Effect of Gonadectomy and Angiotensin II Receptor Blockade in a Mouse Model of Isoproterenol-induced Cardiac Diastolic Dysfunction.

BACKGROUND: Although heart failure (HF) with preserved ejection fraction (HFpEF) is more common in postmenopausal women than in men, the effect of sex hormones on cardiac diastolic function remains unclear. We examined the effect of gonadectomy with or without the angiotensin receptor blocker olmesartan (Olm) in an isoproterenol (ISO) -induced mouse model of left ventricular hypertrophy (LVH) and cardiac diastolic dysfunction. METHODS: ISO or ISO with Olm were administered for 28 days in sham-operated male and female, castrated (CAS), and ovariectomized (OVX) mice. LV ejection fraction (EF) and E/A ratio were analyzed by echocardiography, and the LV and lung weight corrected by tibial length were used as indices of LVH and lung congestion, respectively. RESULTS: On echocardiography, systolic function did not differ between the four groups. LV/tibial length (TL) and Lung/TL significantly increased in all groups. The LV/TL ratio was lower in castrated-ISO vs. Male-Sham-ISO but did not differ between Female-Sham-ISO and OVX-ISO. However, the Lung/TL ratio of OVX-ISO was greater than that of Female-Sham-ISO. Olm prevented LV hypertrophy in all groups. The decrease in E/A and increase in lung weight were improved by Olm in Male-Sham and OVX-ISO but not in the other groups. CONCLUSION: These sex differences suggest that sex hormones play a pivotal role in modulating cardiac hypertrophy and diastolic dysfunction induced by chronic ß-adrenoceptor stimulation, and thus affect the therapeutic potential of angiotensin receptor blockade.

ß 3-Adrenergic Receptor Agonist Prevents Diastolic Dysfunction in an Angiotensin II-Induced Cardiomyopathy Mouse Model.

ß3-Adrenergic receptor expression is enhanced in the failing heart, but its functional effects are unclear. We tested the hypothesis that a ß3-agonist improves left ventricular (LV) performance in heart failure. We examined the chronic effects of a ß3-agonist in the angiotensin II (Ang II)-induced cardiomyopathy mouse model. C57BL/6J mice were treated with Ang II alone or Ang II + BRL 37344 (ß3-agonist, BRL) for 4 weeks. Systolic blood pressure in conscious mice was significantly elevated in Ang II and Ang II + BRL mice compared with control mice. Heart rate was not different among the three groups. Systolic performance parameters that were measured by echocardiography and an LV catheter were similar among the groups. LV end-diastolic pressure and end-diastolic pressure-volume relationships were higher in Ang II mice compared with control mice. However, the increase in these parameters was prevented in Ang II + BRL mice, which suggested improvement in myocardial stiffness by BRL. Pathologic analysis showed that LV hypertrophy was induced in Ang II mice and failed to be prevented by BRL. However, increased collagen I/III synthesis, cardiac fibrosis, and lung congestion observed in Ang II mice were inhibited by BRL treatment. The cardioprotective benefits of BRL were associated with downregulation of transforming growth factor-ß1 expression and phosphorylated-Smad2/3. Chronic infusion of a ß3-agonist has a beneficial effect on LV diastolic function independent of blood pressure in the Ang II-induced cardiomyopathy mouse model. SIGNIFICANCE STATEMENT: Chronic infusion of a ß3-adrenergic receptor agonist attenuates cardiac fibrosis and improves diastolic dysfunction independently of blood pressure in an angiotensin II-induced hypertensive mouse model. This drug might be an effective treatment of heart failure with preserved ejection fraction.

Association between out-of-bed mobilization and complications of immobility in acute phase of severe stroke: A retrospective observational study.

BACKGROUND: Medical complications often occur, particularly in the acute phase of severe stroke, and lead to poor outcomes. However, it is unclear whether out-of-bed mobilization (OM) reduces such complications or not in the acute phase of severe stroke. Thus, we investigated the association between OM and complications of immobility in the acute phase of severe stroke. METHODS: We enrolled 407 patients diagnosed with ischemic stroke or intracerebral hemorrhage and patients with modified Rankin Scale 5 at discharge in this study. Patients were divided into two groups: OM (303 patients) and bed rest (BR; 104 patients) at discharge based on their medical records. Complications of immobility (such as pneumonia, urinary tract infection, pressure sore, and falls) during hospitalization in each group were recorded. RESULTS: The total complication rate of immobility, incidence of pneumonia, and the incidence of pressure sores were significantly lower in the OM group than in the BR group [60.7% vs. 88.5%, 45.5% vs. 62.5%, and 3.6% vs. 12.5%; odds ratio, 0.20, 0.50, and 0.26; and 95% confidence intervals, 0.11-0.39, 0.32-0.79, and 0.11-0.61, respectively]. Urinary tract infection and falls did not differ significantly between the two groups. CONCLUSIONS: In the acute phase of severe stroke, OM was significantly associated with a lower risk of total complication rate of immobility, incidence of pneumonia, and incidence of pressure sore without increasing falls.

Predictors of responders for low-dose carperitide monotherapy in patients with acute heart failure.

Human atrial natriuretic peptide, known as carperitide, is approved for early relief of dyspnea in patients with acute heart failure (AHF). However, the diuretic effect of carperitide is sometimes insufficient for controlling volume overload. We investigated predictors for the carperitide response in patients with AHF. Forty-seven patients (age: 74 ± 10 years; left ventricular ejection fraction: 42.0% ± 15.9%) with AHF were enrolled and treated with carperitide monotherapy at a dose of 0.0125 µg/kg/min. Patients without sufficient diuresis (< 60 ml/h) or improvement of symptoms by 4 h after carperitide administration, despite increasing to twice the dose of carperitide and adding another agent, were defined as non-responders. Twenty-four (51%) patients were defined as responders and treated with low-dose carperitide monotherapy on the first day. Multiple logistic regression analysis showed that the response to carperitide monotherapy was independently predicted by serum creatinine levels and systolic blood pressure (SBP) on admission. The area under the receiver-operating characteristic curve for predicting the response to carperitide by SBP was 0.808 (95% confidence interval [0.686-0.930], sensitivity: 83.3%, specificity: 65.2%, cutoff value: 135 mmHg). Four (8.5%) patients developed asymptomatic transient hypotension. Worsening renal function occurred within 3 days of admission in three (6.4%) patients who received low-dose carperitide therapy. SBP and serum creatinine levels on admission might be useful for predicting the diuretic response to low-dose carperitide monotherapy in patients with AHF. Initial use of low-dose carperitide therapy does not have adverse effects on renal function.

Enhancement of walking ability using a custom-made hinged knee brace in patients who experienced ambient stroke and are in the acute phase.

[Purpose] In this study, we investigated the immediate effect on walking using a custom-made hinged knee brace with adjustable knee flexion and extension support (support brace) in patients in the acute phase of stroke. [Participants and Methods] Thirteen patients (56.8 ± 6.8 years) who experienced stroke and who were able to walk independently participated in the study. The walking speed and mean knee extension strength were evaluated under three conditions: no brace, general brace, and support brace. [Results] The walking speed of patients while using the support brace was significantly faster (0.60 ± 0.11 m/s) than that without brace (0.45 ± 0.16 m/s) and with general brace (0.52 ± 0.14 m/s). The fastest walking speed among all 8 patterns (no brace, general brace, and the support brace with six different patterns of support) was with the support brace. The mean knee extension strength while wearing a support brace (1.01 ± 0.24 Nm/kg) was significantly greater than that without wearing a brace (0.82 ± 0.28 Nm/kg). [Conclusion] The support brace, which allows for customizable adjustment of the flexion and extension strength, enhanced the walking ability of patients who experienced ambient stroke and were in the acute phase.

Transvenous Intravascular Ultrasound-Guided Endovascular Treatment for Chronic Total Occlusion of the Infrainguinal Arteries.

PURPOSE: To investigate the 1-year outcomes of transvenous intravascular ultrasound (IVUS)-guided endovascular therapy (EVT) for chronic total occlusion (CTO) of the lower extremity arteries. METHODS: Transvenous IVUS-guided EVT was performed in 44 patients (50 limbs) with CTO of the femoropopliteal arteries or tibioperoneal trunk. Treatment involved crossing a guidewire through the CTO under the guidance of both fluoroscopic and IVUS imaging, along with insertion of the IVUS catheter into a vein parallel to the target artery. Primary success rate, complications, and target lesion revascularization (TLR) at 12-month follow-up were investigated. RESULTS: Successful recanalization, defined as grade 3 flow (Thrombolysis in Myocardial Infarction score) and no flow-limiting dissection, was observed in 48 (96%) limbs. Two limbs with failed recanalization had a very long CTO lesion from the superficial femoral artery to below the knee. A bidirectional approach was selected in 11 (22%) limbs. Complications at the access site occurred in only 2 patients. The rate of freedom from TLR at 12 months was 77.9% (95% confidence interval 61.4 to 87.9). CONCLUSION: Transvenous IVUS-guided EVT is safe and can provide optimal short-term results for EVT of CTO in the infrainguinal arteries. IVUS-guided EVT may be one of the most effective treatment strategies for CTO of the femoropopliteal arteries or tibioperoneal trunk.

Renal effects of added low-dose dopamine in acute heart failure patients with diuretic resistance to natriuretic peptide.

Worsening renal function during the early phase of hospitalization is related to adverse outcomes in acute heart failure (AHF). This study aimed to clarify whether added low-dose dopamine (DA) is clinically beneficial for AHF patients with diuretic resistance to human atrial natriuretic peptide (hANP). Twenty-four AHF patients, who did not have adequate diuresis by 4 hours after administration of hANP, were randomized to a low dose of DA (1-3 µg·kg·min, n = 12) or a low dose of furosemide (10-30 mg injection, n = 12). The significant increase in mean hourly urine volume from baseline (265% ± 204% with hANP + DA; 187% ± 118% with hANP + furosemide) and improvement of dyspnea were similarly observed in both groups. Significant decreases in serum creatinine levels were observed by -14.0% ± 14.2% in the hANP + DA group compared with the hANP + furosemide group (4.5% ± 9.6%, P = 0.0011) without increases in the renotubular and myocardial markers. The incidence of worsening renal function defined as a rise in serum creatinine of >0.3 mg/dL was not observed within 3 days of admission in both groups. Added low-dose DA might not have a harmful effect on renal function and effects of diuresis and symptom relief without a significant increase in troponin-T in AHF patients with diuretic resistance to hANP.

A case of marked diuresis by combined dopamine and atrial natriuretic peptide administration without renal injury in acute decompensated heart failure.

Renal injury is an important factor for worsening outcome in acute decompensated heart failure (ADHF). An 81-year-old woman was admitted due to ADHF with dyspnea and mild peripheral edema. The patient was managed with intravenous administration of atrial natriuretic peptide (ANP) at a dose of 0.0125 µg/kg/minute, which did not control volume overload even at an increased dose of 0.025 µg/kg/minute. After a low dose of dopamine (DA) of 1.0 µg/kg/ minute was added, urine output increased markedly to 120 from 30 mL/hour. Furthermore, her heart rate decreased to 80-100 from 120 bpm and the congestion improved with a reduced brain natriuretic peptide level. Interestingly, the combination of ANP and DA therapy reduced serum creatinine as well as the levels of urinary liver-type fatty acid binding protein, a novel reno-tubular stress marker, by 98.9%, and an oxidative stress marker, urinary 8-hydroxydeoxyguanosine, by 88.2% from baseline levels. Thus, this ADHF patient, a nonresponder to ANP alone, improved without renal injury when administered combination therapy consisting of low doses of ANP and DA, suggesting that this combined therapy might be useful for better management of ADHF in patients without diuretic responses with ANP alone. Further prospective studies are warranted.

Usefulness of rosuvastatin to prevent periprocedural myocardial injury in patients undergoing elective coronary intervention.

The aim of the present study was to investigate whether percutaneous coronary intervention-related periprocedural myocardial infarction (MI) can be suppressed more significantly with high- compared with low-dose rosuvastatin. A total of 232 patients scheduled to undergo elective percutaneous coronary intervention within 5 to 7 days were assigned to groups that would receive either 2.5 or 20 mg/day of rosuvastatin (n = 116 each). The incidence of periprocedural MI did not significantly differ between the high and low-dose groups (8.7% vs 18.7%, p = 0.052). In patients who were not taking statins at the time of enrollment, high-dose rosuvastatin significantly suppressed periprocedural MI compared with the low dose (10.5% vs 30.0%, p = 0.037). The difference was not significant in patients who were already taking statins (high vs low dose 7.6% vs 10.6%, p = 0.582). In conclusion, the incidence of percutaneous coronary intervention-related periprocedural MI was reduced more effectively by high-dose than by low-dose rosuvastatin in statin-naive patients. However, low-dose rosuvastatin is sufficient for patients who are already taking statins.

Cardiac angiosarcoma diagnosed by transvenous endomyocardial biopsy with the aid of transesophageal echocardiography and intra-procedural consultation.

We report a case who had confirmed tumor cells in the biopsy specimens by transvenous endomyocardial biopsy with intra-procedural consultation and fast smear cytology. A 57-year-old female was admitted to our hospital because of shortness of breath and left back pain. Transthoracic echocardiography (TTE) and contrast-enhanced computed tomography (CT) scans demonstrated a large mass in the right atrium and multiple liver tumors thought to be due to spread of the disease. Coronary angiography showed the right coronary artery was involved in the mass. In order to confirm the histological diagnosis, we attempted transvenous endomyocardial tumor biopsy under fluoroscopic guidance. However, we failed to obtain adequate tissue material. Due to several risks associated with a surgical procedure such as an open surgical biopsy, transvenous endomyocardial tumor biopsy was again attempted with the aid of transesophageal echocardiography (TEE). Intra-procedural consultation and fast smear cytology enabled us to finish the procedure. Hematoxylin-eosin stained sections demonstrated spindle-shaped cells. Immunohistochemical stains of these cells were positive for anti-factor VIII antigen, CD31, and CD34. These findings indicated a definite diagnosis of angiosarcoma. Since there was no surgical indication for this tumor, the patient underwent chemotherapy with docetaxel and radiotherapy. Three months later, CT scans showed a reduction in the size of the cardiac tumor.

Clinical outcome and quality of life of octogenarian patients following percutaneous coronary intervention or surgical coronary revascularization.

BACKGROUND: Thus far, the outcome and effect of percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery on the quality of life of octogenarian patients has not been accurately assessed in Japan. METHODS AND RESULTS: A retrospective analysis of the outcome of invasive coronary revascularization in 130 elderly patients (age, > or =80 years) with ischemic coronary disease was carried out. Their current quality of life was determined by the Seattle Angina Questionnaire. Although the in-hospital death rate was relatively high (21.6% after PCI and 14.3% after CABG surgery), the long-term outcome of the patients who did not die during the in-hospital period after the PCI/CABG surgery was acceptable (5-year survival rate, >60%). All domains of the questionnaire received a favorable score from a majority of the survivors, irrespective of the treatment they received. CONCLUSIONS: The quality of life and longevity of the octogenarian patients following extensive invasive revascularization for ischemic coronary artery disease were satisfactory.

Type I CD36 deficiency associated with metabolic syndrome and vasospastic angina: a case report.

A 54-year-old man was admitted to our hospital for evaluation of chest pain occurring at rest in the morning. ST segment depression was observed during a treadmill exercise test. Coronary angiography identified spontaneous spasm of the proximal right coronary artery, and right coronary obstruction was improved from 90% to about 50% stenosis after intracoronary administration of nitroglycerin. Myocardial iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid uptake was absent, but thallium-201 uptake during single photon emission computed tomography was normal, and neither platelet nor monocyte expression of the CD36 molecule was observed, indicating type I CD36 deficiency. High blood pressure, elevated plasma triglyceride and fasting plasma glucose levels, and low high-density lipoprotein values suggested metabolic syndrome. The final diagnosis was type I CD 36 deficiency associated with metabolic syndrome and vasospastic angina.