Left ventricular stroke volume index following transcatheter aortic valve replacement is an early predictor of 1-year survival.

BACKGROUND: Adverse cardiac events are common following transcatheter aortic valve replacement (TAVR). Our aim was to investigate the low left ventricular stroke volume index (LVSVI) 30 days after TAVR as an early echocardiographic marker of survival. HYPOTHESIS: Steady-state (30-day) LVSVI after TAVR is associated with 1-year mortality. METHODS: A single-center retrospective analysis of all patients undergoing TAVR from 2017 to 2019. Baseline and 30-day post-TAVR echocardiographic LVSVI were calculated. Patients were stratified by pre-TAVR transaortic gradient, surgical risk, and change in transvalvular flow following TAVR. RESULTS: This analysis focuses on 238 patients treated with TAVR. The 1-year mortality rate was 9% and 124 (52%) patients had normal flow post-TAVR. Of those with pre-TAVR low flow, 67% of patients did not normalize LVSVI at 30 days. The 30-day normal flow was associated with lower 1-year mortality when compared to low flow (4% vs. 14%, p = .007). This association remained significant after adjusting for known predictors of risk (adjusted odds ratio [OR] of 3.45, 95% confidence interval: 1.02-11.63 [per 1 ml/m2 decrease], p = .046). Normalized transvalvular flow following TAVR was associated with reduced mortality (8%) when compared to those with persistent (15%) or new-onset low flow (12%) (p = .01). CONCLUSIONS: LVSVI at 30 days following TAVR is an early echocardiographic predictor of 1-year mortality and identifies patients with worse intermediate outcomes. More work is needed to understand if this short-term imaging marker might represent a novel therapeutic target.

A Shocking Case of Pacemaker Lead Perforation.

We report on a 66-year-old man who presented with presyncope, chest discomfort, and pectoralis muscle stimulation after pacemaker implantation. Imaging confirmed lead perforation through the myocardium and reaching the anterior chest wall. (Level of Difficulty: Intermediate.).

Analysis of lumbar spine stenosis specimens for identification of amyloid.

BACKGROUND: Lumbar spinal stenosis (LSS) is a common reason for spine surgery in which ligamentum flavum is resected. Transthyretin (TTR) amyloid is an often unrecognized and potentially modifiable mechanism for LSS that can also cause TTR cardiac amyloidosis. Accordingly, older adult patients undergoing lumbar spine (LS) surgery were evaluated for amyloid and if present, the precursor protein, as well as comprehensive characterization of the clinical phenotype. METHODS: A prospective, cohort study in 2 academic medical centers enrolled 47 subjects (age 69 ± 7 years, 53% male) undergoing clinically indicated LS decompression. The presence of amyloid was evaluated by Congo Red staining and in those with amyloid, precursor protein was determined by laser capture microdissection coupled to mass spectrometry (LCM-MS). The phenotype was assessed by disease-specific questionnaires (Swiss Spinal Stenosis Questionnaire and Kansas City Cardiomyopathy Questionnaire) and the 36-question short-form health survey, as well as biochemical measures (TTR, retinol-binding protein, and TTR stability). Cardiac testing included technetium-99m-pyrophosphate scintigraphy, electrocardiograms, echocardiograms, and cardiac biomarkers as well as measures of functional capacity. RESULTS: Amyloid was detected in 16 samples (34% of participants) and was more common in those aged ≥ 75 years of age (66.7%) compared with those <75 years (22.3%, p < 0.05). LCM-MS demonstrated TTR as the precursor protein in 62.5% of participants with amyloid while 37.5% had an indeterminant type of amyloid. Demographic, clinical, quality-of-life measures, electrocardiographic, echocardiographic, and biochemical measures did not differ between those with and without amyloid. Among those with TTR amyloid (n = 10), one subject had cardiac involvement by scintigraphy. CONCLUSIONS: Amyloid is detected in more than a third of older adults undergoing LSS. Amyloid is more common with advancing age and is particularly common in those >75 years old. No demographic, clinical, biochemical, or cardiac parameter distinguished those with and without amyloid. In more than half of subjects with LS amyloid, the precursor protein was TTR indicating the importance of pathological assessment.

Outcomes of reconstruction after temporal bone resection for malignancy.

Reconstruction after temporal bone resection (TBR) is challenging due to the lack of consensus on an optimal approach. Records of the Keck Hospital of USC were searched to identify, collect and group data on patients who underwent TBR for malignancy. Chi-square analysis was used for categorical variables, and ANOVA was used for continuous variables. Forty TBR including 27 lateral (LTBR), 8 total (TTBR), and 5 subtotal (STBR) temporal bone resections were performed at our institution over a ten year time period (2003-2013) and reconstructed with free, regional, and local flaps and tissue grafts. TTBR was associated with postoperative complications as was presence of a dural defect, though other traditionally poor prognostic factors such as age, comorbidity status, and history of irradiation were not. Patients who underwent auriculectomy or parotidectomy were more likely to require free flap reconstruction. We conclude that TBR and reconstruction can be performed successfully on many patients including those who are older or who have more aggressive disease. We recommend free tissue transfer for the large defects created by TTBR, parotidectomy and auriculectomy.

Changes in the epidemiology and clinical features of acute mastoiditis following the introduction of the pneumococcal conjugate vaccine.

OBJECTIVES: Seven years after the introduction of the pneumococcal conjugate vaccines (PCV) in Israel, its effect on the incidence and severity of episodes of acute mastoiditis (AM) remains unclear. The primary objective of this study was to determine the incidence of AM and describe its clinical features in children during the years that followed the introduction of the PCV13 in comparison with the pre-PCV period. METHODS: Included in this retrospective comparative case series were all pediatric patients diagnosed with AM between Jan. 2007 and Dec. 2015 in one tertiary medical center. The patients were divided into 3 groups: pre-PCV, post-PCV7 (July 2009 through Dec. 2010) and post-PCV13 (Jan. 2011 through Dec. 2015). The patients' medical records were reviewed, and data on age at presentation, gender, presenting signs, bacterial ear cultures, hospitalization course, complications, surgical interventions, inflammatory response and outcome were retrieved and compared between the groups. Comparison was made between the pre-PCV and the post-PCV13 groups. RESULTS: 216 children were identified for analysis, 80 children in the pre-PCV period, 31 in the post-PCV7 period and 105 in the post-PCV13 period. Their mean age was 2.6 years. The number of AM cases per 1000 visits at the emergency room decreased by 46% in the post-PCV13 period compared to the pre-PCV period. There was no difference in the rate of AM between the post-PCV7 and post-PCV13 periods. No differences were found in age, gender, hospitalization length, C-reactive protein level, white blood cell count, rate of surgical interventions (mastoidectomy and incision and drainage) and rate of complications between the 3 groups. CONCLUSION: The incidence of AM was lower in the post-PCV13 period compared to the pre-PCV period. The rate of AM complications, however, has not changed, nor has the number of mastoidectomies.

Exosomes secreted by cardiosphere-derived cells reduce scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine myocardial infarction.

Aims: Naturally secreted nanovesicles known as exosomes are required for the regenerative effects of cardiosphere-derived cells (CDCs), and exosomes mimic the benefits of CDCs in rodents. Nevertheless, exosomes have not been studied in a translationally realistic large-animal model. We sought to optimize delivery and assess the efficacy of CDC-secreted exosomes in pig models of acute (AMI) and convalescent myocardial infarction (CMI). Methods and Results: In AMI, pigs received human CDC exosomes (or vehicle) by intracoronary (IC) or open-chest intramyocardial (IM) delivery 30 min after reperfusion. No-reflow area and infarct size (IS) were assessed histologically at 48 h. Intracoronary exosomes were ineffective, but IM exosomes decreased IS from 80 ± 5% to 61 ± 12% (P= 0.001) and preserved left ventricular ejection fraction (LVEF). In a randomized placebo-controlled study of CMI, pigs 4 weeks post-myocardial infarction (MI) underwent percutaneous IM delivery of vehicle (n = 6) or CDC exosomes (n = 6). Magnetic resonance imaging (MRI) performed before and 1 month after treatment revealed that exosomes (but not vehicle) preserved LV volumes and LVEF (−0.1 ± 2.2% vs. −5.4 ± 3.6%, P= 0.01) while decreasing scar size. Histologically, exosomes decreased LV collagen content and cardiomyocyte hypertrophy while increasing vessel density. Conclusion: Cardiosphere-derived cell exosomes delivered IM decrease scarring, halt adverse remodelling and improve LVEF in porcine AMI and CMI. While conceptually attractive as cell-free therapeutic agents for myocardial infarction, exosomes have the disadvantage that IM delivery is necessary.

Cardiosphere-derived cells reverse heart failure with preserved ejection fraction (HFpEF) in rats by decreasing fibrosis and inflammation.

BACKGROUND: The pathogenesis of HFpEF is unclear, but fibrosis, inflammation and hypertrophy have been put forth as likely contributors. CDCs are heart-derived cell products with anti-fibrotic and anti-inflammatory properties. OBJECTIVES: We questioned whether allogeneic rat CDCs might be able to decrease manifestations of HFpEF in hypertensive rats. METHODS: Starting at 7 weeks of age, Dahl salt-sensitive rats were fed a high-salt diet for 6-7 weeks and randomized to receive intracoronary CDCs or placebo. Dahl rats fed normal chow served as controls. RESULTS: High-salt rats developed hypertension, left ventricular (LV) hypertrophy and diastolic dysfunction, without impairment of ejection fraction. Four weeks after treatment, diastolic dysfunction resolved in CDC-treated rats but not in placebo. The improved LV relaxation was associated with lower LV end-diastolic pressure, decreased lung congestion and enhanced survival in CDC-treated rats. Histology and echocardiography revealed no decrease in cardiac hypertrophy after CDC treatment, consistent with the finding of sustained, equally-elevated blood pressure in CDC- and placebo-treated rats. Nevertheless, CDC treatment decreased LV fibrosis and inflammatory infiltrates. Serum inflammatory cytokines were likewise decreased after CDC treatment. Whole-transcriptome analysis revealed major HFpEF-related, CDC-reversed changes in numerous transcripts, including many involved in inflammation and/or fibrosis. CONCLUSION: CDCs normalized LV relaxation and LV diastolic pressure while improving survival in a rat model of HFpEF. The benefits of CDCs occurred despite persistent hypertension and cardiac hypertrophy. By selectively reversing inflammation and fibrosis, CDCs may be beneficial in the treatment of HFpEF.