Clinical significance of corrected relative flow reserve derived from 13N-ammonia positron emission tomography combined with coronary computed tomography angiography.

BACKGROUND: This study evaluated corrected relative flow reserve (RFR) derived from 13N-ammonia positron emission tomography (PET) combined with coronary computed tomography angiography (CTA). METHODS: We analyzed 61 patients who underwent coronary CTA, 13N-ammonia PET, and invasive coronary angiography. Triple-vessel disease were excluded. Conventional RFRs were calculated as the ratio of hyperemic myocardial blood flow (hMBF) of hypoperfusion areas to those of non-ischemic lesions. Corrected RFRs were calculated using PET and coronary CTA to adjust coronary territories to their feeding vessels. Diagnostic performance was compared to detect obstructive coronary lesions. RESULTS: Of the 180 vessels analyzed, 50 were diagnosed as obstructive lesions (≥ 70% stenosis and/or fractional flow reserve value ≤ 0.8). The coronary flow reserve (CFR), hMBF, conventional RFR, and corrected RFR of obstructive lesions were significantly lower than those of non-obstructive lesions. In receiver operating characteristic curve analysis, these quantitative PET measurements had area under the curve of 0.67, 0.71, 0.89, and 0.92, respectively. Diagnostic performance differences between corrected and conventional RFR were not statistically significant. CONCLUSION: In patients with single or double vessel disease, indices of RFR, with or without coronary angiographic guidance of the reference coronary territory, are better discriminators of flow-limiting stenoses than hMBF and CFR.

Clinical Usefulness of Coronary Flow Reserve Ratio for the Detection of Significant Coronary Artery Disease on 13N-Ammonia Positron Emission Tomography.

BACKGROUND: This study aimed to evaluate the diagnostic performance of coronary flow reserve (CFR), hyperemic myocardial blood flow (hMBF), and CFR ratio for detecting significant coronary artery disease (CAD) on 13N-ammonia positron emission tomography (PET).Methods and Results:We analyzed 63 patients (mean age, 71±9 years; 43 males) with suspected CAD who underwent both pharmacological stress/rest 13N-ammonia PET and coronary angiography. CFR and hMBF for PET were calculated automatically using quantitative PET software, and the CFR ratio was defined as the ratio of per-vessel CFR to maximum CFR in a standard 17-segment model. We compared the diagnostic performance among the 3 quantitative values. In the per-vessel analysis, 55 vessels were diagnosed as significant CAD (≥70% stenosis and/or fraction flow reserve ≤0.8). CFR, hMBF, and CFR ratio of significant CAD were significantly lower than for non-significant CAD (1.85±0.69 vs. 2.38±0.69; P<0.01, 1.67±0.54 vs. 2.19±0.52 mL·min-1·g-1; P<0.01, and 0.66±0.15 vs. 0.82±0.09; P<0.01, respectively). In the receiver-operating characteristic curve analysis, CFR, hMBF, and CFR ratio had areas under the curve of 0.71, 0.75, and 0.85 respectively, and the CFR ratio was significantly higher than CFR and hMBF (P<0.05). The sensitivity, specificity, and accuracy of the CFR ratio with an optimal cutoff value of 0.75 were 75%, 85%, and 82%, respectively. CONCLUSIONS: Clinically, the CFR ratio in 13N-ammonia PET was more effective in detecting significant CAD.

Favorable effects of early tolvaptan administration in very elderly patients after repeat hospitalizations for acute decompensated heart failure.

Tolvaptan (TLV) is an oral selective vasopressin 2 receptor antagonist that acts on the distal nephrons, causing a loss of electrolyte-free water. To date, its early administration in very elderly patients after repeat hospitalizations for acute decompensated heart failure (ADHF) despite receiving optimal medical therapy has not been evaluated. Fifty-six ADHF patients who were >80 years old and had been repeatedly hospitalized were retrospectively enrolled in this study. Twenty-five patients (14 men; mean age 86.7 ± 5.3 years; control group) received standard therapy and 31 patients (15 men; mean age 85.5 ± 4.5 years; TLV group) received oral TLV within 24 h of admission. The rate of worsening renal function was significantly lower in the TLV group than in the control group (13 vs. 40%, P < 0.05). The duration of the return to body weight at a steady state was significantly shorter in the TLV group (5.3 ± 2.8 days) than in the control group (13.9 ± 9.2 days, P < 0.01). Consequently, the hospitalization period in the TLV group (13.5 ± 5.9 days) was significantly shorter than that in the control group (24.7 ± 12.3 days, P < 0.01). In conclusion, the early administration of TLV to very elderly patients who underwent repeat hospitalizations for ADHF resulted in immediate decongestion and thus reduced the hospitalization period with a lower incidence of worsening renal function.

Beneficial effects of adaptive servo-ventilation therapy on readmission and medical costs in patients with chronic heart failure.

Adaptive servo-ventilation (ASV) therapy is a novel modality of noninvasive positive pressure ventilation and is now widely utilized to treat patients with chronic heart failure (CHF). However, there has been no clinical study of the effect of ASV therapy on readmission and cost-effectiveness for the treatment of CHF. The present study was conducted to evaluate the clinical efficacy and cost-effectiveness of home ASV therapy in 45 patients with a history of two or more admissions a year for worsening CHF. Seven patients refused to undergo chronic ASV therapy and three died. Thus, 35 patients were eventually enrolled in the present study. New York Heart Association class (2.8 ± 0.4 versus 2.3 ± 0.5, p < 0.001), log plasma B-type natriuretic peptide level (2.53 ± 0.44 versus 2.29 ± 0.40 pg/mL, p < 0.0001), left atrial dimension (47.5 ± 7.0 versus 44.9 ± 7.6 mm, p = 0.014), and mitral regurgitation area ratio (20.3 ± 12.1 versus 16.9 ± 8.9%, p = 0.007) decreased significantly after 12 months of ASV therapy. The frequency of hospitalization after ASV was significantly lower than before ASV (1.0 ± 1.0 versus 2.3 ± 0.5 times/year/patient, p < 0.0001). ASV also decreased the duration of hospitalization from 64.4 ± 46.5 to 22.8 ± 27.5 days/year/patient (p < 0.0001). Consequently, the total medical costs were reduced by 37% after ASV (1.95 ± 1.37 versus 3.11 ± 1.75 million yen/patient, p = 0.003). ASV therapy reduced readmissions and medical costs in patients with CHF.

The feasibility of substituting left atrial wall strain for flow velocity of left atrial appendage.

OBJECTIVE: Non-valvular atrial fibrillation (NVAF) is frequently complicated by thromboembolism. Left atrial appendage (LAA) flow is a predictor of LAA thrombosis. LAA flow is measured by transesophageal echocardiography (TEE), which is a semi-invasive diagnostic tool. Recently, speckle-tracking methods have been adapted for the evaluation of local cardiac function. We hypothesised that if we could determine LAA wall motion utilising a speckle tracking technique, we could non-invasively analyse LAA flow. METHODS: Sixty-three NVAF patients including 38 with chronic atrial fibrillation (CAF), 14 with paroxysmal AF (PAF) and 11 with atrial flutter (AFL) were enrolled in this study. Normal sinus rhythm (NSR) patients with non-thromboembolic cerebral infarction were also included. Immediately after obtaining a 2D movie of the LAA through the aortic oblique short axis view by transthoracic echocardiography, LAA flow velocity was measured by TEE. Mean strains between the posterior and anterior walls were measured using a speckle-tracking technique. RESULTS: Ten patients exhibited a thrombus and 11 had spontaneous echo contrast (SEC) in the auricle. Mean strain value was similar between CAF and PAF, although LAA flow velocity for CAF was significantly reduced compared with PAF (median value 13.7 cm/s versus 36.1 cm/s, p = <.00001). Mean strain of CAF with thrombus/SEC was significantly reduced compared with NSR patients (median value 1.52% versus 3.17%, p = .00181). Furthermore, mean strain was correlated with LAA flow velocity (R = 0.399, R2 = 0.1595, p = .000615). CONCLUSIONS: LAA wall strain identified via speckle-tracking methods may presage LAA peak flow velocity. This technique may contribute to stratification of thrombosis risks in the LAA.

A unique case of ST-elevation myocardial infarction related to very late stent thrombosis.

A 67-year-old man was transferred to our hospital because of anterior ST elevation myocardial infarction (STEMI). He had a history of a sirolimus-eluting stent implantation from the left main to the left anterior descending coronary artery (LAD) 9 years before and had undergone laparoscopic prostatectomy 8 days before in the setting of discontinuation of dual antiplatelet therapy. Emergent coronary angiography showed total occlusion in the distal LAD that was successfully treated by aspiration alone. Optical coherence tomography (OCT) showed no vulnerable lesion from the occluded lesion to the proximal LAD. OCT demonstrated that the thrombus attached to floating struts at the left main bifurcation and non-apposed struts at the left coronary ostium partly protruding to aorta, while the other struts were covered and well-apposed. Based on OCT findings, this case of STEMI was thought to be caused by distal embolism of a thrombus that formed at the stent site before it evolved into total occlusion. .

Isolated Left Atrial Infective Mural Endocarditis.

A 52-year-old man presented with a fever and malaise. Transthoracic echocardiogram was performed because of a holosystolic murmur, which showed mitral valve prolapse and a regurgitation jet toward the posterior wall of the left atrium. There was no apparent vegetation at any valves. Blood cultures were positive for Streptococcus mitis/oralis. Transesophageal echocardiogram revealed vegetation only at the posterior wall of the left atrium exposed to the mitral regurgitant jet. We diagnosed this condition as infective mural endocarditis. This case highlighted the need for a detailed observation of the valves and the atrial wall when infective endocarditis is suspected.

Beneficial effects of rapid introduction of adaptive servo-ventilation in the emergency room in patients with acute cardiogenic pulmonary edema.

BACKGROUND: Adaptive servo-ventilation (ASV) at home has been used for patients with chronic heart failure. However, its effect on acute cardiogenic pulmonary edema (ACPE) is not clear. The aim of this study was to elucidate the effect of ASV use in the emergency room in patients with ACPE. METHODS: We enrolled 198 consecutive patients with ACPE. Eighty patients received standard therapies, such as oxygen inhalation and vasodilators (conventional therapy group), and 118 received ASV in addition to standard therapy (ASV therapy group). ASV was initiated in the emergency room immediately after diagnosis. The procedure was switched over from ASV to endotracheal intubation (ETI) when oxygenation was insufficient. RESULTS: The ETI rate in the ASV therapy group was significantly lower than that in the conventional therapy group (3% vs. 21%, p<0.01). The intensive care unit and/or high care unit length of stay in the ASV therapy group was also significantly shorter than that in the conventional therapy group (1.9±2.1 days vs. 5.3±6.8 days, p<0.01). Consequently, the hospitalization period in the ASV therapy group was shorter than that in the conventional therapy group (19.3±11.0 days vs. 26.3±16.6 days, p<0.01). CONCLUSION: In patients with ACPE, rapid introduction of ASV in the emergency room reduces the need for ETI and decreases the hospitalization period.

Systemic versus coronary levels of inflammation in acute coronary syndromes.

To address a possible link between systemic and coronary inflammation in the setting of acute coronary syndromes, the authors examined both levels of 3 inflammatory mediators such as high sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, and matrix metalloproteinase (MMP)-9 in patients with the early phase of acute myocardial infarction (AMI). In total, 20 patients with AMI showing minimal elevation of cardiac enzymes were studied. Before angioplasty, peripheral blood and culprit coronary thrombus were sampled to compare systemic and coronary levels of hs-CRP, IL-6, and MMP-9. Relation of systemic levels of hs-CRP and IL-6 to culprit coronary morphology was also evaluated by the use of intravascular ultrasound. Systemic and coronary levels of hs-CRP were nearly equivalent (4.3 +/- 5.0 vs 4.7 +/- 5.4 mg/L, p = 0.279), whereas IL-6 and MMP-9 showed higher in coronary levels than in systemic levels (169 +/- 154 vs 93 +/- 107 microg/mL, p = 0.002 and 164 +/- 116 vs 103 +/- 94 ng/mL, p = 0.018, respectively). Systemic levels of hs-CRP were correlated with coronary levels of IL-6 (r = 0.566, p = 0.009). Culprit coronary plaque area demonstrated a positive relation with systemic levels of hs-CRP (r = 0.466, p = 0.038) and also IL-6 (r = 0.707, p <0.001). The present study may provide an important insight into the link between systemic and coronary levels of inflammation, which is also associated with vulnerable coronary morphology in the setting of acute coronary syndromes.

Prevention of positive coronary artery remodeling with statin therapy in patients with coronary artery diseases.

Since positive coronary artery remodeling with large plaque burden is associated with subsequent coronary events, the authors tested their hypothesis that secondary prevention of coronary events by a statin may be associated with inhibition of the process of positive coronary artery remodeling in underlying coronary atherosclerotic lesions in patients with coronary artery diseases. They evaluated the intravascular ultrasound imaging in angiographically normal coronary lesions at baseline and after 6 months of therapy in 64 patients with coronary artery diseases. External elastic membrane area was defined as the vessel area, and the difference between the vessel and lumen area was calculated as plaque area. The relative echogenicity of coronary plaque to adventitia was evaluated as acoustic characteristics of coronary plaque. Twenty-five patients were treated with a statin and 39 patients did not receive a statin. In patients treated with a statin, plaque area decreased by 12% (p = 0.013) compared to an increase in plaque area of 13% (p = 0.023) in those who did not receive a statin. The vessel area was not enlarged in patients treated with a statin but did show positive remodeling in patients who had plaque progression without a statin. The relative echogenicity of plaque was unchanged in patients treated with a statin but significantly decreased in patients not receiving a statin. A statin may prevent positive coronary artery remodeling via inhibition of plaque progression in underlying coronary atherosclerotic lesions in patients with coronary artery diseases.

Contrast-enhanced ultrasound for the evaluation of acute renal infarction.

A 65-year-old male in the dilated phase of hypertrophic cardiomyopathy and with persistent atrial fibrillation was admitted to our hospital because of an episode of ventricular fibrillation following an appropriate shock from an implantable cardiac defibrillator (ICD). At admission, electrocardiography showed a normal sinus rhythm. He had complained of back pain 7 days after the ICD shock. Renal infarction was suspected, although computed tomography and magnetic resonance imaging could not be performed because of chronic renal failure and the presence of his ICD. We, therefore, used contrast-enhanced ultrasonography with a contrast agent to evaluate his acute kidney injury. This showed the left kidney contained a wedge-shaped area that was not enhanced by the contrast agent, indicating an area of infarction.

A calcified amorphous tumor that developed on both sides of the atrioventricular valve annulus.

We report a rare case of a hemodialysis patient with a calcified amorphous tumor (CAT) on both sides of the atrioventricular valve annulus. A 70-year-old female who had received hemodialysis for 23 years because of chronic glomerulonephritis presented to our hospital with acute heart failure. Echocardiography indicated the presence of mobile cardiac masses on the mitral valve and tricuspid valve annulus. We suspected the presence of a cardiac tumor or vegetation. The patient received 3 g/day sulbactam-ampicillin and 60 mg/day gentamicin. Surgery was performed on the 14th day after hospital admission. The patient underwent mitral valve replacement, tricuspid annuloplasty, and tumor resection. Based on the pathological findings, the cardiac tumor was diagnosed as a CAT.

Remote ischemic preconditioning reduces contrast-induced acute kidney injury in patients with ST-elevation myocardial infarction: a randomized controlled trial.

BACKGROUND: Contrast medium-induced acute kidney injury (CI-AKI) is a cardiovascular complication after myocardial infarction treated with emergency percutaneous coronary intervention. The aim of this randomized, sham-controlled trial was to evaluate the impact of remote ischemic preconditioning (RIPC) on CI-AKI in patients with ST-elevation myocardial infarction who received emergency primary percutaneous coronary intervention. METHODS AND RESULTS: Patients with a suspected ST-elevation myocardial infarction were randomly assigned at a 1:1 ratio to receive percutaneous coronary intervention either with (n=63) or without (n=62) RIPC (intermittent arm ischemia through three cycles of 5min of inflation and 5min of deflation of a blood pressure cuff). A total of 47 RIPC patients and 47 control patients met all study criteria. The primary endpoint was the incidence of CI-AKI, which was defined as an increase in serum creatinine >0.5mg/dL or >25% over the baseline value 48-72h after administration of contrast medium. The incidence of CI-AKI was 10% (n=5) in the RIPC group and 36% (n=17) in the control group (p=0.003). The odds ratio of CI-AKI in patients who received RIPC was 0.18 (95% confidence interval: 0.05-0.64; p=0.008). CONCLUSIONS: In patients with ST-elevation myocardial infarction, RIPC before percutaneous coronary intervention reduced the incidence of CI-AKI.

Brain natriuretic peptide as a risk marker for incident hypertensive cardiovascular events.

We examined the effects of aging and hypertensive left ventricular hypertrophy on the plasma level of brain natriuretic peptide (BNP), and assessed BNP as a risk marker for incident hypertensive cardiovascular events. One hundred and eighty-five hypertensive patients were echocardiographically divided into a hypertensive group with normal left ventricular mass (n=96; age range, 37-86 years; left ventricular mass, 97+/-14 g/m2) and a hypertensive group with left ventricular hypertrophy (n=89; 37-90 years; 140+/-20 g/m2). Forty-four normotensive subjects served as the normotensive group (32-84 years; 91+/-15 g/m2). We examined the association of age with BNP in the three groups and also evaluated BNP as a risk marker for incident cardiovascular events by following up all patients for 40 months. All three groups demonstrated a significant positive relationship between age and BNP. The slope of the relation between age and BNP was steepest in the hypertensive group with left ventricular hypertrophy (p<0.0001 vs. the other two groups). Multiple regression analysis revealed that age, pulse pressure and left ventricular mass index were significantly associated with the increase in BNP. Multivariate Cox proportional hazards regression analysis, which was used to assess the potential association of age, pulse pressure, left ventricular mass index and BNP with the cardiovascular events during follow-up, revealed the highest correlation between BNP and incident cardiovascular events (risk ratio=1.011; p=0.0011). BNP, which is synergistically increased with aging and left ventricular hypertrophy, may be an important risk marker for hypertensive cardiovascular events.

Beneficial Effect of a Long-Term Antihypertensive Therapy on Blood Pressure Response to Isometric Handgrip Exercise in Patients with Essential Hypertension.

To elucidate the effect of a long-term antihypertensive therapy on blood pressure (BP) response to isometric handgrip exercise (IHG) in patients with essential hypertension (EHT, n = 16), IHG was carried out at 30% maximal voluntary contraction of right hand for 3 min before therapy and after a long-term antihypertensive therapy. BP responsiveness to IHG was estimated by the difference between values obtained at rest and at 3 min during IHG (change of systolic BP = DeltaSBP, change of diastolic BP = DeltaDBP. Both DeltaSBP and DeltaDBP before therapy were markedly greater in EHT (DeltaSBP = 64 plus minus 18 mm Hg, DeltaDBP = 33 plus minus 9 mm Hg) than in age-mathced normotensive controls (NT, n = 8, 29 plus minus 4 mm Hg, 18 plus minus 4 mm Hg). By antihypertensive therapy, SBP and DBP in EHT were decreased from 152 plus minus 22 mm Hg to 136 plus minus 14 mm Hg and from 90 plus minus 18 mm Hg to 83 plus minus 10 mm Hg, respectively, but both SBP and DBP in EHT after antihypertensive therapy were still greater than those in NT. Both DeltaSBP and DeltaDBP in EHT after a long-term antihypertensive therapy were significantly smaller than those in EHT before therapy but were still significantly larger than those in NT. These results demonstrate that a long-term antihypertensive therapy reduces the exaggerated BP response to IHG in EHT.