBP compared with BVP . HoweverCardiac resynchronization therapy is the gold standard in the management of patients with systolic heart failure and electromechanical dyssynchrony, as evidenced by a wide QRS duration. For over two decades, the resynchronization method has been through by ventricular pacing. We have strong data using prospective randomized studies that show biventricular pacing improves quality of life New York Heart Association classification, left ventricular ejection fraction, and left ventricular volumes. However, despite strong clinical evidence regarding the efficacy of biventricular pacing, it is estimated that approximately 1/3 of patients have no clinical benefit or response to CRT via LV lead placement . QRS configuration at baseline was left bundle branch block in 39%, and non-left bundle branch block in 46%. Procedure times were 105 ± 54 min, and fluoroscopy time was acceptable at 19 ± 15 min. Importantly, left bundle branch area pacing thresholds were 0.6 ± 0.3 V @0.5 ms, and R wave amplitude was acceptable at 10.6 ± 6 mV at implantation. Sensing and thresholds remain stable during the follow-up of approximately 6 months. The importantly clinical and echocardiographic response was observed in 72 to 73% of the patients who achieved left bundle branch pacing. This study proved that left bundle branch pacing is a feasible alternative for cardiac resynchronization therapy providing acceptable pacing and sensing parameters both in the short and long term with no excessive procedure times and successful clinical outcomes.Recent randomized LBBP-RESYNC study (40 pts) showed that patient randomized to LBBP has higher LVEF improvement. In this study, 10% LBBP patients were crossover to biventricular CRT and 20% of biventricular CRT were crossover to LBBB pacing due to the problems with lead placement. Which on the one hand showed that is not always possible to perform both of techniques in one patient but in case of the impossibility of one of the methods it is possible to change to another. Both HBP and LBAP could be helpful also in patients without HF in whom we expect a high rate of RV stimulation. HBP is the most physiological pacing modality that restores normal ventricular activation and has been demonstrated to achieve greater hemodynamic response over BVP in patients . ConfirmAtrial fibrillation (AF), the most common arrhythmia, increases the risk of death and hospitalization in 76% of HF patients, and the structural and neurohormonal changes in HF make, in turn, the development and progression of AF much more likely . AF ablaIn a study, Molhoek et al. patients with AF showed a milder degree of response to CRT compared to those with sinus rhythm. However, the long-term survival rate was comparable among these two groups of patients , 37. AccAn intrinsic and irregular spontaneous AF rhythm reduces the percentage of effectively biventricular paced captured beats, making CRT delivery more challenging in those patients with AF . NeverthOn the other side, in selected patients with AF and HF, especially with uncontrolled heart rate, the “ablate-and-pace” strategy can be beneficial, resulting in improvement of LVEF and the NYHA functional class . HoweverIn patients with HF and sinus rhythm, PR prolongation is a prospective issue for pacing. A PR ≥ 200 ms is significantly associated with 58% higher mortality in the long term regardless of QRS duration .The benefits of HBP in HF can potentially apply to patients with narrow QRS and PR prolongation by providing AV synchrony without inducing ventricular dyssynchrony . The EurAt present with the development of dedicated tools for direct HBP, the success rate of implantations has become more than 90%. Moreover, in most cases, the acceptable pacing thresholds can be achieved . Su et aThe study by Vinther et al. observed HF patients with LBBB, demonstrated that His-CRT provided similar clinical improvement in comparison with BiV-CRT at the expense of higher pacing thresholds . One morIncrease heart rate (HR) may have the potential to reduce the risk for heart failure hospitalization, atrial fibrillation (AF), and cerebrovascular stroke as these outcomes are increased in patients with a normal or preserved ejection fraction on HR-lowering treatments. Therefore, lower HR elevation employing physiological conduction system pacing in patients with HFpEF will decrease left atrial and left ventricular filling pressures. There is an ongoing randomized trial that is investigating whether pacing with a higher heart rate is beneficial for patients with HFpEF and pacemakers with intrinsic AV conduction or CRT. Also, physiological pacing (CRT or His) could be beneficial in patients with HF, LVEF 35–50%, and indications for pacemaker implantation with high expected percent of pacing (BLOCK HF study) . Again, Implementing physiological pacing techniques directly activating the conduction system has been and continues to be a crucial issue in managing cardiac conduction disease. HBP is the most physiological pacing modality that restores normal ventricular activation and has been demonstrated to achieve greater hemodynamic response over BVP in patients. HBP combined with AV node ablation showed effectiveness in AF patients with drug-refectory HF. Left bundle branch area pacing has been suggested as an effective alternative to overcome the limitations of His bundle pacing. But, left bundle branch pacing and His bundle pacing have a larger target area and somewhat fewer technological implant challenges. In fact, future studies and large-scale clinical trials are expected to validate HBP and LBBP’s safety, reliability, and long-term performance for physiological pacing in several groups of patients.


Assessment of right ventricular (RV) function is crucial for the evaluation of the dyspnoeic patient and/or with systemic venous congestion and provides powerful prognostic insights. It can be performed using different imaging modalities including standard and advanced echocardiographic techniques, cardiac magnetic resonance imaging, computed tomography, and radionuclide techniques, which should be used in a complementary fashion. Each modality has strengths and weaknesses based on which the choice of their use and in which combination may vary according to the different clinical scenarios as will be detailed in this review. The conclusions from multiple studies using different imaging techniques are concordant: RV function can be reliably assessed and is a critical predictor of clinical outcomes.  Heart failure (HF) syndromes have been historically based on LV dysfunction as the source of limitation, and most therapeutic approaches aimed at improving LV remodelling and contractility. However, there are many settings in which an increased load of the RV and/or a decrease in RV contractility can result in a failure to appropriately augment cardiac output.The role of the heart is to provide sufficient cardiac output to meet the metabolic needs of the body at rest and during exercise. To achieve this, both the left ventricle (LV) and right ventricle (RV) must augment their function to meet demand. It may be said that ‘1 and can decrease dramatically particularly during physical activity when increases in RV after-load, work and wall stress are far greater than for the LV.2 Thus, the concept of ventricular–arterial interaction is particularly important for the RV. Increase in RV after-load can be initially accommodated by an increase in RV contractility such that output is maintained. However, when sustained increases in loading cannot be matched by RV contractile reserve, ‘uncoupling’ will occur as the RV is incapable of meeting the demands imposed on it. At first, the uncoupling presents during exercise or acute illness, but is then detectable at rest in more advanced disease stages.Excess loading and limitations in contractile force are therefore the key factors that may combine to limit RV output. Regarding RV load, it is critical to note that the RV sits ‘upstream’ of the systemic circulation, the LV, the left atrium, and pulmonary circulation. Dysfunction at any of these levels can result in increased pulmonary artery pressures and RV after-load, such as in HF with preserved or reduced ejection fraction (EF), valvular heart disease, and pulmonary vascular disease. With an RV mass and a contractile reserve of approximately one-third of the LV, RV output is highly sensitive to increases in after-load,4 and also conditions that have traditionally been regarded as primarily LV pathologies such as congestive HF5–7 and acute myocardial infarction.8–10 The RV can be assessed using a range of imaging modalities including Doppler, 2D and 3D and strain echocardiographic techniques, magnetic resonance imaging (CMR), computed tomography (CT), and radionuclide techniques. Recent technological advances have improved the feasibility and accuracy of each imaging modality for the assessment of RV function, but still there is no single approach able to provide all the necessary information, and their use in a complementary fashion is therefore advised . As summarized in Table 1 and will be detailed in this review, each modality has strengths and weaknesses, based on which the choice of their use and in which combination may vary according to the different clinical scenarios. The conclusions from multiple studies using different imaging techniques are concordant: RV function can be reliably assessed and is a critical predictor of clinical outcomes.These important physiological principles explain why assessment of the RV function is crucial for the evaluation of the dyspnoeic patient and/or with systemic venous congestion, and can provide powerful prognostic insights. RV function has been shown to be a critical determinant of survival in pulmonary vasculature diseases, such as pulmonary arterial hypertension,11In daily clinical practice, RV evaluation is mainly performed by 2D echocardiography. However, there is currently little uniformity in echocardiographic approach to the RV, owing to potential lack of awareness and/or conformity with recommendations.Qualitative evaluation of the RV anatomy should be performed from multiple acoustic windows and is particularly important in the context of ischaemic heart disease or arrhythmogenic right ventricular cardiomyopathy , and suspicion of constriction or pressure/volume overload .12 These measurements are particularly important as part of the criteria for the diagnosis of ARVC. However, the operator should ensure a correct alignment of the views to provide accurate and reproducible values. RV end-systolic area (ESA) and end-diastolic area (EDA) are obtained by manually tracing the ventricular endocardium in the RV-focused apical four-chamber view, excluding the trabeculae: normal values can be found in the ASE/EACVI recommendation paper.12The quantitative assessment of the RV size should include several measurements. RV-free wall thickness can be measured at end-diastole in the subcostal four-chamber view or parasternal view: >5 mm is considered abnormal after exclusion of the trabeculae. RV basal, mid-cavitary diameters, and base-to-apex length are also recommended, together with the RV outflow tract (RVOT) diameter  in the parasternal long-axis view, as well as RVOT proximal and distal diameters in the parasternal short-axis view.13 The ability of FAC to predict major adverse cardiac events has been demonstrated in various cardiovascular conditions including myocardial infarction and pulmonary hypertension.14 2D RVEF is not recommended for clinical use due to the inaccuracy of the method.12 The tricuspid annular plane systolic excursion (TAPSE) quantifies the excursion of the lateral tricuspid annulus from end-diastole to end-systole and reflects only the longitudinal contraction of the RV-free wall. This simple and reproducible measure is considered abnormal when <17 mm. Many assumptions and drawbacks should be considered while using this parameter . Nevertheless, its prognostic value has been demonstrated in several conditions such as HF, coronary artery disease, pulmonary embolism, pulmonary hypertension, and in critically ill patients.16 Tissue Doppler imaging (TDI)-derived tricuspid lateral annular systolic velocity (S′) is another parameter of RV longitudinal function, which correlates with CMR-derived RVEF13: a value <10 cm/s is considered abnormal but may decrease with age. The limitations are similar to those for TAPSE and should be taken into account. RV index of myocardial performance (RIMP) is a ratio between isovolumic contraction and relaxation times and the ejection time. This parameter reflects global RV systolic function and was shown to correlate well with CMR-derived RVEF. RIMP <0.55 is considered abnormal. Another measure of RV function is the RV dp/dt, which represents the rate of change of pressure and is calculated as the slope of the spectrum of tricuspid regurgitation between 1 and 2 m/s: a value <400 is considered abnormal. This parameter is less used due to its high load dependency. Finally, a less load dependent parameter of RV performance is the right isovolumic myocardial acceleration (IVA), which is the peak isovolumic myocardial velocity divided by the time to reach this peak velocity: it is considered abnormal when <2.2 m/s.The quantitative evaluation of RV performance is quite challenging and can be estimated with different parameters. Fractional area change (FAC) is calculated by the formula [(EDA − ESA)/EDA] × 100, and showed fair correlation with RVEF assessed by CMR: a value <35% is considered abnormal.17 Attenuated increase in FAC and S′ with exercise indicated subclinical RV dysfunction in athletes with RV arrhythmias.18Assessment of RV systolic function during exercise stress echocardiography is a promising diagnostic and prognostic tool. Exercise-induced reduction in TAPSE demonstrated important incremental prognostic value in asymptomatic patients with primary mitral regurgitation.19 RV peak systolic longitudinal strain and strain rate are assessed in the (RV-focused) apical four-chamber view, where RV-free wall and septum are each divided into three segments . Regional strain values are generated, and the RV four-chamber longitudinal strain (average of the six segments) and RV-free wall strain (average of the three segments) are derived.19 Current recommendations propose a cut-off value of −20% for RV four-chamber longitudinal strain and of −23% for RV-free wall strain as abnormal. However, some studies showed that a lower cut-off for RV four-chamber strain of −19% was associated with poor prognosis. Overall, RV longitudinal strain has shown important prognostic value in various conditions, including pulmonary hypertension, valvular heart disease, LV dysfunction, and HF.20 Recent studies suggest that the mechanical dispersion of the strain curves could also play a role in the risk stratification of patients with ARVC.212D speckle tracking echocardiography (STE) has recently emerged, enabling a real-time tracking of the frame-to-frame myocardial motion, and overcoming most of the limitations inherent in conventional echocardiography. In particular, STE is less angle- and load-dependent, and less influenced by passive tethering, thus allowing accurate quantification of regional and global myocardial function, reflecting more closely myocardial contractility.Figure 1.Importantly, assessment of the RV size and systolic function by conventional echocardiography should always be performed in a clinical context, including RV loading conditions. Accurate evaluation requires multi-parametric approach and use of different echocardiographic views to ensure correct interpretation of the findings, especially when there is discrepancy between echocardiographic parameters, as illustrated in Figure 2). In particular, RV full-volume dataset can be post-processed using dedicated software packages to obtain tracing of the RV endocardial surface at end-diastole and end-systole and measurement of RV volumes and EF, without using any geometrical assumptions or formulas.Unlike 2D echocardiography, 3D echocardiography enables acquisition of full-volume datasets from either a single beat capture or few consecutive beats with sub-volumes stitched together, allowing for higher temporal and spatial resolution. This full-volume dataset incorporates all three components of the RV  and allows for a detailed analysis of RV size, shape, function, and contraction patterns , moderate (30–40%), or severe (<30%) RV dysfunction have been also prognostically validated to stratify the risk of cardiac death and MACE.27 Prognostic value of RVEF was shown to be superior to conventional echocardiographic parameters of RV systolic function for predicting mortality.28Regarding its prognostic value, 3D echocardiography-derived RVEF has been shown to be independently associated with cardiac and all-cause mortality and major adverse cardiac events (MACE) in patients with various cardiovascular conditions.29 Recently developed software package enables to decompose the wall motion of the 3DE-derived RV model along three anatomical axes: longitudinal (from tricuspid annulus to the apex), radial (perpendicular to the interventricular septum), and anteroposterior  axes and quantify contribution of each motion component separately.30 The inward motion of the free wall  and interestingly, the anteroposterior shortening  was shown to be as important as longitudinal shortening in healthy volunteers.31 Also, RV pressure overload could be detected early if radial motion component was lost, while RV volume overload showed more prominent impact on the longitudinal RV component.32 However, data on the prognostic role of different components of RV systolic function remain scarce. A recent study on a large cohort of patients with left-sided heart disease demonstrated that in a subgroup of patients with preserved RVEF, reduced relative contribution of the anteroposterior component was significantly and independently associated with adverse outcomes, while RVEF or LVEF was not.29Quantification of the individual motion components of the RV using 3D echocardiography enables a comprehensive characterization of RV contraction pattern, which could be abnormal even in the context of normal RVEF.33 In patients with pressure overload, the curvature of the RV inflow tract was a more robust predictor of death than RVEF, RV volumes, or other regional curvature indices. Recently the reference values of 3D echocardiographic values of regional curvature indices were reported in a large group of healthy subjects to facilitate future studies on adverse RV remodelling.34Finally, the role of RV remodelling and RV shape alterations are widely recognized in RV pressure and volume overload conditions. However, till recently there was no evidence supporting association of poor outcomes in patients with adverse RV shape changes independent of those predicted by size and functional parameters. A unique approach by 3D echocardiography to provide RV shape indices based on analysis of the RV curvature was recently developed and evaluated in normal subjects and in patients with pulmonary arterial hypertension.Figure 3).Many conventional measures of RV function, such as FAC, EF, and TAPSE, reflect the interaction between loading conditions and contractility. However, an accurate measure of (load-independent) contractility represents the ideal means of determining the patient’s prognosis and possibly the need for intervention. A load-independent RV function assessment can theoretically be achieved by two means—either a direct load-independent surrogate of contractility or by incorporating load into the measurement of RV function  under a range of varied loading conditions. The theory was intriguing given that IVA is a measure of myocardial motion during the isovolumic contraction period, prior to the ventricle being exposed to its after-load. Whilst the concept is appealing, the measure has not been well validated or widely accepted, perhaps due to difficulties with reproducibility. As mentioned above, STE is another approach promoted as being an approximate of contractility: longitudinal strain is a measure of deformation and, both in theory and in practice, should be interpreted relative to load. However, based on animal and human studies,36 the change in strain relative to time (strain rate) might be a closer approximate of contractility. There is some support for this premise, but strain rate has also failed to make its way into clinical routine due to issues with reproducibility and its impact on a measure with small dynamic range.Only few measures have been proposed as surrogate approximates of RV contractility. Two decades ago, Vogel et al.37 have demonstrated the prognostic utility of expressing TAPSE relative to pulmonary artery systolic pressure (PASP) estimates as a surrogate of contractility. A variant on this concept incorporates the ratio of RV area to PASP and has been validated against a gold-standard hybrid using CMR volumes and invasive pressure measures, both at rest and throughout exercise.38 The utility of these measures during exercise provides an additional strength in that the additional load and work of exercise challenges the contractile reserve of the ventricle. In essence, this provides an insight into whether the compensated RV is starting to fail.An alternate means of dissecting the underlying RV contractility is to express it as the relationship between RV function and load. This is akin to the approach in which contractility can be determined invasively from pressure volume–volume relationships. In a series of elegant studies, Guazzi 39 The same method can be applied for the RV, using the pulmonary pressures as an estimate of myocardial force, and STE-derived RV longitudinal strain to estimate changes in segment length . RV MW therefore provides an integrative analysis of RV function incorporating RV longitudinal strain with pulmonary pressures, as measure of RV after-load, although an accurate estimation of the last one can be challenging in some cases. Cardiac cycle timings are determined by pulmonic and tricuspid valve opening and closure events, identified through either direct visualization of 2D images or by pulsed-wave Doppler interrogation. Any myocardial lengthening occurring during systole and any shortening during isovolumic relaxation is recorded as RV wasted work ; therefore, any inefficient post-systolic shortening will not contribute to estimate the RV constructive work , defined as the work contributing to the shortening of the cardiac myocytes during systole and the lengthening during isovolumic relaxation. A recent study showed a significant correlation of these novel indices derived non-invasively by pressure–strain loops, and in particular RVGCW, with invasively measured stroke volume index.40 The importance of considering after-load in the assessment of RV function has been demonstrated by studies on RV–pulmonary arterial coupling.37 This is particularly relevant even when using RV longitudinal strain, which remains after-load-dependent even more than LV longitudinal strain due to the thinner walls and lower ventricular elastance of the RV. Furthermore, RVMW synchronizes pulmonic and tricuspid valvular events with RV longitudinal strain, accounting also for possible post-systolic shortening (often seen in the setting of pulmonary hypertension) and septal dyssynchrony due to ventricular interdependence.41 RVMW indices have the potential of delivering a more precise estimate of RV systolic function and may enhance the non-invasive understanding of the pathophysiology of patients with HF, pulmonary hypertension, and any other form of RV involvement, also providing a new tool to non-invasively characterize their response to therapies. Further validation of this approach  is necessary to support its application in the clinical practice and studies on its potential prognostic value are warranted.Recently, a non-invasive method to assess LV myocardial work  cine imaging with retrospective ECG gating allowing to fully cover the RV with 10–12 slices acquired in 5–12 short breath-holds. Alternatively, in patients unable to breath-hold or in patients with multiple arrhythmias, images can also be acquired in free-breathing real-time images, but with less spatial and temporal resolution. Recently, using parallel imaging techniques or under-sampling with iterative reconstruction it is also possible to acquire true 3D cine breath-hold imaging.Figure 4). Imaging in axial plane of multiple axially rotated long-axis slices may allow better identification of the tricuspid valve plane and more precise evaluation of RV volumes and EF than imaging in short-axis plane especially in congenital heart diseases. However, this requires separate acquisitions for the RV and lengthens the exam duration.The most commonly used approach for measurement of both RV and LV volumes is to acquire serial slices in short-axis view, covering both ventricles from apex to base , allowing only computation of longitudinal but not of circumferential or radial RV strains.46 Its application in the clinical practice is still limited due to reproducibility issues, for which machine learning models are being currently applied to improve the performance.CMR radiomics is also a novel technique for advanced image phenotyping based on the analysis of multiple quantifiers of shape and tissue texture, which has been applied also to the RV.45 allowing for assessment of pulmonary congestion in various situations of RV pressure overload.Finally, CMR also has the unique advantage of allowing RV myocardial tissue characterization. Fat infiltration in the RV, which is of particular interest in diagnosis or ARVC can be identified by T1 weighted black-blood spin echo imaging and confirmed by fat saturation techniques. RV fibrosis and necrosis may be present in a multitude of RV diseases and can be identified by late-gadolinium imaging (LGE) after injection of contrast. Also, it was also recently shown that after injection of contrast agents CMR also allows for estimation of pulmonary transit time and blood volume,The evaluation of RV function and structure by CMR has shown clinical relevance in multiple diseases, and particularly in congenital heart diseases, in ARVC, in pulmonary hypertension, in ischaemic diseases, and HF.47 The identification of fat or LGE is not currently part of ARVC diagnosis but may be particularly useful in orientating the diagnosis. Two studies demonstrated that presence of such anomalies had additional prognostic value over ECG findings in ARVC patients or mutation carriers.48CMR plays a particular role in determining the aetiology of RV dilatation. An example is the diagnosis and evaluation of severity of atrial septal defects. Also, by assessing global and regional RV dilatation and by revealing structural abnormalities such as fat infiltration and RV fibrosis CMR may confirm diagnosis of ARVC. The current task force criteria rely on CMR volume and EF measurement to define major and minor criterial for ARVC.49 Also, the repair of pulmonary regurgitation in tetralogy of Fallot was shown to improve RV dilatation and clinical status. Although patients improve RV volumes after repair of pulmonary regurgitation, normalization was achieved only when dilatation was not excessive, with indexed RV end-diastolic volumes > 150–170 mL/m2 and systolic volumes >80–90 m/m2.49 Therefore, CMR is currently recommended in all patients with TOF to serially follow RV volumes and eventually provide timely indication for surgery.CMR also plays a particular important role in various congenital heart diseases, from patients with either congenitally corrected transposition of RV or which have undergone atrial (Mustard or Senning) switch repair surgery to patients with complex congenital heart disease such as functional univentricular hearts with various palliation surgeries. In this setting the evaluation of RV fibrosis by LGE imaging has also been shown to provide prognostic value. CMR also plays a fundamental role in the follow-up of patients with tetralogy of Fallot (TOF). Indeed, relief of RVOT obstruction in TOF often involves disruption of pulmonary valve integrity, which leads to residual pulmonary regurgitation of various degrees in most patients. While this condition is often well tolerated, when severe pulmonary regurgitation is longstanding, it leads to progressive dilatation of the RV, causing RV failure and arrhythmias. Because of its high precision, and non-invasiveness CMR is ideally suited for longitudinal follow-up in patients with repaired TOF. It was shown that moderate or severe LV or RV systolic dysfunction by CMR, but not pulmonary regurgitation fraction or RV diastolic dimensions, is independently associated with impaired clinical status in long-term survivors of TOF repair.50 Similarly in other settings of tricuspid regurgitation, CMR also allows precise evaluation of RV dilatation and systolic function, which is of fundamental role to give surgery indication.Moreover, CMR also plays an important role Ebsteins’ anomaly. In this condition, which is characterized by severe tricuspid regurgitation due to anterior displacement of the septal leaflet of the tricuspid valve, it is particularly well suited to precisely distinguish the functional RV from the atrialized part of the RV and to measure their respective sizes.51 Similarly, several recent studies have also highlighted the role of CMR–RV function on outcome of cardiomyopathies and ischaemic heart disease (including RV infarction), as well as in both HF with preserved or reduced EF.52CMR was recently shown to play an important role in pulmonary hypertension. In this setting several studies have shown that RV function assessment by CMR predicts outcome and allows to evaluate response to therapy.Decades ago, radionuclide techniques have been the first imaging modalities used to provide accurate and reproducible measurements of RV structure and function. Nowadays, nuclear imaging still plays a role in selected subgroup of patients, being able to assess RV perfusion and metabolism as well as morphology and EF, and therefore providing new opportunities for comprehensive evaluation of RV from a single study.53 SPECT equilibrium radionuclide angiography, due to its 3D view, improves spatial separation and resolution of cardiac chambers and has been shown to provide accurate and reproducible assessment of RV volumes and EF .53Assessment of RVEF using radionuclide techniques can be performed with either first pass (FPRNA) or equilibrium techniques , in which the radioisotopes in the blood pool can be imaged. Both these approaches have been extensively validated and, since RVEF is derived from end-systolic and end-diastolic count densities, it is independent of the geometric assumption required for other modalities.Nuclear-imaging techniques are emerging as clinically useful tools to assess RV perfusion and metabolism, to detect isolated RV infarction of RV or LV infarction with RV involvement. To improve visualization of RV, it’s possible to use a dedicated computed post-processing technique that can mask activity of LV. Previous studies showed that SPECT provides accurate detection of RV ischaemia in patients with suspected coronary artery disease, identified by reversible defects in the RV and interventricular septum and decreased RVEF during stress. Furthermore, PET allows non-invasive quantification of regional myocardial blood flow and coronary flow reserve in RV mostly using nitrogen-13 ammonia.54Finally, the evaluation of shift in fatty acid metabolism, assessed by SPECT with b-methyl-p-iodine-123 iodophenyl-pentadecanoid acid (BMIPP) and 99Tc sestamibi and by PET with F-18 2-fluoro 2-deoxyglucose (FDG) or carbon-11 labelled palmitate, demonstrated changes in metabolism of RV in response to various stimuli, in particular in patients with RV pressure overload.Although nuclear assessment of the RV cannot be considered as the first-choice imaging modality, in selected clinical situations, it can overcome limitations of other techniques  or replace other modalities, when they are not indicated, as in the case of CMR in patients with implantable devices.55 of particular interest for patients undergoing CT for other clinical indications, such percutaneous intervention of the tricuspid valve or congenital defects or arrhythmias ablation. However, a retrospective ECG-gated acquisition throughout the cardiac cycle is required and ECG-tube current modulation is often implemented to minimize radiation exposure. Previous studies that compared CT measurements of RV volume and function with CMR as the reference standard, showed variable results in terms of agreement,24 partially due to the difference in RV segmentation methods.With the recent improvements in the temporal and spatial resolution of the scanners, cardiac CT can be used to assess RV volume and function,A systematic and thorough evaluation of RV size, shape, and function provides important diagnostic and prognostic information in most of patients with cardiovascular disease and should be performed by using in a complementary fashion the different imaging modalities available, knowing their strengths and weaknesses. For RV function assessment, echocardiography represents the first line imaging modality in most of patients, and correction of the various measurements for after-load (or the use of less load-dependent approaches) should be attempted, especially when an increase in pulmonary pressures is suspected. CMR, although considered the gold standard for RV dimension and function assessment, is often limited by time, costs, and availability, but should be performed particularly when echocardiography is not conclusive, when detailed anatomical information  are necessary and when tissue characterization is required. Cardiac CT is currently used to provide additional RV evaluation in patients undergoing CT for other clinical indications. Finally, nuclear imaging could be performed when information on RV perfusion and metabolism are of importance and the expertise is available.Conflict of interest: Nina Ajmone Marsan received speaker fees from GE Healthcare and Abbott Vascular and has been in the Medical Advisory Board of Philips Ultrasound. Other authors have no conflict of interest to disclose.Data availabilityNo new data were generated or analysed in support of this research.