Appropriateness rating for the application of optimal medical therapy and multidisciplinary care among heart failure patients.

AIMS: Clinical guidelines for improving the patients' quality of care vary in clinical practice, particularly in super-aging societies, like in Japan. We aimed to develop a set of appropriate-use criteria (AUC) for contemporary heart failure (HF) management to assist physicians in decision making. METHODS AND RESULTS: With the use of the RAND methodology, a multidisciplinary writing group developed patient-based clinical scenarios in 10 selected key topics, stratified mainly by HF stage, age, and renal function. Nine nationally recognized expert panellists independently rated the clinical scenario appropriateness twice on a scale of 1-9, as 'appropriate' (7-9), 'may be appropriate' (4-6), or 'rarely appropriate' (1-3). Decisions were based on clinical evidence and professional opinions in the context of available resource use and costs. An interactive round-table discussion was held between the first and second ratings; the median score of the nine experts was then assigned to an appropriate-use category. Most clinical scenarios without strong evidence were evaluated as 'may be appropriate'. Frailty assessments in elderly patients (age ≥ 75 years), regardless of the HF stage, and advanced care planning in patients with stage C/D HF, regardless of age, were considered 'appropriate'. For HF with reduced ejection fraction, beta-blocker administration in elderly patients (age ≥ 75 years) with heart rate < 50 b.p.m. and mineral corticosteroid receptor antagonist use in elderly patients (age ≥ 75 years) with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 were considered 'rarely appropriate'. CONCLUSIONS: The HF management AUC provide a practical guide for physicians regarding scenarios commonly encountered in daily practice.

Prognostic Relevance of Liver Stiffness Assessed by Transient Elastography in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Acute decompensated heart failure (ADHF) is often accompanied by liver congestion through increased right atrial pressure (RAP). Liver stiffness (LS) assessed non-invasively using transient elastography is related to increased RAP and liver congestion in patients with general HF. We investigated the relationship of LS with clinical and echocardiographic variables and outcomes in patients with ADHF.Methods and Results:The subjects were 105 patients with ADHF admitted to hospital between October 2016 and June 2017. Patients were divided into 2 groups based on median LS at admission (low LS <8.8 kPa [n=52] vs. high LS ≥8.8 kPa [n=53]). Death from cardiovascular disease and readmission for HF were primary endpoints. Total bilirubin and γ-glutamyl transpeptidase levels, MELD-XI score, diameters of the inferior vena cava and right ventricle, and severity of tricuspid regurgitation were greater in the high LS group (all P<0.05). During a median (interquartile range) follow-up period of 153 (83-231) days, cardiac events occurred in 29 patients (54%) in the high LS group and in 13 (25%) in the low LS group (P=0.001). After adjusting for variables that influence organ congestion, a high LS ≥8.8 kPa was still significantly associated with cardiac events (all P<0.05). CONCLUSIONS: Increased LS measured by transient elastography reflects RAP elevation, hepatic congestion, and hepatic dysfunction. LS upon admission may be a useful prognostic marker in patients with ADHF.

Calcified Amorphous Tumor-Induced Acute Cerebral Infarction.

We report the case of a 38-year-old woman who was admitted for acute cerebral infarction linked to a cardiac calcified amorphous tumor (CAT) and related mitral annular calcification (MAC). The cardiac mass was removed, and mitral valve replacement surgery was performed. Pathological examination revealed an amorphous accumulation of degenerating material within both lesions, indicating that build-up of calcium along the mitral annulus and subsequent rupture of the fibrotic tissue may be involved in the initiation and progression of CAT.

The Impact of Bronchodilator Therapy on Systolic Heart Failure with Concomitant Mild to Moderate COPD.

In older adults, chronic obstructive pulmonary disease (COPD) is commonly associated with heart failure with reduced ejection fraction (HFrEF), and the high prevalence of this combination suggests that customized treatment is highly necessary in patients with COPD and HFrEF. To investigate whether the treatment of COPD with tiotropium, an anticholinergic bronchodilator, reduces the severity of heart failure in patients with HFrEF complicated by mild to moderate COPD, forty consecutive participants were randomly divided into two groups and enrolled in a crossover design study. Group A inhaled 18 µg tiotropium daily for 28 days and underwent observation for another 28 days. Group B completed the 28-day observation period first and then received tiotropium inhalation therapy for 28 days. Pulmonary and cardiac functions were measured on days 1, 29, and 56. In both groups, 28 days of tiotropium inhalation therapy substantially improved the left ventricular ejection fraction (from 36.3 ± 2.4% to 41.8 ± 5.9%, p < 0.01, in group A; from 35.7 ± 3.8% to 41.6 ± 3.8%, p < 0.01, in group B) and plasma brain natriuretic peptide levels (from 374 ± 94 to 263 ± 92 pg/mL, p < 0.01, in group A; from 358 ± 110 to 246 ± 101 pg/mL, p < 0.01, in group B). Tiotropium inhalation therapy improves pulmonary function as well as cardiac function, and reduces the severity of heart failure in patients with compensated HFrEF with concomitant mild to moderate COPD.

Complete Atrioventricular Block Complicating Mitral Infective Endocarditis Caused by Streptococcus Agalactiae.

BACKGROUND Infective endocarditis (IE) involving the mitral valve can but rarely lead to complete atrioventricular block (CAVB). CASE REPORT A 74-year-old man with a history of infective endocarditis caused by Streptococcus gordonii (S. gordonii) presented to our emergency room with fever and loss of appetite, which had lasted for 5 days. On admission, results of serologic tests pointed to severe infection. Electrocardiography showed normal sinus rhythm with first-degree atrioventricular block and incomplete right bundle branch block, and transthoracic echocardiography and transesophageal echocardiography revealed severe mitral regurgitation caused by posterior leaflet perforation and 2 vegetations (5 mm and 6 mm) on the tricuspid valve. The patient was initially treated with ceftriaxone and gentamycin because blood and cutaneous ulcer cultures yielded S. agalactiae. On hospital day 2, however, sudden CAVB requiring transvenous pacing occurred, and the patient's heart failure and infection worsened. Although an emergent surgery is strongly recommended, even in patients with uncontrolled heart failure or infection, surgery was not performed because of the Child-Pugh class B liver cirrhosis. Despite intensive therapy, the patient's condition further deteriorated, and he died on hospital day 16. On postmortem examination, a 2×1-cm vegetation was seen on the perforated posterior mitral leaflet, and the infection had extended to the interventricular septum. Histologic examination revealed extensive necrosis of the AV node. CONCLUSIONS This rare case of CAVB resulting from S. agalactiae IE points to the fact that in monitoring patients with IE involving the mitral valve, clinicians should be aware of the potential for perivalvular extension of the infection, which can lead to fatal heart block.

Association between plasma concentration of tolvaptan and urine volume in acute decompensated heart failure patients with fluid overload.

BACKGROUND: Tolvaptan (TLV) is a useful diuretic for acute decompensated heart failure (ADHF) with fluid overload, but its clinical response varies between patients. The aim of this study is to investigate whether plasma TLV concentrations correlate with the urine volume. METHODS: ADHF inpatients with evidence of fluid overload and total urine volume < 1,500 mL 24 h after initial intravenous administration of 40 mg furosemide were included in the study. On days 1-7, 7.5 mg oral TLV was added. The plasma TLV concentration, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured on days 1, 3 and 7. RESULTS: In the 52 patients who completed the protocol, the TLV concentration increased significantly from 67.6 ± 30.1 ng/mL on day 1 to 98.3 ± 39.6 ng/mL on day 3 to 144.8 ± 44.2 ng/mL on day 7, and the TLV concentration correlated with total urine volume on days 3 and 7 (r = 0.392, p < 0.01; r = 0.639, p < 0.001, respectively) but not on day 1. The urine volume correlated inversely with PRA and PAC (r = -0.618, p < 0.05; r = -0.547, p < 0.05, respectively). CONCLUSIONS: Plasma TLV concentrations correlated with the urine volume in late phase of treatment but not in early phase, which suggests that the effect of TLV may possibly be inhibited by renin-angiotensin-aldosterone system activity.

Spontaneous Remission in a Case of Giant Cell Myocarditis with Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Giant cell myocarditis (GCM) is rapidly progressive fulminant myocarditis causing death or requiring cardiac transplantation despite various immunosuppression therapies. CASE REPORT: A 28-year-old woman with progressive shortness of breath and palpitation following an upper respiratory infection was referred to our institution. On admission, transthoracic echocardiography (TTE) revealed a preserved left ventricular ejection fraction (LVEF) with mildly impaired LV diastolic function despite extensive ECG abnormalities, a mildly elevated troponin I concentration, and moderately elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) concentration. The diagnosis of GCM was made by endomyocardial biopsy (EMB), which revealed extensive fibrosis and inflammatory infiltration with multinucleated giant cells, as well as scattered eosinophils and lymphocytes in the absence of granuloma formation. However, the patient's symptoms began to improve without any specific therapy within 2 weeks, followed by the normalization of the ECG abnormalities, TTE-determined diastolic function, and troponin I and NT-pro-BNP concentrations. In sub-acute phase, 18F-fluorodeoxyglucose positron emission tomography showed no evidence of inflammation, and repeat EMB showed a significant decrease in the inflammatory infiltration and fibrosis, including absence of giant cells. Given the favorable clinical course, the patient was discharged without medications. At the 6-month follow-up, the patient had no LV functional impairment, cardiovascular events, or arrhythmia. CONCLUSIONS: We encountered a rare case of atypical GCM in which clinical and histologic remission was achieved without immunosuppression therapy. There seems to be a population of GCM patients who improve without immunosuppression therapy. In monitoring GCM patients, clinicians should be aware of the possibility of spontaneous remission.

Right heart function prediction of outcome in heart failure patients after catheter ablation for recurrent ventricular tachycardia.

OBJECTIVES: This study sought to determine the relevance of echocardiographic assessment focusing on right ventricular (RV) function to estimate prognosis in patients with heart failure (HF) and low left ventricular ejection fraction (LVEF) after ablation of ventricular tachycardia (VT). BACKGROUND: Recurrent VT is a marker of increased mortality in HF. Decision making remains challenging as some patients have a poor outcome despite successful catheter ablation of VT due to progressive biventricular HF. METHODS: Retrospective analysis was performed on data from 320 consecutive patients with HF and LVEF ≤40% who underwent ablation for recurrent VT between 1999 and 2008. Baseline clinical and echocardiographic data were analyzed in relation to survival. RESULTS: Among the 320 patients included, the mean age was 63 years, and 86% were male. During follow-up (median: 36 months) 127 patients (40%) died. RV dysfunction (hazard ratio [HR]: 1.4) and tricuspid regurgitation (TR) (HR: 1.7), together with age, New York Heart Association (NYHA) class, and serum creatinine, were independent predictors of death in a Cox regression model. Mortality was more than 2-fold higher in patients with at least moderate RV dysfunction and TR (HR: 2.6; p < 0.001). In patients with at least moderate RV dysfunction, TR, and estimated pulmonary arterial pressure ≥45 mm Hg, mortality was 61% at 2 years, compared with 16% in patients with good RV function without pulmonary hypertension (p < 0.0001). CONCLUSIONS: Despite low LVEF, patients with recurrent VT who had good RV function without elevated pulmonary pressures had a good prognosis after VT ablation. RV dysfunction, TR, and elevated pulmonary pressures identified a high-risk group of VT survivors in whom additional interventions may be necessary to improve survival.

The worst symptom as defined by patients during heart failure hospitalization: implications for response to therapy.

BACKGROUND: Patients perceive different symptoms of heart failure decompensation. It is not known whether the nature of the worst symptom relates to hemodynamic profile, response to therapy, or improvement in clinical trials. METHODS AND RESULTS: Patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial were hospitalized with advanced heart failure, ejection fraction ≤30%, and at least 1 sign and 1 symptom of elevated filling pressures. Visual analog scales (VAS) for symptoms were completed by 371 patients, who selected their worst symptom as difficulty breathing, fatigue, abdominal discomfort, or body swelling and also scored breathing and global condition at baseline and discharge. The dominant symptom identified was difficulty breathing by 193 (52%) patients, fatigue by 118 (32%), and abdominal discomfort and swelling each by 30 (8%) patients, combined as right-sided congestion for analysis. Clinical and hemodynamic assessments were not different between groups except that right-sided congestion was associated with more hepatomegaly, ascites, third heart sounds, and jugular venous distention. This group also had greater reduction in jugular venous distention and trend toward higher blood urea nitrogen after therapy. By discharge, average improvements in worst symptom and global score were 28 points and 24 points. For those with ≥10 points in improvement in worst symptom, 84% also improved global assessment ≥10 points. Initial fatigue was associated with less improvement (P = .002) during and after hospitalization, but improvements in symptom scores were sustained when re-measured during 6 months after discharge. CONCLUSION: In most patients hospitalized with clinical congestion, therapy will improve symptoms regardless of the worst symptom perceived, with more evidence of baseline fluid retention and reduction during therapy for worst symptoms of abdominal discomfort or edema. Improvement in trials should be similar when tracking worst symptom, dyspnea, or global assessment.

Mismatch of right- and left-sided filling pressures in chronic heart failure.

BACKGROUND: In patients with advanced heart failure (HF), elevated jugular venous pressure (JVP) is the most reliable sign of elevated left-sided filling pressures. However, discordance between right- and left-sided filling pressures (R-L mismatch) could lead to inadequate or excessive therapy guided by JVP. We determined the prevalence of R-L mismatch in the current era and investigated whether mismatch might be identified from clinical information. METHODS AND RESULTS: Right-sided heart catheterization was performed in 537 consecutive patients hospitalized with advanced HF during complete transplantation evaluation. Patients with high filling pressures were categorized as matched (right atrial pressure (RAP) ≥10 mm Hg and pulmonary wedge pressure (PCWP) ≥22 mm Hg), high-R mismatch (RAP ≥10 but PCWP <22 mm Hg) or high-L mismatch (PCWP ≥22 but RAP <10 mm Hg). Among all of the patients, 195 (36%) were matched low and 194 (36%) were matched high, and 148 (28%) had R-L mismatch. Among patients with high filling pressures, 194 (57%) were matched high and 82 (24%) had high-L and 66 (19%) high-R mismatch. Mismatches were not associated with differences in demographic or clinical data, including pulmonary and hepatic function, or severity of valvular regurgitation and right ventricular function by echo. However, among all patients with RAP ≥10 mm Hg, pulmonary artery systolic pressure (PASP) was higher in those patients with matched high left- and right-sided pressures (59 ± 12 mm Hg) versus high-R mismatch (41 ± 13 mm Hg; P < .0001). Similarly among all patients with low RAP, PASP was lower in patients with matched low right- and left-side pressures (33 ± 11 mm Hg) versus high-L mismatch (53 ± 13 mm Hg; P < .0001). CONCLUSIONS: R-L mismatch was present in >1 in 4 total patients, and >1 in 3 with elevated filling pressures. Regardless of clinical history, when empiric therapy to optimize volume status to JVP is not effective, additional measurement should be considered to establish the R-L relationship.

Impaired heart rate responses and exercise capacity in heart failure patients with paced baseline rhythms.

BACKGROUND: Conduction system disease and beta-blocker therapy are both common among heart failure (HF) patients and contribute to increasing reliance on paced rhythms. We hypothesized that many HF patients dependent on pacing have suboptimal heart rate responses and associated limitations in exercise capacity. METHODS AND RESULTS: We studied 122 HF patients (left ventricular ejection fractions ≤40%) referred for cardiopulmonary exercise testing, comparing those with pacing at baseline with those with native rhythms. The paced group (PG) had lower resting (71 ± 9 vs 75 ± 15 beats/min; P = .048) and peak heart rates (103 ± 22 vs 127 ± 27 beats/min; P < .0001). Although beta-blockers were prescribed with similar frequency in both groups (90% vs 85%), average dose was higher in the PG. Inotropic reserve (oxygen pulse) was similar in both groups (11.1 ± 3.3 vs 11.1 ± 3.4 mL/beat; P = .94), consistent with equivalent stroke volumes, but chronotropic incompetence was higher (95% vs 71%, P = .001) and peak VO(2) was lower (12.2 ± 3.4 vs 14.2 ± 4.1 mL/kg/min; P = .004) in the PG. CONCLUSIONS: Chronotropic incompetence and exercise capacity are worse in HF patients depending on paced heart rate responses. This has implications for quality of life as well as advanced therapy choices based on exercise capacity. Reevaluating beta-blocker dosing and optimizing pacemaker programming may therefore benefit the growing population of HF patients with device-dependent rhythms.

Right ventricular dysfunction during intensive pharmacologic unloading persists after mechanical unloading.

BACKGROUND: Right ventricular (RV) dysfunction is associated with adverse outcomes in heart failure (HF). Mechanical unloading should be more effective than pharmacologic therapy to reduce RV afterload and improve RV function. We compared RV size and function after aggressive medical unloading therapy to that achieved in the same patients after 3 months of left ventricular assist device (LVAD) support. METHODS AND RESULTS: We studied 20 patients who underwent isolated LVAD placement (9 pulsatile and 11 axial flow). Echocardiograms were performed after inpatient optimization with diuretic and inotropic therapy and compared with studies done after 3 months of LVAD support. After medical optimization right atrial pressure was 11 +/- 5 mm Hg, mean pulmonary artery pressure 36 +/- 11 mm Hg, pulmonary capillary wedge pressure 23 +/- 9 mm Hg, and cardiac index 2.0 +/- 0.6 L.min.m(2). Preoperatively, RV dysfunction was moderate (2.6 +/- 0.9 on a 0 to 4 scale), RV diameter at the base was 3.1 +/- 0.6 cm, and mid-RV was 3.5 +/- 0.6 cm. After median LVAD support of 123 days (92 to 170), RV size and global RV dysfunction (2.6 +/- 0.9) failed to improve, despite reduced RV afterload. CONCLUSIONS: RV dysfunction seen on intensive medical therapy persisted after 3 months of LVAD unloading therapy. Selection of candidates for isolated LV support should anticipate persistence of RV dysfunction observed on inotropic therapy.

Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure.

OBJECTIVES: We investigated the functional relationship between natriuretic peptides and adiponectin by performing both experimental and clinical studies. BACKGROUND: Natriuretic peptides are promising candidates for the treatment of congestive heart failure (CHF) because of their wide range of beneficial effects on the cardiovascular system. Adiponectin is a cytokine derived from adipose tissue with various cardiovascular-protective effects that has been reported to show a positive association with plasma brain natriuretic peptide (BNP) levels in patients with heart failure. METHODS: The expression of adiponectin messenger ribonucleic acid (mRNA) and its secretion were examined after atrial natriuretic peptide (ANP) or BNP was added to primary cultures of human adipocytes in the presence or absence of HS142-1 (a functional type A guanylyl cyclase receptor antagonist). Changes of the plasma adiponectin level were determined in 30 patients with CHF who were randomized to receive intravenous ANP (0.025 microg/kg/min human ANP for 3 days, n = 15) or saline (n = 15). RESULTS: Both ANP and BNP dose-dependently enhanced the expression of adiponectin mRNA and its secretion, whereas such enhancement was inhibited by pre-treatment with HS142-1. The plasma adiponectin level was increased at 4 days after administration of human ANP compared with the baseline value (from 6.56 +/- 0.40 microg/ml to 7.34 +/- 0.47 microg/ml, p < 0.05), whereas there was no change of adiponectin in the saline group (from 6.53 +/- 0.57 microg/ml to 6.55 +/- 0.56 microg/ml). CONCLUSIONS: Natriuretic peptides enhance adiponectin production by human adipocytes in vitro and even in patients with CHF, which might have a beneficial effect on cardiomyocytes in patients receiving recombinant natriuretic peptide therapy for heart failure.

Tiotropium, a novel muscarinic M3 receptor antagonist, improved symptoms of chronic obstructive pulmonary disease complicated by chronic heart failure.

A 77-year-old man was referred to hospital because of dyspnea on exertion. Although the patient had been fully medicated for chronic heart failure (CHF) caused by hypertensive heart disease, the echo-estimated left ventricular end-diastolic pressure (LVEDP) and brain natriuretic peptide (BNP) level had continued to be high for at least 2 years. Pulmonary functional examination revealed concomitant chronic obstructive pulmonary disease (COPD). Because beta-agonists were expected to exacerbate the CHF, inhalation of tiotropium, a non-beta-adrenergic bronchodilator and novel M3 muscarinic receptor antagonist, was used to treat the COPD. Not only did the pulmonary function improved but the treatment also safely ameliorated CHF signs including LVEDP and plasma BNP.

Unusual appearance of mitral annular calcification mimicking intracardiac tumor prompting early surgery.

Although mitral annular calcification (MAC) is usually easy to diagnose by transthoracic echocardiography, we experienced a rare case with MAC which looked like an intracardiac tumor. The patient who had been on chronic hemodialysis for 20 years was admitted to our hospital because of dyspnea. Transthoracic echocardiography showed a mass with severe calcification on the anterior mitral annulus and mean mitral gradient of 20 mm Hg. Because of the suspicion of the intracardiac calcified tumor that restricted mitral valve motion causing mitral obstruction, she underwent resection of the mass and mitral valve replacement. Pathological findings showed that the mass had a calcified envelope containing liquefied necrotic eosinophilic material with lympocytic infiltrate inside consistent with MAC. We should consider a possibility of MAC when we see a severe calcified mass attached to the mitral annulus in a patient on long-term hemodialysis.