Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure with Malnutrition, Frailty, Sarcopenia, or Cachexia.

(1) Background: In patients with heart failure (HF) and impaired nutritional status or decreased muscle mass, sodium-glucose cotransporter-2 inhibitors (SGLT2is) may worsen these conditions and result in poor prognosis, especially worsening of frailty. We aimed to investigate the relationship between SGLT2is and clinical outcomes, including frailty-related events, in patients with HF and malnutrition, frailty, sarcopenia, or cachexia. (2) Methods: In this retrospective observational cohort study, a global federated health research network provided data on patients with HF and malnutrition, frailty, sarcopenia, or cachexia from January 2016 to December 2021. We investigated the incidence of the composite endpoint of death or frailty-related events within one year. (3) Results: Among 214,778 patients included in the analysis, 4715 were treated with SGLT2is. After propensity score matching, 4697 patients in the SGLT2is group were matched with 4697 patients in the non-SGLT2is groups. The incidence of the composite endpoint, mortality, and frailty-related events was lower in the SGLT2is group than in the non-SGLT2is group (composite endpoint, 65.6% versus 77.6%, p < 0.001; mortality, 17.4% vs. 35.5%, p < 0.001; frailty-related events, 59.4% vs. 64.3%, p < 0.001). (4) Conclusions: Patients with HF and malnutrition, frailty, sarcopenia, or cachexia had a high incidence of death and frailty-related events. SGLT2is were associated with a lower incidence of these events.

Diuretic and renal effects of angiotensin receptor-neprilysin inhibitor in patients hospitalized for acute heart failure.

In patients hospitalized for acute decompensation of heart failure (HF), the impact of angiotensin receptor-neprilysin inhibitor (ARNI) on diuresis and renal function has not been fully investigated. Patients with HF and reduced ejection fraction who were hospitalized for acute decompensation and newly initiated ARNI after hemodynamic stabilization were enrolled. Changes in urine volume (UV), body weight, estimated glomerular filtration rate (eGFR), and urine N-acetyl-beta-d-glucosaminidase (uNAG) levels before and after ARNI initiation were investigated. Changes in the diuretic response [DR, calculated as urine volume/(intravenous furosemide volume/40 mg)], N-terminal pro-brain natriuretic peptide (NT-proBNP), hematocrit, and plasma volume (PV) were also evaluated. A total of 60 patients were enrolled. ARNI was initiated at a median of 6 [5, 7] days after hospitalization. After initiation of ARNI, body weight, NT-proBNP, and PV decreased. UV and DR increased only on the day of ARNI initiation (delta UV 400 ± 957 ml and delta DR 1100 ± 3107 ml/40 mg furosemide) and then decreased to baseline levels. In the multivariable linear regression analysis, younger age, higher BMI, and higher NT-proBNP levels were significantly associated with greater UV after ARNI initiation. eGFR and uNAG did not significantly change after the initiation of ARNI [delta eGFR -1.7 ± 12.0 mL/min/1.73 m2 and delta uNAG 2.0 (-5.6, 6.9) IU/L]. In patients hospitalized for HF, the initiation of ARNI was associated with a small and transient increase in UV and DR, and was not associated with worsening of renal function or tubular injury.

Concomitant use of VA-ECMO and Impella with inhaled nitric oxide to treat cardiogenic shock after cardiac surgery: A case report.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to treat cardiogenic shock. However, a lack of left ventricle (LV) unloading and increased systemic afterload can cause pulmonary congestion. Impella (Abiomed, Danvers, MA, USA), a catheter-mounted micro-axial rotary pump, unloads the LV and provides hemodynamic support. However, Impella cannot support the right ventricle (RV), and RV dysfunction impedes weaning from VA-ECMO. A 50-year-old man with heart failure with reduced ejection fraction due to myocardial infarction developed moderate aortic stenosis and regurgitation, moderate mitral regurgitation, and tricuspid regurgitation. Aortic valve replacement, mitral valve replacement, and tricuspid valve replacement were performed. VA-ECMO with intra-aortic balloon pump (IABP) was initiated as he could not be weaned from cardiopulmonary bypass. The patient could not be weaned from IABP and VA-ECMO; therefore, Impella 5.0 was inserted instead of IABP on day 7. However, Impella 5.0 was ineffective due to RV dysfunction. Increased inhaled nitric oxide (iNO) dose lowered pulmonary vascular resistance, decreased RV afterload, and improved RV distension. He was weaned from VA-ECMO after increasing the flow from the Impella 5.0. Combining VA-ECMO with Impella and iNO improved hemodynamics in a patient with RV dysfunction, and Impella with iNO aided weaning from VA-ECMO. Learning objective: Combining venoarterial extracorporeal membrane oxygenation (VA-ECMO) with Impella (Abiomed, Danvers, MA, USA) and inhaled nitric oxide (iNO) can improve hemodynamics in a patient with right ventricular dysfunction, and iNO may aid weaning from VA-ECMO.

Possible Neoangiogenesis in Achilles Tendon Xanthoma with Familial Hypercholesterolemia: A Novel Approach to Achilles Tendon Xanthoma.

Achilles tendon xanthoma (ATX) is one of the typical features of familial hypercholesterolemia (FH). The morphological evaluation of ATX by X-ray radiography is widely recognized; however, the utility of other imaging modalities remains unclear. We herein report two cases of FH in which Doppler ultrasound imaging demonstrated a microvascular flow in ATX that only rarely could be observed in normal Achilles tendons. Neoangiogenesis accompanies chronic inflammation and it may play an important role in the deposition of cholesterol crystals leading to ATX. In addition to the morphological evaluation of ATX, the assessment of neoangiogenesis may therefore be essential for the evaluation of ATX.

Clinical Differences of Recent Myocardial Infarction Compared With Acute Myocardial Infarction　- Insights From the Tokyo CCU Network Multicenter Registry.

BACKGROUND: Characteristics and treatment outcomes of acute myocardial infarction (AMI) patients have been studied; however, those of recent myocardial infarction (RMI) patients remain unclear. This study aimed to clarify characteristics, treatment strategy, and in-hospital outcomes of RMI patients in the Tokyo CCU network database.Methods and Results:In total, 1,853 RMI and 12,494 AMI patients from the Tokyo CCU network database during 2013-2016 were compared. Both RMI and AMI were redefined by onset times of 2-28 days and ≤24 h, respectively. The RMI group had a higher average age (70.4±12.9 vs. 68.0±13.4 years, P<0.001), more women (27.6% vs. 23.6%, P<0.001), lower proportion of patients with chest pain as the chief complaint (75.2% vs. 83.6%, P<0.001), higher prevalence of diabetes mellitus (35.9% vs. 31.0%, P<0.001), and higher mechanical complication incidence (3.0% vs. 1.5%, P<0.001) than did the AMI group. Thirty-day mortality was comparable (5.3% vs. 5.8%, P=0.360); major causes of death were cardiogenic shock and mechanical complications in the AMI and RMI groups, respectively. Death from mechanical complications (not onset time) in the AMI group plateaued almost 1 week after hospitalization, whereas it continued to increase in the RMI group. CONCLUSIONS: Both RMI and AMI patients have distinctive clinical features, sequelae, and causes of death. Although treatment of RMI patients adhered to guidelines, it was insufficient, and death from mechanical complications continues to increase.

Malignant Findings in Candidates for Transcatheter Aortic Valve Implantation.

BACKGROUND: In candidates for transcatheter aortic valve implantation (TAVI), preoperative computed tomography (CT) may detect clinically relevant non-cardiac findings. In particular, when malignant findings are detected, patients may be less likely to undergo the procedure. Additionally, they might require further examinations, which may prolong their time to treatment. We investigated how malignant findings affect candidacy for TAVI. METHODS: In this single-center retrospective study, 98 patients with severe aortic stenosis who had undergone preoperative CT between September 2013 and October 2016 were evaluated for malignant findings. RESULTS: Seven patients (7.1%) had malignant findings. 74 of 91 patients who did not have malignant findings underwent TAVI, SAVR, or balloon aortic valvuloplasty (81.3%). All patients who had malignant findings underwent TAVI or SAVR, and they underwent the procedure sooner after CT than the rest of the patients (mean time to TAVI or SAVR: 24.6 ± 16.8 versus 48.5 ± 45.4 days; P = .003). All 5 patients who had malignant findings without metastatic cancer and who underwent TAVI were still alive during the follow-up period (the mean duration of the follow-up period was 22.3 ± 8.8 months). However, 1 patient who had a malignant finding with metastatic cancer died 7 months after CT. CONCLUSION: Our outcomes indicated that the mean duration before TAVI or SAVR was reduced when malignant findings were detected by CT; and TAVI may be a safe and effective treatment for patients with aortic stenosis and a malignant tumor.

Nivolumab-induced myocardial necrosis in a patient with lung cancer: A case report.

A 74-year-old man with lung adenocarcinoma recurrence was admitted to our hospital because of dyspnea 7 days after receiving initial immunotherapy with nivolumab. Electrocardiography revealed ST-segment elevation in V1-6 and echocardiography showed a markedly reduced left ventricular ejection fraction of 9% and akinesis of the anteroseptal wall and apex. He died from acute heart failure 3 days after admission. Microscopically, multiple small foci of myocardial necrosis with few inflammatory cells were scattered in both ventricles. Obstruction of the coronary artery was not identified. We believed that the cause of death was acute heart failure possibly due to nivolumab-induced myocardial necrosis.

The role of transcatheter aortic valve replacement in the patients with severe aortic stenosis requiring major non-cardiac surgery.

Severe aortic stenosis (AS) is considered as an independent risk factor for perioperative cardiac complications of non-cardiac surgery. Surgical aortic valve replacement should be considered before non-cardiac surgery in patients with symptomatic severe AS. However, recently, transcatheter aortic valve replacement (TAVR) has emerged as an alternative approach for selected AS patients. We sought to determine the safety and efficacy of TAVR in preparation for major non-cardiac surgery. From our retrospective database, seven patients who underwent TAVR in preparation for major non-cardiac surgery were identified, and their clinical and hemodynamic data were collected. After TAVR, a significant reduction in the mean transaortic pressure gradient from 54.0 (Interquartile range (IQR) 47.5-64.5) to 18.0 (IQR 12.5-19.0) mmHg (p = 0.016) and an increase in the calculated aortic valve area from 0.6 (IQR 0.6-0.7) to 1.3 (IQR 1.1-1.5) cm2 (p = 0.022) were noted. Non-cardiac surgery included lung segmentectomy and lymph node dissection, lung lobectomy, ileocecal resection, partial colectomy, partial nephrectomy, nephroureterectomy, laparoscopic nephrectomy, and laparoscopic nephroureterectomy. All the initial non-cardiac surgeries were performed without cardiac complications, under general anesthesia, 37 (IQR 32-74) days after TAVR. Two of the patients eventually needed additional non-cardiac surgery, which was performed uneventfully without the need for additional AS treatment. TAVR was an effective and safe procedure that might reduce the risk of general anesthesia and major non-cardiac surgery in severe AS.

Simultaneous transcatheter aortic valve implantation and endovascular aneurysm repair in a patient with very severe aortic stenosis with abdominal aortic aneurysm.

The safety of non-cardiac surgery is uncertain for asymptomatic patients with very severe aortic stenosis (AS). Herein, we describe a case involving an elderly and frail patient with asymptomatic, very severe AS. The patient was considered a high-risk candidate for aortic valve replacement (AVR); thus, transcatheter aortic valve implantation (TAVI) was planned. On perioperative examination, an abdominal aortic aneurysm (AAA) was observed, which required endovascular aneurysm repair (EVAR). To reduce the risks involved with sequential procedures, TAVI and EVAR were performed simultaneously. In patients with severe AS who are high-risk candidates for AVR, TAVI can be considered as an alternative therapy before non-cardiac surgery. In addition, the combined TAVI and EVAR procedure can reduce the risks associated with the perioperative period. .

Transcatheter aortic valve implantation in a patient with severe aortic valve stenosis, colon cancer, and obstructive ileus: A case report.

An 82-year-old woman with symptomatic severe aortic stenosis (AS) developed an obstructive ileus caused by colon cancer. Colectomy was considered a high-risk surgery due to both the severe AS and obstructive ileus. Therefore, we planned placement of a colonic stent for the obstructive ileus. After stenting, we performed transcatheter aortic valve implantation (TAVI) instead of surgical aortic valve replacement (SAVR), because of the risk of bleeding during extracorporeal circulation and the perioperative risk of AVR (Society of Thoracic Surgery predicted risk of mortality: 7.4%). Successful colonic stenting and TAVI allowed a safer colectomy. The period from TAVI to colectomy was 12 days. TAVI could be useful for symptomatic severe AS in high-risk patients prior to non-cardiac surgery, especially for malignant tumors. .

Transcatheter aortic valve implantation for patients with lung cancer and aortic valve stenosis.

Many patients who require lung resection have cardiovascular and cerebrovascular comorbidities. It has been recommended that surgical aortic valve replacement (SAVR) should precede lung resection in patients with severe aortic valve stenosis (AS). However, by first undergoing transcatheter aortic valve implantation (TAVI), the patient may undergo lung resection more safely. We present two patients with both severe AS and lung cancer who underwent TAVI and lung resection without any complications.

Quantitative measurement of lipid rich plaque by coronary computed tomography angiography: A correlation of histology in sudden cardiac death.

BACKGROUND AND AIMS: Recent advancements in coronary computed tomography angiography (CCTA) have allowed for the quantitative measurement of high-risk lipid rich plaque. Determination of the optimal threshold for Hounsfield units (HU) by CCTA for identifying lipid rich plaque remains unknown. We aimed to validate reliable cut-points of HU for quantitative assessment of lipid rich plaque. METHODS: 8 post-mortem sudden coronary death hearts were evaluated with CCTA and histologic analysis. Quantitative plaque analysis was performed in histopathology images and lipid rich plaque area was defined as intra-plaque necrotic core area. CCTA images were analyzed for quantitative plaque measurement. Low attenuation plaque (LAP) was defined as any pixel < 30, 45, 60, 75, and 90 HU cut-offs within a coronary plaque. The area of LAP was calculated in each cross-section. RESULTS: Among 105 cross-sections, 37 (35.2%) cross-sectional histology images contained lipid rich plaque. Although the highest specificity for identifying lipid rich plaque was shown with <30 HU cut-off (88.2%), sensitivity (e.g. 55.6% for <75 HU, 16.2% for <30 HU) and negative predictive value (e.g. 75.9% for <75 HU, 65.9% for <30 HU) tended to increase with higher HU cut-offs. For quantitative measurement, <75 HU showed the highest correlation coefficient (0.292, p = 0.003) and no significant differences were observed between lipid rich plaque area and LAP area between histology and CT analysis (Histology: 0.34 ±â€¯0.73 mm2, QCT: 0.37 ±â€¯0.71 mm2, p = 0.701). CONCLUSIONS: LAP area by CCTA using a <75 HU cut-off value demonstrated high sensitivity and quantitative agreement with lipid rich plaque area by histology analysis.

High-risk carotid plaque: lessons learned from histopathology.

The pathophysiology and natural history of atherosclerotic carotid disease is predicated on a more extensive knowledge of lesion progression gained in the studies conducted in the coronary arteries, and these will be reviewed. While the precise sequence of lesion progression leading to carotid plaque vulnerability and cerebrovascular events remain less well understood, specific early and more advanced progressive lesion morphologies associated with stroke risk have been characterized. Of late, there has been a conscious effort for stroke prevention in symptomatic and asymptomatic patients to move beyond luminal stenosis as the only guidance to predict future cerebrovascular events. Driving this strategy are recent advances in medical imaging modalities to assess carotid atherosclerosis vulnerability particularly involving molecular imaging, which is now positioned at the forefront to provide a more detailed and mechanistic assessment of stroke risk. As such, we will spotlight the pathology of high-risk carotid plaques in patients with symptomatic and asymptomatic carotid disease with further reference into more recent mechanistic insights involving a recognized macrophage-mediated inflammatory change, intraplaque neoangiogenesis/hemorrhage, hypoxia, and microcalcification, as potential morphologic indicators of stroke risk.

Pathology of balloon-expandable transcatheter aortic valves.

BACKGROUND: The Placement of AoRtic TraNscathetER Valves trials (PARTNER) showed favorable safety and efficacy versus medical or surgical therapy in inoperable, high, and intermediate surgical risk patients with severe aortic stenosis. However, the biological responses to transcatheter aortic valves have not been well characterized. OBJECTIVES: The aim of this study was to perform pathologic assessment of Edwards SAPIEN transcatheter aortic valves removed either at autopsy or surgically during the PARTNER I and II clinical trials. METHODS: Explanted valves and frame were evaluated for pathologic responses including extent of thrombus, inflammation, neointima, and leaflet degeneration/calcification according to semiquantitative grading by implant duration (≤30 days; 31-90 days; >90 days). RESULTS: A total of 22 cases (median age 82.0 years, 45% men) were included, with a duration of implantation that ranged from 0 to 1739 days (median duration 16.5 days [interquartile range, 2.8-68.3]). Valve thrombosis resulting in severe aortic stenosis was observed in one case. Moderate leaflet thrombus was seen in 14% of cases (n = 3) and all were asymptomatic. Calcification was seen in two valves: one with severe leaflet calcification had severe aortic stenosis requiring surgical replacement, while the other showed early calcification. Mild structural leaflet changes were exclusively seen in valve implants >90 days. Valve inflammation and thrombus formation was mild in majority of the cases. CONCLUSIONS: Overall, our study demonstrates moderate thrombus formation in 14% and calcification in only 2 valves, ≥4 years duration. In this short-duration study, acceptable durability and biocompatibility of the Edwards SAPIEN transcatheter valve system was demonstrated; however, further studies are required to confirm the significance and application of our findings.

Comparison of branch and distally focused main renal artery denervation using two different radio-frequency systems in a porcine model.

OBJECTIVES: Anatomic placement of lesions may impact efficacy of radio-frequency (RF) catheter renal denervation (RDN). However, it is unclear if it is necessary to perform treatments post bifurcation with systems that may provide deeper penetration to achieve successful RDN. METHODS: Sixteen domestic swine (n=16) were randomly assigned to 4 groups: 1) 8 lesions created in the branch arteries using the Spyral catheter (SP8); 2) 8 lesions created in the branch arteries plus 4 lesions created in the main artery using the SP catheter (SP12); 3) 8 lesions created in the main artery using the EnligHTN catheter with the distal position as close as possible to the bifurcation (EN8); and 4) 12 lesions created in the main artery using the EN catheter with the distal position as close as possible to the bifurcation (EN12). RESULTS: Each arm showed statistically significant changes in kidney norepinephrine (NE, ng/g) between treated kidneys vs. untreated contralateral control. There were no statistically significant differences in tissue NE% reductions across each arm based on catheter, anatomic location, & number of lesions (p=0.563): EN8 -74±34%, EN12 -95±3%, SP8 -76±16%, SP12 -82±17% (p=0.496). A total of 46 lesions were measured for lesion depth: EN main (3.3±2.8mm) vs. SP branch (2.0±1.0mm, p=0.039), SP main (2.9±1.6mm) vs. SP branch (p=0.052), and EN main vs. SP main (p=0.337). CONCLUSIONS: Distally-focused main renal artery treatment using the EN system appears to be equally efficacious in reducing tissue NE levels compared with SP treatment in the branches plus main renal arteries, advocating for device-specific procedure execution.

Very late scaffold thrombosis of everolimus-eluting bioresorbable scaffold following implantation in STEMI after discontinuation of dual antiplatelet therapy.

A 42-year-old male with a history of smoking and dyslipidemia was admitted due to ST-elevation myocardial infarction. Coronary angiography showed severe stenosis in proximal right coronary artery (RCA) and total occlusion in mid RCA. Absorb everolimus-eluting bioresorbable scaffolds were deployed in mid and proximal RCA. The patient was discharged with dual anti-platelet therapy. Patient was admitted 15-months later due to acute coronary syndrome with scaffold thrombosis. Both aspirin and clopidogrel had been discontinued 1 month prior to the second event because of general malaise. Therefore, either aspirin or clopidogrel should have been continued even after 1 year following stent implantation.

Histopathological Differential Diagnosis of Optical Coherence Tomographic Image Interpretation After Stenting.

OBJECTIVES: The aim of this study was to identify histological features that correlate with terms commonly used to describe optical coherence tomographic (OCT) and optical frequency-domain imaging (OFDI) images of stented vessels, by means of a histopathological validation study using stented human coronary arteries. BACKGROUND: OCT imaging and OFDI are used to evaluate vascular responses to stent implantation. Descriptive terms such as "peristrut low attenuation" and "heterogeneous" have been used to describe neointimal characteristics that may have clinical relevance. However, only limited histopathological correlations are available. METHODS: Using the CVPath stent registry, 19 cases were identified in whom implantation duration was >30 days and OCT imaging or OFDI and histological findings were available. Consecutive OCT or OFDI frames (n = 1,063) of stented coronary arteries were categorized according to their predominant imaging features in 1-mm intervals. Coregistration of OCT or OFDI frames and histopathological cross sections was performed in 111 frames. RESULTS: Seven distinct OCT or OFDI patterns were found: homogenous (45%), layered (15%), high intensity with high attenuation (14%), intraluminal protruding masses (8%), peristrut low attenuation (7%), heterogeneous (2%), and honeycomb (1%). Histopathologically, the homogenous pattern correlated most often with smooth muscle cells within collagenous/proteoglycan matrix and less often with organized thrombus. The layered pattern correlated with healed neointimal rupture or erosion, peristrut neovascularization, or smooth muscle cells within collagen/proteoglycan matrix. High intensity with high attenuation correlated with superficial macrophage accumulation in the majority of cases, but with other histological findings in 30% of cases. The diagnostic accuracy was greater in restenotic lesions. The only OCT or OFDI finding that had a single histological feature was the honeycomb pattern. CONCLUSIONS: This study suggests a lack of correlation between OCT image patterns and distinct histological tissue characteristics.