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Hyperuricemia is an independent predictor of mortality in patients with chronic heart failure (CHF). To determine whether febuxostat, a urate-lowering agent, may improve clinical outcomes in CHF patients, we conducted a multicenter, prospective, randomized, open-label, blinded endpoint study with a treatment period of 24 weeks. We randomly assigned Japanese outpatients diagnosed with both CHF with reduced left ventricular ejection fraction (LVEF < 40%) and asymptomatic hyperuricemia (serum uric acid [UA] levels > 7.0 mg/dl and < 10.0 mg/dl) to either a febuxostat group (n = 51) or a control group (n = 50). The primary efficacy endpoint was the change in log-transformed plasma B-type natriuretic peptide (BNP) levels from baseline to week 24 (or at discontinuation). The secondary efficacy endpoints were the changes in LV systolic or diastolic function evaluated by echocardiography, New York Heart Association (NYHA) class, hemoglobin, and estimated glomerular filtration rate from baseline to week 24, and the change in log-transformed plasma BNP levels or serum UA levels from baseline to weeks 4, 8, 12, 16 and 20 (BNP) or weeks 4, 8, 12, 16, 20 and 24 (serum UA). The primary safety endpoints were occurrence of all-cause death or major cardiovascular events. The mean age of participants was 70 years; 14% were female. The febuxostat group and the control group did not differ with respect to the primary efficacy endpoint (p = 0.13), although the decrease in log-transformed plasma BNP levels from baseline to each of weeks 4, 8, 12, 16 and 20 was greater in the febuxostat group. There were no significant differences between the two groups in the primary safety endpoints or the secondary efficacy endpoints except reduced serum UA levels in the febuxostat group. Febuxostat did not reduce plasma BNP levels at week 24 in patients with CHF, but it appeared safe with no increase in major cardiovascular events and all-cause or cardiovascular mortality.
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Background: Ventricular arrhythmia (VA) is a life-threatening condition associated with cardiac sarcoidosis (CS). Right bundle branch block (RBBB) is a common conduction disorder in CS; however, its association with VA remains unknown. Objectives: This study aimed to investigate the relationship between RBBB and VA in patients with CS. Methods: This was a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients with Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of CS. Eligible patients were divided into two groups based on the presence or absence of RBBB at the time of diagnosis. The primary outcome was serious ventricular arrhythmia events (SVAEs), defined as a combination of sudden cardiac death and documented ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy. Results: Overall, 312 patients were studied, with 155 (49.7%) patients presenting with RBBB (RBBB group). Patients in the RBBB group had a higher prevalence of basal interventricular septum (IVS) thinning and prominent late gadolinium enhancement in the basal IVS on cardiac magnetic resonance imaging than those in the non-RBBB group. During a median follow-up of 3.0 years (IQR: 1.6-6.0 years), 66 patients experienced SVAE. In multivariable Cox regression analysis, the RBBB group was independently associated with a higher incidence of SVAEs (HR: 1.93 [95% CI: 1.14-3.28]; P = 0.015). Conclusions: In patients with CS, RBBB was an independent predictor of SVAEs, which might reflect the specific scar distribution that is predominant in the IVS.
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Background: Nonsteroidal immunosuppressive therapy is a potential therapeutic strategy for cardiac sarcoidosis. However, it is not recommended as an established treatment option. This study aimed to demonstrate the clinical outcomes of patients with cardiac sarcoidosis using nonsteroidal immunosuppressants through the ILLUstration of the Management and PrognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis multicenter retrospective registry. Methods: From a cohort of 512 patients, 426 who received corticosteroid therapy and 26 who received other immunosuppressive therapy were included for analysis. Clinical outcomes included all-cause death, fatal ventricular arrhythmic events (FVAE), and worsening heart failure with hospitalization. Results: Nonsteroidal immunosuppressants were used for retained fluorodeoxyglucose uptake in the heart (n = 14), corticosteroid side effects (n = 7), ventricular arrhythmia (n = 4), complete atrioventricular block (n = 2), worsened extracardiac sarcoidosis (n = 2), and other reasons (n = 2). They comprised of methotrexate (n = 20), cyclosporine (n = 2), cyclophosphamide (n = 2), and azathioprine (n = 3). After the addition of a nonsteroidal immunosuppressant, corticosteroids were reduced in 14 of 26 patients (5 [5-17] mg), although no patient discontinued corticosteroids. Of the 14 patients, decreased fluorodeoxyglucose uptake was observed in seven at follow-up. Clinical outcomes were observed in 11 patients (42.3 %). Detected events included all-cause death in five patients (19.2 %), FVAE in four (15.4 %), and worsening heart failure with hospitalization in five (19.2 %), with some overlap. Conclusions: Nonsteroidal immunosuppressive therapy may be a possible treatment option for patients who are not stabilized with corticosteroids alone or develop corticosteroid side effects.
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Improvements in therapies for heart failure with preserved ejection fraction (HFpEF) are crucial for improving patient outcomes and quality of life. Although HFpEF is the predominant heart failure type among older individuals, its prognosis is often poor owing to the lack of effective therapies. The roles of the spleen and bone marrow are often overlooked in the context of HFpEF. Recent studies suggest that the spleen and bone marrow could play key roles in HFpEF, especially in relation to inflammation and immune responses. The bone marrow can increase production of certain immune cells that can migrate to the heart and contribute to disease. The spleen can contribute to immune responses that either protect or exacerbate heart failure. Extramedullary hematopoiesis in the spleen could play a crucial role in HFpEF. Increased metabolic activity in the spleen, immune cell production and mobilization to the heart, and concomitant cytokine production may occur in heart failure. This leads to systemic chronic inflammation, along with an imbalance of immune cells (macrophages) in the heart, resulting in chronic inflammation and progressive fibrosis, potentially leading to decreased cardiac function. The bone marrow and spleen are involved in altered iron metabolism and anemia, which also contribute to HFpEF. This review presents the concept of an interplay between the heart, spleen, and bone marrow in the setting of HFpEF, with a particular focus on extramedullary hematopoiesis in the spleen. The aim of this review is to discern whether the spleen can serve as a new therapeutic target for HFpEF.
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Medula Óssea , Insuficiência Cardíaca , Hematopoese Extramedular , Baço , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/metabolismo , Hematopoese Extramedular/fisiologia , Baço/imunologia , Baço/metabolismo , Volume Sistólico/fisiologia , Miocárdio/metabolismo , Miocárdio/patologia , Miocárdio/imunologia , InflamaçãoRESUMO
Insufficient exposure to sunlight increases the risk of cardiovascular diseases. Hypertensive left ventricular (LV) hypertrophy exacerbates the risks of myocardial ischemia, ventricular arrhythmias, sudden cardiac death, and heart failure. This study aimed to determine the effects of ultraviolet (UV) irradiation on LV hypertrophy and mitochondrial morphology. Eighteen 7-week-old Dahl salt-sensitive (Dahl S) rats were categorized into three groups (n = 6 each) and fed sodium chloride (NaCl) diets, as follows: UV-irradiated [UVB+A (+), 8% NaCl], non-UV-irradiated [UV (-), 8% NaCl], and control [UV (-), 0.3% NaCl]. UV irradiation was administered at a low intensity of 100 mJ/cm2 for 6 days per week. Echocardiography and mitochondrial analyses were performed to evaluate LV hypertrophy and cardiomyocytes, and skin tissues were stained with hematoxylin and eosin to assess the pathological abnormalities at 12 weeks of age. LV mass was significantly reduced in the UVB+A (+) and control groups compared to that in the UV (-) group. Mitochondrial structural abnormalities in cardiomyocytes were observed only in the UV (-) group, but not in the UVB+A (+) or control group. Pathological skin abnormalities were not observed in any of the three groups. These findings suggest the potential benefits of UV irradiation in hypertensive models.
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Percutaneous mechanical circulatory support utilizing micro-axial flow pumps, such as the Impella group of devices, has become a life-saving technique in the treatment of refractory cardiogenic shock, with ever-increasing success rates. A 30-year-old man presented with acute decompensated heart failure and a severely reduced left ventricular ejection fraction (17%). Despite initial treatment with inotropic drugs and intra-aortic balloon pump support, his hemodynamic status remained unstable. Transition to Impella CP mechanical circulatory support was made on day 6 owing to persistently low systolic blood pressure. A significant decline in platelet count prompted suspicion of heparin-induced thrombocytopenia (HIT), later confirmed by positive platelet-activated anti-platelet factor 4/heparin antibody and a 4Ts score of 6 points. Argatroban was initially used as the purge solution, but owing to complications, a switch to Impella 5.0 and a bicarbonate-based purge solution (BBPS) was performed. Despite additional veno-arterial extracorporeal membrane oxygenation support on day 24, the patient, aiming for ventricular assist device treatment and heart transplantation, died from infection and multiple organ failure. Remarkably, the Impella CP continued functioning normally until the patient's demise, indicating stable Impella pump performance using BBPS. This case highlights the usefulness of BBPS as an alternative to conventional Impella heparin purge solution when HIT occurs.
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BACKGROUND: Myeloproliferative disorders, including monoclonal gammopathy of undetermined significance (MGUS), are often associated with amyloid light-chain (AL)-type cardiac amyloidosis (CA) but occasionally with wild-type transthyretin (ATTR) CA. In recent years, ATTR amyloidosis has attracted necessity for its reliable diagnosis with the addition of new treatments. Usually, both wild-type ATTR CA and AL-type CA present with marked cardiac hypertrophy, but renal dysfunction is milder in wild-type ATTR amyloidosis than in AL-type amyloidosis. Peripheral neurologic and autonomic symptoms such as numbness and dysesthesia are moderately present in AL-type amyloidosis, but less so in wild-type ATTR amyloidosis. Furthermore, the prognosis of ATTR-type amyloidosis is better than that of AL-type amyloidosis. CASE PRESENTATION: A 72-year-old man with cardiac hypertrophy presented with New York Heart Association functional class III dyspnea and leg edema. He had no history of carpal tunnel syndrome. An electrocardiogram showed atrial fibrillation and low voltage. The N-terminal pro-B-type natriuretic peptide level was 3310 pg/mL, and troponin T was elevated to 0.073 ng/mL. However, the glomerular filtration rate was only slightly decreased at 69.0 mL/min/1.73 m2. The serum free light-chain assay revealed a significant increase in the kappa chain, with positive results in Bence Jones proteins and serum immunoelectrophoresis. Bone marrow examination confirmed the diagnosis of monoclonal gammopathy of undetermined significance (MGUS). AL-type amyloidosis associated with a myeloproliferative disorder was suspected, and the prognosis was initially predicted to be poor, classified as Mayo stage IV. Contrary to this prognosis, the patient showed a slow progression of heart failure. Further imaging modalities and cardiac tissue findings confirmed the diagnosis as transthyretin type amyloidosis, and a favorable prognosis was established with the use of tafamidis. CONCLUSIONS: MGUS occasionally coexists with wild-type ATTR CA. Scant autonomic symptoms, mild renal dysfunction, and slow progression of heart failure might be clues that the CA associated with the myeloproliferative disease is wild-type ATTR amyloidosis.
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Backgrounds: Remote cardiac rehabilitation has proven useful in patients with cardiovascular disease; however, the methodology had not been fully validated. This study aimed to investigate the efficacy and safety of remote cardiac rehabilitation (RCR) with real-time monitoring and an ergometer using a bidirectional communication tool during the recovery phase of cardiovascular diseases. Methods: This multicenter, nonrandomized, interventional study was conducted at 29 institutions across Japan and enrolled patients with cardiovascular diseases who met indications for cardiac rehabilitation (CR) after receiving in-hospital treatment. The RCR group exercised at home using an ergometer and was monitored in real-time using interactive video and monitoring tools for 2-3 months. Educational instructions were provided concurrently through e-learning approaches. The safety of the RCR protocol and the improvement in peak oxygen consumption (VO2) were compared with those of the historical control group that participated in center-based CR. Results: Fifty-three patients from the RCR group were compared with 103 historical controls having similar background characteristics. No patients in RCR experienced significant cardiovascular complications while engaging in exercise sessions. After 2-3 months of RCR, the peak VO2 improved significantly, and the increases in the RCR group did not exhibit any significant differences compared to those in the historical controls. During follow-up, the proportion of patients whose exercise capacity increased by 10% or more was also evaluated; this finding did not indicate a statistically significant distinction between the groups. Conclusions: RCR during the recovery phase of cardiovascular diseases proved equally efficient and safe as center-based CR.
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Sepsis is caused by the body's dysregulated response to infection, which can lead to multiorgan injury and death. Patients with sepsis may develop acute cardiac dysfunction, termed septic cardiomyopathy, which is a global but reversible dysfunction of both sides of the heart. This narrative review discusses the mechanistic changes in the heart during septic cardiomyopathy, its diagnosis, existing treatment options regarding severity and course, and emerging treatment approaches. Although no standardized definition for septic cardiomyopathy exists, it is described as a reversible myocardial dysfunction that typically resolves within 7 to 10 days. Septic cardiomyopathy is often diagnosed based on electrocardiography, cardiac magnetic resonance imaging, biomarkers, and direct invasive and noninvasive measures of cardiac output. Presently, the treatment of septic cardiomyopathy is similar to that of sepsis, primarily focusing on acute interventions. Treatments for cardiomyopathy often include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. However, because of profound hypotension in sepsis, many cardiomyopathy treatments are contraindicated in patients with septic cardiomyopathy. Substantial efforts have been made to study the pathophysiological mechanisms and diagnostic options; however, the lack of a uniform definition for septic cardiomyopathy is challenging for physicians when considering treatments. Another challenge for physicians is that the treatment for septic cardiomyopathy has only focused on acute intervention, whereas the treatment for other cardiomyopathies has been provided on a long-term basis. A better understanding of the underlying mechanisms of septic cardiomyopathy may contribute to the development of a unified definition of the condition and novel treatment options.
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Cardiomiopatias , Sepse , Humanos , Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Sepse/diagnóstico , Sepse/complicações , Sepse/fisiopatologia , Sepse/terapia , EletrocardiografiaRESUMO
In this comprehensive state-of-the-art review, we provide an evidence-based analysis of current drug therapies for patients with heart failure with preserved ejection fraction (HFpEF) in the acute and chronic phases with concurrent hypertension. Additionally, we explore the latest developments and emerging evidence on the efficacy, safety, and clinical outcomes of common and novel drug treatments in the management of HFpEF with concurrent hypertension. During the acute phase of HFpEF, intravenous diuretics, mineralocorticoid receptor antagonists (MRAs), and vasodilators are pivotal, while in the chronic phase, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have proven effective in enhancing clinical outcomes. However, the use of calcium channel blockers in HFpEF with hypertension should be approached with caution, owing to their potential negative inotropic effects. We also explored emerging drug therapies for HFpEF, such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, angiotensin receptor-neprilysin inhibitor (ARNI), soluble guanylate cyclase (sGC) stimulators, novel MRAs, and ivabradine. Notably, SGLT2 inhibitors have shown promise in reducing heart failure hospitalizations and cardiovascular mortality in patients with HFpEF, regardless of their diabetic status. Additionally, ARNI and sGC stimulators have demonstrated potential in improving symptoms, functional capacity, and quality of life. Nonetheless, additional research is necessary to pinpoint optimal treatment strategies for HFpEF with concurrent hypertension. Furthermore, long-term studies are essential to assess the durability and sustained benefits of emerging drug therapies. Identification of novel targets and mechanisms underlying HFpEF pathophysiology will pave the way for innovative drug development approaches in the management of HFpEF with concurrent hypertension.
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Insuficiência Cardíaca , Hipertensão , Volume Sistólico , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Doença Crônica , Doença Aguda , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/farmacologiaRESUMO
Troponin (Tn) is a biomarker related to myocardial necrosis and is elevated in patients with myocarditis. This study aimed to investigate the association between cardiac Tn levels and the course of cardiac function, and prognosis in patients with fulminant myocarditis (FM) receiving percutaneous mechanical circulatory support (MCS).We used data from a multicenter retrospective registry, CHANGE PUMP 2, which included 216 patients with FM who required MCS. Among them, 141 patients whose Tn levels were available were analyzed. The patients were divided into low and high Tn groups according to the median values of TnT and TnI.The median age was 54 years, and 59.6% were male. The TnT and TnI on day 1 (at MCS initiation) were 3.8 (1.4-10.0) and 21.4 (8.4-68.8) ng/mL. While the left ventricular ejection fraction (LVEF) was similar on day 1 (25.0% versus 24.5%), the low Tn group showed better LVEF improvement on day 7 than the high Tn group (45.0% versus 25.3%, P < 0.001). LVEF at 1 year after admission was higher in the low Tn group (65.0% versus 59.7%, P = 0.039). The low Tn group had a better 90-day composite endpoint in death, durable left ventricular assist device implantation, and heart transplantation compared to the high Tn group (hazard ratio 0.47, 95% CI 0.23-0.95).Tn levels were associated with short- and long-term cardiac recovery and adverse outcomes in patients with FM receiving MCS due to cardiogenic shock.
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Coração Auxiliar , Miocardite , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico , Prognóstico , Estudos Retrospectivos , Choque Cardiogênico , Volume Sistólico , Resultado do Tratamento , Troponina , Função Ventricular Esquerda , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). METHODS AND RESULTS: We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used: a sex-specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49-7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04-4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. CONCLUSIONS: Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.
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Desfibriladores Implantáveis , Miocardite , Sarcoidose , Masculino , Humanos , Feminino , Função Ventricular Esquerda , Volume Sistólico , Estudos Retrospectivos , Sarcoidose/complicações , Sarcoidose/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/complicações , Desfibriladores Implantáveis/efeitos adversos , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Miocardite/complicaçõesAssuntos
Lipólise , Miocárdio , Humanos , Triglicerídeos/metabolismo , Miocárdio/metabolismo , MutaçãoRESUMO
AIMS: Higher left ventricular (LV) ejection fraction (EF) is related to unfavourable prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). The cause of this finding needs to be haemodynamically explained. Thus, we investigated this crucial issue from the perspective of LV-arterial (A) and right ventricular (RV)-pulmonary arterial (PA) coupling. METHODS AND RESULTS: Study patients were derived from our prospective cohort study of patients hospitalized due to acute decompensated HF and LVEF > 40%. We divided the 255 patients into three groups: HF with mildly reduced EF (HFmrEF), HFpEF with 50% ≤ LVEF < 60%, and HFpEF with LVEF ≥ 60%. We compared LV end-systolic elastance (Ees), effective arterial elastance (Ea), and Ees/Ea as a representative of LV-A coupling among groups and compared the ratio of tricuspid annular plane excursion to peak pulmonary arterial systolic pressure (TAPSE/PASP) as a representative of RV-PA coupling. All-cause death and readmission due to HF-free survival was worse in the group with a higher LVEF range. Ees/Ea was greater in HFpEF patients with LVEF ≥ 60% (2.12 ± 0.57) than in those with 50% ≤ LVEF < 60% (1.20 ± 0.14) and those with HFmrEF (0.82 ± 0.09) (P < 0.001). PASP was increased in the groups with higher LVEF; however, TAPSE/PASP did not differ among groups (n = 168, P = 0.17). In a multivariate Cox proportional hazard model, TAPSE/PASP but not PASP was significantly related to event-free survival independent of LVEF. CONCLUSION: HFpEF patients with higher LVEF have unfavourable prognosis and distinctive LV-A coupling: Ees/Ea is elevated up to 2.0 or more. Impaired RV-PA coupling also worsens prognosis in such patients. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000017725.
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Insuficiência Cardíaca , Artéria Pulmonar , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico por imagem , Masculino , Feminino , Volume Sistólico/fisiologia , Idoso , Estudos Prospectivos , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/diagnóstico por imagem , Prognóstico , Estudos de Coortes , Pessoa de Meia-Idade , Medição de Risco , EcocardiografiaRESUMO
Background: Clinical characteristics and the risk of cardiovascular events in patients with cardiac sarcoidosis (CS) according to the age of initial diagnosis are unclear. Methods: This study is a sub-analysis of the ILLUMINATE-CS registry, which is a retrospective, multicenter registry that enrolled patients with CS between 2001 and 2017. Patients were divided into three groups according to the tertile of age at the time of initial diagnosis of CS. The study compared the clinical background at the time of CS diagnosis and the incidence rate of cardiac events across age categories. Results: A total of 511 patients were analyzed in this study. In baseline, older patients were more likely to be female. History of hypertension, heart failure admission, and atrioventricular block were more common in patients with older age. There was no significant difference in the history of ventricular arrhythmias and left ventricular ejection fraction among all age groups. During a median follow-up period of 3.2 [IQR: 1.7-4.2] years, 35 deaths, 56 heart failure hospitalization, and 98 fatal ventricular arrhythmias was observed. The incidence rate of all-cause death and heart failure hospitalization was significantly higher in patients with older age (p < 0.001), while there was no significant difference in the incidence rate of ventricular arrhythmia among age groups (p = 0.74). Conclusions: In patients with CS, the risk of all-cause death and heart failure hospitalization was higher in older patients compared with other age groups; however, the risk of ventricular arrhythmia was comparable across all age groups.