Acute Reduction in Left Ventricular Function Following Transcatheter Mitral Edge-to-Edge Repair.

Background Little is known about the impact of transcatheter mitral valve edge-to-edge repair on changes in left ventricular ejection fraction (LVEF) and the effect of an acute reduction in LVEF on prognosis. We aimed to assess changes in LVEF after transcatheter mitral valve edge-to-edge repair for both primary and secondary mitral regurgitation (PMR and SMR, respectively), identify rates and predictors of LVEF reduction, and estimate its impact on prognosis. Methods and Results In this international multicenter registry, patients with both PMR and SMR undergoing transcatheter mitral valve edge-to-edge repair were included. We assessed rates of acute LVEF reduction (LVEFR), defined as an acute relative decrease of >15% in LVEF, its impact on all-cause mortality, major adverse cardiac event (composite end point of all-cause death, mitral valve surgery, and residual mitral regurgitation grade ≥2), and LVEF at 12 months, as well as predictors for LVEFR. Of 2534 patients included (727 with PMR, and 1807 with SMR), 469 (18.5%) developed LVEFR. Patients with PMR were older (79.0±9.2 versus 71.8±8.9 years; P<0.001) and had higher mean LVEF (54.8±14.0% versus 32.7±10.4%; P<0.001) at baseline. After 6 to 12 months (median, 9.9 months; interquartile range, 7.8-11.9 months), LVEF was significantly lower in patients with PMR (53.0% versus 56.0%; P<0.001) but not in patients with SMR. The 1-year mortality was higher in patients with PMR with LVEFR (16.9% versus 9.7%; P<0.001) but not in those with SMR (P=0.236). LVEF at baseline (odds ratio, 1.03 [95% CI, 1.01-1.05]; P=0.002) was predictive of LVEFR for patients with PMR, but not those with SMR (P=0.092). Conclusions Reduction in LVEF is not uncommon after transcatheter mitral valve edge-to-edge repair and is correlated with worsened prognosis in patients with PMR but not patients with SMR. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05311163.

Primary cardiac mesothelioma presenting with fulminant recurrent pericarditis: a case report.

Background: Primary pericardial mesothelioma is an extremely rare disease. Prognosis is poor, with little effects of chemo- or radio-therapy. The majority of cases is diagnosed at autopsy. Case summary: A 22-year-old man, who presented with recurrent pericarditis and large pericardial effusion 2 months after a second BNT162b2 COVID-19 vaccine, underwent pericardiocentesis and pericardial window. Pathology specimen of pericardium revealed benign mesothelial inflammation, consistent with acute pericarditis. Four months later, he presented with a large pericardial mass manifesting in heart failure and underwent urgent pericardiectomy. A new pathology specimen immunostaining and fluorescence in situ hybridization analysis revealed pericardial mesothelioma. Despite intensive care, the patient died 3 weeks later. Discussion: Primary pericardial mesothelial should be considered in the differential diagnosis of refractory recurrent pericarditis, even with prior biopsy-proven pericarditis or when a putative trigger (COVID-19 mRNA prior vaccination) is suspected, as was the case in this patient. Tumour diagnosis and identification consist of multimodal imaging and laboratory tests. A multidisciplinary, individualized care approach should be performed.

Increased risk of non-hematological cancer in young patients with aortic stenosis: a retrospective cohort study.

BACKGROUND: We have previously reported an increased risk for non-hematological malignancies in young patients with moderate or severe aortic stenosis (AS). These findings were the result of a post-hoc analysis from a large echocardiography database and needed verification. Our aim was to determine, using a different study population, whether young patients with AS are at increased risk for cancer. METHODS: A large echocardiographic database was used to identify patients (age ≥ 20 years) with moderate or severe AS (study group) and patients without aortic stenosis (comparative group). The new occurrence of non-hematological malignancies was determined after the index date (first echo with moderate or severe AS or first recorded echo in the control group). RESULTS: The final study group included 7013 patients with AS and 98,884 without AS. During a median follow-up of 6.9 years (3.0-11.1) there were 10,705 new cases of non-hematological cancer. The crude incidence rate of cancer was higher in AS compared to non-AS patients (22.3 vs. 13.7 per 1000 patient-year, crude HR 1.58 (95%CI 1.46-1.71). After adjustment for relevant covariates, there was no difference between groups (HR 0.93, 95% CI 0.86-1.01). Only patients in the lowest age quartile (20-49.7 years), had an increased adjusted risk of cancer (HR 1.91, 95%CI 1.08-3.39). The HR for the risk of cancer associated with AS was inversely proportional to age (P < 0.001 for the interaction between AS and age). CONCLUSIONS: Young patients with moderate or severe AS may have an increased risk for cancer. Cancer surveillance should be considered for young patients with AS.

Natural History and Disease Progression of Early Cardiac Amyloidosis Evaluated by Echocardiography.

Since the diagnosis of cardiac amyloidosis (CA) is often delayed, echocardiographic findings are frequently indicative of advanced cardiomyopathy. We aimed to describe early echocardiographic features in patients subsequently diagnosed with CA. Preamyloid diagnosis echocardiographic studies were screened for structural and functional parameters and stratified according to the pathogenetic subtype (immunoglobulin light-chain [AL] or amyloid transthyretin [ATTR]). Abnormalities were defined based on published guidelines. Our cohort included 75 CA patients of whom 42 (56%) were diagnosed with AL and 33 (44%) with ATTR. Forty-two patients had an earlier echocardiography exam available for review. Patients presented with increased wall thickness (1.3 [interquartile range {IQR} 1.0, 1.5] cm) ≥3 years before the diagnosis of CA and relative wall thickness was increased (0.47 [IQR 0.41, 0.50]) ≥7 years prediagnosis. One to 3 years before CA diagnosis restrictive left ventricular (LV) filling pattern was present in 19% of patients and LV ejection fraction ≤50% was present in 21% of patients. Right ventricular dysfunction was detected concomitantly with disease diagnosis. The echocardiographic phenotype of ATTR versus AL-CA showed increased relative wall thickness (0.74 [IQR 0.62, 0.92] versus 0.62 [IQR 0.54, 0.76], p = 0.004) and LV mass index (144 [IQR 129, 191] versus 115 [IQR 105, 146] g/m2, p = 0.020) and reduced LV ejection fraction (50 [IQR 44, 58] versus (60 [IQR 53, 60]%, p = 0.009) throughout the time course of CA progression, albeit survival time was similar. In conclusion, increased wall thickness and diastolic dysfunction in CA develop over a time course of several years and can be diagnosed in their earlier stages by standard echocardiography.

Echocardiographic Assessment of Aortic Stenosis under Sedation Underestimates Stenosis Severity.

BACKGROUND: Sedation can impact aortic stenosis (AS) classification, which depends on left ventricular ejection fraction (<≥ [less than or greater than and/or equal to] 50%), aortic valve area (AVA<≥ 1 cm2), mean pressure gradient (<≥ 40 mm Hg), peak velocity <≥ 400 cm/sec, and stroke volume index (SVI <≥35 mL/m2). We compared AS classification by transthoracic echo (TTE) during wakefulness versus sedation. METHODS: Immediately following a baseline TTE performed during wakefulness, another TTE was done during sedation delivered for a concomitant transesophageal study in 69 consecutive patients with AS (mean age 78 ± 7 years, 32 males). AVA was calculated through the continuity equation using the relevant hemodynamic parameters measured by each TTE study and same left ventricular outflow tract. AS class was defined as moderate, severe high gradient (HG), low ejection fraction low flow low gradient (LF-LG), paradoxical LF-LG (PLFLG), and normal flow low gradient (NF-LG). Based on conservative versus invasive treatment implication, AS classes were aggregated into group A (moderate AS and NFLG) and group B (HG, low-EF LF-LG, and PLFLG). RESULTS: During sedation, systolic and diastolic blood pressure decreased by 14.3 ± 29 and 8 ± 22 mm Hg, respectively, mean pressure gradient from 30.4 ± 10.9 to 27.2 ± 10.8 mm Hg, peak velocity from 345.3 ± 57.7 to 329.3 ± 64.8 cm/m2, and SVI from 41.5 ± 11.3 to 38.3 ± 11.8 mL/m2 (all P < .05). Calculated AVA was similar (delta = -0.009 ± 0.15 cm2). Individual discrepancies in hemodynamic parameters between the paired TTE studies resulted in an overall 17.4% rate of AS intergroup misclassification with sedation, with a relative risk of 1.09 of downgrade misclassification from group B to A versus upgrade misclassification (P < .001). CONCLUSIONS: Sedation TTE assessment downgrades AS severity in a significant proportion of patients, with a conversely smaller proportion of patients being upgraded, and therefore cannot be a substitute for wakefulness assessment.

Long-Term Outcomes After Mitral Valve Replacement and Tricuspid Annuloplasty in Rheumatic Patients.

BACKGROUND: Late tricuspid regurgitation is a common finding in patients with rheumatic valvular disease after mitral valve replacement surgery. However, the long-term benefit of concomitant tricuspid valve annuloplasty has not been established in this population. METHODS: This was a single-center retrospective study in a tertiary hospital. The final cohort included 285 rheumatic patients who underwent either isolated mitral valve replacement (147 patients) or mitral valve replacement with concomitant tricuspid valve annuloplasty (138 patients). Tricuspid regurgitation severity grade was assessed according to current echocardiography guidelines and graded using a 0 to 3 scale (none or trivial, mild, moderate, severe). RESULTS: Patients were followed for a total median duration of 10.8 (interquartile range, 6.8 to 14.5) years. The majority of patients undergoing mitral valve replacement were women, with a median age at operation of 59 (interquartile range, 48 to 68) years. Patients undergoing concomitant tricuspid valve annuloplasty had a 3.4-fold odds of improving their tricuspid regurgitation grade at long-term follow-up by multivariate logistic regression. Furthermore, concomitant tricuspid valve annuloplasty was independently associated with a long-term survival benefit in patients with preoperative moderate or severe tricuspid regurgitation (hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.87; p = 0.018). CONCLUSIONS: This study demonstrates good long-term results in patients with rheumatic heart disease undergoing mitral valve replacement with concomitant tricuspid valve annuloplasty.

Low circulating monocyte count is associated with severe aortic valve stenosis.

BACKGROUND: The pathophysiology of aortic stenosis (AS) involves inflammatory features including infiltration of the aortic valve (AV) by activated macrophages and T cells, deposition of lipids, and heterotopic calcification. OBJECTIVES: To evaluate the correlation between white blood cell (WBC) differential count and the occurrence and progression of AS. METHODS: We identified in our institutional registry 150 patients with AS who underwent two repeated echo studies at least 6 months apart. We evaluated the association between the average of repeated WBC differential counts sampled during the previous 3 years and subsequent echocardiographic AS indices. RESULTS: There was no significant difference in total WBC, lymphocyte or eosinophil count among mild, moderate or severe AS groups. There was a progressive decrease in monocyte count with increasing AS severity (P = 0.046), more prominent when comparing the mild and severe groups. There was a negative correlation between AV peak velocity or peak or mean gradient and monocyte count in the entire group (r = -0.31, -0.24, and -0.25 respectively, all P < 0.01). Similar partial correlations controlling for age, gender, hypertension, smoking, dyslipidemia and ejection fraction remained significant. The median changes over time in peak velocity and peak gradients in AS patients were 0.44 (0-1.3) m/sec/ year and 12 (0-39) mmHg/year, respectively. There was no correlation between any of the WBC differential counts and the change in peak velocity or peak gradient per year. CONCLUSIONS: Severe AS is associated with decreased total monocyte count. These findings may provide further clues to the mechanism underlying the pathogenesis of aortic stenosis.

Regulatory T cells and IL-10 levels are reduced in patients with vulnerable coronary plaques.

BACKGROUND: Despite having a similar large extent of atherosclerotic coronary affliction, some patients suffer of recurrent cardiac events, whereas others remain asymptomatic. HYPOTHESIS: We hypothesized the existence of a systemic "signature" that could distinguish "vulnerable" patients with preexisting coronary atherosclerosis from those having similar risk factors and atheromatous burden, but no history of clinically evident plaque rupture/erosion. METHODS: Twenty three patients who had at least two prior myocardial infarctions ("vulnerable group") were matched in respect to their background and coronary atherosclerosis extent with twenty one patients without a history of previous myocardial infarction who underwent routine coronary angiography before valvular surgery. We studied a panel of cytokines, antibodies and hormones including IL-6, IL-10, IL-12, antibodies to ß2 glycoprotein I (ß2GPI), antibodies to oxidized-LDL, adiponectin and resistin, along with levels of circulating EPCs and Tregs. RESULTS: A significantly higher level of Treg cells was present in the control (73.4%±4) than in the "vulnerable patient" group (62.2%±10.7), p<0.001. IL-10 level was also significantly higher in the control than in the vulnerable patients (2.6±1.2 pg/ml versus 0.9±0.1 pg/ml respectively, p=0.03). There was no significant difference in the circulating levels of the other cytokines, hormones or EPCs between the two groups. CONCLUSION: Regulatory T cells and serum IL-10 may discriminate "vulnerable" versus stable patients and may have a protective role against plaque rupture in patients with coronary atherosclerosis.

Circulating endothelial progenitor cells in cardiovascular disorders.

The role of vascular endothelium in cardiovascular disorders is well recognized. Mature endothelial cells contribute to the repair of endothelial injury, but only with a limited capacity. This has led to growing interest and further investigation into circulating endothelial progenitor cells (EPCs) and their role in vascular healing, repair and postnatal neovascularization. Recent studies have shown that EPCs are affected both in number and function by several cardiovascular risk factors as well as various cardiovascular disease states. Here, we aim to provide an overview of EPCs in humans, from methods of assessment to quantification and functional properties in numerous cardiovascular conditions. In addition, we hope to offer some perspective on the potential diagnostic and therapeutic aspects of EPCs.

Circulating apoptotic progenitor cells: a novel biomarker in patients with acute coronary syndromes.

BACKGROUND: Progenitor CD34 cells are capable of differentiating into endothelial cells and play a role in neoangiogenesis. Circulating CD34+ cells and endothelial progenitor cells are increased in acute coronary syndrome (ACS) patients possibly because of peripheral mobilization. We tested the hypothesis that circulating apoptotic progenitors are detectable in healthy subjects and altered in ACS patients. METHODS AND RESULTS: Peripheral blood mononuclear cells were isolated by Ficoll density gradient from 53 patients with ACS undergoing coronary angiography and 27 healthy subjects. Apoptosis in progenitor CD34+ cells was assessed using the Annexin V-PE/7-AAD detection kit, and fluorescence-activated cell sorter analysis was performed with triple staining for CD34, annexin-V, and 7-AAD. The percentage of apoptotic CD34+ progenitors was determined in the 2 subject groups and correlated with clinical characteristics. The percentage of apoptotic CD34+ progenitor cells was significantly increased in patients with ACS as compared with healthy subjects and was associated with the extent of coronary stenosis by angiography. There was no significant correlation between apoptotic progenitor CD34+ cells and the other parameters that we examined (age, smoking, hypertension, hyperlipidemia, diabetes mellitus, ejection fraction, creatinine levels, or taking any of the various medications, including beta blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium blockers, nitrates, or statins). CONCLUSION: We established for the first time to our knowledge an assay to detect circulating apoptotic progenitor cells using fluorescein isothiocyanate-anti-CD34 MAb, annexin V-PE, and 7-AAD and found that apoptotic CD34+ cells are increased in ACS patients and in patients with more extensive coronary artery disease. This novel assay may shed new light on the factors governing the hemostasis of progenitor CD34+ cells.

Generalized vasculitis, thrombocytopenia, and transient lymphoproliferative disorder caused by idiopathic mixed cryoglobulinemia.

We present a 75-year-old patient with recurrent palpable purpura and multiorgan involvement by leukocytoclastic vasculitis caused by mixed-type cryoglobulinemia. The disease spanned 40 years, with many flare-ups, each associated with thrombocytopenia, and finally culminated in widespread involvement of not only the skin and the kidneys but also the lungs and spleen. Despite extensive investigation, no association with hepatitis C virus or with any malignant or connective tissue disorder was found.