Immediate pharmacotherapy intensification after cardiac resynchronization therapy: incidence, characteristics, and impact.

AIMS: Cardiac resynchronization therapy (CRT) is an established treatment for drug-refractory heart failure (HF) in patients with left bundle branch block (LBBB). Acute haemodynamic improvement after CRT implantation may enable the intensification of HF medication soon thereafter. Immediate pharmacotherapy intensification (IPI) after CRT implantation achieves a synergetic effect, possibly leading to a better prognosis. This study aimed to explore the incidence, characteristics, and impact of IPI on real-world outcomes among CRT recipients with a history of hospitalization for acute HF. METHODS AND RESULTS: This multicentre retrospective study enrolled CRT recipients with LBBB morphology, a QRS width ≥120 ms, a left ventricular ejection fraction ≤35%, and New York Heart Association II-IV HF symptoms. All patients had previous HF hospitalizations within the previous year and received guideline-directed medical therapy before CRT implantation. Patient baseline characteristics, including HF medication, were collected. IPI was defined as the intensification of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists within 30 days of CRT implantation. The primary endpoint was all-cause death or first hospitalization for HF; the secondary endpoint was all-cause death. We enrolled 194 patients (75% male; mean age, 65 ± 13 years; 78% with non-ischaemic cardiomyopathy). One hundred five (54%) patients received IPI. Patients who received IPI exhibited a significantly shorter QRS duration (159 ± 26 vs. 171 ± 32 ms; P = 0.004), higher estimated glomerular filtration rate (55.2 ± 20.0 vs. 47.8 ± 24.7 mL/min/1.73 m2 ; P = 0.022), and more dilated cardiomyopathy. During a median follow-up period of 29 months, 70 (36%) patients reached the primary endpoint and 42 (22%) patients died. Patients with IPI showed significantly better outcomes for the primary and secondary endpoints than patients without IPI. The volumetric responder ratio at 6 months after implantation was not significantly different between patients with and without IPI; however, patients who received IPI had reduced mortality even at 6 months after implantation. In the multivariate analysis, IPI was an independent predictor of the primary endpoint (hazard ratio, 0.51; 95% confidence interval, 0.27-0.97; P = 0.043). CONCLUSIONS: Immediate intensification of HF medication was achieved in 54% of CRT recipients and was significantly higher in patients without excessive QRS prolongation, preserved renal function, and dilated cardiomyopathy than others. In patients with LBBB morphology and QRS ≥ 120 ms, IPI was associated with a significantly better prognosis and fewer HF hospitalizations after CRT implantation than others.

Introduction of pseudo-base benzimidazole derivatives into nucleosides via base exchange by a nucleoside metabolic enzyme.

In alternate organic synthesis, biocatalysis using enzymes provides a more stereoselective and cost-effective approach. Synthesis of unnatural nucleosides by nucleoside base exchange reactions using nucleoside-metabolizing enzymes has previously shown that the 5-position recognition of pyrimidine bases on nucleoside substrates is loose and can be used to introduce functional molecules into pyrimidine nucleosides. Here we explored the incorporation of purine pseudo bases into nucleosides by the base exchange reaction of pyrimidine nucleoside phosphorylase (PyNP), demonstrating that an imidazole five-membered ring is an essential structure for the reaction. In the case of benzimidazole, the base exchange proceeded to give the deoxyribose form in 96 % yield, and the ribose form in 23 % yield. The reaction also proceeded with 1H-imidazo[4,5-b]phenazine, a benzimidazole analogue with an additional ring, although the yield of nucleoside was only 31 %. Docking simulations between 1H and imidazo[4,5-b]phenazine nucleoside and the active site of PyNP (PDB 1BRW) supported our observation that 1H-imidazo[4,5-b]phenazine can be used as a substrate by PyNP. Thus, the enzymatic substitution reaction using PyNP can be used to incorporate many purine pseudo bases and benzimidazole derivatives with various functional groups into nucleoside structures, which have potential utility as diagnostic or therapeutic agents.

Combined use of venoarterial extracorporeal membrane oxygenation and intra-aortic balloon pump after cardiac arrest.

OBJECTIVES: We investigated whether intra-aortic balloon pump (IABP) combined with venoarterial extracorporeal membrane oxygenation (VA-ECMO) was associated with favourable neurological outcomes for patients after the return of spontaneous circulation (ROSC). Moreover, we evaluated the aetiology of cardiac arrest on the effectiveness of this therapy in a sub-study. BACKGROUND: There is insufficient research on the optimal combination of machines for patients after ROSC is not established. METHODS: This is a large-scale, multicentre, 30-day cohort study. Among 80,716 patients who delivered to the emergency room, 935 patients treated with VA-ECMO after ROSC were included using the data from the Tokyo Cardiovascular Care Unit Network Registry between 2010 and 2017. The study patients were stratified according to the use of IABP [the ECMO + IABP group (n = 762) vs. the ECMO-alone group (n = 173)]. We also evaluated the cause of cardiac arrest [acute coronary syndrome (ACS) and non-ACS] in the sub-study. To adjust the patients' backgrounds, we used the propensity score matching for additional analyses. The endpoint was 30-day favourable neurological outcome. RESULTS: The ECMO + IABP group showed significantly better neurological outcomes than the ECMO-alone group (crude; 35% vs. 25%; log-lank P < 0.001). In the ACS subgroup, the ECMO + IABP group showed significantly better neurological outcome (crude; 34% vs. 18%; log-lank P < 0.001), but not in the non-ACS subgroup (crude; 38% vs. 32%; log-lank P = 0.11). These results are similar after adjustments to their backgrounds using propensity matching. CONCLUSIONS: Compared to VA-ECMO alone, the combined use of VA-ECMO and IABP is associated with better neurological outcomes after ROSC, especially in complicated ACS.

An on-demand bench-top fabrication process for fluidic chips based on cross-diffusion through photopolymerization.

In this paper, we propose a novel approach to fabricate fluidic chips. The method utilizes molecular cross-diffusion, induced by photopolymerization under ultraviolet (UV) irradiation in a channel pattern, to form the channel structures. During channel structure formation, the photopolymer layer still contains many uncured molecules. Subsequently, a top substrate is attached to the channel structure under adequate pressure, and the entire chip is homogenously irradiated by UV light. Immediately thereafter, a sufficiently sealed fluidic chip is formed. Using this fabrication process, the channel pattern of a chip can be designed quickly by a computer as binary images, and practical chips can be produced on demand at a benchtop, instead of awaiting production in specialized factories.

Association Between Multivessel Coronary Artery Disease and Return of Spontaneous Circulation Interval in Acute Coronary Syndrome Patients with Out-of-Hospital Cardiac Arrest.

Acute coronary syndrome (ACS) is the major cause of out-of-hospital cardiac arrest (OHCA). The relationship between the findings from the study of coronary images and return of spontaneous circulation (ROSC) interval is still unknown. Hence, we investigated this relationship in ACS patients with OHCA.A cohort of 2779 patients was admitted to our emergency center due to cardiopulmonary arrest (CPA) between April 2011 and March 2015. We included ACS patients who had CPA with ventricular fibrillation (VF) as an initial rhythm, were successfully resuscitated, underwent coronary angiography (CAG), had a culprit lesion, and were diagnosed with ACS (n = 58; age, 63.7 ± 12.0 years; 93.1% male).We divided the 58 patients into two groups, an early ROSC group (ROSC ≤ 20 minutes: E-ROSC) and a late ROSC group (ROSC > 20 minutes: L-ROSC), and then analyzed their characteristics.The finding of a collateral artery for the culprit lesion location, Rentrop II-III, and TIMI III flow on CAG on arrival presented no significant differences between the two groups (Rentrop II-III: 25.0% versus 23.5%, P = 0.90; TIMI III: 33.3% versus 35.3%, P = 0.88). The incidence of multivessel coronary artery disease (MVD) was lower in the E-ROSC group than in the L-ROSC group (16.7% versus 58.8%, P = 0.001).Collateral and TIMI flow were not associated with ease of resuscitation, but MVD may have a negative impact on resuscitation, especially in VF patients.

Clinical impact of the gap-angle ratio in patients with ostial lesions of the right coronary artery undergoing percutaneous coronary intervention.

The aim of this study was to investigate the incidence of binary restenosis and its predictors in patients with ostial lesions of the right coronary artery (RCAos) who underwent percutaneous coronary intervention (PCI). RCAos are associated with a high incidence of restenosis, and the implantations of drug-eluting stents for RCAos have not been fully elucidated. The study participants included 75 patients (72.3 ± 9.5 years, 72% men) who underwent PCI for RCAos at our institution between November 2001 and May 2017. The angle between the greater curvature of the aortic wall and the right coronary artery take-off in the diastolic and systolic phases in the left anterior oblique position view was investigated. Clinical outcome was defined as binary restenosis at follow-up coronary angiography. We also evaluated target lesion failure (TLF) defined as a composite of cardiac mortality, target vessel myocardial infarction, and target lesion revascularization (TLR). The incidence of binary restenosis was 48.0% (n = 36) of the entire cohort. The incidence of TLF was 49.3% (n = 37) of the entire cohort, which was mainly driven by TLR (36.0%, n = 27). The area under the curve of the gap-angle ratio [(difference between the maximum and minimum angles)/(minimum angle); GAR] for binary restenosis was 0.73, and the cutoff value was 0.306 (sensitivity 67%, specificity 82%). The patients were divided into two groups: a low-GAR (< 0.306; n = 30) and high-GAR group (> 0.306; n = 45). Binary restenosis was more frequent in the high-GAR group than in the low-GAR group (76.7% vs. 28.9%, p = 0.007). The cumulative rate of TLF was significantly higher in the high-GAR group when compared with the low-GAR group (53.3% vs. 40.0%, p = 0.01), which was mainly driven by TLR (56.7% vs. 22.2%, p = 0.01). High-GAR (> 0.306) [OR 2.66 (1.34-5.31), p = 0.005] and stent under expansion [OR 2.37 (1.10-5.11), p = 0.03] were found to be independent predictors of binary restenosis after adjustment for multiple confounders. Multivariable analysis also revealed that high-GAR (> 0.306) [OR 2.06 (1.02-4.14), p = 0.03] and stent under expansion [OR 2.82 (1.28-6.19), p = 0.01] were independent predictors of TLF. We suggest that GAR (> 0.306) predicts binary restenosis and TLF in patients undergoing PCI for RCAos.

Exercise-related resuscitated out-of-hospital cardiac arrest due to presumed myocardial ischemia: Result from coronary angiography and intravascular ultrasound.

AIM: Possible causes of exercise-related out-of-hospital cardiac arrest (OHCA) in people with coronary artery disease (CAD) include atherosclerotic plaque rupture (PR) and intra-coronary thrombosis, exercise-induced myocardial ischaemia and other triggers. We investigated whether there are differences in the incidence of PR and/or intra-coronary thrombus and in clinical outcome between 'exercise-related' and 'non-exercise-related' OHCA. METHODS: 219 consecutive resuscitated patients with CAD diagnosed by emergency coronary angiography (CAG) were enrolled. They were divided into the exercise group (≥6 METs; n = 35) and non-exercise group (<6 METs; n = 184), according to estimated METs immediately before OHCA using 2011 Compendium of Physical Activities. We investigated whether culprit lesions had PR and/or thrombus using CAG and intravascular ultrasound. The clinical outcome was 30-day survival with minimal neurologic impairment. RESULTS: Acute PR and/or thrombus occurred in fewer of the exercise group than the non-exercise group (11% vs. 90%; P < 0.001). The exercise group had a higher incidence of favorable neurological outcome (94% vs. 47%; P < 0.001) than the non-exercise group. Multivariable Cox proportional hazards models revealed that exercise immediately before OHCA was one of the predictors of a good neurological outcome (HR, 0.19; P = 0.025). CONCLUSION: The incidence of PR and/or thrombosis was lower in the group taking higher levels of exercise, than in the group taking less or no exercise. "Exercise-related" OHCA with CAD has better clinical outcomes than "non-exercise-related" with a greater proportion of witnessed arrests and early return of spontaneous circulation.

Additive effect of heparin on the photoinactivation of Escherichia coli using tricationic P-porphyrins.

Polycationic porphyrins have received substantial attention in developing singlet oxygen-sensitizers for biological use such as in the photoinactivation of bacteria and photodynamic therapy (PDT) of tumor cells because they have strong binding affinities for DNA and proteins. However, these strong cellular interactions can retard elimination of the drug after PDT. Therefore, the studies on the interactions of porphyrins with other molecules present much interest, in order to modulate the sensitizers' activity or even remove them from the human body after PDT. Here, we studied the additive effect of heparin on the photoinactivation by polycationic porphyrins using Escherichia coli as a model cell. Tricationic P-porphyrin sensitizers substituted with an N-alkylpyridinium group (alkyl = pentyl (1a), hexyl (1b), and heptyl (1c)) or N-hexylammonium (1d) as the axial ligand were used. Additionally, dicationic Sb-porphyrin substituted with an N-hexylpyridinium group (1e) was prepared. We studied the additive effect of heparin on the photoinactivation of E. coli by 1a-1e. The bactericidal activities were evaluated using the half-life (T1/2 in min) of E. coli and the minimum effective concentrations ([P]) of the porphyrin sensitizers. In the absence of heparin, the [P] values were determined to be 0.4-0.5 µM for 1a-1c and 2.0 µM for 1d-1e. The bactericidal activity of 1a-1c was completely retarded by the addition of heparin (1.0 µM). However, the addition of heparin (1.0 µM) could not completely retard the bactericidal activity of 1d-1e whose [P] values were relatively large. It is suggested that tricationic 1a-1c adsorbed onto the anionic heparin through electrostatic interactions. The adsorption of 1 on heparin disturbs the uptake of 1 into E. coli cells. Thus, the addition of heparin was found to be a useful method for retarding photoinactivation.

Photodynamic therapy of human biliary cancer cell line using combination of phosphorus porphyrins and light emitting diode.

A series of phosphorus porphyrin complexes ([(RO)2P(tpp)]Cl, tpp = tetraphenylporphyrinato group, R = -(CH2CH2O)m(CH2)nH; 1a: m = 2, n = 2; 1b: m = 2, n = 4; 1c: m = 2, n = 6; 1d: m = 3, n = 6) were used for the photodynamic therapy (PDT) of human biliary cancer cell line (NOZ) when exposed to the irradiation of light emitting diodes (LEDs). A Dulbecco's modified Eagle's medium (DMEM) containing NOZ cells (2000 cell well-1) and 1 (0-100 nM) was introduced into a 96-well microplate and incubated for 24 h to accumulate 1 into the NOZ cells and to multiply the NOZ cells until the cell number reached 104 cells well-1. After replacing the DMEM medium containing 1 with a fresh DMEM medium without 1, the plates were irradiated for 30 min at 610 nm. After incubation was performed for 24 h in dark conditions, the cell viability of the NOZ cells was determined using the MTT assay. The half maximum inhibitory concentrations 50 (IC50) of 1a-1d were found to be in the range of 33.7-58.7 nM for NOZ. These IC50 values for the NOZ were one hundredth the IC50 value (7.57 µM) for mono-l-aspartyl chlorin e6 (laserphyrin®). Thus, it was found that the PDT activity of 1a-1d was much higher than the mono-l-aspartyl chlorin e6. Similarly, IC50 vales of 1a-1d for HeLa cells were found to be 27.8-52.5 nM. This showed that 1a-1d had high photodynamic activity in cancer cells. At the same time, it was speculated that an LED is a useful light source for deactivating the cancer cells because it can excite the sensitizers with peak width in their absorption spectra using the light of the specified wave length with band width of 10-20 nm; LEDs provide a homogeneous light distribution for the target cells.

Association between delay to coronary reperfusion and outcome in patients with acute coronary syndrome undergoing extracorporeal cardiopulmonary resuscitation.

AIM: The prognostic effect of early coronary reperfusion therapy with extracorporeal cardiopulmonary resuscitation (ECPR) in patients with cardiac arrest due to acute coronary syndrome (ACS) has yet to be clarified. We investigated the relationship between time interval from collapse to start of ECPR (CtoE) and coronary reperfusion (CtoR) time and neurological outcome in patients with cardiac arrest due to ACS. METHODS: A cohort of 119 consecutive patients (63±12 years old) with ACS who underwent ECPR and percutaneous coronary intervention(PCI) at our hospital was registered from January 2005 to June 2016. We analyzed patient clinical outcome, which was defined as survival with good neurological outcome at 30 days. We divided the patients into four groups according to CtoR time: Group 1 (time<60min: n=19), Group 2 (60≤time<90min: n=19), Group 3 (time≥90min: n=70) and Group 4 (unsuccessful coronary reperfusion: n=11). RESULTS: One hundred patients (84%) were successful of PCI. A Kaplan-Meier curve showed that Group 1 had the best outcome among the four groups (good neurological outcome at 30 days; 74% vs 37% vs 23% vs 9%, P<0.0001). In receiver operating characteristics analysis for good neurological outcome at 30 days, the cutoff values for CtoE was 40min. The delay CtoE and CtoR time were independent predictors of poor neurological outcome at 30 days after adjusting multiple confounders (CtoE time; Hazard ratio (HR):1.026, 95% confidential intervals(CI): 1.011-1.042, P=0.001), (CtoR time; HR: 1.004, 95% CI: 1.001-1.008, P=0.020). CONCLUSIONS: A shorter CtoE and CtoR predicts better clinical outcome in patients with ACS undergoing ECPR.

Focused Proteomics Revealed a Novel Rho-kinase Signaling Pathway in the Heart.

Protein phosphorylation plays an important role in the physiological regulation of cardiac function. Myocardial contraction and pathogenesis of cardiac diseases have been reported to be associated with adaptive or maladaptive protein phosphorylation; however, phosphorylation signaling in the heart is not fully elucidated. We recently developed a novel kinase-interacting substrate screening (KISS) method for exhaustive screening of protein kinase substrates, using mass spectrometry and affinity chromatography. First, we examined protein phosphorylation by extracellular signal-regulated kinase (ERK) and protein kinase A (PKA), which has been relatively well studied in cardiomyocytes. The KISS method showed that ERK and PKA mediated the phosphorylation of known cardiac-substrates of each kinase such as Rps6ka1 and cTnI, respectively. Using this method, we found about 330 proteins as Rho-kinase-mediated substrates, whose substrate in cardiomyocytes is unknown. Among them, CARP/Ankrd1, a muscle ankyrin repeat protein, was confirmed as a novel Rho-kinase-mediated substrate. We also found that non-phosphorylatable form of CARP repressed cardiac hypertrophy-related gene Myosin light chain-2v (MLC-2v) promoter activity, and decreased cell size of heart derived H9c2 myoblasts more efficiently than wild type-CARP. Thus, focused proteomics enable us to reveal a novel signaling pathway in the heart.

Atresia of the right atrial ostium of the coronary sinus without persistent left superior vena cava.

We present a case of atresia of the right atrial ostium of the coronary sinus. Recognizing this anomaly is important during catheter ablation or cardiac surgery, which could be noninvasively evaluated by multidetector CT.

Prevalence of amino acid mutation in hepatitis C virus core region among Japanese volunteer blood donors.

It is not known whether there is a trend of increasing or decreasing incidence of new hepatitis C virus (HCV) infections in Japan. From the treatment point of view, it is important to verify HCV genotypes and the prevalence of treatment-resistant clones of HCV. At the Japanese Red Cross blood centers, all blood samples obtained from blood donation have been screened using serological methods and the minipool nucleic acid amplification testing. One hundred and fourteen donors have been identified over the past 10 years to be HCV RNA-only positive without detectable anti-HCV and were considered to be in the acute phase of HCV infection. There was a trend of decreasing incidence of such new infections among the blood donors. HCV RNA-only-positive samples were examined further for genotyping and HCV RNA quantitation. Genotype 2 (2a plus 2b) was predominant (78.2%) among them followed by genotype 1b (21.2%). Direct sequencing was carried out to detect the possible treatment-resistant mutant clones 70Q and 91M, clones with amino acid substitutions at positions 70 and 91 of the HCV core protein, respectively. 70Q and 91M were found regularly in donors with genotype 1b, but not in those with other genotypes. No particular endemic areas for the mutant clones were identified. There was no significant difference in the mean viral titer between the 70Q mutant type and the non-70Q wild-type. Even in newly infected people, the mutant clone 70Q was detected frequently.

Modification of atrioventricular conduction in dogs by laser irradiation of Koch's triangle guided by balloon-tipped cardioscope.

PURPOSE: This study assessed the feasibility of modification of atrioventricular (AV) conduction under direct vision with a new ablation system using laser energy. METHODS AND RESULTS: In 23 anesthetized dogs, a combined laser and balloon-tipped endoscope was introduced into the right atrium after right thoracotomy. Koch's triangle was easily identified in all dogs endoscopically. Nd:YAG laser energy was delivered through an optical fiber positioned inside the saline-filled balloon to the middle portion of Koch's triangle in eight dogs (mid-Koch group) and to the posterior portion in 12 dogs (postero-Koch group). Complete AV block was achieved in five of eight dogs in the mid-Koch group. In the postero-Koch group, anterograde Wenckebach cycle length increased significantly from 178+/-23 ms to 202+/-37 ms (P = 0.008). CONCLUSION: Selective laser ablation of Koch's triangle is feasible with a combined laser and balloon-tipped endoscope.

Sex- and age-specific carriers of hepatitis B and C viruses in Japan estimated by the prevalence in the 3,485,648 first-time blood donors during 1995-2000.

OBJECTIVE: Carriers of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Japan were estimated on a national basis. METHODS: Sera from the first-time blood donors aged 16-64 years in eight jurisdictions of the Japanese Red Cross Blood Center during 1995-2000 were tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV). Viremia with HCV was estimated to be present in 70% of donors with anti-HCV. RESULTS: HBsAg was detected in 22,018 of 3,485,648 (0.63%) blood donors including 12,990 of 1,780,149 (0.73%) men and 9,028 of 1,705,499 (0.53%) women, and anti-HCV in 17,010 (0.49%) including 8,504 (0.48%) men and 8,506 (0.50%) women. Multiplying the carrier rate by the population registered in the Census 2000, the total HBV carriers aged 15-65 years were estimated at 967,753 (95% confidence interval 806,760-1,128,745), of whom 571,210 (479,267-663,152) were men and 396,543 (327,494-465,593) were women. Likewise, the total HCV carriers were estimated at 884,954 (95% confidence interval 725,082-1,044,826), of whom 464,363 (377,927-550,799) were men and 420,591 (347,156-494,027) were women. CONCLUSION: Estimated numbers of HBV and HCV carriers would help plan to prevent the development of hepatocellular carcinoma in Japan.

Clinical study of the efficacy of a cooled-tip catheter ablation system for common atrial flutter.

BACKGROUND: Radiofrequency catheter ablation (RF-CA) of common atrial flutter (AFL) requires the creation of a transmural incision to create a bidirectional conduction block in the cavotricuspid isthmus (ITH). METHODS AND RESULTS: RF-CA of the ITH using a cooled-tip system was carried out in 40 patients. In the 'conventional' mode (CONV) of the system, RF energy was applied for 2 min with the temperature set at 60 degrees C and power of up to 50 W, and in the failed cases the 'cooled-tip' mode (COOL) was utilized at 45 degrees C with up to 30 W (with a 15 ml/min saline flow rate). Of the 40 patients, 29 crossed over from the CONV to the COOL after a failed ablation of the AFL. As a result, in all 40 patients a complete linear incision could be created with either the COOL or the CONV, resulting in the successful abolition of the AFL. Complete bi-directional block was successfully created in all patients. No significant side effects occurred. CONCLUSIONS: The COOL was found to be more effective and just as safe as the CONV for AFL ablation, thus facilitating the rapid and complete elimination of the AFL.

'Tako-Tsubo cardiomyopathy' associated with syndrome malin: reversible left ventricular dysfunction.

A 66-year-old man developed a fever and had a syncopal attack during treatment with imipramine and amantadine for depression and Parkinson's disease. His muscular enzyme levels were very high, so he was diagnosed with incomplete syndrome malin and given hydration therapy. The electrocardiogram recorded an ST segment elevation like acute myocardial infarction in most leads, and the echocardiogram revealed left ventricular dysfunction with severe hypokinesis to dyskinesis of the anterior and apical wall regions, and hyperkinesis of the basal wall. One month from onset, the left ventricular contractility had not changed despite normal coronary arteries. Thallium-201((201)Tl) myocardial scintigraphy showed a perfusion defect and there was no accumulation of iodine-123((123)I) metaiodobenzylguanidine (MIBG) in the entire apex of the heart. Left ventricular function returned to normal and repeat (201)Tl scintigraphy showed recovery by the 4th month. However, there was still an absence of cardiac MIBG uptake. There are a number of reports from Japan of a syndrome demonstrating such reversible left ventricular dysfunction, called 'tako-tsubo cardiomyopathy', but the present case is the first to be associated with syndrome malin. A coronary microvascular abnormality and cardiac sympathetic denervation probably both play an important role in tako-tsubo cardiomyopathy.