Usefulness of hypochloremia at the time of discharge to predict prognosis in patients with chronic heart failure after hospitalization.

BACKGROUND: Hypochloremia has been suggested as a strong marker of mortality in hospitalized patients with heart failure (HF). This study aimed to clarify whether incorporating hypochloremia into pre-existing prognostic models improved the performance of the models. METHODS: We tested the prognostic value of hypochloremia (<97 mEq/L) measured at discharge in hospitalized patients with HF registered in the REALITY-AHF and NARA-HF studies. The primary outcome was 1-year mortality after discharge. RESULTS: Among 2496 patients with HF, 316 (12.6 %) had hypochloremia at the time of discharge, and 387 (15.5 %) deaths were observed within 1 year of discharge. The presence of hypochloremia was strongly associated with higher 1-year mortality compared to those without hypochloremia (log-rank: p < 0.001), and this association remained even after adjustment for the Get With the Guideline-HF risk model (GWTG-HF), anemia, New York Heart Association (NYHA) classification, and log-brain natriuretic peptide (BNP) [hazard ratio (HR) 1.64; p < 0.001]. Furthermore, adding hypochloremia to the prediction model composed of GWTG-HF + anemia + NYHA class + log-BNP yielded a numerically larger area under the curve (0.740 vs 0.749; p = 0.059) and significant improvement in net reclassification (0.159, p = 0.010). CONCLUSIONS: Incorporating the presence of hypochloremia at discharge into pre-existing risk prediction models provides incremental prognostic information for hospitalized patients with HF.

Right Ventricular to Pulmonary Artery Uncoupling Is Associated With Impaired Exercise Capacity in Patients With Transthyretin Cardiac Amyloidosis.

BACKGROUND: Exercise capacity is related to mortality and morbidity in heart failure (HF) patients. Determinants of exercise capacity in transthyretin cardiac amyloidosis (ATTR-CA) have not been established. METHODS AND RESULTS: This single-center study retrospectively evaluated ATTR-CA patients and patients with non-amyloidosis HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) (n=32 and n=51, respectively). In the ATTR-CA group, the median age was 75.5 years (interquartile range [IQR] 71.3-78.8 years), 90.6% were male, and the median left ventricular (LV) ejection fraction was 53.5% (IQR 41.4-65.6%). Cardiopulmonary exercise tests revealed a median peak oxygen consumption and anaerobic threshold of 15.9 (IQR 11.6-17.4) and 10.6 (IQR 8.5-12.0] mL/min/kg, respectively, and ventilatory efficiency (minute ventilation/carbon dioxide production [V̇E/V̇CO2] slope) of 35.5 (IQR 32.0-42.5). Among exercise variables, V̇E/V̇CO2slope has the greatest prognostic value. Univariate analysis revealed a significant correlation between V̇E/V̇CO2slope and age, LV global longitudinal strain, tricuspid annular plain systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and mixed venous oxygen saturation. In multivariate analyses, the TAPSE/PASP ratio was an independent predictor of V̇E/V̇CO2slope (95% confidence interval -44.5, -10.8; P=0.0067). In non-amyloidosis HFpEF/HFmrEF patients, the TAPSE/PASP ratio was not independently correlated with V̇E/V̇CO2slope. CONCLUSIONS: Right ventricular-pulmonary artery coupling estimated by the TAPSE/PASP ratio determines exercise capacity in ATTR-CA patients. This highlights the importance of early therapeutic intervention against underappreciated right ventricular dysfunction associated with ATTR-CA.

Impact of center volume on in-hospital mortality in adult patients with out­of­hospital cardiac arrest resuscitated using extracorporeal cardiopulmonary resuscitation: a secondary analysis of the SAVE-J II study.

Recently, patients with out-of-hospital cardiac arrest (OHCA) refractory to conventional resuscitation have started undergoing extracorporeal cardiopulmonary resuscitation (ECPR). However, the mortality rate of these patients remains high. This study aimed to clarify whether a center ECPR volume was associated with the survival rates of adult patients with OHCA resuscitated using ECPR. This was a secondary analysis of a retrospective multicenter registry study, the SAVE-J II study, involving 36 participating institutions in Japan. Centers were divided into three groups according to the tertiles of the annual average number of patients undergoing ECPR: high-volume (≥ 21 sessions per year), medium-volume (11-20 sessions per year), or low-volume (< 11 sessions per year). The primary outcome was survival rate at the time of discharge. Patient characteristics and outcomes were compared among the three groups. Moreover, a multivariable-adjusted logistic regression model was applied to study the impact of center ECPR volume. A total of 1740 patients were included in this study. The center ECPR volume was strongly associated with survival rate at the time of discharge; furthermore, survival rate was best in high-volume compared with medium- and low-volume centers (33.4%, 24.1%, and 26.8%, respectively; P = 0.001). After adjusting for patient characteristics, undergoing ECPR at high-volume centers was associated with an increased likelihood of survival compared to middle- (adjusted odds ratio 0.657; P = 0.003) and low-volume centers (adjusted odds ratio 0.983; P = 0.006). The annual number of ECPR sessions was associated with favorable survival rates and lower complication rates of the ECPR procedure.Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041577 (unique identifier: UMIN000036490).

External Validation of the CAST and rCAST Score in Patients With Out-of-Hospital Cardiac Arrest Who Underwent Extracorporeal Cardiopulmonary Resuscitation: A Secondary Analysis of the SAVE-J II Study.

BACKGROUND: Risk stratification is important in patients with post-cardiac arrest syndrome. The Post-Cardiac Arrest Syndrome for Therapeutic Hypothermia (CAST) and revised CAST (rCAST) scores have been well validated for predicting neurological outcomes, particularly for conventionally resuscitated patients with post-cardiac arrest syndrome. However, no studies have evaluated patients undergoing extracorporeal cardiopulmonary resuscitation. METHODS AND RESULTS: Adult patients with out-of-hospital cardiac arrest who underwent extracorporeal cardiopulmonary resuscitation were analyzed in this retrospective observational multicenter cohort study. We validated the accuracy of the CAST/rCAST scores for predicting neurological outcomes at 30 days. Moreover, we compared the predictive performance of these scores with the TiPS65 risk score derived from patients with out-of-hospital cardiac arrest who were resuscitated using extracorporeal cardiopulmonary resuscitation. A total of 1135 patients were analyzed. The proportion of patients with favorable neurological outcomes was 16.6%. In the external validation, the area under the receiver operating characteristic curve of the CAST score was significantly higher than that of the rCAST score (area under the receiver operating characteristic curve 0.677 versus 0.603; P<0.001), but there was no significant difference with that of the TiPS65 score (versus 0.633; P=0.154). Both CAST/rCAST risk scores showed good calibration (Hosmer-Lemeshow test: P=0.726 and 0.674), and the CAST score showed significantly better predictability in net reclassification compared with the rCAST (P<0.001) and TiPS65 scores (P=0.001). CONCLUSIONS: The prognostic accuracy of the CAST score was significantly better than that of other risk scores in net reclassification. The CAST score may help to predict neurological outcomes in patients with out-of-hospital cardiac arrest who undergo extracorporeal cardiopulmonary resuscitation. However, the predictive value of the CAST score was not sufficiently high for clinical application. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041577; Unique identifier: UMIN000036490.

Derivation and validation of a machine learning-based risk prediction model in patients with acute heart failure.

BACKGROUND: Risk stratification is important in patients with acute heart failure (AHF), and a simple risk score that accurately predicts mortality is needed. The aim of this study is to develop a user-friendly risk-prediction model using a machine-learning method. METHODS: A machine-learning-based risk model using least absolute shrinkage and selection operator (LASSO) regression was developed by identifying predictors of in-hospital mortality in the derivation cohort (REALITY-AHF), and its performance was externally validated in the validation cohort (NARA-HF) and compared with two pre-existing risk models: the Get With The Guidelines risk score incorporating brain natriuretic peptide and hypochloremia (GWTG-BNP-Cl-RS) and the acute decompensated heart failure national registry risk (ADHERE). RESULTS: In-hospital deaths in the derivation and validation cohorts were 76 (5.1 %) and 61 (4.9 %), respectively. The risk score comprised four variables (systolic blood pressure, blood urea nitrogen, serum chloride, and C-reactive protein) and was developed according to the results of the LASSO regression weighting the coefficient for selected variables using a logistic regression model (4 V-RS). Even though 4 V-RS comprised fewer variables, in the validation cohort, it showed a higher area under the receiver operating characteristic curve (AUC) than the ADHERE risk model (AUC, 0.783 vs. 0.740; p = 0.059) and a significant improvement in net reclassification (0.359; 95 % CI, 0.10-0.67; p = 0.006). 4 V-RS performed similarly to GWTG-BNP-Cl-RS in terms of discrimination (AUC, 0.783 vs. 0.759; p = 0.426) and net reclassification (0.176; 95 % CI, -0.08-0.43; p = 0.178). CONCLUSIONS: The 4 V-RS model comprising only four readily available data points at the time of admission performed similarly to the more complex pre-existing risk model in patients with AHF.

Lacosamide Intoxication-induced Wide QRS Tachycardia Successfully Treated with Veno-arterial Extracorporeal Membrane Oxygenation.

Lacosamide is an antiepileptic drug that acts on voltage-gated sodium channels and was approved as an antiepileptic by the Food and Drug Administration in 2008. Although the efficacy and safety of lacosamide have been established in many previous trials, some case reports have shown that it may lead to cardiovascular side effects, especially in patients with electrical conduction system disorders. We herein report a case of life-threatening cardiac arrhythmia caused by lacosamide intoxication that was successfully treated with veno-arterial extracorporeal membrane oxygenation.

Usefulness of Incorporating Hypochloremia into the Get With The Guidelines-Heart Failure Risk Model in Patients With Acute Heart Failure.

Although hypochloremia is strongly associated with adverse prognosis in acute heart failure (AHF), it is unknown whether incorporating hypochloremia into the preexisting risk model improves the model performance. We calculated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score in 1,428 patients with AHF (derivation cohort) and developed 2 risk scores incorporating brain natriuretic peptide (BNP) into the GWTG-HF risk score (GWTG-BNP risk score) and incorporating both BNP and hypochloremia (GWTG-BNP-Cl risk score). Hypochloremia was defined as <98 mmol/L. The external validation and comparison of model performance were performed in an independent group of 1,256 patients with AHF (validation cohort). All models were tested for in-hospital mortality. Hypochloremia was observed in 9.4% and 12.2% of the derivation and validation cohorts, respectively. Hypochloremia was an independent predictor of in-hospital mortality in the derivation cohort (odds ratio 2.02; p = 0.028). In the validation cohort, the GWTG-HF, GWTG-BNP, and GWTG-BNP-Cl risk scores demonstrated good discrimination (area under the curve: 0.742, 0.749, and 0.763, respectively). However, the GWTG-BNP-Cl risk score was more reliable than the GWTG-HF and GWTG-BNP risk scores in risk reclassification (net reclassification improvement: 0.491 and 0.408, respectively; p <0.01 for both). Moreover, this score demonstrated a good calibration of the GWTG-BNP-Cl model (Hosmer-Lemeshow test: p = 0.479). In conclusion, incorporating hypochloremia into the preexisting risk model improves the model performance.

Exercise-Based Cardiac Rehabilitation Improves Exercise Capacity Regardless of the Response to Cardiac Resynchronization Therapy in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: In patients with chronic heart failure with reduced ejection fraction (HFrEF), cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) and exercise-based cardiac rehabilitation (ECR) enhances exercise capacity. This study examined the relationship between the 2 responses.Methods and Results:Sixty-four consecutive HFrEF patients who participated in a 3-month ECR program after CRT were investigated. Patients were categorized according to a median improvement in peak oxygen uptake (PV̇O2) after ECR of 7% as either good (n=32; mean percentage change in PV̇O2[%∆PV̇O2]=23.2%) or poor (n=32; mean %∆PV̇O2=2.5%) responders. There was no significant difference in baseline characteristics between the good and poor responders, except for PV̇O2(51% vs. 59%, respectively; P=0.01). The proportion of good CRT responders was similar between the good and poor responders (%∆LVEF ≥10%; 53% vs. 47%, respectively; P=NS). Overall, there was no significant correlation between %∆LVEF after CRT and %∆PV̇O2after ECR. Notably, among poor CRT responders (n=32), the prevalence of atrial fibrillation (0% vs. 29%; P<0.03) and baseline PV̇O2(48% vs. 57%; P<0.05) were significantly lower among those with a good (n=15) than poor (n=17) response to ECR. CONCLUSIONS: In patients with HFrEF, good ECR and CRT responses are unrelated. A good PV̇O2response to ECR can be achieved even in poor CRT responders, particularly in those with a sinus rhythm or low baseline PV̇O2.

Development of Pulmonary Arterial Hypertension in a Patient Treated with Qing-Dai (Chinese Herbal Medicine).

Pulmonary arterial hypertension (PAH) is a rare, devastating disease, characterized by elevated pulmonary arterial pressure due to pulmonary microvascular obstruction, which can result in heart failure and death. PAH can be associated with exposure to certain drugs or toxins. We herein report a case in which PAH developed in a patient with refractory ulcerative colitis during treatment with "Qing-Dai," a Chinese herbal medicine. The patient's PAH improved after the discontinuation of Qing-Dai.

Cardiac arrest caused by landiolol in a patient in thyroid crisis.

In the acute phase of a thyroid crisis, the cardiovascular mortality rate is high and the likelihood of death and severity of heart failure increase significantly with an increasing heart rate. Thus, heart rate control is essential to avoid cardiac death. Propranolol has been used to manage thyroid crisis, but worsening heart failure and cardiac arrest have been previously reported when using propranolol in such cases. Thus, short-acting beta-blockers, such as landiolol and esmolol, are recommended, especially in patients with a low ejection fraction and severe heart failure. Our patient was a 49-year-old woman with a medical history of Graves' disease, who stopped attending her control visits 1 year earlier. She presented with symptoms of heart failure, atrial fibrillation, and tachycardia. She was diagnosed with thyroid storm and low-ejection-fraction heart failure. After 2.5 h of treatment with landiolol, her heart suddenly arrested. Cardiopulmonary resuscitation was performed immediately and circulation was re-established. After receiving treatment for the thyroid crisis and heart failure, she was discharged without any sequelae. To the best of our knowledge, cardiac collapse caused by landiolol has not been previously reported. We wish to emphasize the importance of close hemodynamic monitoring when using landiolol in such cases. .