Kenichi Kusuhara

The synergistic combined effect of anemia with high plasma levels of B-type natriuretic peptide significantly predicts an enhanced risk for major adverse cardiac events

The prevalence of anemia in patients with heart failure (HF) increases according to disease severity as a consequence of renal insufficiency, cytokine production, plasma volume expansion, and/or malnutrition. B-type natriuretic peptide (BNP) has been recognized as a biochemical marker of ventricular dysfunction. The aim of this study was to evaluate the clinical significance of anemia in HF patients and furthermore, to investigate whether a significant correlation exists between anemia, BNP, and poor clinical outcomes in HF patients. We studied 185 consecutive HF patients. We assessed the occurrence of major adverse cardiac events (MACE) post hospital discharge. Anemia was defined as Hb concentrations <12.9 g/dl in men and <11.3 g/dl in women, respectively. Kaplan-Meier analysis revealed that anemia and high BNP levels (>259 pg/ml) were significantly associated with the occurrence of MACE. Multiple logistic analysis revealed that the most predictive independent risk factor for the occurrence of MACE was high BNP levels, followed by anemia (relative risk [RR] = 2.803 and 2.241, respectively). We divided the patients with or without anemia and high or low BNP levels into four groups according to their respective Hb and BNP levels. The hazard ratio for MACE in the group with anemia and high BNP levels was 10.3 in comparison to the group without anemia and with low BNP levels (P = 0.0002). Both anemia and high plasma levels of BNP are significantly and independently associated with the occurrence of MACE in HF patients; furthermore, the synergistic effect of anemia combined with high BNP levels significantly predicts an enhanced risk for MACE.

Pump failure death and sudden cardiac death in patients with cardiac dysfunction: A search for prognostic predictive factors-A long-term follow-up study

BACKGROUND There have been few reports that have analyzed the predictive factors for heart failure death, which is sub-divided into pump failure death and sudden cardiac death, in the long term. METHODS AND RESULTS We followed 186 consecutive patients with myocardial infarction (MI) and 115 consecutive patients with non-ischemic heart failure (NIHF) during 73+/-3 months. In the MI group, 26 died from pump failure and 12 died from sudden cardiac death. In the NIHF group, 21 died from pump failure and 9 died from sudden cardiac death. Multivariate analysis revealed that the log B-type natriuretic peptide (BNP) was an independent predictor for pump failure death in both groups. In the MI group, the estimated glomerular filtration rate (eGFR) was an independent predictor for sudden cardiac death. Kaplan-Meier analysis revealed that a high BNP level was a risk factor for pump failure death in either MI or NIHF patients. On the other hand, the sudden cardiac death rate was significantly higher in the MI patients with low eGFR than in those with high eGFR. CONCLUSIONS The plasma BNP level is an independent predictor for pump failure death in both MI and NIHF patients. The eGFR is an independent predictor for sudden cardiac death in MI patients.

Clinical factors affecting serum potassium concentration in cardio-renal decompensation syndrome

BACKGROUND Renin-angiotensin-aldosterone system (RAAS) inhibitors are currently indispensable for the treatment of heart failure. It is well known that hyperkalemia is likely to occur in renal failure; however, it has not yet been clarified how the serum potassium concentration changes as heart failure progresses. Currently, the cardio-renal decompensation syndrome holds that the serum potassium concentration is altered similarly by both heart failure and renal failure; however, there are no definitive reports on this. In order to use RAAS inhibitors more safely and effectively in heart failure, it is necessary to understand the factors affecting serum potassium concentration in the clinical setting. METHODS AND RESULTS We examined the clinical factors affecting serum potassium concentration in 1035 consecutive patients with cardiovascular disease who were hospitalized in our institution. Multiple regression analysis showed that the independent factors associated with an elevated serum potassium concentration were renal insufficiency evaluated by estimated glomerular filtration rate (eGFR) (P<0.0001), diabetes mellitus evaluated by HbA(1c) (P=0.0005) and the use of RAAS inhibitors (P=0.0010). The independent factors associated with a decreased serum potassium concentration were mean blood pressure (P<0.0001), heart failure evaluated by log BNP (P=0.0164) and the use of diuretics (P=0.0232). CONCLUSIONS The serum potassium concentration decreases with the severity of heart failure if renal function is preserved. From the perspective of potassium homeostasis, we could use the RAAS inhibitors more aggressively in patients with heart failure who do not have renal failure.

Early diastolic overinflation in diastolic mitral regurgitation.

An 81-year-old man presented with exertional dyspnea at our hospital. An electrocardiogram was recorded, which showed 2:1 atrioventricular (AV) block. Transthoracic 2-dimensional echocardiography showed that the left ventricular (LV) wall thickness and wall motion were normal. Color Doppler echocardiography showed no significant valvular heart disease. Pulsed Doppler echocardiography at the mitral valve showed a high early diastolic inflow (E) wave (111 cm/s) with a short deceleration time (125 ms) and diastolic mitral regurgitation (MR) in early diastole (Fig. 1, right panel, arrow). By raising the baseline to reveal the full profile of the diastolic regurgitant flow, pulsed Doppler echocardiography showed that the pressure gradient at the mitral cusp was 8.3 mmHg (Fig. 1, left panel, arrow). There have been reports about the mechanisms of diastolic MR. As coaptation of the mitral valve is not isolated to the tips but, rather, is the result of the overlap of several millimeters of tissue, LV contraction is necessary for definite mitral valve closure. Thus, AV block of any degree may become a cause of diastolic MR [1]. The reversed AV pressure gradient during atrial relaxation may also contribute to this. Without AV block, diastolic MR may be present in a high LV diastolic pressure setting, such as that during aortic regurgitation [2]. In the present case, a longitudinal global strain from speckle tracking showed that the left ventricle was already dilated to the level of end-diastole (Fig. 2, dotted line, arrow). This suggests that LV early diastolic pressure might be as high as end-diastolic pressure. Along with the decrease in left atrial pressure after atrial contraction, there might be a reversed pressure gradient between the left ventricle and the left atrium. The global strain decreased during mid-diastole, suggesting gradual decrease in LV size due to diastolic MR (Fig. 2). Thus, global strain was useful in estimating the LV volume change during diastole in this patient.

Deceased left ventricular compliance contributing to diastolic mitral regurgitation in a patient with atrioventricular block

A 79-year-old woman temporarily lost consciousness and was admitted to our hospital. She had been treated for hypertension and diabetes mellitus. Upon admission, her blood pressure was 112/51 mm Hg; pulse rate, 37/min; and pulse oxygen saturation, 95 %. On auscultation, her heart and breath sounds were normal. Blood examination results showed normal cardiac enzyme levels but high plasma B-type natriuretic peptide levels (381.7 pg/mL). A 12-lead electrocardiogram showed advanced atrioventricular (AV) block. Slight ST-segment elevation and terminal T inversion were observed in leads III and aVF. A chest radiograph showed a cardiothoracic ratio of 57 %. Twodimensional transthoracic echocardiography showed normal left ventricular (LV) wall thickness and hypokinesis at the inferior wall. LV end-diastolic and end-systolic dimensions and fractional shortening were normal (44 mm, 26 mm, and 41 %, respectively). A pulsed Doppler echocardiogram of the mitral inflow (Fig. 1, arrows) and color Doppler imaging (Fig. 2, top, arrow) showed diastolic mitral regurgitation (DMR). The estimated peak pressure gradient of DMR was 8 mm Hg. The patient underwent cardiac catheterization. Simultaneous recording of pulmonary artery wedge (PAW) and LV pressures showed that the LV pressure was elevated abruptly by atrial contraction and remained elevated until late diastole (Fig. 2, bottom). As the PAW pressure decreased after the atrial contraction, AV pressure reversal occurred and continued to late diastole. Coronary arteriography revealed severe stenosis at the right coronary artery, for which percutaneous coronary intervention was performed. The next day, the AV block was abolished. A transthoracic echocardiogram showed that the DMR had disappeared. Complete mitral valve closure needs effective LV contraction, and mitral regurgitation may occur whenever the LV pressure exceeds the left atrial (LA) pressure during diastole. In any degree of AV block, atrial relaxation without succeeding LV contraction may cause reversed AV pressure gradient and DMR [1]. In the present case, we recorded the PAW and LV pressures simultaneously. The LV pressure abruptly elevated to higher than 15 mm Hg in mid-diastole by atrial contraction and decreased LV compliance owing to myocardial ischemia. However, the LA volume was already so small in atrial systole that the LA and PAW pressures became lower in mid-diastole. This case suggests that early atrial emptying and decreased LV compliance might play pivotal roles in the DMR in AV block.

Paradoxical increase in E/e′ ratio after treatment of heart failure in two patients with preserved ejection fraction

We report an increase in E/e′ ratio after treatment of heart failure (HF) in two patients. In case 1, the E/e′ ratio increased from 15 to 18 after treatment of HF. In case 2, the E/e′ ratio also increased from 24 to 35. Although a high E/e′ ratio suggests high pulmonary artery wedge pressure and worsening HF, the ratio may increase after improvement of HF.In the present cases of diastolic dysfunction, the high E wave did not change, but the e′ wave decreased relatively. This report may suggest difficulty in evaluating hemodynamic status based on the E/e′ ratio in patients with diastolic dysfunction.

Mid-systolic flow reversal in a patient with mid-ventricular obstructive hypertrophic cardiomyopathy

An 80-year-old man with palpitations presented to our hospital. A 12-lead electrocardiogram showed atrial fibrillation, complete right bundle branch block (CRBBB), right axis deviation, and negative T waves in leads II, III, aVF, and V1–V4. A chest radiograph showed a cardiothoracic ratio of 58 %. A 2D transthoracic echocardiography showed LV hypertrophy (the interventricular septum was 14 mm thick and the LV posterior wall was 9 mm thick), mid-ventricular obstruction, and apical aneurysm. A pulsed Doppler echocardiogram showed systolic mid-ventricular obstruction and paradoxical jet flow typical for MVOCM [2]. Moreover, additional mid-systolic flow reversal was intermittently observed at the obstruction. This flow was observed between the systolic flow and paradoxical jet flow (Figs. 1, 2a). The patient underwent cardiac catheterization to enable visualization of the mechanism of this flow reversal and to examine whether the apical aneurysm was caused by myocardial infarction. Simultaneous LV pressure recordings showed that the basal pressure intermittently surpassed the apical pressure in mid-systole, which corroborated the echocardiographic data (Fig. 2b). Coronary arteriography yielded normal results. The patient was discharged with beta-blocker, calcium channel blocker, and anticoagulation.

Mid-diastolic mitral regurgitation in a patient with diastolic heart failure.

A 94-year-old woman who had been treated with hypertension was referred to our department because of paroxysmal nocturnal dyspnea. Her blood pressure was 154/84 mmHg and her pulse rate was 67/min. A chest radiograph showed pulmonary congestion and high cardiothoracic ratio (65 %). Blood test results indicated a high plasma B-type natriuretic peptide level (521.3 pg/ mL). A 12-lead electrocardiogram showed a sinus rhythm with high voltage in the left ventricle (S in V1 ? R in V5 = 4.1 mV). A transthoracic echocardiogram showed left ventricular hypertrophy (interventricular septal thickness was 13.0 mm and posterior wall thickness was 12.5 mm) with normal systolic function (left ventricular end-diastolic and end-systolic dimensions, 49 and 32 mm, respectively; ejection fraction, 63 %). Left ventricular mass was 294 g and left atrial volume was 81 cm. Thickening of both the anterior and posterior mitral valves and moderate systolic mitral regurgitation (MR) were observed. A continuous Doppler echocardiogram indicated that the estimated peak pressure gradient at the tricuspid regurgitation (TR) was 44 mmHg. The pulsed Doppler echocardiogram of the mitral inflow revealed a short E-wave deceleration time (131 ms) and mid-diastolic mitral regurgitation (Fig. 1, top panel, arrows). In addition, a color Doppler M-mode echocardiogram also demonstrated diastolic MR (Fig. 1, bottom panel, arrows). Tissue Doppler echocardiography at the mitral annulus revealed left ventricular diastolic dysfunction (e0 wave of 6.6 cm/s and E/e0 ratio of 15.9). After diuretics were administered for treating heart failure, the patient improved in terms of estimated peak pressure gradient at the TR (27 mmHg). Diastolic MR was no longer observed in both pulsed Doppler (Fig. 2, top panel) and color Doppler M-mode (Fig. 2, bottom panel) echocardiograms. Effective left ventricular contraction is essential to complete mitral valve closure, and diastolic MR occurs whenever the left ventricular pressure exceeds the left atrial (LA) pressure. In the present case, degenerative thickening of the mitral valve might have contributed to diastolic MR. In atrioventricular (AV) block of any degree, lowering the LA pressure during atrial diastole may cause diastolic MR [1]. In cases of atrial flutter with a variable advanced AV block, to-and-fro diastolic transmitral flow may be observed [2]. In severe aortic regurgitation or left ventricular diastolic failure, high left ventricular pressure may cause end-diastolic MR [3, 4]. As mid-diastole is a quiescent phase, the left ventricular pressure does not usually exceed the LA pressure between the early diastolic E wave and atrial systolic A wave. However, in the present case, diastolic MR was observed immediately after the end of the E-wave, suggesting an overshoot of the diastolic left ventricular pressure after H. Usuku I. Misumi (&) K. Kusuhara T. Rokutanda R. Akahoshi M. Matsumoto Internal Medicine, Kumamoto Saisyunsou Hospital, 2659 Suya, Koushi, Kumamoto 861-1196, Japan e-mail: misumi@saisyunsou1.hosp.go.jp

Hemodynamic influence of triphasic mitral inflow velocity: A case report

A 56-year-old woman with chest discomfort was brought to our hospital by ambulance. Her blood pressure was 138/74 mmHg, and her pulse rate was 99 beats/min. Results of blood sampling showed a high plasma brain natriuretic peptide level (103.7 pg/ml). The chest radiograph showed a cardiothoracic ratio of 45 % without pulmonary congestion. A 12-lead electrocardiogram demonstrated sinus rhythm with a normal QRS wave. A transthoracic echocardiogram at the echocardiography laboratory revealed normal LV wall thickness, no regional wall motion abnormality, and a preserved ejection fraction. Pulsed Doppler echocardiography recordings of mitral inflow showed a high E/A ratio of 2.0, suggesting a high LV preload. It also revealed a mid-diastolic regurgitant

Mid-diastolic mitral flow vectors in complete atrioventricular block

An 81-year-old man who was treated for prostate cancer was referred to our department because of bradycardia. He had a 1-month history of shortness of breath. A 12-lead electrocardiogram (ECG) showed complete atrioventricular (AV) block. His blood pressure was 165/78 mmHg and pulse rate was 38 beats/ min. Results of blood sampling were normal. A transthoracic echocardiogram revealed normal left ventricular (LV) wall thickness (interventricular septal thickness, 8 mm; LV posterior wall thickness, 8 mm) and normal LV systolic function (LV end-diastolic dimension, 39 mm; LV end-systolic dimension, 22 mm; LV ejection fraction, 76 %). A color-coded 2-dimensional echocardiogram showed no significant valvular disease. During mid-diastole, mitral forward and regurgitant flows were intermittently observed (Fig. 1). Color-coded M-mode echocardiography also showed intermittent mitral forward and regurgitant flows (Fig. 2). Simultaneous ECG recording indicated a relationship between the timing of the P wave and the T wave and the direction of mid-diastolic flow. Middiastolic mitral inflow was observed when the P wave was on the T wave, while diastolic mitral regurgitation (MR) was observed when the P wave emerged after the T wave (Figs. 1, 2). After treatment of complete AV block by pacemaker implantation, neither type of mitral flow was observed. Mid-diastolic mitral forward flow can be observed in some patients with advanced LV diastolic dysfunction. In these cases, mid-diastolic flow may be a result of interruption of early diastolic mitral inflow (E wave) by transient elevation of LV pressure [1, 2]. In the present case of complete AV block, mid-diastolic forward flow was observed when the P wave overlapped with the T wave. It is probable that mid-diastolic flow in this case might be a result of E wave interruption by transient fall of left atrial (LA) pressure by atrial relaxation. Diastolic MR is observed when the AV pressure gradient is reversed because the mitral valve does not close firmly during diastole. In complete AV block, diastolic MR can be observed when atrial relaxation occurs during ventricular diastole [3]. Moreover, decreased LV compliance [4] and early diastolic LV hyperinflation [5] may also play a part. In this patient with complete AV block, the timing of atrial relaxation might have played a decisive role in the mid-diastolic mitral inflow velocity and diastolic MR.