Lifestyle Modification or Medication to Improve Condition of Patients With Asymptomatic Heart Failure　- Monitoring and Management of OptiVol Alert to Reduce Heart Failure Hospitalization II (MOMOTARO II) Study.

BACKGROUND: In heart failure (HF) patients implanted with high-energy devices, worsening of HF can be diagnosed from intrathoracic impedance (ITI) before symptoms appear. Early therapeutic intervention can prevent HF worsening, but the optimal intervention remains unknown. This study aimed to examine which lifestyle modifications or medications can improve HF indicators in asymptomatic HF patients diagnosed from ITI.Methods and Results:This multicenter, prospective, randomized study included patients with high-energy devices, left ventricular ejection fraction <40%, or with a history of HF hospitalization. After the OptiVol alert was evoked by decreased ITI, patients underwent examinations. If they were diagnosed with HF, they were randomly assigned to 3 groups: lifestyle modification, diuretic, or nitrate. After 1 week, they underwent the same examinations. The primary endpoint was change in ITI and serum B-type natriuretic peptide (BNP). Totally, 57 patients were randomized. In all 3 groups, ITI was significantly increased post-intervention compared with pre-intervention. In the diuretic and nitrate groups, logBNP post-intervention was significantly lower than pre-intervention, but not in the lifestyle modification group. CONCLUSIONS: Compared with lifestyle modifications, diuretic and nitrate therapy for 1 week may be more effective management of HF detected by decreased ITI. However, lifestyle modification may have the additional benefits of reducing the workload or cost.

Structure-Activity Relationship of Anti-malarial Allylpyrocatechol Isolated from Piper betle.

Malaria disease remains a serious worldwide health problem. In South-East Asia, one of the malaria infection "hot-spots," medicinal plants such as Piper betle have traditionally been used for the treatment of malaria, and allylpyrocatechol (1), a constituent of P. betle, has been shown to exhibit anti-malarial activities. In this study, we verified that 1 showed in vivo anti-malarial activity through not only intraperitoneal (i.p.) but also peroral (p.o.) administration. Additionally, some analogs of 1 were synthesized and the structure-activity relationship was analyzed to disclose the crucial sub-structures for the potent activity.

Analysis of arrhythmic events is useful to detect lead failure earlier in patients followed by remote monitoring.

BACKGROUND: Remote monitoring (RM) has been advocated as the new standard of care for patients with cardiovascular implantable electronic devices (CIEDs). RM has allowed the early detection of adverse clinical events, such as arrhythmia, lead failure, and battery depletion. However, lead failure was often identified only by arrhythmic events, but not impedance abnormalities. OBJECTIVE: To compare the usefulness of arrhythmic events with conventional impedance abnormalities for identifying lead failure in CIED patients followed by RM. METHODS: CIED patients in 12 hospitals have been followed by the RM center in Okayama University Hospital. All transmitted data have been analyzed and summarized. RESULTS: From April 2009 to March 2016, 1,873 patients have been followed by the RM center. During the mean follow-up period of 775 days, 42 lead failure events (atrial lead 22, right ventricular pacemaker lead 5, implantable cardioverter defibrillator [ICD] lead 15) were detected. The proportion of lead failures detected only by arrhythmic events, which were not detected by conventional impedance abnormalities, was significantly higher than that detected by impedance abnormalities (arrhythmic event 76.2%, 95% CI: 60.5-87.9%; impedance abnormalities 23.8%, 95% CI: 12.1-39.5%). Twenty-seven events (64.7%) were detected without any alert. Of 15 patients with ICD lead failure, none has experienced inappropriate therapy. CONCLUSIONS: RM can detect lead failure earlier, before clinical adverse events. However, CIEDs often diagnose lead failure as just arrhythmic events without any warning. Thus, to detect lead failure earlier, careful human analysis of arrhythmic events is useful.

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.

Essential role of the PSI-LHCII supercomplex in photosystem acclimation to light and/or heat conditions by state transitions.

Light and temperature affect state transitions through changes in the plastoquinone (PQ) redox state in photosynthetic organisms. We demonstrated that light and/or heat treatment induced preferential photosystem (PS) I excitation by binding light-harvesting complex II (LHCII) proteins. The photosystem of wheat was in state 1 after dark overnight treatment, wherein PQ was oxidized and most of LHCII was not bound to PSI. At the onset of the light treatment [25 °C in the light (100 µmol photons m-2 s-1)], two major LHCIIs, Lhcb1 and Lhcb2 were phosphorylated, and the PSI-LHCII supercomplex formed within 5 min, which coincided with an increase in the PQ oxidation rate. Heat treatment at 40 °C of light-adapted wheat led to further LHCII protein phosphorylation of, resultant cyclic electron flow promotion, which was accompanied by ultrafast excitation of PSI and structural changes of thylakoid membranes, thereby protecting PSII from heat damage. These results suggest that LHCIIs are required for the functionality of wheat plant PSI, as it keeps PQ oxidized by regulating photochemical electron flow, thereby helping acclimation to environmental changes.

Regulation of photochemical energy transfer accompanied by structural changes in thylakoid membranes of heat-stressed wheat.

Photosystems of higher plants alleviate heat-induced damage in the presence of light under moderate stressed conditions; however, in the absence of light (i.e., in the dark), the same plants are damaged more easily. (Yamauchi and Kimura, 2011) We demonstrate that regulating photochemical energy transfer in heat-treated wheat at 40 °C with light contributed to heat tolerance of the photosystem. Chlorophyll fluorescence analysis using heat-stressed wheat seedlings in light showed increased non-photochemical quenching (NPQ) of chlorophyll fluorescence, which was due to thermal dissipation that was increased by state 1 to state 2 transition. Transmission electron microscopy revealed structural changes in thylakoid membranes, including unstacking of grana regions under heat stress in light. It was accompanied by the phosphorylation of thylakoid proteins such as D1 and D2 proteins and the light harvesting complex II proteins Lhcb1 and Lhcb2. These results suggest that heat stress at 40 °C in light induces state 1 to state 2 transition for the preferential excitation of photosystem I (PSI) by phosphorylating thylakoid proteins more strongly. Structural changes of thylakoid membrane also assist the remodeling of photosystems and regulation of energy distribution by transition toward state 2 probably contributes to plastoquione oxidation; thus, light-driven electrons flowing through PSI play a protective role against PSII damage under heat stress.

Usefulness of right ventriculography compared with computed tomography for ruling out the possibility of lead perforation before lead extraction.

PURPOSE: High-risk patients can be identified by preprocedural computed tomography (CT) before lead extraction. However, CT evaluation may be difficult especially for lead tip identification due to artifacts in the leads. Selective right ventriculography (RVG) may enable preprocedural evaluation of lead perforation. We investigated the efficacy of RVG for identifying right ventricular (RV) lead perforation compared with CT in patients who underwent lead extraction. METHODS: Ninety-five consecutive patients who were examined by thin-section non-ECG-gated multidetector CT and RVG before lead extraction were investigated retrospectively. Newly recognized pericardial effusion after lead extraction was used as a reference standard for lead perforation. We analyzed the prevalence of RV lead perforation diagnosed by each method. The difference in the detection rates of lead perforation by RVG and CT was evaluated. RESULTS: Of the 115 RV leads in the 95 patients, lead perforation was diagnosed for 35 leads using CT, but the leads for 29 (83%) of those 35 leads diagnosed as lead perforation by CT were shown to be within the right ventricle by RVG. Three patients with 5 leads could not be evaluated by CT due to motion artifacts. The diagnostic accuracies of RVG and CT were significantly different (p < 0.001). There was no complication of pericardial effusion caused by RV lead extraction. CONCLUSION: RVG for identification of RV lead perforation leads to fewer false-positives compared to non-ECG-gated CT. However, even in cases in which lead perforation is diagnosed, most leads may be safely extracted by transvenous lead extraction.

A Low Critical Event Rate Despite a High Abnormal Event Rate in Patients with Cardiac Implantable Electric Devices Followed Up by Remote Monitoring.

Objective Remote monitoring (RM) of cardiac implantable electric devices (CIEDs) has been advocated as a healthcare standard. However, expert consensus statements suggest that all patients require annual face-to-face follow-up consultations at outpatient clinics even if RM reveals no episodes. The objective of this study was to determine the critical event rate after CIED implantation through RM. Methods This multicenter, retrospective, cohort study evaluated patients with pacemakers (PMs), implantable cardioverter defibrillators (ICDs), or cardiac resynchronization therapy defibrillator (CRT-Ds) and analyzed whether or not the data drawn from RM included abnormal or critical events. Patients A total of 1,849 CIED patients in 12 hospitals who were followed up by the RM center in Okayama University Hospital were included in this study. Results During the mean follow-up period of 774.9 days, 16,560 transmissions were analyzed, of which 11,040 (66.7%) were abnormal events and only 676 (4.1%) were critical events. The critical event rate in the PM group was significantly lower than that in the ICD or CRT-D groups (0.9% vs. 5.0% or 5.9%, p<0.001). A multivariate analysis revealed that ICD, CRT-D, and a low ejection fraction were independently associated with critical events. In patients with ICD, the independent risk factors for a critical event were old age, low ejection fraction, Brugada syndrome, dilated phase hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Conclusion Although abnormal events were observed in two-thirds of the transmitted RM data, the critical event rate was <1% in patients with a PM, which was lower in comparison to the rates in patients with ICDs or CRT-Ds. A low ejection fraction was an independent predictor of critical events.

Prognosis after lead extraction in patients with cardiac implantable electronic devices infection: Comparison of lead-related infective endocarditis with pocket infection in a Japanese single-center experience.

BACKGROUND: The increase in the use of cardiac implantable electronic devices (CIEDs) has been associated with an increase in CIED-related infections. Transvenous lead extraction is safe and effective for patients with CIED-related infections; however, the mortality rate in these patients is high. The prognosis after transvenous lead extraction in Japanese patients, especially those with lead-related infective endocarditis, has not been evaluated. Then, the purpose of this study is to clarify the prognosis after transvenous lead extraction in Japanese patients with CIED-related infections at a single Japanese center. METHODS: A total of 107 patients who underwent transvenous lead extraction were retrospectively reviewed. The patients were divided into a lead-related infective endocarditis group (n = 32) and a pocket infection group (n = 75). Procedure success rate and prognosis after lead extraction were evaluated between the two groups. RESULTS: Procedure success rate was not significantly different between the groups. There were no deaths associated with the procedure or with infection. The survival rate was not significantly different at 1 year or at a median of 816 days (lead-related infective endocarditis vs pocket infection; 93.7% vs 94.7%, P = 1.000; 78.1% vs 81.3%, P = 0.791) Time to reimplantation and duration of hospital stay and antibiotics therapy were significantly longer for patients with lead-related infective endocarditis. CONCLUSION: In this study, the prognosis for patients with lead-related infective endocarditis after transvenous lead extraction was favorable. Thus, extraction should be strongly recommended, even if the general condition of the patient is poor.

Two cases of inappropriate implantable cardioverter-defibrillator therapies due to T wave oversensing induced by body twisting.

T wave oversensing (TWOS) is a common cause of inappropriate implantable cardioverter-defibrillator (ICD) therapies. Various algorithms to avoid inappropriate ICD therapy are available; however, they are not helpful to avoid TWOS. Although the reproduction of TWOS is useful to resolve the problem of TWOS, it is sometimes difficult to reproduce TWOS. We report two cases of inappropriate ICD therapy due to TWOS, which were induced only by body twisting. We can successfully manage the device based on the evidence of reproduced TWOS.

Comparison of longevity and clinical outcomes of implantable cardioverter-defibrillator leads among manufacturers.

BACKGROUND: An early failure of the Biotronik Linox S/SD implantable cardioverter-defibrillator (ICD) lead has been reported. We have also experienced several cases with early failure of Linox leads. OBJECTIVE: Our aim was to assess the longevity of Linox S/SD (Biotronik, Berlin, Germany) compared with Sprint Fidelis (Medtronic, Minneapolis, MN), Sprint Quattro (Medtronic), and Endotak Reliance (Boston Scientific, Natick, Massachusetts) leads. METHODS: We retrospectively reviewed patients who had undergone implantation of Linox S/SD (n = 90), Sprint Fidelis (n = 37), Sprint Quattro (n = 27), or Endotak Reliance (n = 50) leads between June 2000 and December 2013 at our hospital. Variables associated with lead failure were assessed by the Kaplan-Meier method and Cox survival modeling. RESULTS: Failure rates of Linox, Sprint Fidelis, and Endotak leads were 3.2%/year (7-year survival rate, 81.0%), 3.4%/year (7-year survival rate, 77.2%), and 0.61%/year (7-year survival rate, 95.8%), respectively. No lead failure was found with Sprint Quattro leads. The survival probability of Linox leads was significantly lower than that of Endotak leads (P = .049) and comparable to that of Sprint Fidelis leads (P = .69). In univariate analysis, age was the only predictor of Linox lead failure. Patients <58 years old were at significantly increased risk of lead failure compared with patients ≥58 years old (hazard ratio, 9.0; 95% confidence interval, 1.13-71.3; P = .037). CONCLUSION: In our single-center experience, the survival rate of Linox leads was unacceptably low. The only predictor of Linox lead failure was age at implantation. This is the first description of a lower survival rate for Linox leads in an Asian population.

Epicardially placed implantable cardioverter-defibrillator for a child with congenital long QT syndrome.

A 7-year-old boy presented at our hospital with syncope. At birth, electrocardiography had shown a long QT interval with torsade de pointes (TdP). Congenital long QT syndrome (LQTS) had been diagnosed by genetic testing, and was successfully controlled with oral propranolol. At age 7, TdP had recurred with syncope. Electrocardiography revealed a prominent long QT interval with T-wave alternans. The propranolol dose was increased, but TdP remained uncontrolled. A cardioverter-defibrillator (ICD) was implanted epicardially, and TdP completely resolved with atrial pacing. We report this rare case of ICD implantation in a child with LQTS.

Complete right bundle branch block and QRS-T discordance can be the initial clue to detect S-ICD ineligibility.

BACKGROUND: In order to minimize inappropriate shocks of subcutaneous implantable cardioverter-defibrillators (S-ICD), it is important to recognize who is suitable for S-ICD indication. This study aimed to clarify what types of cardiac disease are likely to fulfill the S-ICD screening criteria and ineligible factors for S-ICD in the standard 12-lead electrocardiogram (ECG). METHODS: A total of 348 patients with heart disease were enrolled. They were assessed by supine and standing ECG recording to simulate the 3 S-ICD sensing vectors and standard 12-lead ECG, simultaneously. Clinical and ECG characteristics were analyzed to compare the patients who are eligible and ineligible with S-ICD screening ECG indication. RESULTS: The mean age of study patients was 49±21 years and 244 (70%) were men. Nineteen percent of patients were unsuitable for S-ICD. There was no significant difference in ineligibility for S-ICD among cardiac diseases (p=0.48). Univariate analysis showed complete right bundle branch block (CRBBB), QRS-T discordance in lead II, and QRS-T discordance in 3 leads (I, II, and aVF) were more frequent in patients who were ineligible for S-ICD than in the eligible group. Multivariate regression analysis showed CRBBB and QRS-T discordance in 3 leads were independent predictors for ineligibility of S-ICD. CONCLUSION: There are no differences in eligibility of S-ICD among types of cardiac diseases. CRBBB and QRS-T discordance were independent predictors for ineligibility.

Initial experience with the subcutaneous implantable cardioverter-defibrillator in a single Japanese center.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is recognized as a viable alternative to the transvenous ICD. The safety and efficacy of this device has been demonstrated in Western countries, but studies with S-ICD implantation in Japanese patients have not been reported. METHODS AND RESULTS: Twelve patients received an S-ICD implant in our institute between February and September 2016. All S-ICDs were successfully implanted without complications. One appropriate and one inappropriate therapy was identified. CONCLUSIONS: S-ICD implantation appears to provide a viable alternative to transvenous ICD implantation for some Japanese patients. However, we should perform careful follow-up of patients to eliminate inappropriate therapy.

An improved algorithm calculated from intrathoracic impedance can precisely diagnose preclinical heart failure events: Sub-analysis of a multicenter MOMOTARO (Monitoring and Management of OptiVol Alert to Reduce Heart Failure Hospitalization) trial study.

BACKGROUND: Ambulatory measurement of intrathoracic impedance (ITI) with an implanted device has potential to assess fluid accumulation in patients with heart failure (HF), but it has failed to reduce HF-related hospitalization because of a high false-positive rate. OBJECTIVE: We aimed to examine whether a modified algorithm (OptiVol 2.0) could reduce false-positive HF events documented in our multicenter trial (MOMOTARO). METHODS: The MOMOTARO trial assessed the potential that fluid index could predict fluid accumulation and therefore HF. The MOMOTARO trial assessed whether HF events could be detected based on fluid accumulation as assessed by fluid index. We re-analyzed raw data of ITI trends of the threshold-crossing events with the modified algorithm. RESULTS: The study consisted of 195 patients who had been implanted with a high-energy device. During a mean follow-up period of 658±165 days, there were 154 primary HF events detected by the previous algorithm (OptiVol 1.0). With the previous algorithm, there was no significant difference in log concentration of brain natriuretic peptide (BNP) between baseline and alert (p=0.21). Among 150 alerts of the previous algorithm, only 37 reached the threshold by the modified algorithm, and log BNP was significantly higher in these 37 events compared with the baseline value (2.40±0.46 vs. 2.27±0.52, p<0.01). CONCLUSION: Our simulation study demonstrates that fluid index calculated with the modified algorithm reduces the number of false-positive threshold-crossing HF events and is promising for accurate diagnosis of fluid accumulation in patients.

Organic synthesis using a hypervalent iodine reagent: unexpected and novel domino reaction leading to spiro cyclohexadienone lactones.

The reaction of 1-(p-hydroxyaryl)cyclobutanols and phenyl iodide(III) diacetate in hexafluoroisopropanol and water produced spiro cyclohexadienone lactones via a domino reaction.