Elevated blood bicarbonate levels and long-term adverse outcomes in patients with chronic heart failure.

AIMS: The bicarbonate (HCO3 -) buffer system is crucial for maintaining acid-base homeostasis and blood pH. Recent studies showed that elevated serum HCO3 - levels serve as an indicator of the beneficial effects of acetazolamide in improving decongestion in acute heart failure. In this study, we sought to clarify the clinical relevance and prognostic impact of HCO3 - in chronic heart failure (CHF). METHODS: This cohort study enrolled 694 hospitalized patients with CHF (mean age 68.6 ± 14.6, 62% male) who underwent arterial blood sampling and exhibited neutral pH ranging from 7.35 to 7.45. We characterized the patients based on HCO3 - levels and followed them to register cardiac events. RESULTS: Among the patients, 17.3% (120 patients) had HCO3 - levels exceeding 26 mmol/L. Patients presenting HCO3 - > 26 mmol/L were more likely to use loop diuretics and had higher serum sodium and lower potassium levels, but left ventricular ejection fraction did not differ compared with those with HCO3 - between 22 and 26 (379 patients) or those with HCO3 - < 22 mmol/L (195 patients). During a median follow-up period of 1950 days, Kaplan-Meier analysis revealed that patients with HCO3 - > 26 mmol/L had the lowest event-free survival rate from either cardiac deaths or heart failure-related rehospitalization (P < 0.01 and 0.03, respectively). In the multivariable Cox model, the presence of HCO3 - > 26 mmol/L independently predicted increased risks of each cardiac event with a hazard ratio of 2.31 and 1.69 (P < 0.01 and 0.02, respectively), while HCO3 - < 22 mmol/L was not associated with these events (hazard ratios, 0.99 and 1.19; P = 0.98 and 0.43, respectively). CONCLUSIONS: Elevated blood HCO3 - levels may signify enhanced proximal nephron activation and loop diuretic resistance, leading to long-term adverse outcomes in patients with CHF, even within a normal pH range.

Associations of the fibrosis-4 index with left atrial low-voltage areas and arrhythmia recurrence after catheter ablation: cardio-hepatic interaction in patients with atrial fibrillation.

Background: The relationship between liver fibrosis and left atrial (LA) remodeling in atrial fibrillation (AF) remains uncertain. We examined the associations between the fibrosis-4 (FIB4) index, an indicator of liver fibrosis, and both LA low-voltage areas (LVAs) on electroanatomic mapping and AF recurrence postablation. Methods: We recruited 343 patients who underwent radiofrequency catheter ablation (RFCA) or cryoballoon ablation (CBA) for AF. First, the association between the FIB4 index and LA LVAs (<0.5 mV) was evaluated in RFCA using electroanatomic mapping (n = 214). Next, the utility of a FIB4 index ≥1.3, recommended cut-off value of liver fibrosis, was verified to assess the risk for AF recurrence in CBA without additional LVA ablation (n = 129). Results: Patients with a FIB4 index ≥1.3 had a higher prevalence of LA LVAs (>5 cm2) compared to those without. Additionally, the quantitative size of LVAs showed a positive correlation with the FIB4 index (R = .642, p < .001). In multivariate logistic models, a FIB4 index ≥1.3 was related to the presence of LVAs after adjusting for LA diameter, right atrial end-systolic area, and nonparoxysmal AF (odds ratio 2.508; p = 0.039). In CBA, AF recurrence rate was 13.1% during 3-12 months postablation. In multivariate Cox models, a FIB4 index ≥1.3 was an important predictor of AF recurrence (hazard ratio 3.796; p = .037), suggesting that LVAs might be associated with AF recurrence after CBA. Conclusion: The FIB4 index was a novel predictor of the existence of LA LVAs on electroanatomic mapping and AF recurrence after CBA.

Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy.

BACKGROUND: The immune systems and chronic inflammation are implicated in the pathogenesis of dilated cardiomyopathy (DCM) and heart failure. However, the significance of neutrophil extracellular traps (NETs) in heart failure remains to be elucidated. METHODS: We enrolled consecutive 62 patients with heart failure with idiopathic DCM who underwent endomyocardial biopsy. Biopsy specimens were subjected to fluorescent immunostaining to detect NETs, and clinical and outcome data were collected. Ex vivo and in vivo experiments were conducted. RESULTS: The numbers of NETs per myocardial tissue area and the proportion of NETs per neutrophil were significantly higher in patients with DCM compared with non-DCM control subjects without heart failure, and the numbers of NETs were negatively correlated with left ventricular ejection fraction. Patients with DCM with NETs (n=32) showed lower left ventricular ejection fraction and higher BNP (B-type natriuretic peptide) than those without NETs (n=30). In a multivariable Cox proportional hazard model, the presence of NETs was independently associated with an increased risk of adverse cardiac events in patients with DCM. To understand specific underlying mechanisms, extracellular flux analysis in ex vivo revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of cardiomyocytes, while these effects were abolished when PAD4 (peptidyl arginine deiminase 4) in neutrophils was genetically ablated. In a murine model of pressure overload, NETs in myocardial tissue were predominantly detected in the acute phase and persisted throughout the ongoing stress. Four weeks after transverse aortic constriction, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4-deficient mice displayed preserved left ventricular ejection fraction without inducing NET formation. CONCLUSIONS: NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes.

Collagen Triple Helix Repeat-Containing Protein 1 Is a Novel Biomarker of Right Ventricular Involvement in Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension leads to right ventricular failure, which is a major determinant of prognosis. Circulating biomarkers for right ventricular function are poorly explored in pulmonary hypertension. This study aimed to clarify the significance of collagen triple helix repeat-containing protein 1 (CTHRC1) as a biomarker of right ventricular failure in pulmonary hypertension. METHODS: A monocrotaline-induced pulmonary hypertension rat model was used to evaluate right ventricular CTHRC1 expression and its relationship with fibrosis. Next, human plasma CTHRC1 levels were measured in controls (n = 20), pulmonary arterial hypertension (n = 46), and patients with chronic thromboembolic pulmonary hypertension (CTEPH) (n = 64) before the first and after the final balloon pulmonary angioplasty. RESULTS: CTHRC1 expression was higher in the right ventricles of rats with monocrotaline-induced pulmonary hypertension than in those of controls. CTHRC1 was colocalized with vimentin and associated with fibrosis in the right ventricles. Plasma CTHRC1 levels were higher in human patients with pulmonary arterial hypertension (P = 0.006) and CTEPH (P = 0.011) than in controls. Plasma CTHRC levels were correlated with B-type natriuretic peptide (R = 0.355, P < 0.001), tricuspid lateral annular peak systolic velocity (R = -0.213, P = 0.029), and right ventricular fractional area change (R = -0.225, P = 0.017). Finally, plasma CTHRC1 levels were decreased after the final balloon pulmonary angioplasty (P < 0.001) in CTEPH. CONCLUSIONS: CTHRC1 can be a circulating biomarker associated with right ventricular function and fibrosis in pulmonary hypertension and might reflect the therapeutic efficacy of balloon pulmonary angioplasty in CTEPH.

Heart Failure Post-Myocardial Infarction Promotes Mammary Tumor Growth Through the NGF-TRKA Pathway.

Background: Epidemiological investigations suggest that patients with heart failure have a higher incidence of cancer; however, the causal role of cardiac disease on cancer progression remains unclear. Objectives: This study aimed to investigate the impact and underlying mechanisms of myocardial infarction (MI)-induced heart failure on tumor cell growth. Methods: We generated a syngeneic mouse model by implanting mammary tumor-derived 4T1 cells into BALB/c mice with MI resulting from ligation of the left anterior descending artery. Results: Mice with MI exhibited increased tumor volume, tumor weight, and Ki67-positive proliferative cells in the tumor tissue compared with the sham-operated mice. Furthermore, RNA sequencing analysis in the tumor tissue revealed significant enrichment of pathways related to tumor progression, particularly the PI3K-AKT pathway in the MI mice. Upregulation of tropomyosin receptor kinase A (TRKA) phosphorylation, an upstream regulator of PI3K-AKT signaling, was observed in the tumor tissue of the MI mice. We also observed elevated levels of circulating nerve growth factor (NGF), a ligand of TRKA, and increased NGF expressions in the myocardium after MI. In in vitro experiments, NGF stimulation led to increased cell proliferation, as well as phosphorylation of TRKA and AKT. Notably, inhibition of TRKA by small interfering RNA or the chemical inhibitor GW441756 effectively blocked these effects. Administration of GW441756 resulted in the suppression of tumor volume and cell proliferation in the MI mice. Conclusions: Our study demonstrates that MI promotes mammary tumor growth through the NGF-TRKA pathway. Consequently, inhibiting TRKA could represent a therapeutic strategy for breast cancer patients concurrently experiencing heart failure after MI.

Predictive Value of Aortic Valve Calcium Volume Measured by Computed Tomography for Paravalvular Leakage After Transcatheter Aortic Valve Implantation.

Paravalvular leakage (PVL) is a complication of transcatheter aortic valve implantation (TAVI) for aortic stenosis, leading to an adverse prognosis. We investigated whether aortic valve calcium volume (Ca-Vol) measured by preoperative cardiac computed tomography had a predictive value for PVL after TAVI using a third-generation self-expandable valve.We retrospectively analyzed 59 consecutive patients who underwent TAVI using a third-generation self-expandable valve. We measured Ca-Vol in the aortic valve and each cusp (non-coronary cusp [NCC], right-coronary cusp [RCC], and left-coronary cusp [LCC]). We divided the patients into 2 groups: a PVL group (32.2%) and a non-PVL group (67.8%). Total Ca-Vol was significantly higher in the PVL group than in the non-PVL group (P < 0.001). Ca-Vol in each cusp was also significantly higher in the PVL group ([NCC] P < 0.001, [RCC] P = 0.001, [LCC] P < 0.001). Univariate logistic regression analysis for PVL indicated that the total and per-cusp Ca-Vols were predictors for PVL (total, odds ratio [OR] 4.0, P < 0.001; NCC, OR 12.5, P = 0.002; RCC, OR 16.0, P = 0.008; LCC, OR 44.5, P < 0.001).Receiver operating characteristic curve analysis of Ca-Vol for predicting PVL revealed the optimal cut-off values of Ca-Vol were 2.4 cm3 for the total, 0.74 cm3 for NCC, 0.73 cm3 for RCC, and 0.56 cm3 for LCC (area under the curve, 0.85, 0.79, 0.76, and 0.83, respectively).Preoperative total, NCC, RCC, and LCC calcium volumes were significant predictors for PVL after TAVI using third-generation self-expandable valves.

Calcium-Phosphorus Product Is Associated with Adverse Prognosis in Hospitalized Patients with Heart Failure and Chronic Kidney Disease.

It has been reported that high levels of calcium-phosphorus (Ca-P) product are an indicator of coronary calcification and mortality risk in patients undergoing chronic hemodialysis. In the present study, we aimed to evaluate the significance of Ca-P product to predict the prognosis of patients with heart failure (HF) and chronic kidney disease (CKD). We conducted a prospective observational study of 793 patients with decompensated HF and CKD, and measured the value of Ca-P product. The cut-off value was obtained from the survival classification and regression tree (CART) analysis to predict post-discharge all-cause mortality and/or worsening HF, and the patients were divided into 2 groups: a high group (Ca-P product > 28, n = 594) and a low group (Ca-P product ≤ 28, n = 199). We compared the patient baseline characteristics and post-discharge prognosis between the 2 groups. The age as well as the prevalence of male sex, ischemic etiology, and anemia were significantly higher in the low group than in the high group. In contrast, there was no difference in echocardiographic parameters between the 2 groups. In the Kaplan-Meier analysis (mean follow-up 1089 days), all-cause mortality and/or worsening HF event rates were higher in the low group than in the high group (log-rank P = 0.001). In the multivariable Cox proportional hazard analysis, lower Ca-P product was found to be an independent predictor of all-cause mortality and/or worsening HF (hazard ratio 0.981, P = 0.031). Lower Ca-P product predicts adverse prognosis in patients with HF and CKD.

Geriatric Nutritional Risk Index predicts bleeding event in patients with heart failure.

AIMS: We aimed to elucidate the association between malnutrition and the occurrence of bleeding events in patients with heart failure. METHODS AND RESULTS: We evaluated the nutritional status of patients with heart failure [n = 2044, median (inter-quartile range) age 69.0 (59.0-78.0) years, 1209 (59.1%) males] using the Geriatric Nutritional Risk Index (GNRI). The primary endpoint was a composite of bleeding events such as haemorrhagic stroke or gastrointestinal bleeding. According to the survival classification and regression tree analysis, the accurate cut-off point of GNRI for predicting the primary endpoint was 106.2. We divided the patients into two groups based on GNRI levels: high GNRI group (GNRI ≥ 106.2, n = 606, 29.6%) and low GNRI group (GNRI < 106.2, n = 1438, 70.4%). We compared the patients' characteristics and prognosis between the two groups. The low GNRI group was older [72.0 (63.0-79.0) vs. 63.0 (53.0-73.0) years, P < 0.001] and had a lower prevalence of male sex (56.9% vs. 64.5%, P = 0.001). There were no differences in the use of antiplatelet agents and anticoagulants between the two groups. Levels of B-type natriuretic peptide were higher [321.1 (123.3-667.4) vs. 111.6 (42.6-235.4) pg/mL, P < 0.001] and levels of haemoglobin were lower [12.4 (10.8-13.7) vs. 14.2 (12.9-15.4) g/dL, P < 0.001] in the low GNRI group. The Kaplan-Meier analysis demonstrated that bleeding event rates were higher in the low GNRI group (log-rank P < 0.001). The multivariable Cox proportional hazard analysis revealed that low GNRI (hazard ratio 1.952, 95% confidence interval 1.002-3.805, P = 0.049) was associated with bleeding events. CONCLUSIONS: Heart failure patients with poor nutritional status, determined by GNRI under 106.2, experienced high bleeding event rates. Comprehensive management is required to avoid bleeding event in those populations.

Acute coronary syndrome with severe coronary calcification in a patient with pseudo-pseudohypoparathyroidism.

A 40-year-old female with a history of steroid therapy for juvenile rheumatoid arthritis was brought to our hospital because of chest pain. A diagnosis of non-ST elevation myocardial infarction was made, and emergency coronary angiography revealed stenotic lesions with severe calcification in the left anterior descending artery and the right coronary artery. Percutaneous coronary intervention with rotational atherectomy followed by a drug-coated balloon was performed to the lesion in the left anterior descending artery. The patient had characteristic physical findings including short stature, a round face, and 'knuckle-dimple sign'. Whole-body computed tomography showed many ectopic calcifications, indicating Albright's hereditary osteodystrophy. Ellsworth-Howard test revealed that urinary cyclic adenosine monophosphate response was positive, thus a diagnosis of pseudo-pseudohypoparathyroidism (PPHP) was made. Here, we describe a rare case of PPHP complicated by acute coronary syndrome with severely calcified coronary arteries. Learning objective: Pseudo-pseudohypoparathyroidism (PPHP) presents with several characteristic physical findings and ectopic calcifications. Since PPHP involves coronary artery calcification as in the present case, it may be considered as a cause of coronary artery disease.

A Case of Giant Goiter Associated with Airway Stenosis Caused by Long-Term Intravenous Epoprostenol Therapy for Idiopathic Pulmonary Arterial Hypertension.

Idiopathic pulmonary arterial hypertension is a progressive and life-threatening disease with pulmonary vasculature remodeling, leading to right-sided heart failure. Epoprostenol (prostaglandin I2) is highly recommended for patients with severe pulmonary arterial hypertension (PAH) categorized by the World Health Organization as functional class III or IV. It has been reported that prostaglandin I2 analogs can cause thyroid gland swelling and abnormal thyroid function. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she began complaining of neck swelling and was diagnosed with Graves' disease. The patient's thyroid function was controlled by thiamazole and levothyroxine; nevertheless, her thyroid gland enlargement worsened as the epoprostenol dose was titrated. After 20 years, she developed respiratory failure with a giant goiter leading to airway stenosis, and she passed away. The pathological autopsy confirmed a massive goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension:its history and development, and regional medical cooperation in Fukushima.

Chronic thromboembolic pulmonary hypertension (CTEPH) is designated as an intractable disease by the Ministry of Health, Labour and Welfare of Japan, and has an extremely poor prognosis if untreated. Surgical pulmonary endarterectomy is the curative treatment for cases in which the organized thrombi are located in the central part of the pulmonary artery, but there had been no effective treatment for cases in which the thrombi are located in the peripheral part of the pulmonary artery. Recently, balloon pulmonary angioplasty (BPA), a transcatheter procedure to dilate stenotic or occluded lesions in the peripheral pulmonary artery, has been rapidly developed. Although BPA was once a globally abandoned procedure due to hemorrhagic complications, Japanese experts have improved the technique, and its safety and efficacy have been enhanced. As a result, BPA is now being reevaluated worldwide. This review describes the history and development of BPA in the treatment of CTEPH, as well as the status of this treatment in Fukushima Prefecture.

Prognostic Role of Circulating LTBP-2 in Patients With Dilated Cardiomyopathy: A Novel Biomarker Reflecting Extracellular Matrix LTBP-2 Accumulation.

BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening disease related to heart failure. Extracellular matrix proteins have an important role in the pathogenesis of DCM. Latent transforming growth factor beta-binding protein 2 (LTBP-2), a type of extracellular matrix protein, has not been investigated in DCM. METHODS: First, we compared plasma LTBP-2 levels in 131 patients with DCM who underwent endomyocardial biopsy and 44 controls who were matched for age and sex and had no cardiac abnormalities. Next, we performed immunohistochemistry for LTBP-2 on endomyocardial biopsy specimens and followed the DCM patients for ventricular assist device (VAD) implantation, cardiac death, and all-cause death. RESULTS: Patients with DCM had elevated plasma LTBP-2 levels compared with controls (P < 0.001). Plasma LTBP-2 levels were positively correlated with LTBP-2-positive fraction in the myocardium from the biopsy specimen. When patients with DCM were divided into 2 groups according to LTBP-2 levels, Kaplan-Meier analysis demonstrated that patients with high plasma LTBP-2 were associated with increased incidences of cardiac death/VAD and all-cause death/VAD. In addition, patients with high myocardial LTBP-2-positive fractions were associated with increased incidences of these adverse outcomes. Multivariable Cox proportional hazard analysis showed that plasma LTBP-2 and myocardial LTBP-2-positive fraction were independently associated with adverse outcomes. CONCLUSIONS: Circulating LTBP-2 can serve as a biomarker to predict adverse outcomes, reflecting extracellular matrix LTBP-2 accumulation in the myocardium in DCM.

Hepatic Venous Stasis Index Reflects Hepatic Congestion and Predicts Adverse Outcomes in Patients With Heart Failure.

Background It has been reported that the hepatic vein waveforms determined by abdominal ultrasonography can assess hepatic congestion in patients with heart failure (HF). However, the parameter that quantifies hepatic vein waveforms has not been established. We suggest the hepatic venous stasis index (HVSI) as the novel indicator to evaluate hepatic congestion quantitatively. To examine the clinical significance of HVSI in patients with HF, we aimed to clarify the associations of HVSI with the parameters of cardiac function and right heart catheterization, as well as that with prognosis, in patients with HF. Methods and Results We performed abdominal ultrasonography, echocardiography, and right heart catheterization in patients with HF (n=513). The patients were divided into 3 groups based on HVSI as follows: HVSI 0 (HVSI=0, n=253), low HVSI (HVSI 0.01-0.20, n=132), and high HVSI (HVSI>0.20, n=128). We examined the associations of HVSI with parameters of cardiac function and right heart catheterization and followed up for cardiac events defined as cardiac death or worsening HF. There was a significant increase in level of B-type natriuretic peptide, inferior vena cava diameter, and mean right atrial pressure with increasing HVSI. During the follow-up period, cardiac events occurred in 87 patients. In the Kaplan-Meier analysis, cardiac event rate increased across increasing HVSI (log-rank, P=0.002). Conclusions HVSI assessed by abdominal ultrasonography reflects hepatic congestion and right-sided HF and is associated with adverse prognosis in patients with HF.

Prognostic significance of spleen shear wave elastography and dispersion in patients with heart failure: the crucial role of cardio-splenic axis.

INTRODUCTION: The interaction between the heart and spleen plays a crucial role among cardiac and multiple organ networks, particularly in heart failure (HF). Ultrasound shear wave imaging is a non-invasive technology capable of quantifying tissue quality, but its significance in the spleen in patients with HF is poorly understood. METHODS AND RESULTS: This prospective observational study enrolled hospitalized 232 patients with HF undergoing abdominal ultrasonography. We used shear wave elastography (SWE) to assess spleen tissue elasticity and shear wave dispersion (SWD) to assess spleen tissue viscosity. Clinical, echocardiography, right heart catheterization, and outcome data were collected. Spleen SWE was negatively correlated with right ventricular fractional area change (R = - 0.180, P = 0.039), but not with right-sided pressure or congestion indices. When patients were divided into three groups based on tertile values of splenic parameters, Kaplan-Meier analysis demonstrated that patients with the highest spleen SWE and SWD had lower event-free survival rates from cardiac deaths and decompensated HF over a median 494-days follow-up period (P < 0.0001 and P < 0.0001, respectively). In a multivariable Cox proportional hazard model, both spleen SWE and SWD were independently associated with increased risks of adverse cardiac events (hazard ratio, 4.974 and 1.384; P = 0.003 and P < 0.0001). Mechanistically, we evaluated mRNA expressions of CD36, a monocyte/macrophage-associated molecule, in peripheral leukocytes, and found that enhanced spleen stiffness was associated with the upregulation of CD36 expressions. CONCLUSION: Share wave imaging of the spleen is useful for stratifying the prognosis of HF patients and may suggest a role of the cardio-splenic axis in HF pathogenies.

A case of COVID-19-associated fulminant myocarditis due to SARS-CoV-2 omicron BA.2 sub-lineage in an unvaccinated female.

COVID-19-associated myocarditis can be a lethal complication in previous variants, but it is not well understood in the Omicron variant. We present an unvaccinated case of COVID-19-associated fulminant myocarditis due to the Omicron BA.2 sub-lineage requiring mechanical circulatory support (MCS). A 66-year-old female without vaccination against SARS-CoV-2 was hospitalized due to COVID-19. On the next day, she was transferred to our hospital due to the development of fulminant myocarditis. After arrival, she was treated with Impella CP and venoarterial extracorporeal membrane oxygenation due to unstable hemodynamics. In addition to MCS, we treated her with inotropes, methylprednisolone, tocilizumab, and remdesivir. Left ventricular contraction gradually improved, and MCS was removed on day 8. Endomyocardial biopsy showed mild interstitial infiltration of CD3+-T lymphocytes and CD68+-macrophages with no remarkable necrosis or fibrosis. This case showed similar histological characteristics to COVID-19-associated myocarditis before the Omicron variant. The vaccination against the Omicron variant should be considered to prevent the development of severe illness, including fulminant myocarditis. Learning objective: Although the Omicron variant is thought to be generally less severe, COVID-19-associated fulminant myocarditis, as in this case, can occur. The vaccination against the Omicron variant should be considered to prevent from developing severe illness.

Persistent Hypochloremia Is Associated with Adverse Prognosis in Patients Repeatedly Hospitalized for Heart Failure.

BACKGROUND: Hypochloremia reflects neuro-hormonal activation in patients with heart failure (HF). However, the prognostic impact of persistent hypochloremia in those patients remains unclear. METHODS: We collected the data of patients who were hospitalized for HF at least twice between 2010 and 2021 (n = 348). Dialysis patients (n = 26) were excluded. The patients were divided into four groups based on the absence/presence of hypochloremia (<98 mmol/L) at discharge from their first and second hospitalizations: Group A (patients without hypochloremia at their first and second hospitalizations, n = 243); Group B (those with hypochloremia at their first hospitalization and without hypochloremia at their second hospitalization, n = 29); Group C (those without hypochloremia at their first hospitalization and with hypochloremia at their second hospitalization, n = 34); and Group D (those with hypochloremia at their first and second hospitalizations, n = 16). RESULTS: a Kaplan-Meier analysis revealed that all-cause mortality and cardiac mortality were the highest in Group D compared to the other groups. A multivariable Cox proportional hazard analysis revealed that persistent hypochloremia was independently associated with both all-cause death (hazard ratio 3.490, p < 0.001) and cardiac death (hazard ratio 3.919, p < 0.001). CONCLUSIONS: In patients with HF, prolonged hypochloremia over two hospitalizations is associated with an adverse prognosis.

Cancer therapeutics-related cardiovascular dysfunction: Basic mechanisms and clinical manifestation.

Although recent advances in cancer treatment improve cancer prognosis, cancer therapeutics-related cardiovascular dysfunction (CTRCD) significantly contributes to the global burden of cardiovascular disease. CTRCD causes two crucial issues: first, premature treatment interruption or discontinuation of chemotherapy; second, the development of congestive heart failure during and after cancer treatment. Thus, early detection and prompt treatment of CTRCD may improve the prognosis in cancer patients. This review covers representative anticancer drugs, including anthracyclines, human epidermal growth factor 2 inhibitors, tyrosine kinase inhibitors, proteasome inhibitors, and immune checkpoint inhibitors. We focus on the molecular mechanisms of CTRCD and various approaches to diagnosis, prevention, monitoring, and treatment.

Successful management of unstable angina in a ravulizumab-treated patient with paroxysmal nocturnal hemoglobinuria.

Ravulizumab is an anti-C5 antibody approved for treating paroxysmal nocturnal hemoglobinuria (PNH). In August 2019, a 77-year-old Japanese man with PNH, who had been on ravulizumab treatment for 2 years, was hospitalized for chest discomfort and malaise. Electrocardiography identified a right bundle block, and elevated serum troponin I and d-dimer suggested ischemic heart disease. Cardiac catheterization revealed severe stenosis in the left anterior descending coronary artery, and intracoronary stenting relieved his chest discomfort. The final diagnosis was unstable angina unrelated to ravulizumab, and the patient's ravulizumab treatment was uninterrupted with no significant complications of PNH. This case report highlights the importance of continuing complement inhibition therapy during acute coronary events.