Mari Sakamoto

Non-linear Equation using Plasma Brain Natriuretic Peptide Levels to Predict Cardiovascular Outcomes in Patients with Heart Failure.

Brain natriuretic peptide (BNP) is the most effective predictor of outcomes in chronic heart failure (CHF). This study sought to determine the qualitative relationship between the BNP levels at discharge and on the day of cardiovascular events in CHF patients. We devised a mathematical probabilistic model between the BNP levels at discharge (y) and on the day (t) of cardiovascular events after discharge for 113 CHF patients (Protocol I). We then prospectively evaluated this model on another set of 60 CHF patients who were readmitted (Protocol II). P(t|y) was the probability of cardiovascular events occurring after >t, the probability on t was given as p(t|y) = −dP(t|y)/dt, and p(t|y) = pP(t|y) = αyβP(t|y), along with p = αyβ (α and β were constant); the solution was p(t|y) = αyβ exp(−αyβt). We fitted this equation to the data set of Protocol I using the maximum likelihood principle, and we obtained the model p(t|y) = 0.000485y0.24788 exp(−0.000485y0.24788t). The cardiovascular event-free rate was computed as P(t) = 1/60Σi=1,…,60 exp(−0.000485yi0.24788t), based on this model and the BNP levels yi in a data set of Protocol II. We confirmed no difference between this model-based result and the actual event-free rate. In conclusion, the BNP levels showed a non-linear relationship with the day of occurrence of cardiovascular events in CHF patients.

The impact of creating mathematical formula to predict cardiovascular events in patients with heart failure

Since our retrospective study has formed a mathematical formula, α = f(x1, …, x252), where α is the probability of cardiovascular events in patients with heart failure (HF) and x1 is each clinical parameter, we prospectively tested the predictive capability and feasibility of the mathematical formula of cardiovascular events in HF patients. First of all, to create such a mathematical formula using limited number of the parameters to predict the cardiovascular events in HF patients, we retrospectively determined f(x) that formulates the relationship between the most influential 50 clinical parameters (x) among 252 parameters using 167 patients hospitalized due to acute HF; the nonlinear optimization could provide the formula of α = f(x1, …, x50) which fitted the probability of the actual cardiovascular events per day. Secondly, we prospectively examined the predictability of f(x) in other 213 patients using 50 clinical parameters in 3 hospitals, and we found that the Kaplan–Meier curves using actual and estimated occurrence probabilities of cardiovascular events were closely correlated. We conclude that we created a mathematical formula f(x) that precisely predicted the occurrence probability of future cardiovascular outcomes of HF patients per day. Mathematical modelling may predict the occurrence probability of cardiovascular events in HF patients.

Elucidation of the Strongest Predictors of Cardiovascular Events in Patients with Heart Failure

Background In previous retrospective studies, we identified the 50 most influential clinical predictors of cardiovascular outcomes in patients with heart failure (HF). The present study aimed to use the novel limitless-arity multiple-testing procedure to filter these 50 clinical factors and thus yield combinations of no more than four factors that could potentially predict the onset of cardiovascular events. A Kaplan–Meier analysis was used to investigate the importance of the combinations. Methods In a multi-centre observational trial, we prospectively enrolled 213 patients with HF who were hospitalized because of exacerbation, discharged according to HF treatment guidelines and observed to monitor cardiovascular events. After the observation period, we stratified patients according to whether they experienced cardiovascular events (rehospitalisation or cardiovascular death). Findings Among 77,562 combinations of fewer than five clinical parameters, we identified 151 combinations that could potentially explain the occurrence of cardiovascular events. Of these, 145 combinations included the use of inotropic agents, whereas the remaining 6 included the use of diuretics without bradycardia or tachycardia, suggesting that the high probability of cardiovascular events is exclusively determined by these two clinical factors. Importantly, Kaplan–Meier curves demonstrated that the use of inotropes or of diuretics without bradycardia or tachycardia were independent predictors of a markedly worse cardiovascular prognosis. Interpretation Patients treated with either inotropic agents or diuretics without bradycardia or tachycardia were at a higher risk of cardiovascular events. The uses of these drugs, regardless of heart rate, are the strongest clinical predictors of cardiovascular events in patients with HF.

Prosthetic valve dysfunction 35 years after mitral valve replacement with a Starr-Edwards caged-disc valve

A 49-year-old man was admitted to our hospital with a chief complaint of dyspnea. He had a history of mitral valve replacement (MVR) with a Starr-Edwards (SE) caged-disc valve at the age of 14. Echocardiography revealed elevated trans-valvular pressure gradient of the mitral prosthetic valve with neither disk motion abnormality nor abnormal structure. Catheterization confirmed an elevation of the mean diastolic gradient of the mitral valve to 12.3 mmHg. Re-MVR was performed, and abnormal tissue attached to the cage of the valve and proliferating beneath the valve was observed. Histologic examination revealed them as fibrinous tissue and mild pannus proliferation, respectively. This rare case report focuses on long-term follow-up and the complication of a SE caged-disc valve. A SE caged-disc valve may become stenotic, only detected with a trans-valvular pressure gradient without any disk motion abnormality or abnormal structure during a prolonged follow-up period.

Does the pathophysiology of heart failure prime the incidence of cancer|[quest]|

Both chronic heart failure (CHF) and cancer are among the most frequent causes of death in developed countries. Given that CHF activates neurohumoral factors, such as cytokines, the pathophysiology of CHF could prime the onset or progression of cancer. We consecutively enrolled 5238 patients with CHF who had been hospitalized in the Department of Cardiovascular Medicine in our institute between 2001 and 2013. We followed these patients until April 2015. We examined the cohort of patients from our hospital and compared it with a control cohort derived from the 2008 cancer database ‘Monitoring of Cancer Incidence in Japan’ from the National Cancer Center, Japan. The incidence of cancer in CHF patients (198 cases out of the 5238 patients) was approximately four times higher than that in control patients (2.27% vs 0.59%, P<0.0001; 95% confidence interval, 1.89–2.71). When we omitted the patients whose cancer diagnosis occurred prior to their diagnosis of CHF, we still observed a significantly higher incidence of cancer in patients with CHF than in controls. Based on our results, we suggest that there is a strong correlation between the pathophysiology of CHF and cancer. Given that CHF could prime the onset of cancers, we recommend that clinicians should be vigilant regarding cancer comorbidity in patients with CHF.

MORE IMPAIRED DIASTOLIC FUNCTION OF LIGHT CHAIN AMYLOIDOSIS CONTRIBUTE TO POOR PROGNOSIS COMPARED WITH TRANSTHYRETIN AMYLOIDOSIS: RESULT FROM LONGITUDINAL STUDY OF BIOPSY-PROVEN CARDIAC AMYLOIDOSIS

Immunoglobulin light chain (AL) amyloidosis is associated with higher mortality than transthyretin (TTR) amyloidosis, however, few data exist regarding the relationship between difference of type of amyloidosis and cardiac mortality, especially in hemodynamic and echocardiographic parameters. We