When Is Cardiac Resynchronization Therapy with a Defibrillator Indicated in Patients with Heart Failure, Especially Elderly Patients?

One benefit of an implantable cardioverter-defibrillator is the prevention of sudden cardiac death (SCD). It is recommended for patients with a low left ventricular ejection fraction (LVEF). However, the choice of cardiac resynchronization therapy (CRT) with or without a defibrillator (CRT-D and CRT-P) in elderly patients is controversial. To understand the current situation for proper device selection, we investigated the impact of defibrillators on mortality in elderly patients with heart failure.Consecutive patients who underwent CRT implantation were retrospectively recruited. Baseline characteristics, all-cause mortality, cardiac death, and defibrillator implantation rates were investigated in patients aged > 75 or ≤ 75 years.A total of 285 patients (79 patients aged > 75 years) were analyzed. Elderly patients had more comorbidities, but a lower proportion had ventricular arrhythmia. During the mean follow-up of 47 months, 109 patients died (67 due to cardiac death). Kaplan-Meier analysis showed higher mortality in elderly patients (P = 0.0428) but no significant difference in cardiac death by age group (P = 0.7472). There were no significant differences in mortality between patients with CRT-D versus CRT-P (P = 0.3386).SCD was rare. A defibrillator had no significant impact on mortality. In elderly patients, comorbidities are common and related to mortality. The selection of CRT-D versus CRT-P should take those factors into account.

AV timing in pacemaker patients with first-degree AV block: which is preferable, intrinsic AV conduction or pacing?

Some patients with pacemakers present with first-degree atrioventricular (AV) block. To avoid right ventricular (RV) pacing, preserving intrinsic AV conduction as much as possible is recommended. However, there is no clear cutoff AV interval to determine whether intrinsic AV conduction should be preserved or RV pacing should be delivered. This study aimed to compare a pacing mode-preserving, intrinsic AV conduction with the DDD mode delivering RV pacing in terms of echocardiographic parameters in patients with first-degree AV block and to investigate whether RV pacing induces heart failure (HF). Stroke volume (SV) was measured to determine the optimal AV delay with the intrinsic AV conduction rhythm and the DDD pacing delivering RV pacing. Echocardiographic evaluation was performed for 6-month follow-up period. Seventeen patients were studied. At baseline, mean intrinsic PQ interval was 250 ± 40 ms. SV was greater with RV pacing with optimal AV delay of 160 ms than with intrinsic AV conduction rhythm in all patients. Therefore, pacemakers were set to the DDD to deliver RV pacing. During follow-up, seven patients developed HF. Mean baseline E/E' ratio in patients who developed HF (HF group) during RV pacing was higher than in patients without HF (non = HF group; 17.9 ± 8 versus 11.5 ± 2, P = 0.018) Even within HF group patients without a high baseline E/E' ratio, it increased with RV pacing (22.2 ± 6 versus 11.6 ± 2; P < 0.001). In patients with pacemaker and first-degree AV block, RV pacing with the optimal AV delay of 160 ms increased SV. However, the risk of HF may be increased with RV pacing if the E/E' ratio is > 15 during intrinsic AV conduction or RV pacing. RV pacing should be avoided in patients with high E/E' ratio under intrinsic AV conduction or RV pacing.

Clinical significance of the albumin-bilirubin score in patients with heart failure undergoing cardiac resynchronization therapy.

Despite emerging recognition of interactions between heart failure (HF) and liver dysfunction, the impact of cardiac hepatopathy on patients with HF undergoing cardiac resynchronization therapy (CRT) has not been fully elucidated. Albumin-bilirubin (ALBI) score is a new assessment of liver function. The relationship between liver dysfunction severity based on ALBI score and clinical outcomes of patients with HF receiving CRT is unclear. Clinical records of 274 patients who underwent CRT device implantation between March 2003 and October 2020 were retrospectively investigated. ALBI score was calculated based on serum albumin and total bilirubin levels obtained before CRT device implantation. Patients were divided into three groups based on ALBI score: first tertile (ALBI ≤ - 2.62, n = 91)), second tertile (- 2.62 < ALBI < - 2.13, n = 92), and third tertile (ALBI ≥ - 2.13, n = 91). The study endpoint was all-cause mortality. The third tertile group had more advanced NYHA functional class, lower hemoglobin levels, and higher total bilirubin, aspartate aminotransferase, γ-glutamyl transferase, and N-terminal Pro-B-type natriuretic peptide levels (all p < 0.05). The third tertile group also had a higher prevalence of moderate or severe tricuspid regurgitation and higher tricuspid regurgitation pressure gradient (all p < 0.05). CRT response rates were significantly lower in the third tertile group. During a median (interquartile range) follow-up of 30 (9-60) months, 104 (37.9%) patients died. The third tertile group had significantly higher rates of all-cause mortality (log-rank p < 0.001). Higher ALBI score was significantly associated with all-cause mortality, even after adjusting for clinically relevant factors, a conventional validated risk score, and echocardiographic parameters related to right HF (all p < 0.01). Higher ALBI score before CRT device implantation is associated with HF severity, hepatic congestion and impairment due to right HF, lower CRT response, and higher all-cause mortality in CRT recipients.

Bradyarrhythmia Suspected to be Associated with Sleep Apnea Syndrome.

Sleep apnea syndrome (SAS) is a condition in which apnea and hypoventilation at night cause hypoxemia and impaired wakefulness during the day, resulting in a general malaise and dozing. Sleep apnea has been implicated in the development of hypertension, ischemic heart disease, arrhythmia, heart failure, and cerebrovascular disease.1) Approximately 50% of patients with sleep-disordered breathing have an arrhythmia. In severe cases with an apnea-hypopnea index (AHI) of 30 or more, the frequency of arrhythmias during sleep is two to four times that of individuals without SAS. Bradyarrhythmias such as sinus bradycardia, sinus arrest, and atrioventricular block occurs at night in about 5%-10% of patients with sleep-disordered breathing.2)During nocturnal sleep, vagal excitation causes excessive muscle relaxation of the upper airway, leading to periodic airway diameter reduction, which increases snoring and obstructive apnea. As a result, hypoxemia is likely, further increasing vagal tone and leading to bradycardia. An increase in ventilation rate and volume quickly compensates for the decrease in arterial partial pressure of oxygen during apnea, which leads to new bradycardia due to a decrease in the partial pressure of oxygen in arterial blood, which suppresses vagal tone and respiration.3)We experienced a case of a 44-year-old patient with bradyarrhythmia that might be associated with SAS. After continuous positive airway pressure treatment, AHI decreased, and very long cardiac arrests resolved.

Gastrointestinal Bleeding From Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA Atrial Fibrillation Registry.

BACKGROUND: In the Japanese clinical setting, the prevalence, potential cofounders of gastrointestinal (GI) bleeding from anticoagulant therapy, including direct oral anticoagulants (DOACs) and warfarin, and prognosis after GI bleeding are unclear.Methods and Results:We examined about GI bleeding from anticoagulant therapy using data from the SAKURA AF Registry, a prospective multicenter registry in Japan. Among 3,237 enrollees, 48.8% (n=1,561) were warfarin users and 51.2% (n=1,676) DOAC users. GI bleeding was identified in 68 patients (2.1%). No incidental differences in GI bleeding were observed between the DOAC and warfarin users (32 [1.9%] patients [0.67 events per 100 person-years] vs. 36 [2.3%] patients [0.75 events per 100 person-years], respectively; P=0.43). Multivariate Cox proportional hazard model analysis revealed that creatinine (hazard ratio [HR] 1.379, 95% confidence interval [CI] 1.091-1.743 P=0.007) and hemoglobin (HR 0.814, 95% CI 0.705-0.941, P=0.005) remained independent determinants of GI bleeding. Patients experiencing GI bleeding events had a higher risk of all-cause death (18%) than those without GI bleeding (6%) (P=0.045). CONCLUSIONS: GI bleeding was strongly associated with anemia and renal impairment. Patients experiencing GI bleeding had higher risk for all-cause death than those without GI bleeding.

Association of renal resistance index and arterial stiffness on clinical outcomes in patients with mild-to-moderate renal dysfunction and presence or absence of heart failure with preserved ejection fraction.

The renal arterial resistance index (RI) and the brachial-ankle pulse wave velocity (baPWV) are known as indicators of renal vascular resistance/systemic vascular damage and systemic arterial stiffness. The clinical significance of those parameters on clinical outcomes is poorly known in patients with and without heart failure with preserved ejection fraction (HFpEF). Baseline clinical data and the RI assessed by renal Doppler data, baPWV were obtained in patients with (HFpEF group, n = 60) and without HFpEF (non-HFpEF group, n = 51) who had a reduced estimated glomerular filtration rate (eGFR) of > 30 and < 60 mL/min/1.73 m2). We investigated the association between the RI and baPWV and major clinical outcomes including hospitalization for heart failure, cardiovascular death, myocardial infarction or unstable angina or other cardiovascular events and death from another cause. The RI and baPWV were greater in the HFpEF group than in the non-HF group (0.75 ± 0.07 vs. 0.69 ± 0.08, p < 0.001; 2002 ± 430 vs. 1762 ± 300 cm/s, p = 0.001). The RI correlated significantly with baPWV in the HFpEF (r = 0.382, p = 0.003) and non-HFpEF groups (r = 0.414, p = 0.002). During the median follow-up period of 54 months, major clinical outcomes occurred in 41 (36.9%) patients. The RI value, statin use and the presence of HFpEF were major factors for predicting clinical outcomes by multivariate analysis. Among the patients who had mild-to-moderate renal dysfunction, an increased RI and baPWV were observed in HFpEF patients as compared to non-HFpEF patients, but the baPWV similarly correlated with the RI value regardless of HFpFE patients or not. The strong association between the high RI value and presence of HFpEF and major clinical outcomes, suggests that not only the presence of HFpEF but also the high RI value may help to identify the high-risk patients leading to poor clinical outcomes.

Narrower QRS may be enough to respond to cardiac resynchronization therapy in lightweight patients.

A prolonged QRS duration (QRSd) is promising for a response to cardiac resynchronization therapy (CRT). The variation in human body sizes may affect the QRSd. We hypothesized that conduction disturbances may exist in Japanese even with a narrow (< 130 ms)-QRS complex; such patients could be CRT candidates. We investigated the relationships between QRSd and sex and body size in Japanese. We retrospectively analyzed the values of 338 patients without heart failure (HF) (controls) and 199 CRT patients: 12-lead electrocardiographically determined QRSd, left ventricular diastolic and systolic diameters (LVDd and LVDs), body surface area (BSA), body mass index (BMI), and LVEF. We investigated the relationships between the QRSd and BSA, BMI, and LVD. The men's and women's BSA values were 1.74 m2 and 1.48 m2 in the controls (p < 0.0001), and 1.70 m2 and 1.41 m2 in the CRT patients (p < 0.0001). The men's and women's QRSd values were 96.1 ms and 87.4 ms in the controls (p < 0.0001), and 147.8 ms and 143.9 ms in the CRT group (p = 0.4633). In the controls, all body size and LVD variables were positively associated with QRSd. The CRT response rate did not differ significantly among narrow-, mid-, and wide-QRS groups (83.6%, 91.3%, 92.4%). An analysis of the ROC curve provided a QRS cutoff value of 114 ms for CRT responder. The QRSd appears to depend somewhat on body size in patients without HF. The CRT response rate was better than reported values even in patients with a narrow QRSd (< 130 ms). When patients are considered for CRT, a QRSd > 130 ms may not be necessary, and the current JCS guidelines appear to be appropriate.

Benefit of Rate Response with Closed-Loop Stimulation in Patients with Difficult Hemodialysis.

Rate-responsive pacing is known to improve quality of life (QOL) in patients with sick sinus syndrome and chronotropic incompetence. However, the sensors for rate response include accelerometers, closed-loop stimulation (CLS), and minute ventilation sensors (MV sensors), each of which has a different mode of action. For this reason, it is important to select appropriate sensors that match the daily habits and behavioral patterns of the patient. For example, young and active patients are expected to have a rate increase when an accelerometer is used, while elderly patients and patients with a physical disability who are only able to move slowly often have a poor response to the accelerometer. MV sensors are therefore better suited to these patients. Furthermore, CLS is considered effective for patients who require an increase in heart rate when at rest, for example, patients undergoing maintenance dialysis.We describe a representative case, demonstrating the effectiveness of closed-loop stimulation in a patient with hypotension during dialysis.

Clinical Outcomes of Off-Label Dosing of Direct Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA AF Registry.

BACKGROUND: Off-label dosing of direct oral anticoagulants (DOACs) is encountered clinically among patients with atrial fibrillation (AF), although data on the clinical outcomes of over- and under-dosing are lacking in Japan. Methods and Results: We examined the clinical outcomes of off-label DOAC dosing using the SAKURA AF Registry, a prospective multicenter registry in Japan. Among 3,237 enrollees, 1,676 under any of the 4 DOAC regimens were followed up for a median of 39.3 months: 746 (45.0%), appropriate standard-dose; 477 (28.7%), appropriate low-dose; 66 (4.0%), over-dose; and 369 (22.2%) under-dose. Compared with the standard-dose group, patients in the under- and over-dose groups were significantly older and had a higher stroke risk. After multivariate adjustment, stroke/systemic embolism (SE) and death events were equivalent between the standard- and under-dose groups, but major bleeding events tended to be lower in the under-dose group (hazard ratio [HR] 0.474, P=0.0739). Composite events (stroke/SE, major bleeding, or death) were higher in the over-dose than in the standard-dose group (HR 2.714, P=0.0081). CONCLUSIONS: Clinical outcomes were not worse for under-dose than for standard-dose users among patients with different backgrounds. Over-dose users, however, were at higher risk for all clinical events and required careful follow-up. Further studies are needed to clarify the safety and effectiveness of off-label DOAC dosing in Japan.

Three-Year Clinical Outcomes Associated With Warfarin vs. Direct Oral Anticoagulant Use Among Japanese Patients With Atrial Fibrillation　- Findings From the SAKURA AF Registry.

BACKGROUND: Although direct oral anticoagulants (DOACs) are widely used in Japanese patients with atrial fibrillation (AF), large-scale investigations into their use, with suitable follow-up times and rates, are lacking. Methods and Results: The SAKURA AF Registry is a prospective multicenter registry created to investigate therapeutic outcomes of oral anticoagulant (OAC) use in Japanese AF patients. We conducted a study involving 3,237 enrollees from 63 institutions in the Tokyo area being treated with any of 4 DOACs (n=1,676) or warfarin (n=1,561) and followed-up for a median of 39.3 months (range 28.5-43.6 months). Analyses of 1- and 2-year follow-up data available for 3,157 (97.5%) and 2,952 (91.2%) patients, respectively, showed no significant differences in rates of stroke or systemic embolism (SE), major bleeding, and all-cause mortality for DOAC vs. warfarin users (1.2 vs. 1.8%/year, 0.5 vs. 1.2%/year, and 2.1 vs. 1.7%/year, respectively). Under propensity score matching, the incidence of stroke or SE (P=0.679) and all-cause death (P=0.864) remained equivalent, but the incidence of major bleeding was significantly lower (P=0.014) among DOAC than warfarin users. CONCLUSIONS: A high follow-up rate allowed us to obtain reliable data on the status of OAC use and therapeutic outcomes among AF patients in Japan. Warfarin and DOACs appear to yield equivalent 3-year stroke and all-cause mortality rates, but DOACs appear to reduce the risk of major bleeding.

Patient Satisfaction with Direct Oral Anticoagulants and Warfarin.

The burden of anticoagulation treatment affects patient satisfaction, which in turn affects adherence to treatment. Thus, we must thoroughly understand the advantages of direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs)/warfarin given for stroke prevention in patients with atrial fibrillation (AF). We compared satisfaction with anticoagulation therapy between 654 DOAC and 821 warfarin users enrolled in the SAKURA AF Registry. Satisfaction was assessed by means of the Anti-Clot Treatment Scale (ACTS), which includes 12-item burdens and 3-item benefits scales, and the treatment satisfaction questionnaire for medication II (TSQM II), which includes 2-item effectiveness, 3-item side effects, 3-item convenience, and 2-item global satisfaction domains. There were no significant between-group differences in TSQM II convenience (67.6 ± 14.5 versus 68.9 ± 14.5, P = 0.280), effectiveness (65.0 ± 13.3 versus 66.0 ± 15.0, P = 0.422), side effects (93.6 ± 13.7 versus 92.8 ± 14.4, P = 0.067), and global satisfaction (64.7 ± 14.9 versus 66.0 ± 14.6, P = 0.407) scores. In contrast, although there was no significant between-group difference in the ACTS benefits scores (9.8 ± 3.1 versus 10.1 ± 3.2, P = 0.051), the ACTS burdens scores (54.5 ± 6.3 versus 52.7 ± 6.9, P < 0.0001) were significantly higher in the DOAC users, independent of age, sex, and DOAC type. We can expect greater burden satisfaction with anticoagulation treatment in patients given a DOAC versus VKA/warfarin. The reduced burden of treatment will translate to greater patient adherence to their treatment plans and a positive effect on clinical outcomes.

MRI Mode Programming for Safe Magnetic Resonance Imaging in Patients With a Magnetic Resonance Conditional Cardiac Device.

Although diagnostically indispensable, magnetic resonance imaging (MRI) has been, until recently, contraindicated in patients with an implantable cardiac device. MR conditional cardiac devices are now widely used, but the mode programming needed for safe MRI has yet to be established. We reviewed the details of 41 MRI examinations of patients with a MR conditional device. There were no associated adverse events. However, in 3 cases, paced beats competed with the patient's own beats during the MRI examination. We describe 2 of the 3 specific cases because they illustrate these potentially risky situations: a case in which the intrinsic heart rate increased and another in which atrial fibrillation occurred. Safe MRI in patients with an MR conditional device necessitates detailed MRI mode programming. The MRI pacing mode should be carefully and individually selected.

Assessment of Efficacy and Necessity of Routine Defibrillation Threshold Testing in Patients Undergoing Implantable Cardioverter-Defibrillator (ICD) Implantation.

Defibrillation threshold (DFT) testing is performed routinely in patients undergoing implantable cardioverter-defibrillator (ICD) implantation to verify the ability of the ICD to terminate ventricular fibrillation (VF). However, neither the efficacy nor the safety of DFT testing has been proven; thus, the necessity of such testing is controversial. We conducted a retrospective study of the efficacy of DFT testing, particularly with respect to long-term outcomes of ICD implantation.The study included 150 patients (125 men, 25 women, aged 59.0 ± 17.6 years) who underwent ICD or cardiac resynchronization therapy defibrillator implantation, with (n = 73) or without (n = 77) intraoperative DFT testing, between June 1996 and September 2007. VF was induced by delivery of a T-wave shock, and a 20-25-J shock was then delivered. If the 20-25-J shock failed to terminate VF, 30 J was delivered. We assessed whether undersensed VF events occurred during DFT testing and/or during patient follow-up and checked for any association between undersensing and delayed shock delivery. During DFT testing, fine VF was sensed, and shocks were delivered in a timely manner. Nevertheless, 2 patients in the DFT testing group died from VF within 3 years after device implantation.DFT testing, in comparison to non-DFT testing, appeared to have no influence on the long-term outcomes of our patients, suggesting that DFT testing at the time of ICD implantation is limited.

Dramatic Response to Cardiac Resynchronization Therapy With AV Delay Optimization in Narrow QRS Heart Failure.

Cardiac resynchronization therapy (CRT) has been shown to be effective for heart failure. However, as outlined in the AHA/ACC/HRS Appropriate Use Criteria, CRT is not strongly recommended for patients with a narrow QRS complex. We describe a case of dilated cardiomyopathy and narrow QRS complex in which we obtained a dramatic response to CRT by optimizing the atrioventricular (AV) delay. The patient was a 61-year-old man with intractable heart failure. Echocardiography showed a low ejection fraction of 22% but no dyssynchrony. Because he had been hospitalized many times for congestive heart failure despite ß-blocker and diuretic treatment, we decided to use CRT. However, after implantation of the CRT device, the QRS complex widened abnormally, and his symptoms worsened. He was re-admitted 2 months after CRT implantation. We examined the pacemaker status and optimized the AV delay to obtain a "narrow" QRS complex. The patient's condition improved dramatically after the AV delay optimization. His clinical status has been good, and there has been no subsequent hospitalization. Our case points to the effectiveness of CRT in patients with a narrow QRS complex and to the importance of AV optimization for successful CRT.

Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study.

Background: Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods: We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results: Not applicable. Conclusion: This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

A novel heart failure mice model of hypertensive heart disease by angiotensin II infusion, nephrectomy, and salt loading.

Although the mouse heart failure (HF) model of hypertensive heart disease (HHD) is useful to investigate the pathophysiology and new therapeutic targets for HHD, the model using simple experimental procedures and stable phenotypes has not been established. This study aimed to develop a novel mouse HF model of HHD by combining salt loading and uninephrectomy with ANG II infusion. Eight-week-old C57BL/6 male mice were treated with ANG II infusion (AT), ANG II infusion and uninephrectomy (AN), ANG II infusion and salt loading (AS), or ANG II infusion, uninephrectomy, and salt loading (ANS). Systolic blood pressure was significantly elevated and left ventricular (LV) hypertrophy was found in AT, AN, AS, and ANS mice, and there were no significant differences in those parameters between the four groups. At 6 wk after the procedures, only ANS mice showed significant decreases in LV fractional shortening and increases in lung weight with a high incidence. This phenotype was reproducible, and there were few perioperative or early deaths in the experimental procedures. Severe LV fibrosis was found in ANS mice. Oxidative stress was enhanced and small GTPase Rac1 activity was upregulated in the hearts of ANS mice. After the addition of salt loading and uninephrectomy to the ANG II infusion mouse model, cardiac function was significantly impaired, and mice developed HF. This might be a novel and useful mouse HF model to study the transition from compensated LV hypertrophy to HF in HHD.

Cardiac resynchronization therapy: Current status and near-future prospects.

Cardiac resynchronization therapy (CRT) has been established as a standard treatment for heart failure. The effectiveness of CRT has been shown in many clinical trials and realized in actual clinical practice. Nevertheless, underutilization of CRT is a major problem in the treatment of heart failure. One factor leading to underutilization is the existence of CRT non-responders. CRT non-response has been discussed for approximately 20 years, since CRT was introduced. Since the beginning, the CRT non-response rate has been reported to be 30%. However, we are now undergoing a major transformation in the thinking about CRT response. First, heart failure is a progressive disease. Like many medications for heart failure, CRT does not cure the underlying disease of heart failure. Considering the natural course of heart failure, it is easy to understand that there will definitely be non-responders. There might have been misunderstandings about how to determine CRT response. Although CRT is a treatment for heart failure, it does not cure heart failure or myocardial tissue damage. Instead, by correcting conduction disorders and dyssynchrony, it modifies factors that exacerbate heart failure, which contributes to improvement. In addition, it is important to realize that pacing is the only treatment for correcting conduction disorders. Thus, in theory, CRT is an essential treatment for heart failure at any stage, regardless of severity, when it is accompanied by conduction disorder. Here, we consider the current state of CRT and the causes of underutilization. Returning to the origin of CRT, reconsidering the effects of CRT and the thinking about response, and spreading a new way of thinking will lead to the proper utilization of CRT.

Prognostic value of the MELD-XI score in patients undergoing cardiac resynchronization therapy.

AIMS: Multi-organ dysfunction was recently reported to be a common condition in patients with heart failure (HF). The Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) score reflects liver and kidney function. The prognostic relevance of this score has been reported in patients with a variety of cardiovascular diseases who are undergoing interventional therapies. However, the relationship between the severity of hepatorenal dysfunction assessed by the MELD-XI score and the long-term clinical outcomes of HF patients receiving cardiac resynchronization therapy (CRT) has not been evaluated. METHODS AND RESULTS: Clinical records of 283 patients who underwent CRT implantation between March 2003 and October 2020 were retrospectively evaluated (mean age 67 ± 12, 22.6% female). Blood samples were collected before CRT implantation. Patients were divided into three groups based on tertiles of the MELD-XI score: first tertile (MELD-XI = 9.44, n = 95), second tertile (9.44 < MELD-XI < 13.4, n = 94), and third tertile (MELD-XI ≥ 13.4, n = 94). The primary endpoint was all-cause mortality. Compared with the other groups, the third tertile group exhibited significantly older age, higher prevalence of diabetes mellitus and hypertension, lower haemoglobin level, and higher N-terminal pro-brain natriuretic peptide level (all P < 0.05). The functional CRT response rate was also significantly lower in the third tertile group (P = 0.011). During a median follow-up of 30 months (inter-quartile range, 9-67), 105 patients (37.1%) died. Kaplan-Meier analysis revealed that patients with a higher MELD-XI score had a greater risk of all-cause mortality (log-rank test: P < 0.001). Even after adjustment for clinically relevant factors and a conventional risk score, the MELD-XI score was still associated with mortality (adjusted hazard ratio: 1.04, 95% confidence interval: 1.00-1.07, P = 0.014, and adjusted hazard ratio: 1.04, 95% confidence interval: 1.01-1.09, P = 0.005, respectively). A higher MELD-XI score was associated with a greater risk of all-cause mortality than a lower MELD-XI score regardless of whether a pacemaker or defibrillator was implanted (log-rank test: P = 0.010 and P < 0.001, respectively). CONCLUSIONS: Impaired hepatorenal function assessed by the MELD-XI score was associated with older age, higher prevalence of multiple co-morbidities, severity of HF, lower CRT response rates, and subsequent all-cause mortality in HF patients undergoing CRT implantation. These results suggest that the MELD-XI score can provide additional prognostic information and may be useful for improving risk stratification in this population.

What Are the Expectations for Cardiac Resynchronization Therapy? A Validation of Two Response Definitions.

BACKGROUND: The definition of response to cardiac resynchronization therapy (CRT) varies across clinical trials. There are two main definitions, i.e., echocardiographic response and functional response. We assessed which definition was more reasonable. METHODS: In this study of 260 patients who had undergone CRT, an echocardiographic response was defined as a reduction in a left ventricular end-systolic volume of greater than or equal to 15% or an improvement in left ventricular ejection fraction of greater than or equal to 5%. A functional response was defined as an improvement of at least one class category in the New York Heart Association functional classification. We assessed the response to CRT at 6 months after device implantation, based on each definition, and investigated the relationship between response and clinical outcomes. RESULTS: The echocardiographic response rate was 74.2%. The functional response rate was 86.9%. Non-responder status, based on both definitions, was associated with higher all-cause mortality. Cardiac death was only associated with functional non-responder status (hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.19-5.46, p = 0.0186) and heart failure hospitalization (HR 2.78, 95% CI, 1.29-5.26, p = 0.0111). CONCLUSION: After CRT implantation, the functional response definition of CRT response is associated with a higher response rate and better clinical outcomes than that of the echocardiographic response definition, and therefore it is reasonable to use the functional definition to assess CRT response.

Prognostic importance of the Controlling Nutritional Status (CONUT) score in patients undergoing cardiac resynchronisation therapy.

AIMS: Malnutrition is common and associated with worse clinical outcomes in patients with heart failure (HF). The Controlling Nutritional Status (CONUT) score is an integrated index for evaluating diverse aspects of the complex mechanism of malnutrition. However, the relationship between the severity of malnutrition assessed by the CONUT score and clinical outcomes of HF patients receiving cardiac resynchronisation therapy (CRT) has not been fully clarified. METHODS: Clinical records of 263 patients who underwent pacemaker or defibrillator implantation for CRT between March 2003 and October 2020 were retrospectively evaluated. The CONUT score was calculated from laboratory data obtained before CRT device implantation. Patients were divided into three groups: normal nutrition (CONUT scores 0-1, n=58), mild malnutrition (CONUT scores 2-4, n=132) and moderate or severe malnutrition (CONUT scores 5-12, n=73). The primary endpoint was all-cause mortality. RESULTS: The moderate or severe malnutrition group had a lower body mass index, more advanced New York Heart Association functional class, higher Clinical Frailty Scale score, lower levels of haemoglobin and higher levels of N-terminal probrain natriuretic peptide (all p<0.05). In the moderate or severe malnutrition group, the CRT response rate was significantly lower than for the other two groups (p=0.001). During a median follow-up period of 31 (10-67) months, 103 (39.1%) patients died. Kaplan-Meier analysis revealed that the moderate or severe malnutrition group had a significantly higher mortality rate (log-rank p<0.001). A higher CONUT score and CONUT score ≥5 remained significantly associated with all-cause mortality after adjusting for previously reported clinically relevant factors and the conventional risk score (VALID-CRT risk score) (all p<0.05). CONCLUSIONS: A higher CONUT score before CRT device implantation was strongly associated with HF severity, frailty, lower CRT response rate and subsequent long-term all-cause mortality.