Autopsy Case Report of Severe COVID-19 Pneumonia at a General Municipal Hospital.

We present the autopsy procedure and findings of severe coronavirus disease 2019 (COVID-19) pneumonia in an 85-year-old man. The patient required intubation immediately after admission for severe COVID-19 pneumonia. He had severe hypoxia that did not improve despite treatment with remdesivir, corticosteroids, and appropriate mechanical ventilation. On day 13, the patient developed sudden hypercapnia. His renal dysfunction subsequently worsened and became associated with hyperkalemia, and he passed away on day 15. An autopsy was performed to clarify the cause of the hypercapnic hypoxia. None of the medical personnel involved in the autopsy developed symptoms of COVID-19. Histologic examination showed various stages of diffuse alveolar damage throughout the lungs, with intra-alveolar hemorrhage in the upper zones. Microscopic examination of the kidneys revealed acute tubular necrosis. There was no significant systemic thrombosis. The autopsy findings were consistent with those typical of COVID-19.

The urinary albumin-to-creatinine ratio is a potential predictor of target lesion revascularization after percutaneous coronary intervention with coronary stents.

The association between the urinary albumin-to-creatinine ratio (UACR) and target lesion revascularization (TLR) is unknown in patients who are implanted with drug-eluting stents (DESs) or bare metal stents (BMSs) for the treatment of coronary artery disease. Of 231 Japanese patients who were implanted with DESs and/or BMSs during percutaneous coronary intervention (PCI) between July 2009 and January 2011, 118 underwent follow-up coronary angiography at 6 to 9 months after PCI; 103 were negative for qualitative tests for urine protein: 32 (31.0%)/103 patients underwent TLR for severe in-stent restenosis (ISR) and 71 did not. On the next day after admission to the hospital, first-morning-void spot urine samples were collected to calculate UACR based on urinalysis results. Pearson's product-moment correlation coefficients indicated positive associations of UACR with late loss as assessed by quantitative coronary analysis in the overall cohort, (r = +0.515, P < 0.0001), the DES subgroup (r = +0.443, P < 0.0001), and the BMS subgroup (r = +0.652, P < 0.0001). The incidence of multivessel lesions was significantly higher (P < 0.05) in the TLR group. UACR was significantly higher (P < 0.01) in the TLR group (23.88 ± 31.8 mg/gCr) than in the control group (6.29 ± 7.46 mg/gCr). Multivariate logistic regression analysis revealed UACR (odds ratio: 1.07; 95% confidence interval: 1.02-1.12; P < 0.01) to be associated with TLR. UACR was suggested to be a potential predictor of TLR required for severe ISR after PCI with coronary stents.

Prediction of inappropriate implantable cardioverter-defibrillator therapies through parameters obtained in a simple exercise stress test.

Although the clinical benefits of implantable cardioverter-defibrillators (ICDs) have been demonstrated, inappropriate therapies (IATs) cannot be completely avoided even with the most advanced devices. Recently, IATs are considered to decrease the ventricular function and prognosis of a patient. The aim of this study was to investigate the predictors of IAT with parameters during cardiopulmonary exercise stress test (CPX). Sixty consecutive ICD patients underwent symptom-limited CPX, and were divided into IAT (+) and IAT (-) groups. During and after CPX, ECG and hemodynamic parameters of systemic blood pressure, heart rate, and maximal O2 consumption (max VO2) were evaluated every minute. In selected patients, sympathetic and parasympathetic activities were evaluated with analyses of heart rate variability (HRV). No significant differences were observed in clinical background parameters. In the CPX parameters, only the maximal heart rate exhibited a significant difference between the IAT (+) group and the IAT (-) group (154.8 ± 5.9 versus 137.9 ± 4.2 beats per minute, P = 0.032), and LF/HF was higher during the recovery phase 4 minutes after peak exercise in the former group (4.5 ± 1.0 versus 2.4 ± 0.9, P = 0.021). In ICD patients, IAT can be predicted using simple parameters of increased sympathetic activity such as increased maximal heart rate and increased LF/HF ratio during and after the exercise stress test.

N-acetylcysteine suppresses the progression of ventricular remodeling in acute myocarditis: studies in an experimental autoimmune myocarditis (EAM) model.

BACKGROUND: Electrical and structural remodeling, characterized by prolonged action potential duration (APD), Kv4.2 downregulation and cellular infiltration were studied in rat experimental autoimmune myocarditis (EAM). Because the reactive oxygen species (ROS) has been speculated to play a role in the promotion of such remodeling, the effect of N-acetylcysteine (NAC) on the progression of ventricular remodeling was evaluated. METHODS AND RESULTS: Six-week-old Lewis rats were immunized with porcine cardiac myosin. On Days 10-11 after the immunization, NAC (0, 1, 10, or 100mg) was injected intraperitoneally to EAM and control rats. On Day 14, the electrophysiological parameters were evaluated and the expression levels of the mRNA were examined by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR).The EAM rats exhibited a typical acute myocarditis with prolonged APD and reduced Kv4.2 expression as previously reported. The myocarditis and electrical changes were significantly suppressed by NAC-treatment in a dose-dependent manner (P<0.05). In rats with 100mg NAC, the myocarditis was almost totally negated although the mortality increased. In rats with 1mg NAC, the suppression of myocarditis was not obvious, but APD prolongation and Kv4.2 reduction was attenuated (P<0.05). CONCLUSIONS: The NAC treatment suppressed ventricular remodeling in the EAM rats. This may indicate the role of oxidative stress in causing remodeling and myocarditis itself in the acute phase of myocarditis.

Role of electrophysiologic study (EPS)-guided preventive therapy for the management of ventricular tachyarrhythmias in patients with heart failure.

BACKGROUND: Ventricular tachyarrhythmias (VT/VF) are 1 of the most important factors determining the prognosis of patients with heart failure (HF). Although priority is given to implantable cardioverter defibrillator (ICD) therapy for the prevention of sudden cardiac death, electrophysiologic-study (EPS)-guided preventive therapy could be important for reducing the number of cardiac events. METHODS AND RESULTS: Of 864 patients with a history of HF, an EPS was performed in 168 and 121 had inducible VT/VF. Under the basic therapy of an ICD, additional catheter ablation was attempted for 95 of 124 monomorphic VT foci in 74 patients, and 78 of the VT were successfully ablated. The prognoses were compared among 5 patient groups with different results for the EPS and catheter ablation: (1) success group (n=43), (2) failure group (n=15), (3) not attempted group (n=16), (4) VF group (n=47), and (5) no inducible VT/VF group. During a follow-up period of 31+/-22 months, the incidence of VT/VF was lower in the success and no inducible VT/VF groups than in the other groups (p=0.0018), although a significant difference was not observed for the total deaths. CONCLUSION: EPS-guided preventive therapy using an ICD and catheter ablation can be useful, at least for the reduction of arrhythmic events in patients with HF.

Clinical usefulness of electrophysiologic study (EPS)-guided risk stratification for life-threatening arrhythmia in patients with heart failure.

BACKGROUND: Ventricular tachyarrhythmia is one of the most important factors determining the prognosis of patients with heart failure and sudden death can be observed even during stable therapy controlling clinical heart failure. In this study, the usefulness of electrophysiologic study (EPS) for the prediction of a future arrhythmic event was evaluated in patients with heart failure. METHODS AND RESULTS: The patient population consisted of 474 patients with a history of clinical heart failure but without an episode of spontaneous sustained ventricular tachycardia or fibrillation (VT/VF). A Holter ECG was performed in all patients, and 177 of the 474 patients underwent EPS because of a recording of nonsustained VT (NSVT, > 5 beats). When sustained VT/VF was inducible in EPS, the patient was assigned to implantation of a defibrillation device. The patients were divided into 3 groups, ie, 1) no NSVT (n = 297), 2) NSVT + no inducible VT/VF (n = 134), and 3) NSVT + inducible VT/VF (n = 43), and were followed-up for > 12 months. All patients were followed-up under standard therapy for heart failure. There were no significant differences in basic clinical characteristics and therapies among the 3 groups. During the follow-up period of 32 +/- 18 months, 56/474 patients suffered a VT/VF episode, ie, 21/297 in no NSVT, 14/134 in NSVT + no inducible VT/VF, and 21/43 in NSVT + inducible VT/VF patients (P = 0.032). All patients were rescued from sudden death among patients with an implanted defibrillator, but 11 patients without a defibrillator died. CONCLUSION: In patients with heart failure, future arrhythmic events could be predicted by EPS and Holter ECG. EPS-guided risk stratification seems to be useful in managing patients with heart failure.

Predictive impact of the inducibility of ventricular fibrillation in patients with Brugada-type ECG.

The natural history of asymptomatic individuals with a Brugada-type electrocardiogram (ECG) is still controversial. In this study, we evaluated ventricular fibrillation (VF) inducibility in Brugada-type ECG patients and compared it with other risk factors to clarify the significance of these data on their prognosis. The study population consisted of 38 patients who presented with a typical ST-segment elevation in the precordial leads and underwent an electrophysiological study (EPS). The patients were divided into 3 groups; group A: patients with spontaneous ventricular fibrillation (VF) (n = 5), group B: patients without clinical VF but with inducible VF in EPS (n = 16), and group C: patients with neither clinical nor inducible VF (n = 17). The clinical features, diagnostic results, and prognosis were compared among these groups. During the follow-up period of 26 +/- 19 months, 2/5 (group A), 1/16 (group B), and 0/17 (group C) patients suffered fatal arrhythmic events. None of the clinical features showed any significant difference, although the incidence of positive results in a drug challenge test was higher in groups A and B than in group C (P < 0.05). On the other hand, VF inducibility was higher in patients with positive results in the drug challenge test than in patients with negative results (59% versus 13%; P < 0.05). No VF episodes were observed in patients without VF induction, although one was observed in 1 of 16 patients with VF induction in asymptomatic Brugada syndrome. The drug challenge test appears to be useful for predicting VF inducibility even though it is a noninvasive test.

Tumor necrosis factor-alpha downregulates the voltage gated outward K+ current in cultured neonatal rat cardiomyocytes: a possible cause of electrical remodeling in diseased hearts.

BACKGROUND: Inflammatory cytokines have been reported to contribute to the progression of cardiac remodeling in various heart diseases and a remarkable prolongation of the monophasic action potential duration and reductions in the expression of Kv4.2 and K+ channel-interacting protein-2 (KChIP-2) in a rat autoimmune myocarditis model have been documented. In this study, the effect of tumor necrosis factor-alpha (TNF-alpha) on cultured cardiomyocytes was evaluated, focusing on the change in the voltage-gated outward K+ current and expression of related molecules. METHODS AND RESULTS: Cardiomyocytes isolated from 1-day-old Lewis rats were cultured for 72 h and treated with TNF-alpha (50 ng/ml) for an additional 48 h. The myocytes treated with TNF-alpha showed a 22% reduction in the peak K+ current, which consisted of a transient outward K+ current (Ito) and 1.4-fold enhancement of the cell-capacitance in comparison with the control. Among the cardiac ion channel related molecules evaluated in this study, Kv4.2 and KChIP-2 mRNA exhibited remarkable reductions (p < 0.05). CONCLUSIONS: Treatment with TNF-alpha induced reductions in Ito as well as cellular hypertrophy in neonatal cultured myocytes, which indicates that TNF-alpha might play a role in promoting electrical remodeling of cardiomyocytes under inflammatory conditions.

Clinical significance of the electrophysiologic study (EPS)-guided therapy for the secondary prevention of ventricular tachycardia.

BACKGROUND: Although electrophysiologic study (EPS) is one of the most reliable methods for selecting preventive therapy for patients with sustained ventricular tachycardia (VT), VT may recur during EPS-guided effective therapy; therefore, the importance of implantable cardioverter-defibrillator (ICD) has been emphasized. In this study, the prognoses of VT patients were evaluated to clarify the importance of EPS-guided therapy for the secondary prevention of VT. METHODS AND RESULTS: The study population consisted of 99 consecutive patients with a history of sustained VT, which was inducible in EPS. The VT induction protocol used 1-3 extrastimuli and rapid ventricular pacing at 2 right ventricular sites and included additional isoproterenol infusion. ICD implantation was applied to all patients with an episode of hemodynamically unstable VT, regardless of the result of preventive therapy. For preventive therapy, an antiarrhythmic drug and/or catheter ablation were selected, and they were defined as being effective in the EPS-guided therapy when the induction of VT was completely prevented. When no therapy was effective for prevention, an antiarrhythmic drug was prescribed under ICD implantation. During the follow-up period of 19+/-20 months, VT recurred in 17 of 32 patients (53%) in the ineffective group and in 10 of 67 patients (15%) in the effective group (p=0.0001). The therapies used in the effective group were class I antiarrhythmic drug in 9, class III in 15, and catheter ablation in 35 patients. Between the patients with and without VT recurrence, there were no significant differences in the left ventricular ejection fraction and the maximum number of repetitive ventricular responses that remained in VT induction in EPS. CONCLUSIONS: Although VT may recur in up to 15% of patients with EPS-guided effective therapy, the recurrence rate was significantly reduced in comparison to that in the ineffective group. EPS-guided therapy may be useful to reduce the clinical recurrence of VT, as well as the action of ICD.

Long-term follow-up of changes in fibrillation waves in patients with persistent atrial fibrillation: spectral analysis of surface ECG.

BACKGROUND: Little is known about the shortening of atrial refractoriness as a result of electrical remodeling in atrial fibrillation (AF) in clinical cases, especially in terms of long-term follow-up, because of a lack of noninvasive testing methods. METHODS AND RESULTS: The present study population comprised 38 consecutive patients with persistent AF (PAF, >1 month). Before and after the follow-up period of 1-14 months, surface ECGs were recorded for analysis. In each case, the fibrillation wave was purified by subtracting the QRS-T complex template and then power spectral analysis was performed. The mean fibrillation cycle length (FCL) and FCL coefficient of variation (FCL-CV) were determined from peak power frequency in 20 epochs in each recording. The change in FCL (FCL) was calculated by subtracting the baseline FCL from the FCL after the follow-up period. To correct for the difference in the follow-up period, DeltaFCL was divided by the follow-up period in each case. In 38 cases, mean FCL decreased from 160+/-20 ms to 151+/-19 ms (p<0.05), and the FCL-CV also decreased from 15+/-9% to 12+/-5% (p<0.05). The corrected DeltaFCL was -2.4+/-7.6 (ms/month) and there was a significant negative correlation between corrected DeltaFCL and baseline FCL (p<0.01). CONCLUSION: Shortening of the FCL during a relatively long-term follow-up period was observed in patients with PAF.

Bepridil inhibits sub-acute phase of atrial electrical remodeling in canine rapid atrial stimulation model.

Background The effect of bepridil, a multichannel blocker, on atrial electrical remodeling was evaluated in a canine rapid atrial stimulation model. Methods and Results In 10 beagle dogs, the right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. The atrial electrophysiological parameters, including effective refractory period (AERP), were evaluated at three atrial sites: RAA, the right atrium close to the inferior vena cava (IVC) and the left atrium (LA), during the time course of rapid pacing. Five of the dogs were given bepridil (10 mg . kg (-1) . day(-1) po). In the control group, AERP was significantly shortened at all atrial sites and the AERP shortening (DeltaAERP) was larger for the RAA and LA than at the IVC site (p<0.05). In the bepridil group, DeltaAERP was smaller than that of the controls at all atrial sites, and the AERP started to return slowly to the pre-pacing level in the second week, regardless of the continuation of rapid pacing. Conclusions In a canine rapid atrial stimulation model, bepridil suppressed AERP shortening. Bepridil might have a reverse electrical remodeling effect, at least for AERP shortening, because it showed slow recovery of AERP in the subacute phase of rapid atrial pacing. (Circ J 2006; 70: 206 - 213).

Mexiletine protects myocardium during acute ischemia by opening sarcolemmal K-ATP channel: studies in closed-chest acute ischemia model in rabbits.

OBJECTIVES: Although we have previously shown that mexiletine might protect myocardium during acute ischemia, the precise mechanism was unclear. In the present study, the mechanism of this effect was examined by using selective K-ATP channel blockers in closed-chest acute ischemia model in rabbits. METHODS: In 40 rabbits, the large left ventricular branch (LLVB) of the left coronary artery was occluded for 30 minutes by inserting a catheter bead (varphi0.5-0.7 x 1.5 mm) through the left carotid artery and was then reperfused. The rabbits were divided into the following 5 groups: (1) control group (n = 8); (2) mexiletine (Mex) group (n = 8, continuous infusion of Mex 24 mg/kg/h); (3) Mex + 5-hydroxydecanoate (5HD) group (n = 8, preadministration of 5HD, 5 mg/kg, followed by Mex infusion); (4) Mex + HMR1098 (selective sarcolemmal K-ATP channel blocker) group (n = 8, preadministration of HMR1098, 3 mg/kg, followed by Mex infusion); and (5) pilsicainide (Pil) group (n = 8, continuous infusion of Pil 18 mg/kg/h). The incidence of ventricular arrhythmia, hemodynamics, left ventricular ejection fraction (LVEF), and infarction size were evaluated and compared among the 5 groups. RESULTS: The incidence of ventricular arrhythmia was lower in groups treated with Mex than the control. The hemodynamics did not show significant differences among the 5 groups. Although the LVEF at 30 minutes after reperfusion was lower in the Mex group (41 +/- 3%, P < 0.001) than the control group (48 +/- 3%), the LVEF at 360 minutes after reperfusion had recovered and became higher in the Mex group (62 +/- 3%, P < 0.001) than the control group (55 +/- 3%). The infarction size was smaller in the Mex group (30 +/- 5%, P = 0.028) than the control group (51 +/- 8%). These effects of Mex were negated by HMR1098 but not by 5HD and were larger than the effects of Pil. CONCLUSIONS: Mex showed improvement in the LVEF in the later phase after reperfusion as well as a reduction in ventricular arrhythmia. The cardioprotective effect of Mex was considered to appear through its action on the sarcolemmal K-ATP channel.