Early Safety and Efficacy of Sapien 3 20 mm Transcatheter Heart Valve Implantation in Small Japanese Body Size.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is effective in treating severe aortic stenosis in inoperable or high-risk surgical patients, however, the little is known about outcomes after Sapien 3 20 mm transcatheter heart valve (THV) implantation. The purpose of this study was to investigate the short term outcomes of Sapien 3 20 mm THV implantation in Japanese people with a small body size. METHODS: We retrospectively collected the hospital records of consecutive patients who underwent TAVI using the Sapien 3 20 mm THV between October 2016 and March 2017. Clinical and echocardiographic data from before and one week after TAVI were collected. RESULTS: Six Japanese patients (all female, mean age 89 ± 5 years, body surface area [BSA] 1.29 ± 0.16m2) received a Sapien 3 20 mm THV. All the procedures were feasible and successful, and the 30-day mortality rate was 0%. The functional class and the echocardiographic findings significantly improved (aortic valve area, 0.5 ± 0.1 cm2 to 0.8 ± 0.1cm2; mean pressure gradient, 55 ± 15 mmHg to 19 ± 7 mmHg; P = .043, respectively). However, the values of the indexed effective orifice area in all patients after Sapien 3 20 mm THV implantation were less than 0.85 cm2/m2, suggesting prosthesis-patient mismatch (PPM). CONCLUSIONS: The implantation of a Sapien 3 20 mm THV was safe and effective in high surgical risk elderly Japanese patients with a small body size. PPM after Sapien 3 20mm THV may be prevalent among Asians with small body sizes. Careful clinical follow-up will be necessary after Sapien 3 20 mm THV implantation.

Hemodilution after Initial Treatment in Patients with Acute Decompensated Heart Failure.

Decongestion is an important goal of heart failure (HF) management. Blood cell concentration is a recognized indicator for guiding decongestive treatment for HF. We aimed to assess the clinical impact of hemodilution and hemoconcentration after initial treatment in acute decompensated HF (ADHF) patients. We retrospectively evaluated hemoglobin levels and body weight obtained before admission, on admission, 3 days after admission, and at discharge in 102 consecutive patients admitted with ADHF. Patients were then stratified into hemodilution (n = 55) and hemoconcentration (n = 47) groups based on whether their hemoglobin levels decreased or increased, respectively, during the first 3 days after admission. From before admission to admission, hemoglobin levels decreased less in the hemodilution group (-0.16 ± 0.98 g/dL) than in the hemoconcentration group (-0.88 ± 1.11 g/dL) (P < 0.001); however, there was no significant difference in body weight (P≥ 0.05). More patients in the hemodilution group (85%) had grade III/IV pulmonary edema (Turner's criteria) compared with the hemoconcentration group (63%) (P < 0.01). Rate of readmission for HF within 180 days of discharge was higher in the hemodilution group (34%) compared with the hemoconcentration group (9%) (P < 0.01). Hemodilution after initial treatment for ADHF was associated with severe pulmonary edema at admission and higher readmission rates.

Portal congestion and intestinal edema in hospitalized patients with heart failure.

An interaction between the intestine and cardiovascular disease has been suggested. We thought to clarify the association between intestinal conditions and clinical outcomes in patients with heart failure (HF). Hemodynamic parameters in intestinal vessels [superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and portal vein (PV)] and average colon wall thickness (aCWT) from the ascending colon to sigmoid colon were evaluated in 224 hospitalized HF patients. Echocardiographic parameters and composite event rates (all-cause mortality, readmission for HF deterioration, major ventricular arrhythmias) were also examined. Higher PV congestion index (CI) and aCWT were observed in patients with New York Heart Association (NYHA) class III/IV. Higher PVCI [hazard ratio (HR) per + 1 standard deviation (SD) 1.50, p < 0.01] and aCWT (HR per + 1 SD 1.45, p < 0.01) were independently associated with higher composite event rates during the follow-up of 122 ± 68 days. None of SMA/IMA hemodynamic parameters were associated with NYHA class or composite event rates. Higher right ventricular end-diastolic dimension (38 ± 7 vs 34 ± 9 mm, p < 0.01) and lower tricuspid annual plane systolic excursion (15 ± 5 vs 19 ± 5 mm, p < 0.001) were observed in patients with higher PVCI (> 0.031 cm s) and aCWT (> 2.8 mm) relative to those in others. In conclusion, increased portal congestion and intestinal edema were associated with severe HF symptoms and poor outcomes in hospitalized HF patients, in addition to being associated with impaired right-sided cardiac function.

Prognostic impact of intestinal wall thickening in hospitalized patients with heart failure.

BACKGROUND: Intestine-cardiovascular relationship has been increasingly recognized as a key factor in patients with heart disease. We aimed to identify the relationships among intestinal wall edema, cardiac function, and adverse clinical events in hospitalized heart failure (HF) patients. METHODS AND RESULTS: Abdominal computed tomographic images of 168 hospitalized HF patients were retrospectively investigated for identification of average colon wall thickness (CWT) from the ascending to sigmoid colon. Relationships between average CWT and echocardiographic parameters, blood sampling data, and primary outcomes including readmission for deteriorated HF and all-cause mortality were evaluated. Among the echocardiographic parameters, lower left ventricular diastolic function was correlated with higher average CWT. In multivariate analysis, higher logarithmic C-reactive protein level, lower estimated glomerular filtration rate, lower peripheral blood lymphocyte count, higher E/E' ratio, and extremely higher/lower defecation frequency were independently correlated with higher average CWT. Multivariate Cox-hazard analysis demonstrated that higher average CWT was independently related to higher incidence of primary outcomes. CONCLUSION: In hospitalized HF patients, increased CWT was associated with lower cardiac performance, and predicted poorer long-term clinical outcomes.

Non-occlusive mesenteric ischemia accompanied by aortic regurgitation after transcatheter aortic valve implantation.

An 81-year-old male with severe symptomatic aortic stenosis with ventricular tachycardia was referred for treatment. Balloon aortic valvuloplasty was performed under cardiopulmonary resuscitation. Though transcatheter aortic valve implantation (TAVI) was considered high risk for annulus rupture and aortic regurgitation due to annular calcification, TAVI was performed because of extremely high surgical risk. Moderate-to-severe aortic regurgitation (AR) remained and progression of acidosis could not be managed with continuous hemodiafiltration. His autopsy revealed the development of non-occlusive mesenteric ischemia (NOMI) as the cause of progressive acidosis. AR and hemodynamic instability might contribute to the development and progression of NOMI after TAVI.

Higher hemoglobin A1c levels are associated with impaired left ventricular diastolic function and higher incidence of adverse cardiac events in patients with nonischemic dilated cardiomyopathy.

We aimed to elucidate the relationship between glycated hemoglobin (HbA1c), cardiac systolic/diastolic function, and heart failure (HF) prognosis during guideline-directed medical therapy in patients with nonischemic dilated cardiomyopathy (NIDCM). We evaluated 283 hospitalized NIDCM patients, who were grouped according to baseline (BL) and 1-year (1Y) levels of HbA1c (<6.0, 6.0-6.9, and ≥7.0 %). The primary endpoint was defined as either readmission for HF worsening or cardiac death. Approximately half of the patients had BL- or 1Y-HbA1c ≥6.0 % (31 % at BL, 34 % at 1Y had 6.0-6.9 %; 12 % at BL, 12 % at 1Y had ≥7.0 %). The absolute value of left ventricular ejection fraction (LVEF) and its improvement during 1 year showed no significant difference among the 1Y-HbA1c groups (p = 0.273), whereas a lower absolute value and a more significant reduction in the early diastolic velocity of the mitral annulus (E a) were seen in the group with 1Y-HbA1c ≥7.0 % (both p < 0.001). In multiple regression analysis, higher 1Y-plasma B-type natriuretic peptide and lower 1Y-Ea were independently associated with higher 1Y-HbA1c (both adjusted p < 0.05). The cumulative incidence of the primary endpoint was highest in the group with 1Y-HbA1c ≥7.0 % (log-rank p = 0.001). Multivariate analysis demonstrated that higher 1Y-HbA1c was independently associated with a higher incidence of the primary endpoint (adjusted p = 0.005). In conclusion, hyperglycemia during clinical follow-up is a risk factor for progression of concomitant LV abnormal relaxation, leading to poor HF prognosis in patients with NIDCM.

Clinical significance of endomyocardial biopsy in conjunction with cardiac magnetic resonance imaging to predict left ventricular reverse remodeling in idiopathic dilated cardiomyopathy.

Endomyocardial biopsy (EMB) and cardiac magnetic resonance (CMR) are useful modalities to study the characteristics of myocardial tissue. However, the prognostic impact of both diagnostic tools to predict subsequent left ventricular reverse remodeling (LVRR) has not been well elucidated. A total of 187 consecutive patients with idiopathic dilated cardiomyopathy (IDCM) who were treated by optimal pharmacotherapy (OPT) and underwent EMB of the LV wall were investigated. The myocardial specimens were semiquantitatively evaluated measuring cardiomyocyte degeneration (CD), interstitial fibrosis (IF), and hypertrophy. In addition, late gadolinium enhancement (LGE)-CMR was performed in 78 (48 %) patients. Seventy-eight (48 %) patients developed LVRR, defined as a ≥10 % increase in LV ejection fraction with a ≥10 % decrease in indexed LV end-diastolic dimension at 12 months after OPT. Multivariate regression analysis revealed that CD (P = 0.003), but not IF (P = 0.320), was an independent predictor of LVRR. In the patients with not only EMB but also CMR, the CD score and LGE area were independent predictors of LVRR (odds ratios/P values 0.268/0.010, 0.855/<0.001, respectively). The patients with mild CD and negative LGE had a better achievement rate of LVRR than those with severe CD and positive LGE (74 vs. 19 %). A combination of CD score on EMB and LGE-CMR is useful to predict subsequent LVRR in IDCM patients.

Cardiac fibrosis detected by magnetic resonance imaging on predicting time course diversity of left ventricular reverse remodeling in patients with idiopathic dilated cardiomyopathy.

This study aimed to identify the association between the time course of left ventricular reverse remodeling (LVRR) and late gadolinium enhancement in cardiac magnetic resonance imaging (LGE-cMRI) in patients with idiopathic dilated cardiomyopathy (IDCM). We identified 214 IDCM patients treated by optimal pharmacotherapies. LVRR was defined as ≥10 % increment in LV ejection fraction along with ≥10 % reduction in LV end-diastolic dimension. Findings of LGE-cMRI focusing on presence and extent of LGE were evaluated at baseline. Echocardiographic evaluation for detecting LVRR was performed in all patients for 3 years. The primary endpoint was defined as composite events (CEs) including readmission for heart failure, detection of major ventricular arrhythmia, and all-cause mortality. LVRR was found at <1 year in 59 patients (28 %, early responder), ≥1 year in 56 patients (26 %, late responder), and was absent in 99 patients (46 %, non-responder). Multivariate Cox-proportional hazards analysis revealed that both early responders (P = 0.02) and late responders (P < 0.001) had lower incidence of CEs than non-responders. Among 66 subjects (23 %) with complete cMRI evaluation, LGE was detected more often in late and non- than early responders (65, 83 vs. 23 % P < 0.001, respectively), whereas the LGE area was smaller in both early and late than non-responders (2 ± 3, 4 ± 3 vs. 12 ± 10 %, P < 0.001, respectively). In conclusion, evaluating the presence and the extent of LGE is useful for predicting the clinical differences of LVRR time course and subsequent long-term outcomes.

Time course of left ventricular reverse remodeling in response to pharmacotherapy: clinical implication for heart failure prognosis in patients with idiopathic dilated cardiomyopathy.

The present study aimed to identify the clinical significance of differences in detection timings of left ventricular reverse remodeling (LVRR) on heart failure (HF) prognosis in patients with idiopathic dilated cardiomyopathy (IDCM). We investigated 207 patients with IDCM who underwent pharmacotherapeutic treatment. LVRR was defined as improvements in both LV ejection fraction ≥10 % and indexed LV end-diastolic dimension (LVEDDi) ≥10 %. Patients were stratified into 3 groups by LVRR timing: patients with LVRR <24 months (Early LVRR), those with LVRR ≥24 months (Delayed LVRR), and those without LVRR during the entire follow-up period (No LVRR). The major endpoint was first detection of composite event including readmission for decompensated HF, major ventricular arrhythmias, or all-cause mortality. LVRR was recognized in 108 patients (52 %): Early LVRR in 83 (40 %), Delayed LVRR in 25 (12 %), and No LVRR in 99 (48 %). The survival rate for the major endpoint was significantly higher for Delayed LVRR than for No LVRR (P = 0.001); there was no significant difference between Early and Delayed LVRR. Among patients without LVRR <24 months (Delayed + No LVRR), receiver operating characteristic curve analysis showed that the area under the curve for improvement in LVEDDi during the first 6 months for predicting subsequent LVRR (Delayed LVRR) [0.822 (95 % confidence interval, 0.740-0.916; P = 0.038)] was greater than that for improvement in LVEF. In conclusion, LVRR was a favorable prognostic indicator in patients with IDCM irrespective of its detection timing. Reduced LVEDDi during the first 6 months was predictive for subsequent LVRR in the later phase.

Impact of Doctor Car with Mobile Cloud ECG in reducing door-to- balloon time of Japanese ST-elevation myocardial infarction patients.

Early reperfusion by percutaneous coronary intervention (PCI) is the current standard therapy for ST-elevation myocardial infarction (STEMI). To achieve better prognoses for these patients, reducing the door-to-balloon time is essential. As we reported previously, the Kitasato University Hospital Doctor Car (DC), an ambulance with a physician on board, is equipped with a novel mobile cloud 12-lead ECG system. Between September 2011 and August 2013, there were 260 emergency dispatches of our Doctor Car, of which 55 were for suspected acute myocardial infarction with chest pain and cold sweat. Among these 55 calls, 32 patients received emergent PCI due to STEMI (DC Group). We compared their data with those of 76 STEMI patients who were transported directly to our hospital by ambulance around the same period (Non-DC Group). There were no differences in patient age, gender, underlying diseases, or Killip classification between the two groups. The door-to-balloon time in the DC group was 56.1 ± 13.7 minutes and 74.0 ± 14.1 minutes in the Non-DC Group (P < 0.0001). Maximum levels of CPK were 2899 ± 308 and 2876 ± 269 IU/L (P = 0.703), and those of CK-MB were 292 ± 360 and 295 ± 284 ng/mL (P = 0.423), respectively, in the 2 groups. The Doctor Car system with the Mobile Cloud ECG was useful for reducing the door-to-balloon time.

No accumulation of globotriaosylceramide in the heart of a patient with the E66Q mutation in the α-galactosidase A gene.

BACKGROUND: Fabry disease is an X-linked lysosomal disorder resulting from mutations in the α-galactosidase A (GLA) gene. Recent reports described that the E66Q mutation of GLA is not a disease-causing mutation. However, no pathological study was reported. We carried out pathological studies using a cardiac biopsy specimen from a patient with the E66Q mutation. MATERIALS AND METHODS: The case was a 34 year old male patient with end-stage renal failure and cardiomegaly. He was diagnosed with gout at 15 years of age and hemodialysis was started for gouty nephropathy from 31 years of age. He was suspected of having Fabry disease as the result of a screening study for Fabry disease in patients with end-stage renal failure and was referred to our hospital for mutation analysis of the GLA gene. We carried out enzymatic and genetic analysis for GLA and pathological studies of a cardiac biopsy specimen. RESULTS: The patient had the E66Q mutation in the GLA gene. GLA activity in leukocytes was 36.2% of the average of normal controls. The pathological study of the cardiac biopsy sample showed no characteristic findings of Fabry disease. The immunohistochemistry for GL3 of the cardiac biopsy sample showed no positive cells. CONCLUSION: Although the E66Q mutation reduced enzyme activity, the characteristic pathological findings of Fabry disease and the abnormal accumulation of GL3 were not detected in cardiac tissues. The E66Q mutation of the GLA gene is thought to be a functional polymorphism based on enzymatic and pathological studies.

Clinical significance of corticosteroid therapy for eosinophilic myocarditis.

The recommended treatment for eosinophilic myocarditis (EM), pathologically defined as myocardial inflammation with eosinophil infiltration, is corticosteroids. Although EM has a wide variety of clinical features including the degree of eosinophilic infiltration, there have been no reports on how patients with EM should be treated with corticosteroids irrespective of their pathological findings.Thirty-seven consecutive patients with acute myocarditis hospitalized in our institute between 1996-2009 were enrolled. Excluding those with secondary EM such as Loeffler's endocarditis, hypereosinophilic syndrome, and Churg-Strauss Syndrome, together with drug-induced allergic myocarditis, the subjects were divided into 2 groups according to the existence of eosinophils in the myocardial interstitium observed in endomyocardial biopsy specimens. There were no differences in the clinical characteristics on admission between the 2 groups: with (group EM, n = 22) and without (group lymphocytic myocarditis (LM), n = 7) eosinophilic infiltrates irrespective of pathological differences. The treatment policy has been consistent in our institution: intensive hemodynamic observation and support without corticosteroid administration, not only in LM but also in idiopathic EM. There was no significant difference in clinical recovery in the acute phase as indicated by the hospitalization period, left ventricular ejection fraction, or long-term prognosis in EM compared to LM.A conventional management strategy for idiopathic EM without corticosteroid administration can improve the prognosis in the acute and chronic phases, similar to that of LM.

Comparison of nitrite compounds and carperitide for initial treatment of acute decompensated heart failure.

Human atrial natriuretic peptides and nitrite compounds (NC) are infused for the initial management of acute heart failure (HF). However, there have been few studies comparing their hemodynamic effects.Fifty-two patients in acute decompensated HF (ADHF) who received carperitide (0.07 ± 0.05 µg/kg/minute, n = 23, group C) or NC (0.39 ± 0.24 µg/kg/minute, n = 29, group N) during the initial 24 hours in the intensive care unit between 1997 and 2007 were studied. We measured and compared hemodynamic parameters by pulmonary artery catheter monitoring before and after drug administration. Heart rate (HR), diastolic pulmonary artery pressure (DPAP), and central venous pressure (CVP) after the 24-hour administration were lower (HR: 92 ± 18 versus 79 ± 13 bpm, DPAP: 17 ± 6 versus 11 ± 5 mmHg, CVP: 6 ± 4 versus 3 ± 3 mmHg, P < 0.05, respectively) and the reduction of DPAP and systemic vascular resistance index were higher in group N than in group C. However, there was no significant difference regarding other indicators of preload and afterload. Although the serum B-type natriuretic peptide (BNP) level at discharge was lower in group N than group C (382 ± 434 versus 207 ± 201 pg/mL, P < 0.05), there was no significant difference in either the in-hospital reduction of BNP, the duration of hospitalization, or total cardiac events during 1-year follow-up.Although NC tended to improve the hemodynamics of ADHF more than carperitide, both drugs had a similar prognostic impact in patients with ADHF.

Prognostic significance of right ventricular dimension on acute decompensation in chronic left-sided heart failure.

Right ventricular (RV) dysfunction has been discussed in relation to an adverse outcome in heart failure (HF). The aim of this study was to analyze the relationship between RV function with HF exacerbation and its subsequent long-term outcome in patients with chronic left-sided HF.We studied 122 consecutive patients who were admitted for dyspnea due to exacerbated left-sided HF with a left ventricular (LV) ejection fraction of less than 40%. Conventional echocardiography was performed in the study subjects on admission and at discharge. Cox proportional hazards analysis revealed that RV end-diastolic dimension (RVDd) (hazard ratio 1.131, P = 0.005, 95% confidence interval 1.039-1.231) and the serum level of creatinine on admission were independent predictors of subsequent cardiac-related death, but RVDd at discharge and other LV parameters were not. Thus, patients were divided into tertiles on the basis of RVDd on admission: < 32 mm (n = 37), 32-40 mm (n = 43), and ≥ 40 mm (n = 42). According to the increase in the RVDd category, the cardiac-related death-free rate significantly decreased. Among the 3 groups, the pulse pressure and serum total bilirubin levels that demonstrated low cardiac output syndrome (LOS) parameters had significant differences.RVDd on admission could be measured noninvasively and easily to predict a worse long-term prognosis of chronic left-sided HF on admission, and showed correlations with LOS parameters.

End-tidal carbon dioxide concentration can estimate the appropriate timing for weaning off from extracorporeal membrane oxygenation for refractory circulatory failure.

Although extracorporeal membrane oxygenation (ECMO) is widely used as temporary circulation support, there are no reports of direct parameters indicating cardiac recovery to determine the timing of weaning off. Twenty-five patients supported by ECMO due to hemodynamic deterioration were divided into 2 groups according to their outcome: weaned ECMO (W: n = 18) or not (NW: n = 7). In the W group, we examined the differences in parameters between the 2 time points, ECMO introduction, and the reduction in ECMO flow to 40% of the initial setting known as the conventional recovery point (C-point). Significant differences were observed in systolic pulmonary artery pressure, the cardiac index measured by the thermodilution method, C-reactive protein, lactate, base excess, and the end-tidal CO(2) concentration (ETCO(2)). Next, by closely examining these 6 parameters measured every 12 hours, we found that only ETCO(2) had always changed steeply, like a 'flexion point' (E-point), in all W cases, but not in NW. The E-point was defined as an initial increase in ETCO(2) of >or= 5 mmHg over the preceding 12 hours with a continued rise over the next 12 hours. E-points appeared as much as 95 +/- 60 hours earlier than C-points and also preceded weaning off of ECMO. ETCO(2) can be a useful continuous parameter for predicting the adequate timing of weaning off of ECMO for circulatory failure at the bedside.

Myocardial infarction in a premenopausal woman with a decreased serum estrogen level due to leuprorelin acetate.

A 45-year-old premenopausal woman was admitted with acute myocardial infarction. Her serum estrogen level was decreased because of leuprorelin acetate administration, 3 months prior to admission for the treatment of uterine myoma. Emergency coronary angiography revealed diffuse narrowing of the distal half of the left anterior descending artery (LAD). The second coronary angiography after anti-anginal medication revealed significant improvement in LAD narrowing, which suggested prolonged coronary vasospasm. She had no coronary risk factors except for a positive family history. This case suggests that a decreased serum estrogen level could cause ischemic heart disease even in premenopausal women.

Prognostic utility of B-type natriuretic peptide assessment in stable low-risk outpatients with nonischemic cardiomyopathy after decompensated heart failure.

OBJECTIVES: We investigated the clinical utility of B-type natriuretic peptide (BNP) assay in stable outpatients with nonischemic dilated cardiomyopathy (NICM) after decompensated heart failure (HF). BACKGROUND: Patients with NICM admitted for decompensated HF frequently experience sudden death or redecompensation after hospital discharge. The prognostic value of BNP during hospitalization has been demonstrated. However, clinical utility of BNP in stable outpatient setting has been poorly investigated. METHODS: Eighty-three NICM outpatients who were clinically stable in New York Heart Association functional class 1 to 2 for 6 months after discharge for decompensated HF were enrolled, and then followed for an additional 18 months. The main end point was first readmission for decompensated HF or death. B-type natriuretic peptide levels were measured at 3-month intervals from discharge to enrollment, and echocardiographic dimensions at discharge and enrollment. RESULTS: Mean discharge BNP level was 210 +/- 148 pg/ml. Twenty-eight patients were readmitted for decompensated HF or suddenly died at a median time of 11 months from the time of discharge. Among various variables including BNP measurements, clinical parameters and echocardiographic dimensions, a 6-month post-discharge BNP of >190 pg/ml was most closely associated with combined event in the Cox proportional hazards model (hazard ratio 2.29; 95% confidence interval 1.42 to 3.56; p = 0.0005), and had the best discriminatory power (area under the receiver operating characteristic curve 0.91, sensitivity 96%; specificity 76%). CONCLUSIONS: Even in stable low-risk outpatients with NICM at 6 months after hospital discharge for decompensated HF, BNP assessment predicts a long-term risk of redecompensation.