Feasibility of self-measurement telemonitoring using a handheld heart sound recorder in patients with heart failure - SELPH multicenter pilot study.

BACKGROUND: Multi-parametric assessment, including heart sounds in addition to conventional parameters, may enhance the efficacy of noninvasive telemonitoring for heart failure (HF). We sought to assess the feasibility of self-telemonitoring with multiple devices including a handheld heart sound recorder and its association with clinical events in patients with HF. METHODS: Ambulatory HF patients recorded their own heart sounds, mono­lead electrocardiograms, oxygen saturation, body weight, and vital signs using multiple devices every morning for six months. RESULTS: In the 77 patients enrolled (63 ±â€¯13 years old, 84 % male), daily measurements were feasible with a self-measurement rate of >70 % of days in 75 % of patients. Younger age and higher Minnesota Living with Heart Failure Questionnaire scores were independently associated with lower adherence (p = 0.002 and 0.027, respectively). A usability questionnaire showed that 87 % of patients felt self-telemonitoring was helpful, and 96 % could use the devices without routine cohabitant support. Six patients experienced ten HF events of re-hospitalization and/or unplanned hospital visits due to HF. In patients who experienced HF events, a significant increase in heart rate and diastolic blood pressure and a decrease in the time interval from Q wave onset to the second heart sound were observed 7 days before the events compared with those without HF events. CONCLUSIONS: Self-telemonitoring with multiple devices including a handheld heart sound recorder was feasible even in elderly patients with HF. This intervention may confer a sense of relief to patients and enable monitoring of physiological parameters that could be valuable in detecting the deterioration of HF.

Changes in cardiac acoustic biomarkers before and after cardiac events in a patient with right-sided heart failure due to cor pulmonale.

Chronic heart failure (HF) has various phenotypes. It is accompanied by repeated hospitalizations over a long period. Therefore, accumulating long-term observational data of patients with various backgrounds is important to establish a prediction technology for the exacerbation of HF. In a patient with chronic right-sided HF caused by cor pulmonale, heart sounds and electrocardiograms were recorded at home or our hospital twice a week for 7 months including the stable (31 days), pre-exacerbation (2 weeks just before the onset of exacerbation), and hospitalization periods and quantified as cardiac acoustic biomarkers (CABs) using AUDICOR technology (Inovise Medical, Inc., Portland, OR, USA). The relationship between the change in CABs and hospitalization events due to HF were investigated. During the pre-exacerbation period just before the onset of exacerbation of HF leading to hospitalization, inaudible changes in the third heart sound (S3) strength that were probably derived from the right heart were observed. Although the values of the fourth heart sound (S4) strength were high during the stable and pre-exacerbation period, values decreased markedly during hospitalization. These findings suggest that CABs including S3 and S4 are useful for the early detection of signs of HF exacerbation. Learning Objective: In a case of chronic right-sided heart failure, the change in the third heart sound (S3) caused by the right ventricle could be detected using cardiac acoustic biomarkers in exacerbations of heart failure. Even if S3 is inaudible by auscultation, it is possible to observe its changes using quantification technology.

Temporal changes of cardiac acoustic biomarkers and cardiac function in acute decompensated heart failure.

AIMS: Relationships between cardiac acoustic biomarkers (CABs) measured by acoustic cardiography and clinical outcomes have been reported in heart failure (HF) patients. However, no studies have investigated the temporal change of CABs and the corresponding changes in HF status. The purpose of this study was to assess whether the temporal changes of CABs in patients with acute decompensated heart failure (ADHF) reflect changes in cardiac function and status. METHODS AND RESULTS: Sixty ADHF patients were enrolled prospectively. CABs and echocardiography data were collected at admission, before discharge, and at the first clinic visit. CABs included electromechanical activation time (EMAT); the time interval from Q wave onset on electrocardiography to the first heart sound (S1), QoS2; the time interval from Q wave onset on electrocardiography to the second heart sound (S2); and third heart sound (S3) and fourth heart sound (S4) intensities, defined as the peak-to-peak amplitudes of S3 and S4. EMATc (EMAT/RR) (P = 0.001), S3 intensity (P < 0.001), and S4 intensity (P < 0.001) were significantly decreased, and QoS2 (P = 0.005) was significantly increased from admission to discharge. The change in S3 intensity was significantly correlated with that of E/A (ρ = 0.571, P < 0.001), and the extended QoS2 was also significantly correlated with the increase in the stroke volume index (ρ = 0.383, P = 0.004). CONCLUSIONS: Some CABs in ADHF patients changed significantly in the normal direction throughout the treatment course and could be useful biomarkers in ADHF management.

Concise asymmetric total synthesis of scyphostatin, a potent inhibitor of neutral sphingomyelinase.

The concise asymmetric total synthesis of scyphostatin has been achieved by condensation of the optically active cyclohexane unit, prepared from the commercially available 1,4-cyclohexadiene by our own method, and the side chain, prepared by the method developed by Hoye and Tennakoon (T. R. Hoye, M. A. Tennakoon, Org. Lett. 2000, 2, 1481-1483). The modification of the epoxy cyclohexenone unit was achieved in a late stage of the total synthesis, and deprotection of the primary alcohol was conducted in the final step. During the synthesis several key reactions were attained: 1) intramolecular bromoetherification of the cyclohexadiene acetal; 2) stereoselective introduction of the tertiary alcohol, 3) deprotection of the acetal function to the aldehyde by combination with silyl triflate/2,4,6-collidine and the one-pot synthesis of the disilyl aldehyde compounds, with different types of silyl groups, from the dihydroxy acetal compounds; and 4) facile deprotection of the 2,4-dimethoxyphenylmethyl ((2,4)DMPM) protecting group of the primary alcohol.

Reaction of the acetals with TESOTf-base combination; speculation of the intermediates and efficient mixed acetal formation.

We report here unexpected highly chemoselective deprotection of the acetals from aldehydes. Treatment of acetal compounds from aldehydes with TESOTf-2,6-lutidine or TESOTf-2,4,6-collidine in CH2Cl2 at 0 degrees C followed by H2O workup at the same temperature caused the conversion of the acetal functions to aldehyde functions. The reaction had generality and was applied to many acetal compounds. Study using various bases revealed the reaction and reached the best combination of TESOTf-base. It was very mild and highly chemoselective and proceeded under weakly basic conditions. Then, many functional groups such as allyl alcohol, silyl ether, acetate, methyl ether, triphenylmethyl (Tr) ether, 1,3-dithiolane, methyl ester, and tert-butyl ester could survive under these conditions. Furthermore, this methodology could selectively deprotect the acetals in the presence of ketals as the most characteristic feature, although this chemoselectivity is difficult to achieve by other previously reported methods. A detailed study of the reaction including MS and NMR studies revealed the reaction mechanism for determining the structures of the intermediates, pyridinium-type salts. These intermediates had a weak electrophilicity and were successfully applied to the efficient formation of the mixed acetals in high yields.

Unexpected highly chemoselective deprotection of the acetals from aldehydes and not ketones: TESOTf-2,6-lutidine combination.

Acetal functions are recognized as good protecting groups of carbonyl groups. Although many deprotecting methods of acetals to carbonyl functions have already been developed, there is no methodology which can deprotect acetals in the presence of ketals because the usual acidic or radical reactions occur more easily via the more stable cationic or radical intermediates from the ketals. On the other hand, this new method can proceed in a reverse manner to that described in previous reports. That is, the method can deprotect aliphatic acetals in the presence of ketals. The reaction condition is common for silylation, i.e., the TESOTf-2,6-lutidine combinations. Although the TMSOTf-2,6-lutidine combination can also deprotect acetals, it lacks chemoselectivity in deprotection of the acetals from aldehydes and ketones. The treatment of acetals with TESOTf and 2,6-lutidine in CH2Cl2 followed by a H2O workup gave the corresponding aldehydes. Of course, the compounds, which have both acetal and hydroxyl functions afforded the compounds obtained by the usual silylation of an alcohol and deprotection of an acetal without any problem. However, deprotection of the ketals from ketones was not observed during the conversion reaction of acetals from aldehydes. This chemoselectivity was confirmed in the reactions of the compounds that have the acetal and ketal in the same molecule. In both cases, the acetal functions were deprotected to give aldehydes with intact ketals. Furthermore, under the conditions described here, many functional groups such as methoxy, acetoxy, allyl alcohol, and silyloxy ether are intact. This method is very mild and available for many compounds.