A cost-effectiveness analysis of remote monitoring after pacemaker implantation for bradycardia in Japan.

BACKGROUND: Although remote monitoring (RM) after pacemaker implantation is common, its cost-effectiveness has not been fully investigated. Therefore, we assessed the cost-effectiveness of RM compared with conventional follow-up (CFU) in Japanese patients with pacemakers. METHODS: A Markov model was constructed to analyze costs and quality-adjusted life years after pacemaker implantation. The target population was Japanese patients implanted with a dual-chamber pacemaker for bradycardia. Transition probabilities (e.g. atrial fibrillation, stroke, and device trouble) were obtained from literature and expert sources. Additionally, stroke risk was determined according to anticoagulation and CHADS2 scores. We used a 10-year horizon with sensitivity analyses for significant variables. RESULTS: Compared to CFU, RM was more effective; however, it was also more expensive. When the range of the Japanese willingness-to-pay threshold was considered to be ¥5,000,000, RM was at least cost-neutral relative to the CFU in all elderly patients with pacemakers for bradycardia. The cost-effectiveness of RM relative to CFU could be higher for patients with high CHADS2 scores, especially in patients with a CHADS2 score ≥ 3. Scenario analyses changing the interval between visits to an in-office evaluation in the CFU also demonstrated the same conclusions. In particular, when the interval between office visits was 1 year for the CFU, the RM could be more cost-effective. CONCLUSIONS: This study demonstrated that RM can be a cost-effective option for Japanese patients, especially those with high CHADS2 scores and long-term intervals between office visits.

Usefulness of intravascular ultrasound assessment after development of the slow flow phenomenon during percutaneous coronary intervention.

The slow flow phenomenon is a critical complication during percutaneous coronary intervention (PCI) that leads to poor outcomes. We aimed to evaluate the mechanisms underlying the slow flow phenomenon using intravascular ultrasound (IVUS). We retrospectively analyzed IVUS data from 62 lesions in 58 consecutive patients who experienced the slow flow phenomenon during PCI. IVUS was performed immediately after the development of the slow flow phenomenon to assess its cause. No IVUS-based evidence of mechanical obstruction was categorized as distal embolization. Distal embolization was observed in 46 lesions (74%). The slow flow phenomenon occurred in all these lesions after stent implantation. In addition to distal embolization, three different mechanisms underlying the induction of the slow flow phenomenon due to mechanical obstructions (16 lesions, 26%) were detected on IVUS, namely, medial dissection/hematoma (6 lesions), intimal flap (6 lesions), and thrombus obstruction (4 lesions). Most mechanical obstructions (13 lesions, 81%) could not be identified by angiography alone. In 15/16 lesions (94%) with mechanical obstruction, deteriorated flow improved immediately after balloon dilatation or bail-out stent implantation, although intracoronary vasodilator administration could not reestablish coronary flow. The frequency of mechanical obstruction as the cause of the slow flow phenomenon was relatively high. Given the difficulty in angiographical differentiation, IVUS-guided management of slow flow may be a useful strategy.

Cost-Effectiveness of long-term tolvaptan administration for chronic heart failure treatment in Japan.

BACKGROUND: Tolvaptan (TLV) is effective for acute heart failure (HF) with congestion, but its long-term administration in patients with chronic HF (CHF) remains controversial. Moreover, the cost-effectiveness of TLV for CHF treatment has not yet been investigated. Thus, we sought to validate the cost-effectiveness of TLV for CHF treatment in Japan. METHODS: A Markov model was developed to compare total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) between long-term TLV strategy and the standard strategy using furosemide for CHF. The target population included 75-year-old patients with CHF. The effectiveness of the TLV strategy for CHF treatment was determined based on a systematic review and meta-analysis. We used a 10-year horizon, with sensitivity analyses for significant variables and a scenario analysis for patients with CHF receiving high-dose furosemide (≥60 mg per day). RESULTS: In the base case analysis, the total cost of the long-term TLV strategy was higher than that of the standard strategy (¥3,243,779 vs. ¥1,179,964). The total QALYs of the long-term TLV strategy were lower than those of the standard strategy (4.52 vs 4.59). Thus, a standard TLV prescription for CHF treatment has no clinical or economic benefit. In the scenario analysis (i.e. in patients with CHF receiving high-dose furosemide), the long-term TLV strategy was more effective (total QALYs, 5.10 vs. 4.41) but more expensive (total costs, ¥3,540,558 vs. ¥1,272,208) than the standard strategy. The ICER of the TLV strategy against the standard strategy (¥3,289,579/QALY) was below the willingness-to-pay of ¥5,000,000, which suggests that the long-term TLV strategy is cost-effective relative to the standard strategy in patients with CHF receiving high-dose furosemide. CONCLUSIONS: Long-term TLV administration did not provide a clear benefit for all patients with CHF. However, this treatment strategy may be a cost-effective therapeutic option for patients who require high-dose furosemide.

Semiquantitative assessment of the relative apical sparing pattern of longitudinal strain for cardiac amyloidosis identification.

BACKGROUNDS: The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, the visual assessment of RASP is inconsistent, and the quantitative assessment of RASP is time-consuming. This study aimed to compare assessments of RASP for the identification of CA with conventional assessments and investigate their reproducibility and relevance on the assessments. METHODS: Forty patients with biopsy-proven CA were compared with 80 hypertrophied patients matched for mean LV wall thickness. We compared the discriminative abilities of three assessments of RASP to identify CA (visual, quantitative, and semiquantitative). Nine patterns of semiquantitative RASP were investigated; finally, it was defined as "reduction of LS" (≥ -10%) in ≥5 (of 6) basal segments, relative to "preserved LS" (< -15%) in at least one apical segment. RESULTS: The concordance between the two observers for visual RASP was modest (κ = 0.65). On the other hand, the consistency for semiquantitative RASP was perfect (κ = 1.00). The discriminative ability of semiquantitative RASP (area under the curve [AUC]  = 0.74) was significantly better than that of visual RASP (AUC = 0.65) and equivalent to that of binary quantitative RASP. CONCLUSION: Semiquantitative RASP assessment is reproducible and accurately discriminates CA. This simple assessment may help readily refine the risk stratification of patients with diffuse LV hypertrophy.

Combined assessment of subtended myocardial volume and myocardial blood flow for diagnosis of obstructive coronary artery disease using cardiac computed tomography: A feasibility study.

BACKGROUND: This study aimed to evaluate the combined diagnostic performance of coronary artery stenosis-subtended myocardial volume (Vsub) and myocardial blood flow (MBFsub) on computed tomography (CT) for detecting obstructive coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) and fractional flow reserve (FFR). METHODS: Thirty-nine patients who underwent coronary CT angiography (CTA) and stress dynamic myocardial CT perfusion (CTP) prior to ICA were enrolled. Obstructive CAD was defined as severe (≥70%) or moderate (30-69%) stenosis with FFR ≤0.8 on ICA. The Vsub was semi-automatically calculated from coronary CTA data using Voronoi diagram-based myocardial segmentation. The standard CT-MBF based on the 17-segment model was calculated using dynamic stress CTP data and deconvolution analysis. The CT-MBFsub was automatically analyzed by integrating the CT-MBF and Voronoi diagram-based myocardial segmentation analyses. The diagnostic performance of combined CT-MBFsub and Vsub assessment was determined using receiver operating characteristic analysis and compared with standard CT-MBF and CT-MBFsub. RESULTS: Of 117 vessels in 39 patients, 72 vessels were suspected of significant stenosis on CTA and 33 vessels had obstructive CAD on ICA and FFR. The sensitivity and specificity for identifying obstructive CAD were 67% and 82% for standard CT-MBF, 70% and 77% for CT-MBFsub, and 85% and 82% for combined CT-MBFsub and Vsub assessment. The area under the receiver operating characteristic curve of the combined CT-MBFsub and Vsub assessment was significantly higher than those of standard CT-MBF and CT-MBFsub (0.89 vs. 0.75, 0.77; p<0.05). CONCLUSIONS: The Vsub may aid in increasing the diagnostic performance of CT-MBFsub for detecting obstructive CAD.

Cost-Effectiveness of Obstructive Sleep Apnea Screening and Treatment Before Catheter Ablation for Symptomatic Atrial Fibrillation.

Background: Although management of obstructive sleep apnea (OSA) has been recommended to improve outcomes of catheter ablation (CA) in patients with symptomatic atrial fibrillation (AF), the most cost-effective way of preprocedural OSA screening is undetermined. This study assessed the cost-effectiveness of OSA management before CA for symptomatic AF. Methods and Results: A Markov model was developed to assess the cost-effectiveness of 3 OSA detection strategies before CA: no screening; Type 3 portable monitor (PM)-guided screening; and polysomnography (PSG)-guided screening. The target population consisted of a hypothetical cohort of patients aged 65 years with symptomatic AF, with 50% prevalence of OSA. We used a 5-year horizon, with sensitivity analyses for significant variables and scenario analyses for lower and higher OSA prevalence (30% and 70%, respectively). In the base-case, both types of OSA screening were dominant (less costly and more effective) relative to no screening. Although PSG-guided management was more effective than PM-guided management, it was more costly and therefore did not show clear benefit. These findings were replicated in cohorts with lower and higher OSA risks. Conclusions: OSA screening before CA is cost-effective in patients with symptomatic AF, with PM screening being the most cost-effective. Physicians should consider OSA management using this simple tool in the decision making for treatment of symptomatic AF.

Impact of the sampling rate of dynamic myocardial computed tomography perfusion on the quantitative assessment of myocardial blood flow.

BACKGROUND: The relationship between shot-to-shot sampling rates for dynamic myocardial computed tomography perfusion (CTP) and robustness of CTP-derived myocardial blood flow (CT-MBF) is debatable. We retrospectively investigated the influence of a reduced sampling rate for dynamic CTP on CT-MBF computation and diagnostic performance for detecting myocardial perfusion abnormalities. METHODS: Pharmacological stress dynamic whole-heart CTP was performed in 120 patients suspected with coronary artery disease. Dynamic CTP data were obtained for 30 continuous heartbeats during the R-peak to R-peak (1RR) interval on electrocardiography. Three additional datasets were created with sub-sampling acquisitions every 2, 3, and 4 heartbeats from the original dataset as interval times of 2RR, 3RR, and 4RR, respectively. CT-MBF was calculated using deconvolution analysis and determined as the mean value of the whole heart (global CT-MBF) and using the 16-segment model (segmental CT-MBF). The diagnostic performance of segmental CT-MBF for detecting perfusion abnormalities was compared to that of cardiac magnetic resonance imaging as the gold standard in 32 of 120 patients. These results were compared among the four CTP datasets. RESULTS: Global CT-MBFs for 1RR, 2RR, 3RR, and 4RR sampling were 1.57 ±â€¯0.34, 1.54 ±â€¯0.36, 1.51 ±â€¯0.37, and 1.41 ±â€¯0.33 mL/g/min, respectively. Areas under the receiver operating characteristic curves of segmental CT-MBF for 1RR, 2RR, 3RR, and 4RR sampling were 0.84, 0.83, 0.79, and 0.76, respectively (1RR versus [vs.] 2RR, non-significant; 1RR vs. 3RR or 4RR, p < 0.05). CONCLUSION: CT-MBF with 2RR sampling has similar performance with regard to quantification and detecting myocardial perfusion abnormalities as that with 1RR sampling.

Intravascular Ultrasound-Derived Virtual Fractional Flow Reserve for the Assessment of Myocardial Ischemia.

BACKGROUND: Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging method that provides information about lumen and vessel morphology. Previous studies on the expanded use of IVUS to identify functional ischemia have noted an association between anatomy and physiology, but IVUS-derived minimum lumen area (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR. We developed a method to calculate FFR using IVUS-derived anatomical information for the assessment of myocardial ischemia. The aims of this study were to investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS-FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for functional assessment.Methods and Results:We retrospectively analyzed 50 lesions in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously. IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean percent diameter stenosis determined on quantitative coronary angiography and on FFR was 56.4±10.7 and 0.69±0.08, respectively. IVUS-FFR had a stronger linear correlation with FFR (R=0.78, P<0.001; root mean square error, 0.057 FFR units) than with IVUS-derived MLA (R=0.43, P=0.002). CONCLUSIONS: IVUS-FFR may be a more valuable method to identify myocardial ischemia, compared with IVUS-derived MLA.

Cardiovascular Outcomes in Patients With Previous Myocardial Infarction and Mild Diabetes Mellitus Following Treatment With Pioglitazone: Reports of a Randomised Trial From The Japan Working Group for the Assessment Whether Pioglitazone Protects DM Patients Against Re-Infarction (PPAR Study).

BACKGROUND: Secondary prevention in patients with myocardial infarction (MI) is critically important to prevent ischaemic heart failure and reduce social burden. Pioglitazone improves vascular dysfunction and prevents coronary atherosclerosis, mainly via anti-inflammatory and antiatherogenic effects by enhancing adiponectin production in addition to antihyperglycemic effects, thus suggesting that pioglitazone attenuates cardiovascular events in patients with mild (HbA1c levels < 6·5%) diabetes mellitus (DM). Therefore, we evaluated the effects of pioglitazone on cardiovascular events in patients with both previous MI and mild DM. METHODS: In this multicentre, prospective, randomised, open, blinded-endpoint trial, we randomly assigned 630 patients with mild DM with a history of MI to undergo either DM therapy with (pioglitazone group) or without (control group) pioglitazone. DM was diagnosed using the 75-g oral glucose tolerance test, and mild DM was defined if HbA1c level was < 6·5%. The primary endpoint was the composite of cardiovascular death and hospitalisation caused by acute MI, unstable angina, coronary revascularisation (including percutaneous coronary intervention and cardiac bypass surgery), and stroke. FINDINGS: HbA1C levels were 5·9 and 5·8% (p = 0·71) at baseline and 6·0 and 5·8% (p < 0·01) at 2 years for the control and pioglitazone groups, respectively.The primary endpoint was observed in 14·2% and 14·1% patients in the control and pioglitazone groups during two years (95% confidential interval (CI):0.662-1·526, p = 0·98), respectively; the incidence of MI and cerebral infarction was 0·3% and 2·2% (95%CI: 0·786-32·415, p = 0·09) and 1·0% and 0·3% (95%CI: 0·051-3·662, p = 0·44), respectively. Post-hoc analyses of the 7-year observation period showed that these trends were comparable (21·9% and 19·2% in the control and pioglitazone groups, 95%CI: 0.618-1·237, p = 0·45). INTERPRETATION: Pioglitazone could not reduce the occurrence of cardiovascular events in patients with mild DM and previous MI.

Intracoronary Optical Coherence Tomography-Derived Virtual Fractional Flow Reserve for the Assessment of Coronary Artery Disease.

Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Optical coherence tomography (OCT) provides accurate visualization of coronary artery morphology. The aim of this study was to investigate the relation between FFR and OCT-derived FFR. We retrospectively analyzed 31 lesions (25 left anterior descending arteries, 2 left circumflex arteries, and 4 right coronary arteries) in 31 patients with moderate-to-severe coronary stenosis, who underwent OCT and FFR measurements simultaneously. OCT-derived FFR was calculated by the original algorithm, which was calculated using the following equation based on fluid dynamics: ΔP = FV + SV2, where V is the flow velocity, F is the coefficient of pressure loss because of viscous friction (Poiseuille resistance), and S is the coefficient of local pressure loss because of abrupt enhancement (flow separation). Mean values of % diameter stenosis by quantitative coronary angiography and FFR were 55.2 ± 14.0% and 0.70 ± 0.14, respectively. OCT-derived FFR showed a stronger linear correlation with FFR measurements (r = 0.89, p <0.001; root mean square error = 0.062 FFR units) than quantitative coronary angiography % diameter stenosis (r = -0.65, p <0.001), OCT measurements of minimum lumen area (r = 0.68, p <0.001), and % area stenosis (r = -0.70, p <0.001). OCT-derived FFR has the potential to become an alternative method for the assessment of functional myocardial ischemia, and may elucidate the relation between coronary morphology and FFR.