New Conversion Formula Between B-Type Natriuretic Peptide and N-Terminal-Pro-B-Type Natriuretic Peptide　- Analysis From a Multicenter Study.

BACKGROUND: Although B-type natriuretic peptide (BNP) and N-terminal (NT)-proBNP are commonly used markers of heart failure, a simple conversion formula between these peptides has not yet been developed for clinical use.Methods and Results: A total of 9,394 samples were obtained from Nara Medical University, Jichi Medical University, and Osaka University. We randomly selected 70% for a derivation set to investigate a conversion formula from BNP to NT-proBNP using estimated glomerular filtration rate (eGFR) and body mass index (BMI); the remaining 30% was used as the internal validation set and we used a cohort study from Nara Medical University as an external validation set. Multivariate linear regression analysis revealed a new conversion formula: log NT-proBNP = 1.21 + 1.03 × log BNP - 0.009 × BMI - 0.007 × eGFR (r2=0.900, P<0.0001). The correlation coefficients between the actual and converted values of log NT-proBNP in the internal and external validation sets were 0.942 (P<0.0001) and 0.891 (P<0.0001), respectively. We applied this formula to samples obtained from patients administered with sacubitril/valsartan. After treatment initiation, NT-proBNP levels decreased and actual BNP levels increased. However, the calculated BNP levels decreased roughly parallel to the NT-proBNP levels. CONCLUSIONS: This new and simple conversion formula of BNP and NT-proBNP with eGFR and BMI is potentially useful in clinical practice.

Early Detection of Worsening Heart Failure in Patients at Home Using a New Telemonitoring System of Respiratory Stability.

BACKGROUND: Early detection of worsening heart failure (HF) with a telemonitoring system crucially depends on monitoring parameters. The present study aimed to examine whether a serial follow up of all-night respiratory stability time (RST) built into a telemonitoring system could faithfully reflect ongoing deterioration in HF patients at home and detect early signs of worsening HF in a multicenter, prospective study.Methods and Results: Seventeen subjects with New York Heart Association class II or III were followed up for a mean of 9 months using a newly developed telemonitoring system equipped with non-attached sensor technologies and automatic RST analysis. Signals from the home sensor were transferred to a cloud server, where all-night RSTs were calculated every morning and traced by the monitoring center. During the follow up, 9 episodes of admission due to worsening HF and 1 episode of sudden death were preceded by progressive declines of RST. The receiver operating characteristic curve demonstrated that the progressive or sustained reduction of RST below 20 s during 28 days before hospital admission achieved the highest sensitivity of 90.0% and specificity of 81.7% to subsequent hospitalization, with an area under the curve of 0.85. CONCLUSIONS: RST could serve as a sensitive and specific indicator of worsening HF and allow the detection of an early sign of clinical deterioration in the telemedical management of HF.

Long-term outcomes of autologous skeletal myoblast cell-sheet transplantation for end-stage ischemic cardiomyopathy.

We evaluated the cardiac function recovery following skeletal myoblast cell-sheet transplantation and the long-term outcomes after applying this treatment in 23 patients with ischemic cardiomyopathy. We defined patients as "responders" when their left ventricular ejection fraction remained unchanged or improved at 6 months after treatment. At 6 months, 16 (69.6%) patients were defined as responders, and the average increase in left ventricular ejection fraction was 4.9%. The responders achieved greater improvement degrees in left ventricular and hemodynamic function parameters, and they presented improved exercise capacity. During the follow-up period (56 ± 28 months), there were four deaths and the overall 5-year survival rate was 95%. Although the responders showed higher freedom from mortality and/or heart failure admission (5-year, 81% versus 0%; p = 0.0002), both groups presented an excellent 5-year survival rate (5-year, 93% versus 100%; p = 0.297) that was higher than that predicted using the Seattle Heart Failure Model. The stepwise logistic regression analysis showed that the preoperative estimated glomerular filtration rate and the left ventricular end-systolic volume index were independently associated with the recovery progress. Approximately 70% of patients with "no-option" ischemic cardiomyopathy responded well to the cell-sheet transplantation. Preoperative renal and left ventricular function might predict the patients' response to this treatment.

Heart Failure Association, Heart Failure Society of America, and Japanese Heart Failure Society Position Statement on Endomyocardial Biopsy.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumors. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved the diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (1) an overview of the practical approach to EMB, (2) an update on indications for EMB, (3) a revised plan for heart transplant rejection surveillance, (4) the impact of multimodality imaging on EMB, and (5) the current clinical practice in the worldwide use of EMB.

Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure.

In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as follows. At-risk for HF (Stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). The classification includes HF with reduced EF (HFrEF): HF with an LVEF of ≤40%; HF with mildly reduced EF (HFmrEF): HF with an LVEF of 41% to 49%; HF with preserved EF (HFpEF): HF with an LVEF of ≥50%; and HF with improved EF (HFimpEF): HF with a baseline LVEF of ≤40%, a ≥10-point increase from baseline LVEF, and a second measurement of LVEF of >40%.

Relationship of Central Venous Pressure to Body Fluid Volume Status and Its Prognostic Implication in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Although central venous pressure (CVP) is a surrogate measure of preload in patients with acute decompensated heart failure (ADHF), it is a multifactorial index influenced not only by fluid volume status, but also by cardiac pump function and other factors. We aimed to elucidate the individual pathophysiological factors of CVP elevation in patients with ADHF by assessing the relationship between CVP and extracellular fluid volume status (EVS). METHODS AND RESULTS: We quantified EVS in 100 patients with ADHF with the use of bioelectrical impedance analysis. CVP was also measured at the same time point. Subjects were categorized into tertiles according to their CVP-EVS ratios, and patient characteristics and clinical outcomes were compared among these tertiles. The upper-tertile group had a higher incidence of impaired right ventricular pump function, whereas the lower-tertile group had higher incidences of severe inflammation, hypoalbuminemia, and renal dysfunction. Patients in both the upper and lower tertiles had a significantly higher cardiac event rate than those in the middle tertile. CONCLUSIONS: The combined assessment of CVP and EVS provides insight into both the total volume status and distribution of body fluid in ADHF patients, and it may have applications in guiding decongestive therapy and improving prognostic predictions.

Diagnostic performance of coronary angiography utilizing intraprocedural 320-row computed tomography with minimal contrast medium.

Recently developed coronary angiography with intraprocedural 320-row computed tomography can be performed in a catheterization laboratory (XACT) by injecting contrast medium from a place close to the coronary arteries, thereby requiring a minimal amount of contrast medium. However, its clinical application has not yet been established. This study aimed to evaluate the diagnostic accuracy of XACT angiography with a minimal volume of contrast medium in patients with suspected coronary artery disease (CAD). A total of 167 coronary segments were analyzed in 14 patients (9 males, median age 70 years) with suspected CAD by XACT angiography with 7.5 ml of contrast medium and invasive coronary angiography (ICA) with standard techniques. The segmental-based diagnostic accuracy of XACT angiography in detecting stenosis of ≥ 50% and ≥ 75% and visualized by ICA was good (sensitivity: 74% and 62%, specificity: 99% and 99%, positive predictive value: 93% and 80%, and negative predictive value: 97% and 97%, respectively). These results suggest that XACT angiography with a very low amount of contrast medium may have strong clinical utility for screening coronary arteries in patients with renal dysfunction or undergoing clinical procedures such as pacemaker implantation.

Possible associations between palliative care conferences and positive outcomes when performing palliative care for patients with end-stage heart failure: a nationwide cross-sectional questionnaire survey.

Palliative care for end-stage heart failure should be provided by a multidisciplinary team. However, the influence of each occupational category on patients receiving palliative care for end-stage heart failure remains unclear. Thus, this study investigated the relationships between palliative care conferences and positive outcomes of palliative care for end-stage heart failure patients. We sent questionnaires to all cardiology training hospitals authorized by the Japanese Circulation Society (n = 1004); of these, responses from the directors at 554 institutions were analyzed. We divided the responding institutions into two groups according to their implementation of palliative care conferences for patients with end-stage heart failure. The institutions that had held such conferences (n = 223) had a larger number of hospital beds, beds in the cardiovascular department, and patients admitted to the cardiovascular department, compared with institutions that had not held these conferences (n = 321). The usage rates of opioids, non-steroidal anti-inflammatory drugs, and sedatives were significantly higher in institutions that held these conferences. Multivariate analysis revealed that nutritionists and medical social workers had greater involvement in the improvement of mental symptoms and ensuring that patients could stay where they wished, respectively. The presence of palliative care physicians, physical therapists, or pharmacists was associated with multiple positive outcomes. This study indicated that there are possible associations between palliative care conferences and positive outcomes when performing palliative care for patients with end-stage heart failure.

Nationwide Survey of Palliative Care for Patients With Heart Failure in Japan.

BACKGROUND: Palliative care for heart failure (HF) patients is recommended in Western guidelines, so this study aimed to clarify the current status of palliative care for HF patients in Japan.Methods and Results:A survey was sent to all Japanese Circulation Society-authorized cardiology training hospitals (n=1,004) in August 2016. A total of 544 institutions (54%) returned the questionnaire. Of them, 527 (98%) answered that palliative care is necessary for patients with HF. A total of 227 (42%) institutions held a palliative care conference for patients with HF, and 79% of the institutions had <10 cases per year. Drug therapy as palliative care was administered at 403 (76%) institutions; morphine (87%) was most frequently used. Among sedatives, dexmedetomidine (33%) was administered more often than midazolam (29%) or propofol (20%). Regarding the timing of end-of-life care, most institutions (84%) reported having considered palliative care when a patient reached the terminal stage of HF. Most frequently, the reason for the decision at the terminal stage was "difficulty in discontinuing cardiotonics." A major impediment to the delivery of palliative care was "difficulty predicting an accurate prognosis." CONCLUSIONS: This large-scale survey showed the characteristics of palliative care for HF in Japan. The present findings may aid in the development of effective end-of-life care systems.

Non-Ischemic Heart Failure With Reduced Ejection Fraction Is Associated With Altered Intestinal Microbiota.

BACKGROUND: Research suggests that heart failure with reduced ejection fraction (HFrEF) is a state of systemic inflammation that may be triggered by microbial products passing into the bloodstream through a compromised intestinal barrier. However, whether the intestinal microbiota exhibits dysbiosis in HFrEF patients is largely unknown.Methods and Results:Twenty eight non-ischemic HFrEF patients and 19 healthy controls were assessed by 16S rRNA analysis of bacterial DNA extracted from stool samples. After processing of sequencing data, bacteria were taxonomically classified, diversity indices were used to examine microbial ecology, and relative abundances of common core genera were compared between groups. Furthermore, we predicted gene carriage for bacterial metabolic pathways and inferred microbial interaction networks on multiple taxonomic levels.Bacterial communities of both groups were dominated by the Firmicutes and Bacteroidetes phyla. The most abundant genus in both groups wasBacteroides. Although α diversity did not differ between groups, ordination by ß diversity metrics revealed a separation of the groups across components of variation.StreptococcusandVeillonellawere enriched in the common core microbiota of patients, whileSMB53was depleted. Gene families in amino acid, carbohydrate, vitamin, and xenobiotic metabolism showed significant differences between groups. Interaction networks revealed a higher degree of correlations between bacteria in patients. CONCLUSIONS: Non-ischemic HFrEF patients exhibited multidimensional differences in intestinal microbial communities compared with healthy subjects.

Clinical Outcomes and Bioprosthetic Valve Function After Transcatheter Aortic Valve Implantation Under Dual Antiplatelet Therapy vs. Aspirin Alone.

BACKGROUND: Dual antiplatelet therapy (DAPT) is commonly used after transcatheter aortic valve implantation (TAVI); however, the supporting evidence is limited. To determine if aspirin alone is a better alternative to DAPT, we compared the outcomes of patients treated with DAPT or aspirin alone after TAVI.Methods and Results:We analyzed a total of 144 consecutive patients (92 females, mean age 83±6 years) who underwent implantation of a balloon-expandable transcatheter valve (SAPIEN or SAPIEN XT, Edwards Lifesciences). Patients were divided into DAPT (n=66) or aspirin-alone treatment groups (n=78). At 1 year after TAVI, the composite endpoint, which consisted of all-cause death, myocardial infarction, stroke, and major or life-threatening bleeding complications, occurred significantly less frequently (Kaplan-Meier analysis) in the aspirin-alone group (15.4%) than in the DAPT group (30.3%; P=0.031). Valve function assessed by echocardiography was similar between the 2 treatment groups with respect to effective orifice area (1.78±0.43 cm2in DAPT vs. 1.91±0.46 cm2in aspirin-alone group; P=0.13) and transvalvular pressure gradient (11.1±3.5 mmHg in DAPT vs. 10.3±4.1 mmHg in aspirin-alone group; P=0.31). CONCLUSIONS: Treatment with aspirin alone after TAVI had greater safety benefits and was associated with similar valve function as DAPT. These results suggest that treatment with aspirin alone is an acceptable regimen for TAVI patients.

Clinical Significance of Pulmonary Arterial Capacitance Calculated by Echocardiography in Patients With Advanced Heart Failure.

BACKGROUND: Advanced left heart failure (HF) often accompanies post-capillary pulmonary hypertension related to RV afterload. Although pulmonary arterial capacitance (PAC), a measure of pulmonary artery compliance, reflects right ventricular (RV) afterload, the clinical utility of PAC obtained by echocardiography (echo-PAC) is not well established in advanced HF.Methods and Results:We performed right heart catheterization in advanced HF patients (n=30), calculating echo-PAC as stroke volume/(tricuspid regurgitation pressure gradient-pulmonary regurgitation pressure gradient). The difference between the echo-PAC and catheter-measured PAC values was insignificant (0.21±0.17 mL/mmHg, P=0.23). Echo-PAC values predicted both pulmonary arterial wedge pressure (PAWP) ≥18 mmHg and pulmonary vascular resistance ≥3 Wood units (P=0.02, area under the curve: 0.88, cutoff value: 1.94 mL/mmHg). Next, we conducted an outcome study with advanced HF patients (n=72). Patients with echo-PAC <1.94 mL/mmHg had more advanced New York Heart Association functional class, higher B-type natriuretic peptide plasma levels, larger RV and lower RV fractional area change than those with echo-PAC ≥1.94 mL/mmHg. They also had a significantly higher rate of ventricular assist device implantation or death, even after adjustment for indices related to HF severity or RV function during a 1-year follow-up period (P<0.01). CONCLUSIONS: Decreased PAC as measured by echocardiography, indicating elevated PAWP and RV dysfunction, predicted poorer outcomes in patients with advanced HF.

Transtubular Potassium Concentration Gradient as a Surrogate Measure of Arterial Underfilling in Acute Decompensated Heart Failure.

BACKGROUND: The monitoring of tissue hypoperfusion and the subsequent neurohumoral activation (ie, arterial underfilling) during decongestion is important for the management of acute decompensated heart failure (ADHF). The transtubular potassium concentration gradient (TTKG) has been reported to be a marker of renal aldosterone bioactivity. This study tested the hypothesis that TTKG can be a surrogate of arterial underfilling in patients with ADHF. METHODS AND RESULTS: We measured TTKG at discharge in 100 ADHF patients. The primary outcome measure was the occurrence of tissue hypoperfusion events (defined according to the "Cold Modified 2014" definition criteria) within 1 month after discharge. The secondary outcome measure was the occurrence of cardiac death or ADHF readmission within 3 months after discharge. On receiver operating characteristic curve analysis, TTKG predicted tissue hypoperfusion events with high accuracy (C-statistic, 0.889) for a cut-off of 6.0. Multivariate Cox regression analyses demonstrated independent relationships between TTKG and both the primary and secondary outcomes. CONCLUSIONS: TTKG has utility as a surrogate of arterial underfilling, and spot TTKG at discharge may be a prognostic marker in ADHF patients. (Circ J 2016; 80: 1965-1970).

Cardiac AAV9 Gene Delivery Strategies in Adult Canines: Assessment by Long-term Serial SPECT Imaging of Sodium Iodide Symporter Expression.

Heart failure is a leading cause of morbidity and mortality, and cardiac gene delivery has the potential to provide novel therapeutic approaches. Adeno-associated virus serotype 9 (AAV9) transduces the rodent heart efficiently, but cardiotropism, immune tolerance, and optimal delivery strategies in large animals are unclear. In this study, an AAV9 vector encoding canine sodium iodide symporter (NIS) was administered to adult immunocompetent dogs via epicardial injection, coronary infusion without and with cardiac recirculation, or endocardial injection via a novel catheter with curved needle and both end- and side-holes. As NIS mediates cellular uptake of clinical radioisotopes, expression was tracked by single-photon emission computerized tomography (SPECT) imaging in addition to Western blot and immunohistochemistry. Direct epicardial or endocardial injection resulted in strong cardiac expression, whereas expression after intracoronary infusion or cardiac recirculation was undetectable. A threshold myocardial injection dose that provides robust nonimmunogenic expression was identified. The extent of transmural myocardial expression was greater with the novel catheter versus straight end-hole needle delivery. Furthermore, the authors demonstrate that cardiac NIS reporter gene expression and duration can be quantified using serial noninvasive SPECT imaging up to 1 year after vector administration. These data are relevant to efforts to develop cardiac gene delivery as heart failure therapy.

Endovascular aortic repair increases vascular stiffness and alters cardiac structure and function.

BACKGROUND: Endovascular aortic repair (EVAR) is performed in patients with thoracic or abdominal aortic aneurysm because it is less invasive than conventional open repair. However, the effects of EVAR on vascular and cardiac function remain to be clarified. METHODS AND RESULTS: We studied the effects of EVAR on several outcome variables in 40 consecutive patients undergoing EVAR for abdominal and/or thoracic aneurysm with preserved ejection fraction. Echocardiography and brachial-ankle pulse wave velocity (baPWV) data were collected before, 1 week, and 1 year after EVAR. Although no changes in blood pressure were found, baPWV, left ventricular mass index (LVMI), and left atrial volume index were significantly elevated at both post-op time periods after EVAR compared with baseline data. The changes in LVMI correlated with those in baPWV (R=0.32, P<0.05). Among the 22 patients who were successfully followed up, 13 showed deterioration in exercise tolerance 1 year after EVAR. Diastolic wall strain, an index for LV distensibility, was lower at baseline in patients with worsening exercise tolerance than in those with unchanged tolerance. CONCLUSIONS: EVAR increased vascular stiffness and induced LV hypertrophy and diastolic dysfunction without a corresponding elevation of blood pressure in the acute and chronic phases. In addition, low LV distensibility at baseline was associated with the impairment of exercise tolerance. EVAR-induced stiffness of arteries leads to limited clinical symptoms.