Biopsy-Proven Fulminant Myocarditis Requiring Mechanical Circulatory Support Following COVID-19 mRNA Vaccination.

A 48-year-old woman suffered from cardiogenic shock with fulminant myocarditis following the second dose of COVID-19 vaccine (mRNA-1273). Venoarterial extracorporeal membrane oxygenation and Impella support were essential in achieving hemodynamic stability. Endomyocardial biopsy revealed lymphocytic infiltration with predominant immunostaining for CD8- and CD68-positive cells. The left ventricular ejection fraction improved significantly after treatment with mechanical circulatory support. Myocarditis following COVID-19 mRNA vaccination may also occur in middle-aged women; it may be fulminant and require mechanical circulatory support. Although our results suggest the involvement of cytotoxic T lymphocytes and macrophages, further investigation is needed before these can be established as pathogenetic mechanisms.

Une femme de 48 ans a souffert d'un choc cardiogène accompagné d'une myocardite fulminante après avoir reçu la deuxième dose du vaccin contre la COVID-19 (ARNm-1273). L'oxygénation par membrane extracorporelle veino-artérielle et l'assistance par Impella ont joué un rôle essentiel pour atteindre la stabilité hémodynamique. Une biopsie endomyocardique a révélé la présence d'infiltrats lymphocytaires avec une immunocoloration prédominante pour les cellules exprimant CD8 et CD68. La fraction d'éjection ventriculaire gauche s'est améliorée considérablement après un traitement par assistance circulatoire mécanique. Des cas de myocardite peuvent également survenir chez des femmes d'âge moyen après l'administration d'un vaccin à ARNm contre la COVID-19; ils peuvent être fulminants et nécessiter une assistance circulatoire mécanique. Bien que nos résultats laissent croire à une participation des lymphocytes T cytotoxiques et des macrophages, une étude approfondie s'impose avant de pouvoir cerner les mécanismes pathogènes.

Early detection of twiddler syndrome due a congestion alert by remote monitoring.

There are often false-positive alerts of thoracic impedance monitoring; however, the "false-positive alerts" might indicate any clinical problem of patient. In the present case, an alert for a drop in intrathoracic impedance, which generally indicates exacerbation of heart failure, enabled early detection of twiddler syndrome.

Review of High-intensity Interval Training in Cardiac Rehabilitation.

For the secondary prevention of cardiovascular disease, comprehensive cardiac rehabilitation is required. This involves optimal medical therapy, education on nutrition and exercise therapy, and smoking cessation. Of these, efficient exercise therapy is a key factor. A highly effective training protocol is therefore warranted, which requires a high rate of compliance. Although moderate-intensity continuous training has been the main training regimen recommended in cardiac rehabilitation guidelines, high-intensity interval training has been reported to be more effective in the clinical and experimental setting from the standpoint of peak oxygen uptake and central and peripheral adaptations. In this review, we illustrate the scientific evidence for high-intensity interval training. We then verify this evidence and discuss its significance and the remaining issues.

Fatal Intraperitoneal Bleeding after Intravenous Administration of Tissue Plasminogen Activator.

We report a case of acute ischemic stroke, which developed fatal intraperitoneal bleeding after intravenous administration of alteplase. An 86-year-old woman developed acute infarction of the right middle cerebral artery during admission for chronic heart failure. Two days before the stroke, liver biopsy was performed; the result was benign. Although rivaroxaban was prescribed for atrial fibrillation, the rivaroxaban had been discontinued for liver biopsy until the time when she developed the stroke. A condition of recent biopsy required careful determination of eligibility of intravenous alteplase; however, we considered that the benefit of intravenous alteplase outweighed the hemorrhagic adverse effects. Alteplase (0.6 mg/kg) was started 2 hours after the stroke onset, however, no clinical improvement was obtained. One hour after the completion of alteplase, she suddenly developed a shock state. Emergent computed tomography disclosed massive intraperitoneal hemorrhage. She died 8 hours after the completion of alteplase. In the present case, mechanical thrombectomy without intravenous alteplase can be an alternative therapeutic option.

Coronary angioscopic imaging of in-stent restenosis after biolimus-eluting coronary stent implantation.

A 69-year-old man underwent repeat percutaneous coronary intervention for in-stent restenosis in the obtuse marginal artery 8 months after biolimus-eluting stent (2.5 × 28 mm Nobori stent, Terumo, Tokyo, Japan) implantation. Coronary angiography showed focal stenosis in the distal part of the stent. Intravascular ultrasound revealed low echoic heterogeneous intimal tissue. Optical coherence tomography also revealed a heterogeneous finding classified as a layered pattern. Coronary angioscopy detected a white mass with a paste-like appearance at the stenosis extending around the in-stent restenosis as a thin membrane where stent strut could be seen transparently. A small part of the mass was swinging in the blood stream. Coronary angioscopic imaging was beneficial for the understanding of the suspected mechanism and feature of the in-stent restenosis after second-generation stent implantation, which was apparently different from neointimal hyperplasia after bare-metal stent implantation. .

Resolution of left ventricular thrombus secondary to tachycardia-induced heart failure with rivaroxaban.

A 42-year-old man was admitted to our hospital because of lumbago and tachycardia-induced heart failure. Transthoracic echocardiography revealed impaired left ventricular function and a ball mass of thrombus in the left ventricle (LV). He was found to have systemic embolism in the spleen, kidneys, brain, and limbs. The patient was treated with limb thrombectomy followed by anticoagulation. Seven days after the direct factor Xa inhibitor, rivaroxaban, was initiated, transthoracic echocardiography was repeated, revealing disappearance of the LV thrombus without any clinical signs of cardiogenic embolism. His heart failure responded well and the LV wall motion had improved. This case suggests rivaroxaban has fibrinolytic effects on thrombi even in the LV.

Compound heterozygotes for a novel mutation, apo E1 Nagoya (Arg142Ser) and Apo E2 (Arg158Cys), with severe type III hyperlipoproteinemia and familial hypercholesterolemia.

AIM: A patient with severe type III hyperlipoproteinemia and familial hypercholesterolemia (FH) was previously reported (Metabolism, 44,1995:460-465). In the current study, the patient's apolipoprotein (apo) E gene was analyzed. METHODS: An apo E isoform analysis was performed using isoelectric focusing and immunoblotting. In addition, after DNA preparation, a restriction fragment length polymorphism analysis and DNA sequence analysis were performed. RESULTS: The patient's apo E phenotype was E2/E1, and the genotype was ε2/ε2. The sequence analysis of the patient's DNA revealed a new variant of apo E, which involves a single substitution of one serine (AGC) for one arginine (CGC) at position 142, thereby adding one negatively charged unit to apo E2. Therefore, the patient was compound heterozygous for apo E1 (Arg142Ser) and apo E2 (Arg158Cys). CONCLUSIONS: A novel mutation, apo E1 Nagoya (Arg142Ser) in a patient with severe type III hyperlipoproteinemia with heterozygous FH was characterized. Since the presence of arginine at the amino acid residue 142 of apo E is considered to play an important role in binding to LDL receptors, the mutation apo E1 Nagoya (Arg142Ser) likely contributed to the expression of severe type III hyperlipoproteinemia in this patient.

Acute effect of sodium nitroprusside on microvascular dysfunction in patients who underwent percutaneous coronary intervention for acute ST-segment elevation myocardial infarction.

Even in the era of thrombus aspiration and distal protection for ST-segment elevation acute myocardial infarction (STEMI), microvascular dysfunction does exist and improvement of microvascular dysfunction can improve the prognosis and/or left ventricular dysfunction. We evaluated the acute effects of nitroprusside (NTP) on coronary microvascular injury that occurred after primary percutaneous coronary intervention (PCI) for STEMI in 18 patients. The final Thrombolysis in Myocardial Infarction trial (TIMI) flow grade after PCI was 3 in 17 patients and 2 in 1 patient. The index of microcirculatory resistance (IMR) was improved significantly from 76 ± 42 to 45 ± 37 (P = 0.0006) by intracoronary NTP administration. IMR improved to the normal range (IMR < 30) in 9 patients (50%). Higher TIMI flow grade and lower IMR at baseline were observed more frequently in patients whose IMR recovered to normal range after NTP administration. NTP improved the microcirculatory dysfunction at the acute phase in patients who underwent PCI for STEMI and had final TIMI 3 flow in almost all cases.

HDL2 can inhibit further oxidative modification of partially oxidized LDL.

AIM: To investigate whether HDL(2) can inhibit further oxidative modification of partially oxidized LDL (ox-LDL) by interrupting the chain oxidation reaction after lipid hydroperoxides (LOOH) formation. METHODS: Following incubation of LDL 400 microg protein/mL phosphate-buffered saline with Cu(2+) for 1.75 h (defined as 0 min), incubation was continued after adding HDL(2) 200 microg protein/mL or HDL(2) 800 microg protein/mL to give both ox-LDL+HDL(2) 200 microg protein/mL or ox-LDL+HDL(2) 800 microg protein/mL. As a control, ox-LDL 200 microg protein/mL and native LDL were prepared. Each sample was subjected to agarose gel electrophoresis and the LOOH in each sample was measured. RESULTS: When the electrophoretic mobility of native LDL was designated 1, the relative electrophoretic mobility (REM) of ox-LDL increased significantly over time. The REMs of ox-LDL+HDL(2) 800 microg protein/mL from 10 min to 9 h were significantly lower than the REM of ox-LDL at the respective times (p<0.01). LOOH of ox-LDL+HDL(2) 800 microg protein/mL at 1, 3, 6 and 9 h was significantly higher than LOOH in ox-LDL at the respective times (p<0.01). The results of ox-LDL+HDL(2) 200 microg protein/mL were almost the same but to a lesser extent than the results of ox-LDL+HDL(2) 800 microg protein/mL. CONCLUSION: The present findings suggest that HDL(2) can inhibit further oxidative modification of partially oxidized LDL by interrupting the chain oxidation reaction after LOOH formation in a concentration-dependent manner.

Elevated plasma levels of B-type natriuretic Peptide but not C-reactive protein are associated with higher red cell distribution width in patients with coronary artery disease.

Although higher red cell distribution width (RDW) has recently been reported to be associated with increased mortality independent of anemia in patients with heart failure and those with coronary artery disease (CAD), the mechanism underlying this association is unknown. We hypothesized that higher RDW may reflect neurohumoral activation and a chronic inflammatory state that each contribute to adverse clinical outcomes in these populations. We measured RDW and plasma levels of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hs-CRP) in 226 consecutive patients undergoing cardiac catheterization for CAD (age, 67 +/- 8 years; males, 77%; RDW, 45.8 +/- 3.3 fL; hemoglobin, 13.2 +/- 1.4 g/dL; BNP, median [interquartile range], 26.0 [9.0-58.4] pg/mL; hs-CRP, 679 [345-1920] ng/mL). Plasma BNP (r = 0.21, P < 0.01) but not hs-CRP (r = 0.04, P > 0.1) levels correlated with RDW. After adjustment for potential confounders including age, gender, body mass index, glomerular filtration rate, hemoglobin, and known hemodynamic determinants of BNP, including elevated left ventricular end-diastolic pressure and volume and slow left ventricular relaxation, RDW was independently predicted by BNP (r(2) = 0.058, P < 0.001). In conclusion, elevated BNP levels are independently associated with higher RDW in patients with CAD. Neurohumoral activation may be a mechanistic link between increased RDW and adverse clinical outcomes in this population.

Low incidence of cardiac events in statin-administered patients in CAG study.

AIM: The effect of statins in preventing cardiac events in Japanese coronary artery disease (CAD) patients was studied in a retrospective investigation of 148 patients diagnosed with CAD by coronary angiography (CAG). METHODS: Sixty-five patients received statins within 2 weeks after CAG, and 83 patients did not receive statins after CAG. RESULTS: In the statin group, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were reduced significantly with statin administration (p<0.01). In the non-statin group, baseline levels of TC, LDL-C and high-density lipoprotein cholesterol were not changed significantly at the end of the follow-up period. As for the effect of statin in preventing cardiac events, the incidence of cardiac events was significantly lower (p<0.0003) in the statin group (n=5: 8%) than in the non-statin group (n=28: 34%). In subanalysis of 37 patients whose TC at the time of initial CAG was less than 200 mg/dL, none of the statin group (n=17) suffered a cardiac event. This was significantly lower than the incidence of cardiac events in the non-statin group (n=5: 25%; p<0.05). CONCLUSION: The present study demonstrated that lowering LDL-C of Japanese CAD patients by statin administration is effective to prevent cardiac events, particularly, a second percutaneous coronary intervention (PCI) for restenosis of a coronary artery following the initial PCI whether or not these patients had hypercholesterolemia.

Anemia is an independent predictor for elevated plasma levels of natriuretic peptides in patients undergoing cardiac catheterization for coronary artery disease.

BACKGROUND: It is unknown whether the association of anemia with elevated plasma levels of B-type and atrial natriuretic peptides (BNP and ANP) is mediated by the hemodynamic effects of anemia. METHODS AND RESULTS: The study group comprised 237 consecutive patients (BNP, median [interquartile range], 28.3 [9.5-77.1] pg/ml; ANP, 17.8 [8.5-39.0] pg/ml) undergoing determination of hemoglobin (Hb) and natriuretic peptide levels and cardiac catheterization for evaluation of coronary artery disease (CAD). Hb correlated with BNP (r=-0.36, p<0.001) and ANP (r=-0.35, p<0.001). Patients with anemia (Hb <12 g/dl for females; <13 g/dl for males, n=63) were more likely to be older with reduced body mass index and renal function, greater severity of CAD and to have higher heart rate, mean pulmonary capillary wedge pressure, and cardiac output. Anemia was a significant predictor for elevated (>third quartile value) natriuretic peptide levels and the predictive value remained significant after adjustment for other predictors, including increased left ventricular end-diastolic pressure and differences in clinical and hemodynamic variables between patients with and without anemia (adjusted odds ratio [95% confidence interval] for elevated BNP and ANP levels, 7.39 [2.76-19.8] and 2.56 [1.08-6.07], respectively). CONCLUSION: Anemia is an independent predictor for elevated natriuretic peptide levels in patients with known or suspected CAD.

Relationship between blood pressure obtained from the upper arm with a cuff-type sphygmomanometer and central blood pressure measured with a catheter-tipped micromanometer.

Recently, the importance of central blood pressure for cardiovascular risk stratification has been emphasized. Accordingly, the differences in peak systolic and bottom diastolic pressures between the ascending aorta and the brachial artery should be clarified. Study subjects consisted of 82 consecutive patients with suspected coronary artery disease who underwent cardiac catheterization, and in whom ascending aortic pressure waveform was obtained using a catheter-tipped micromanometer, and at the same time systolic and diastolic pressures were measured (single measurement) from the right upper arm with a cuff-type sphygmomanometer based on the oscillometric technique. No significant systematic difference (bias) was found between the peak pressure obtained in the ascending aorta and the systolic pressure from the right upper arm (133.6 +/- 25.1 vs 131.8 +/- 21.5 mmHg, not significant). Bland-Altman analysis showed only a small bias of +1.8 mmHg, and the limits of agreement were 25.4 mmHg and -21.8 mmHg. In contrast, the bottom pressure in the ascending aorta was significantly lower compared with the diastolic pressure from the upper arm (68.5 +/- 10.7 vs 73.0 +/- 12.4 mmHg, P < 0.0001). Bland-Altman analysis showed a small but significant bias of -4.5 mmHg, and the limits of agreement were 14.1 mmHg and -23.1 mmHg. The observed biases seemed to remain within practical range. However, random variation in the two measurements was rather large. This is considered to be caused by the random error in the single measurement with the cuff-type sphygmomanometer.

Lack of inertia force of late systolic aortic flow is a cause of left ventricular isolated diastolic dysfunction in patients with coronary artery disease.

OBJECTIVES: We investigated whether a lack of inertia force of late systolic aortic flow and/or apical asynergy provoke early diastolic dysfunction in patients with coronary artery disease (CAD). BACKGROUND: Left ventricular (LV) isolated diastolic dysfunction is a well-recognized cause of heart failure. METHODS: We evaluated LV apical wall motion and obtained left ventricular ejection fraction (LVEF) by left ventriculography in 101 patients who underwent cardiac catheterization to assess CAD. We also computed the LV relaxation time constant (Tp) and the inertia force of late systolic aortic flow from the LV pressure (P)-first derivative of left ventricular pressure (dP/dt) relation. Using color Doppler echocardiography, we measured the propagation velocity of LV early diastolic filling flow (Vp). Patients with LVEF > or =50% (preserved systolic function [PSF], n = 83) were divided into 2 subgroups: patients with inertia force (n = 53) and without inertia force (n = 30). No patient with systolic dysfunction (SDF) (LVEF <50%) had inertia force (n = 18). RESULTS: The Tp was significantly longer in patients with SDF (85.7 +/- 21.0 ms) and with PSF without inertia force (81.1 +/- 23.6 ms) than in those with PSF with inertia force (66.3 +/- 12.8 ms) (p< 0.001). The Vp was significantly less in the former 2 groups than in the last group. In patients with PSF, LV apical wall motion abnormality was less frequently observed in those with inertia force than in those without (p < 0.0001). CONCLUSIONS: An absence of inertia force in patients with PSF is one of the causes of isolated diastolic dysfunction in patients with CAD. Normal LV apical wall motion is substantial enough to give inertia to late systolic aortic flow.

Both HDL3 and HDL2 exert a powerful anti-oxidative and protective effect against acceleration of oxidative modification of LDL by ascorbic acid.

The objective of the present study was to establish whether high-density lipoprotein 3 (HDL3) or high-density lipoprotein 2 (HDL2) might show an anti-oxidative effect on the acceleration of the oxidative modification of low-density lipoprotein (LDL) by ascorbic acid from measurement of the agarose gel electrophoretic mobility of LDL. LDL was incubated without adding transitional-metal ions for 48 or 96 h in phosphate-buffered saline (PBS) alone, with ascorbic acid (20 microg/mL), or with both ascorbic acid (20 microg/mL) and HDL3 (200 microg protein/mL). The LDL autoxidation occurred in PBS alone. Although ascorbic acid significantly suppressed oxidative modification of LDL after incubation for 48 h, the opposite was true after 96 h. However, since the anti-oxidative ability of HDL2 shows a weaker tendency than that of HDL3, both HDL3 and HDL2 significantly inhibited this acceleration of oxidative modification of LDL by ascorbic acid as assessed by electrophoretic mobility. If there is an augmented oxidative modification of LDL due to ascorbic acid in vivo, HDL3 or HDL2 may thus have an important role in inhibiting this ascorbic acid-accelerated oxidation of LDL.