Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

Fibrinolytic markers could be useful predictors of severity in patients with pulmonary arterial hypertension: a retrospective study.

BACKGROUND: The severity of pulmonary arterial hypertension (PAH) is classified based on mean pulmonary artery pressure (mPAP) levels. However, other markers have not been elucidated. Fibrinolytic markers, such as total plasminogen activator inhibitor-1 (tPAI-1) and thrombomodulin (TM), are known to reflect arterial endothelial function. However, the relationship between serum tPAI-1, TM and pulmonary circulation has not been completely determined. METHODS: This study included 100 consecutive patients (38 men), with a mean age of 68.9 ± 12.0 years, with cardiac diseases who underwent right heart catheterization. Serum coagulation and fibrinolytic marker levels were measured. RESULTS: The average mPAP value was 25.1 ± 13.1 mmHg for all patients. The mPAP levels revealed a significant positive correlation with serum tPAI-1 (ρ = 0.24, p = 0.042) and uric acid (ρ = 0.29, p = 0.0031) levels. In the group with mPAP levels less than 25 mmHg (n = 58, ave. 17.3 ± 4.3 mmHg), mPAP levels showed a significant positive correlation with serum tPA-1 (ρ = 0.34, p = 0.034) and TM (ρ = 0.34, p = 0.043) values. The mean tPAI-1 (29.8 ± 23.3 ng/ml, p = 0.047) and uric acid (5.7 ± 1.8 mg/dl, p = 0.026) levels were significantly less in those with lower mPAP levels. A multivariate analysis revealed that tPAI-1 alone was a significant independent characteristic marker of PAH (odds ratio 1.02, 95%CI 1.000-1.036, p = 0.034). CONCLUSIONS: These results indicate that serum tPAI-1 and TM may be useful predictors of severity, similar to mPAP in patients with PAH. They could be beneficial in predicting PAH among patients in the early stage of the disease.

Intracardiac Thrombosis and Heart Failure in a Patient with Hepatocellular Carcinoma and Cardiac Amyloidosis and an Implanted Cardiac Resynchronization Therapy Device.

BACKGROUND Intracardiac thrombosis has been known to be associated with not only hepatocellular carcinoma but also with amyloidosis and use of a cardiac implantable electronic device. We report a case of a continuous tumor thrombus with hepatocellular carcinoma from the portal vein and hepatic vein to the right atrium via the inferior vena cava in a patient with a cardiac amyloidosis and an implanted cardiac resynchronization therapy (CRT) device. CASE REPORT A 68-year-old female first admitted to our hospital because of heart failure with an AL type primary cardiac amyloidosis. After 3 years, she underwent an implantation of a CRT device for biventricular pacing following repeated episodes of heart failure and low left ventricular ejection fraction of 34% with NYHA class III. Again, she presented with symptoms of heart failure and cardiomegaly on chest x-ray at 7 years after the CRT device implantation. The echocardiography showed a huge echogenic mass occupying the right atrium, and 64 multi-detector computed tomography showed a lobulated heterogeneously enhancing mass of hepatocellular carcinoma in the right upper lobe of her liver and a continuous tumor thrombus from the portal vein and hepatic vein to the right atrium via the inferior vena cava. CONCLUSIONS Intracardiac thrombosis and heart failure occurred in a patient with hepatocellular carcinoma and cardiac amyloidosis, who had an implanted CRT device, which resulted not only in hypercoagulability by the hepatocellular carcinoma itself and the accumulation of various risk factors, but also the progression of myocardial damage with the development of amyloidosis.

Dataset of calcified plaque condition in the stenotic coronary artery lesion obtained using multidetector computed tomography to indicate the addition of rotational atherectomy during percutaneous coronary intervention.

Our data shows the regional coronary artery calcium scores (lesion CAC) on multidetector computed tomography (MDCT) and the cross-section imaging on MDCT angiography (CTA) in the target lesion of the patients with stable angina pectoris who were scheduled for percutaneous coronary intervention (PCI). CAC and CTA data were measured using a 128-slice scanner (Somatom Definition AS+; Siemens Medical Solutions, Forchheim, Germany) before PCI. CAC was measured in a non-contrast-enhanced scan and was quantified using the Calcium Score module of SYNAPSE VINCENT software (Fujifilm Co. Tokyo, Japan) and expressed in Agatston units. CTA were then continued with a contrast-enhanced ECG gating to measure the severity of the calcified plaque condition. We present that both CAC and CTA data are used as a benchmark to consider the addition of rotational atherectomy during PCI to severely calcified plaque lesions.

Regional calcified plaque score evaluated by multidetector computed tomography for predicting the addition of rotational atherectomy during percutaneous coronary intervention.

BACKGROUND: Rotational atherectomy (rotablation) has been proposed as a potentially superior strategy for percutaneous coronary intervention (PCI) in complex and severely calcified lesions. OBJECTIVES: We hypothesized that a per-lesion coronary artery calcium score determined by multidetector computed tomography (MDCT) would be useful for predicting the requriement for rotablation during PCI. METHODS: MDCT was performed in patients with stable angina pectoris who were scheduled for first PCI. In 116 consecutive subjects (168 target lesions) with successful PCI, MDCT and quantitative coronary angiography (QCA) data were retrospectively evaluated regarding their ability to predict rotablation. RESULTS: PCI without rotablation was performed in 105 patients (154 lesions), and rotablation was added in 11 patients (14 lesions). Patients with rotablation had significantly higher SYNTAX scores (p = 0.007) and total calcium scores (p < 0.001) than those without rotablation. Per-lesion, a lesion length ≥20 mm and diameter stenosis ≥74% on QCA as well as a per-lesion calcium score ≥453 and calcification arc ≥270 in MDCT predicted rotablation. After adjustment for potential confounding variables, a high per-lesion calcium score was an independent predictor of rotablation (odds ratio 31.3, 95% confidence interval 2.8-345, p = 0.005, sensitivity 93% and specificity 88%). CONCLUSION: The extent of target lesion calcification in MDCT, a simple marker of calcified plaque, is useful for predicting the need for rotablation during PCI.

Reversible T-wave inversions and neurogenic myocardial stunning in a patient with recurrent stress-induced cardiomyopathy.

A 72-year-old female was diagnosed as a stress-induced cardiomyopathy from apical ballooning pattern of left ventricular dysfunction without coronary artery stenosis after the mental stress. ECG showed the transient T-wave inversions after the ST-segment elevations. By the mental stress after 1 year, she showed a transient dysfunction with similar ECG changes again. T-wave inversions recovered earlier, and cardiac sympathetic dysfunction showed a lighter response corresponding to the less severe dysfunction than those after the first onset. Wellens' ECG pattern was associated with the degree of neurogenic myocardial stunning with sympathetic hyperinnervation caused by mental stress.

A combination of P wave electrocardiography and plasma brain natriuretic peptide level for predicting the progression to persistent atrial fibrillation: comparisons of sympathetic activity and left atrial size.

PURPOSE: Development of atrial fibrillation (AF) is complexly associated with electrical and structural remodeling and other factors every stage of AF development. We hypothesized that P wave electrocardiography with an elevated brain natriuretic peptide (BNP) level would be associated with the progression to persistence from paroxysmal AF. METHODS: P wave electrocardiography such as a maximum P wave duration (MPWD) and dispersion by 12-leads ECG, heart/mediastinum (H/M) ratio by delayed iodine-123 metaiodobenzylguanidine scintigraphic imaging, left ventricular ejection fraction (LVEF), and left atrial dimension (LAD) by echocardiography, and plasma BNP level were measured to evaluate the electrical and structural properties and sympathetic activity in 71 patients (mean ± standard deviation, age: 67 ± 13 years, 63.4 % males) with idiopathic paroxysmal AF. RESULTS: Over a 12.9-year follow-up period, AF developed into persistent AF in 30 patients. A wider MPWD (>129 ms) (p = 0.001), wider P wave dispersion (>60 ms) (p = 0.001), LAD enlargement (>40 mm) (p = 0.001), higher BNP level (>72 pg/mL) (p = 0.002), lower H/M ratio (≤2.7) (p = 0.025), and lower LVEF (≤60 %) (p = 0.035) were associated with the progression to persistent AF, and the wide MPWD was an independently powerful predictor of the progression to persistent AF with a hazard ratio (HR) of 5.49 [95 % confidence interval (CI) 2.38-12.7, p < 0.0001] after adjusting for potential confounding variables, such as age and sex. The combination of wide MPWD and elevated BNP level was additive and incremental prognostic power with 13.3 [2.16-13, p < 0.0001]. CONCLUSION: The wide MPWD with elevated BNP level was associated with the progression to persistent AF.

Usefulness of severe cardiac sympathetic dysfunction to predict the occurrence of rapid atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

Atrial fibrillation (AF) can be a potentially life-threatening arrhythmia when it conducts rapidly through the accessory pathway, which was not predicted by the noninvasive method. We evaluated the cardiac sympathetic activity for predicting the occurrence of AF in patients with Wolff-Parkinson-White (WPW) syndrome. Iodine-123 metaiodobenzylguanidine scintigraphy was performed under stable sinus rhythm conditions at rest <1 week before an electrophysiologic study (EPS) to assess the sympathetic activity using the heart/mediastinum (H/M) ratio in 45 consecutive patients with WPW who had a history of supraventricular tachycardia (mean ± SD, age: 47 ± 17 years, 42.2% women). The study also included 15 normal healthy volunteers (56 ± 17 years, 40% women). The H/M ratio was lower in patients with WPW syndrome than in the normal control group, and in the 15 patients with AF induced during EPS than in the 30 patients without AF (p <0.0001). The sensitivity of H/M ratio ≤2.8 for predicting the AF induced during EPS was 75% in 12 of 16 patients, and the specificity was 89.7% in 26 of 29 patients. The H/M ratio was positively correlated with anterograde effective refractory period (r = 0.514, p <0.0001). The sensitivity of H/M ratio ≤2.75 for predicting the AF with a short anterograde effective refractory period (≤250 ms) was 91.7% in 11 of 12 patients, and the specificity was 90.9% in 30 of 33 patients. In conclusion, the severe cardiac sympathetic dysfunction was associated with the occurrence of AF, particularly in those with rapid AF and in patients with WPW syndrome.

Association between left and right atrial remodeling with atrial fibrillation recurrence after pulmonary vein catheter ablation in patients with paroxysmal atrial fibrillation: a pilot study.

BACKGROUND: Left atrial (LA) remodeling is a factor in atrial fibrillation (AF) recurrence after pulmonary vein catheter ablation (CA), but right atrium (RA) remodeling has not been investigated for possible associations to AF recurrence. METHODS AND RESULTS: Using 64-slice multidetector computed tomography, RA and LA volumes were measured 3-dimensionally before CA in 65 patients with initially proven idiopathic paroxysmal AF (mean age, 60±10 years, 81.5% men). The CA procedure was guided by CARTO Merge atrial electroanatomic mapping. Sixteen patients (24.6%) had AF recurrence within the 6-month period after the CA. The recurrence was associated with a large RA volume [odds ratio, 1.04; 95% confidence interval (CI), 1.02 to 1.07, P<0.0001], a large LA volume with 1.04 [95% CI, 1.01 to 1.06, P=0.002], and low LA mean voltage with 1.03 [95% CI, 1.01 to 1.05, P=0.002]. After adjustment for potential confounding variables, RA and LA volumes remained predictive of AF recurrence. Large atrial volumes (mL) (RA ≥87 or LA ≥99) predicted AF recurrence (sensitivity of RA volume: 81.3% in 13 of 16 patients with AF recurrence; specificity: 75.5% in 37 of 49 patients without AF recurrence; sensitivity of LA volume: 81.3% in 13 of 16 patients with AF recurrence; specificity: 69.4% in 34 of 49 patients without AF recurrence), and the combined estimate of both atrial volumes was incremental and additive prognostic power (sensitivity: 75% in 12 of 16 patients with AF recurrence; specificity: 93.9% in 46 of 49 patients without AF recurrence). CONCLUSIONS: Both LA and RA remodeling are equally associated with post-CA AF recurrence.

Iodine-123 mIBG Imaging for Predicting the Development of Atrial Fibrillation.

OBJECTIVES: we investigated whether cardiac sympathetic nervous system (SNS) activity measured by iodine-123 meta-iodobenzylguanidine ((123)I-mIBG) imaging would be associated with both the occurrence of heart failure (HF) and the transit to permanent atrial fibrillation (AF) in patients with paroxysmal AF. BACKGROUND: atrial fibrillation occurs suddenly and transiently and can persist, and results in the occurrence of HF. An important feature of AF and HF is their propensity to coexist not only because they share antecedent risk factors, but also because the one may directly predispose the heart to the other. However, a useful modality for predicting the occurrences of both those has not been established in patients with paroxysmal AF. METHODS: the (123)I-mIBG scintigraphy was performed to evaluate cardiac SNS activity presented as the heart/mediastinum ratio in 98 consecutive patients (age 66 ± 13 years, 63.3% male) with idiopathic paroxysmal AF and preserved left ventricular ejection fraction (≥ 50%). RESULTS: during 4 ± 3.6 years of follow-up, the transit to permanent AF was associated with the occurrence of HF (34.3% in 12 of 35 patients with permanent AF vs. 6.3% in 4 of 63 patients without, p < 0.0001). Lower heart/mediastinum ratio and lower left ventricular ejection fraction were the independent predictors of the transit to permanent AF with adjusted hazard ratios of 3.44 (95% confidence interval [CI]: 1.9 to 6.2, p < 0.0001) and 1.04 (95% CI: 1.01 to 1.08, p = 0.014). Further, these factors and higher plasma brain natriuretic peptide concentration were the independent predictors of the occurrence of HF with permanent AF, with adjusted hazard ratios of 5.08 (95% CI: 1.5 to 17.5, p = 0.011), 1.11 (95% CI: 1.03 to 1.19, p = 0.004), and 1.004 (95% CI: 1.001 to 1.008, p = 0.014). CONCLUSIONS: cardiac SNS abnormality was associated with the occurrence of both HF and permanent AF in paroxysmal AF patients, and (123)I-mIBG imaging may be a useful modality for predicting the development of AF.

Sympathetic dysfunction of systemic right ventricle in congenitally corrected transposition of the great arteries.

We evaluate the systemic right ventricle (SRV) failure of congenitally corrected transposition of the great arteries using the scintigraphic studies in a case with 32-year-old male who improved the heart failure by the use of beta-adrenergic blockers. The myocardial perfusion sympathetic nervous system activity mismatch with preserved coronary flow and wall thickness indicates a distinctive feature as SRV cardiomyopathy, suggesting the importance of recovery of SRV sympathetic dysfunction for improving the prognosis.

Significance of cardiac sympathetic nervous system abnormality for predicting vascular events in patients with idiopathic paroxysmal atrial fibrillation.

PURPOSE: Neuronal system activity plays an important role for the prognosis of patients with atrial fibrillation (AF). Using (123)I metaiodobenzylguanidine ((123)I-MIBG) scintigraphy, we investigated whether a cardiac sympathetic nervous system (SNS) abnormality would be associated with an increased risk of vascular events in patients with paroxysmal AF. METHODS: (123)I-MIBG scintigraphy was performed in 69 consecutive patients (67 + or - 13 years, 62% men) with paroxysmal AF who did not have structural heart disease. SNS integrity was assessed from the heart to mediastinum (H/M) ratio on delayed imaging. Serum concentration of C-reactive protein (CRP) was measured before (123)I-MIBG study. RESULTS: During a mean of 4.5 + or - 3.6 years follow-up, 19 patients had myocardial infarction, stroke or heart failure (range: 0.2-11.5 years). SNS abnormality (H/M ratio <2.7) and high CRP (> or = 0.3 mg/dl) were associated with the vascular events (58.3% in 14 of 24 patients with SNS abnormality vs 11.1% in 5 of 45 patients without SNS abnormality, p < 0.0001, 52.4% in 11 of 21 patients with high CRP vs 16.7% in 8 of 48 patients without high CRP, p < 0.0001). After adjustment for potential confounding variables such as age, left atrial dimension and left ventricular function, SNS abnormality was an independent predictor of vascular events with a hazard ratio of 4.1 [95% confidence interval (CI): 1.3-12.6, p = 0.014]. Further, SNS abnormality had an incremental and additive prognostic power in combination with high CRP with an adjusted hazard ratio of 4.1 (95% CI: 1.5-10.9, p = 0.006). CONCLUSION: SNS abnormality is predictive of vascular events in patients with idiopathic paroxysmal AF.

Electrocardiographic change after recanalization in a patient with recent extensive anterior wall myocardial infarction.

In a 66-year-old male with subacute extensive anterior wall myocardial infarction, we report a change in ST vector orientation from a basal anterior to a mid anterior after coronary artery recanalization of the proximal left anterior descending coronary artery with rotational atherectomy. The ST vector shift on the frontal plane after recanalization was consistent with a change toward more distal location of the ischemia on thallium-201 single photon emission computed tomography images compared to the findings during an exercise test before intervention. These findings may be correlated with local occlusion caused by distal microvascular embolization which was not visualized on coronary angiography following recanalization.

Thallium-201 and I-123 beta-methyl iodophenyl-pentadecanoic acid dual isotope single photon emission computed tomography for evaluating reperfusion injury after successful reperfusion therapy.

We report a reperfusion injury after rotational coronary atherectomy (RA) in a 66-year-old man with coronary artery disease. Submaximal exercise with thallium-201 single photon emission computed tomography (SPECT) imaging before reperfusion showed partially reversible perfusion defects in the apex and reversible perfusion defects in the anteroseptal area. Thallium-201 and I-123 beta-methyl iodophenyl-pentadecanoic acid (BMIPP) dual isotope SPECT was performed 5 days before and 1 hour after RA, and 1 month after RA. SPECT images at 1 hour after recovery of no reflow phenomenon after RA revealed enlargement of the defect sizes on thallium-201 and BMIPP uptakes in the anteroseptal area including the apex compared with those before RA. The defect size of thallium-201 uptake was progressively improved on 5 hour delayed redistribution imaging and 1 month after reperfusion compared with that of BMIPP uptake. In conclusion, the changes for the worse of thallium-201 uptake and fatty acid metabolism immediately after the no reflow phenomenon may indicate an injured membrane integrity with altered myocardial metabolism rather than myocardial ischemia. Thallium-201 and I-123 BMIPP dual isotope SPECT is useful for evaluating reperfusion injury after successful reperfusion therapy in a patient with acute coronary syndrome.

Comparison of bare metal stent with pioglitazone versus sirolimus-eluting stent for percutaneous coronary intervention in patients with Type 2 diabetes mellitus.

BACKGROUND: Drug-eluting stents (DESs) have been shown to decrease restenosis as compared with bare-metal stents. Recently, thiazolidinediones effectively reduced restenosis and the risk of repeat target vessel revascularization. We conducted a study to compare the performance of a DES with that of a bare-metal stent with pioglitazone in patients with Type 2 diabetes mellitus (DM). METHODS: The study was a prospective cohort trial involving 38 Type 2 diabetic patients referred for coronary stenting who were assigned to either the sirolimus-eluting stent (SES) group or the pioglitazone group. Quantitative coronary angiography was performed at study entry and at 6 months of follow-up to evaluate in-stent late luminal loss and the percentage of the luminal diameter and the rate of restenosis. We also analyzed major adverse cardiac events (MACE) at 12 months. RESULTS: There were no significant differences in glycemic control levels or in lipid levels in the two groups at follow up. The insulin and homeostasis model assessment insulin resistance at follow-up were significantly lower in the pioglitazone group than in the SES group. The percentage of restenosis was similar between the SES group and the pioglitazone group. The incidence of MACE at 1 year tended to be lower in the pioglitazone group than in the SES group. CONCLUSIONS: The bare-metal stent with pioglitazone is not inferior to the SES in the present study and is one of therapeutic strategies of percutaneous coronary intervention for patients with DM.