Initiating ivabradine during hospitalization in patients with acute heart failure: A real-world experience in China.

BACKGROUND: Initiating ivabradine in acute heart failure (HF) is still controversial. HYPOTHESIS: Ivabradine might be effective to be added in acute but hemodynamically stable HF. METHODS: A retrospective cohort of hemodynamically stable acute HF patients was enrolled from January 2018 to January 2020 and followed until July 2020. The primary endpoints were all-cause mortality and rehospitalization for HF. Secondary endpoints included heart rate (HR), cardiac function measured by New York Heart Association (NYHA) class, and left ventricular ejection fraction (LVEF) and adverse events, which were compared between patients with or without ivabradine. RESULTS: A total of 126 patients were enrolled (50 males, median age 54 years, 81% with decompensated HF, median follow-up of 9 months). In patients treated with ivabradine, although baseline HRs were higher than the reference group (96 vs. 80 bpm), they were comparable after 3 months; more patients tolerated high doses of ß-blockers (27% vs. 7.9%), improved to NYHA class I function (55.6% vs. 23.8%) and exhibited normal LVEFs (37.8% vs. 14.3%) than the reference group (all p < .05). Ivabradine was associated with a significant reduction of rehospitalization for HF than the reference group (25.4% vs.61.9%), with longer event-free survival times (hazard ratio: 0.45, 95% confidence interval [CI]: 0.25-0.79), and was related with primary endpoints negatively (hazard ratio 0.51, 95% CI: 0.28-0.91) (all p < .05). CONCLUSION: In patients with acute but hemodynamically stable HF, ivabradine may significantly reduce HR, improve cardiac function, and reduce HF rehospitalization.

PD-1 inhibitor induces myocarditis by reducing regulatory T cells, activating inflammatory responses, promoting myocardial apoptosis and autophagy.

The present study aimed to explore the pathogenesis of autoimmune myocarditis induced by PD-1 inhibitors and their potential therapeutic targets. Mouse models of autoimmune myocarditis induced by PD-1 inhibitor in mouse models of polymyositis were established. The expression level of PD-1 and regulatory T cells (Tregs), CD4, CD8 + T cells, inflammation, apoptosis and autophagy-related factors, including IL-6, TGF-ß, AMA-M2, Fas/FasL, LC3 and p62 were detected in peripheral blood, muscle or myocardium of mice in each group, using ELISA, RT-PCR, Western Blot and immunofluorescence. In addition, HE and TUNEL staining and ultrastructural scanning were performed on the myocardium of mice in each group. Results showed that the expression level of PD-1 in the two myositis groups was significantly lower than that in the control group, and the level of PD-1 was lower in the myocarditis group than that in the polymyositis group. In the myocardium, TGF-ß, p62, and Tregs proportion showed the same expression level trend as PD-1, while CD8, IL-6, IL-10 and LC3 showed the opposite trend. Levels of Fas/FasL were significantly higher in both myositis groups, but were slightly lower in the myocarditis group, as was AMA-M2. Inflammation, apoptosis, and autophagy were observed in both myositis groups, but were more severe in the myocarditis group. In summary, the decreased expression level of PD-1 leads to decreased Tregs level in the myocardium, aggravated inflammatory response, apoptosis and autophagy, which may be the pathological mechanism of myocarditis induced by PD-1 inhibitors.

Sex-specific pattern of left ventricular hypertrophy and diastolic function in patients with type 2 diabetes mellitus.

AIMS: Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodelling, and diastolic dysfunction in patients with type 2 diabetes (T2DM). The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodelling, and diastolic dysfunction in patients with T2DM. Further, the prognostic value of diastolic function in women and men was also evaluated. METHODS AND RESULTS: A total of 350 patients with T2DM (mean age 61 ± 11 years; women, 48.3%) was recruited. Detailed echocardiography was performed at baseline and after 25 months. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization, or myocardial infarction. Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 21 patients developed MACE (5 cardiovascular death, 9 hospitalization for heart failure, and 7 myocardial infarction) during a median follow-up of 56 months. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women [hazard ratio = 6.30; 95% confidence interval (CI) = 1.06-37.54; P < 0.05] but not men (hazard ratio = 2.29, 95% CI = 0.67-7.89; P = 0.19). CONCLUSION: LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men.

Nonapical Right Ventricular Pacing Is Associated with Less Tricuspid Valve Interference and Long-Term Progress of Tricuspid Regurgitation.

BACKGROUND: Tricuspid regurgitation (TR) is a well-known complication after permanent pacemaker implantation. The aim of this study was to compare the degree of TR and the relationship of lead position across the tricuspid valve (TV) between patients with right ventricular apical (RVA) and non-RVA pacing determined by three-dimensional echocardiography. METHODS: Conventional and three-dimensional echocardiography was performed in 284 patients to determine the change in TR severity following permanent pacemaker implantation. Transvenous lead locations were based on fluoroscopic images. This was a retrospective study, and the selected pacing mode was not randomized. RESULTS: RVA pacing had more frequent severe TR (37.9% vs 25.7%, P = .03) compared with non-RVA pacing. Severe TR occurred in 9.7%, 12.6%, and 58.8% of patients when the lead passed through the middle, between the commissures, and impinging the TV leaflets, respectively. Non-RVA leads were more likely to be positioned in the middle of the TV (30.3% vs 12.1%, P < .01) and had the lowest chance of leaflet impingement (33.6% vs 51.5%, P < .01) compared with RVA leads. RVA pacing was associated with worsening of grade ≥2 TR severity compared with non-RVA pacing (42.4% vs 27.6%, P < .01). A TV lead passage angle of -15° to 15° minimized TR. CONCLUSIONS: Pacing-induced TR is more prevalent with RVA than non-RVA pacing. Preferential lead impingement on the TV leaflet, as determined by TV lead passage angle, can explain the development and progression of pacing-induced TR.

The quest for diagnostic approaches of cardiac involvement in polymyositis and dermatomyositis.

Polymyositis (PM) and dermatomyositis (DM) are autoimmune diseases characterized by inflammation of skeletal muscle, primarily manifesting as chronic muscle weakness. Extramuscular organs can also be affected. Cardiac involvement is one of the visceral organ damages whose prevalence is underestimated and is a marker of poor prognosis leading to irreversible dysfunction or even death. Although early and accurate recognition of cardiac involvement remains a key barrier to improving survival in PM/ DM patients, considerable progress has been made, and an overview will be provided in this review. The new concept of multimodality imaging, which involves an integrated approach of echocardiography (Echo), cardiac magnetic resonance and sometimes positron emission tomography (PET), can facilitate diagnosis. The development of ultrasound technology, including strain analysis, stress Echo and contrast-enhanced Echo, helps disclose early cardiac dysfunction more sensitively than conventional Echo. Cardiac magnetic resonance unveils silent, acute or chronic myocarditis in PM/DM and is used to monitor treatment efficacy due to its excellent tissue characterization. PET can be useful thanks to the appearance of new tracers that can eliminate the effects of glucose uptake by normal cardiomyocytes. The sensitivity of endomyocardial biopsy may be increased by targeted sampling with the guidance of cardiac imaging. Troponin I is specific to cardiac injury, and investigations into antibodies against cardiac tissue are being carried out. Disease-specific mechanisms and therapies are also discussed to give more insights into cardiac involvement in PM and DM.

Prognostic Value of Tricuspid Valve Geometry and Leaflet Coaptation Status in Patients Undergoing Tricuspid Annuloplasty: A Three-Dimensional Echocardiography Study.

BACKGROUND: The advent of three-dimensional echocardiography (3DE) enables detailed evaluation of the tricuspid valve (TV) apparatus; nonetheless, the clinical value of preoperative 3DE is unknown in patients undergoing tricuspid annuloplasty (TA). The aim of this study was to evaluate the prognostic value of TV geometric parameters and leaflet coaptation status evaluated by 3DE in patients undergoing TA. METHODS: A total of 122 patients who underwent TA during left-sided heart valve surgery were prospectively evaluated. Detailed 3DE was performed before surgery. Adverse outcome was defined as the occurrence of heart failure requiring hospital admission or all-cause mortality following TA. RESULTS: A total of 33 adverse events (17 heart failures and 16 deaths) occurred during a median follow-up of 36 months. Tethering volume (hazard ratio = 1.32; 95% CI = 1.05-1.66; P = .01) and ratio of total leaflet length to closure length (hazard ratio = 1.07; 95% CI = 1.03-1.12; P < .01) were associated with adverse events after adjustment for age, sex, and tricuspid regurgitation vena contracta width. Receiver-operator characteristic curve analysis revealed that tethering volume (area under curve = 0.73) and ratio of total leaflet length to closure length (area under curve = 0.75) were most associated with adverse events at 1-year follow-up. The presence of either a large tethering volume or a low ratio of total leaflet length to closure length was predictive of an adverse outcome 1 year following TA. CONCLUSIONS: Our study suggests that 3DE-derived TV tethering volume and ratio of total leaflet length to closure length are important preoperative measures associated with adverse events in patients undergoing TA.

Impact of obesity on longitudinal changes to cardiac structure and function in patients with Type 2 diabetes mellitus.

AIMS: Few prospective studies have evaluated the natural progression of left ventricular (LV) remodelling in patients with Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the impact of obesity on longitudinal cardiac structural and functional changes in patients with T2DM. METHODS AND RESULTS: This study comprised of 274 patients with T2DM (mean age, 62.2 ± 11.4 years; male, 51.5%). Echocardiographic parameters including LV geometry, systolic, and diastolic functions were measured at baseline and follow-up. The median follow-up was 24 months (from 12 months to 48 months). The entire cohort showed a significant increase in LV wall thickness, LV mass (LVM), and prevalence of concentric hypertrophy (19.6-27.3%). Further, systolic function and diastolic function had deteriorated at follow-up assessment. Multivariable adjusted linear regression demonstrated that baseline body mass index (BMI) predicted longitudinal change to LVM (ß = 0.29, P < 0.01) and LV ejection fraction (ß = -0.15, P < 0.05). Patients were divided into three groups according to their BMI: normal weight (BMI <23 kg/m2), overweight (BMI between 23 kg/m2 and 27.5 kg/m2), or obese (BMI ≥27.5 kg/m2). Importantly, obesity at baseline predicted a greater longitudinal increase in LVM and decrease in LV ejection fraction compared with overweight and normal weight patients. CONCLUSION: Being obese at baseline was associated with greater longitudinal increase in LV mass and greater deterioration in LV systolic function.

Color Doppler ultrasound and contrast-enhanced ultrasound in the diagnosis of lacrimal apparatus tumors.

Color Doppler ultrasound and contrast-enhanced ultrasound (CEUS) in the diagnosis of lacrimal apparatus tumors were investigated. In total, 48 patients undergoing preoperative two-dimensional and color Doppler ultrasound and CEUS examinations were included in this study. Conventional ultrasound and CEUS characteristics of 48 patients pathologically and clinically diagnosed with lacrimal apparatus tumors were retrospectively analyzed. Results of conventional ultrasound of 29 cases with pleomorphic adenoma of lacrimal gland showed moderate-hypoechogenic solid masses in lacrimal gland; CEUS displayed two enhancement modes: High, fast-developed slow-extinct and overall uniform enhancement (20/29, 68.97%) and high, fast-developed slow-extinct, centripetal, uniform or non-uniform enhancement (9/29, 31.03%); after enhancement, the mass edge was clear without changes in size. Results of conventional ultrasound of 6 cases with adenoid cystic carcinoma of lacrimal gland showed hypoechogenic solid masses with unclear edge, irregular form, non-uniform echo, and abundant blood flow signals; the CEUS displayed high, fast-developed fast-extinct and overall uniform enhancement; after enhancement, mass edge was unclear and masses were larger than that in two-dimensional ultrasound. Results of conventional ultrasound of 10 cases with lacrimal sac cyst showed non-uniform, hypoechogenic masses, or cystic solid mixed masses with clear edge but no blood flow signal; the CEUS displayed peripheral circular enhancement and no enhancement inside. Results of conventional ultrasound of 3 cases with adenocarcinoma of lacrimal sac showed hypoechogenic solid masses with unclear edge, irregular form, non-uniform echo inside, and abundant blood flow signals in lacrimal sac; CEUS displayed high, fast-developed fast-extinct and overall uniform enhancement; after enhancement, masses with irregular shapes were obviously larger than that in two-dimensional ultrasound. CEUS shows the microcirculation of tumors and surrounding tissues. Combination of two-dimensional and color Doppler ultrasound can improve the preoperative qualitative diagnosis of tumors and provide references for the selection of operation methods and determination of tumor resection scope.

Prognostic Value of Hepatorenal Function By Modified Model for End-stage Liver Disease (MELD) Score in Patients Undergoing Tricuspid Annuloplasty.

BACKGROUND: The Model for End-stage Liver Disease excluding international normalized ratio (MELD-XI) score and the modified MELD score with albumin replacing international normalized ratio (MELD-Albumin) score, which reflect both liver and renal function, have been reported as predictors of adverse events in liver and heart disease. Nonetheless, their prognostic value in patients undergoing tricuspid annuloplasty has not been addressed. METHODS AND RESULTS: A total of 394 patients who underwent tricuspid annuloplasty were evaluated. Baseline clinical, laboratory, and echocardiographic parameters were recorded. Adverse outcome was defined as the occurrence of heart failure requiring admission or all-cause mortality. Patients who underwent tricuspid annuloplasty had a high prevalence of preoperative hepatorenal dysfunction that was more common in patients with severe tricuspid regurgitation than those with mild to moderate tricuspid regurgitation. The MELD-XI and MELD-Albumin scores were excellent predictors of 1-year adverse outcome (area under the curve: 0.69 and 0.75, respectively). Kaplan-Meier survival curve demonstrated that a high score on MELD-XI (≥12.0) and MELD-Albumin (≥10.7) was associated with an increased risk of adverse events. During a median follow-up of 40 months, both MELD-XI and MELD-Albumin scores were significantly associated with adverse outcome, even after adjusting for potential confounding factors. Significant improvement of hepatorenal function at 1 year postoperation was noted only in patients who had no adverse events, not in those who experienced an adverse outcome. CONCLUSIONS: Both MELD-XI score and MELD-Albumin score can provide useful information to predict adverse outcome in patients undergoing tricuspid annuloplasty. The present study supports monitoring of modified MELD score to improve preoperative risk stratification of these patients.

Cerebral embolism secondary to cardiac amyloidosis: A case report and literature review.

Cardiac amyloidosis (CA) describes a group of heterogeneous diseases that are characterized by the extracellular fibril deposition of amyloid protein in the myocardium. The abnormal protein is usually derived from light-chain amyloidosis, mutant transthyretin amyloidosis and wild-type transthyretin. Patients with ischemic strokes and amyloidosis have been sporadically reported, however, they are not well summarized. In the present study, a case of cerebral ischemic stroke, secondary to CA was described. This patient presented with dyspnea on exertion, without any evidence of atrial fibrillation. A biopsy revealed deposition of amyloid in the myocardium and Congo Red staining was positive. He suffered from acute infarction of left basal ganglia, resulting from occlusion of the left middle cerebral arterial 6 months prior to admission. However, re-examination of cerebral magnetic resonance imaging in the present hospital revealed an old infarction in the region of the left basal ganglia with a normal appearance of the left middle cerebral artery. Transesophageal echocardiography (TEE) and cardiac magnetic resonance (CMR) both discovered intra-cardiac thrombi, confirming the diagnosis of cardiogenic cerebral embolism. The present study indicates that patients with CA may additionally present with cardiogenic cerebral embolism, and TEE and CMR imaging may help to avoid missing the presence of intra-cardiac thrombi.

A Silent Asymptomatic Solid Pancreas Tumor in a Nonsmoking Athletic Female: Pancreatic Ductal Adenocarcinoma.

A silent solid endocrine tumor of pancreas, intraductal adenocarcinoma of pancreas, is the fourth leading cancer-related death in the US. However, it is expected to become the third leading cause by 2030 owing to delayed diagnosis and slow progress in management. Chronic pancreatitis is at risk for pancreatic ductal adenocarcinoma (PDAC). PDAC is diagnostic with transabdominal sonogram, blood test such as carbohydrate antigen 19-9 (CA 19-9), and imaging. PDAC has a dismal prognosis. The survival rate in 5 years is barely 6%, while late detection rate is 80-85% with unresectable stage upon diagnosis. Here, we present a 51-year-old asymptomatic female with intermittent constipation and abdominal pain for 1 month with obstructive jaundice with PDAC with liver metastasis.

Quantitative diagnosis of salivary gland tumors with contrast-enhanced ultrasound--a preliminary study.

OBJECTIVE: To quantitatively analyze the value of qualitative diagnosis of salivary gland masses with contrast-enhanced ultrasound (CEUS). STUDY DESIGN: The enhanced sonographic features of 68 salivary gland masses were analyzed to differentiate them. The final diagnoses were confirmed by biopsy pathology. RESULTS: We observed from the perfusion kinetics of CEUS that most pleomorphic adenomas manifested lower enhancement and well-defined margins; most Warthin tumors presented with higher enhancement and well-defined margins; and most malignant tumors had higher enhancement and poorly defined margins. Their time-intensity curves showed pleomorphic adenomas were hypovascularized with a poor perfusion, whereas Warthin tumors and malignant tumors were hypervascularized with a rich perfusion. Additionally, malignant tumors showed significantly shortened time to peak and richer maximum signal intensity compared with Warthin tumors. CONCLUSIONS: The features of salivary gland masses identified with CEUS were helpful in the differential diagnosis of salivary gland masses.