Does Sustained Reduction of Functional Mitral Regurgitation Impact Survival?

Functional mitral regurgitation (FMR) is associated with increased mortality and has been considered a marker for advanced heart disease, yet the value of mitral valve repair (MVr) in this population remains unclear. This study aims to evaluate the impact of reducing FMR burden through surgical MVr on survival. Patients with severe FMR who underwent MVr with an undersized, complete, rigid, annuloplasty between 2004 and 2017 were assessed (n = 201). Patients were categorized based on grade of recurrent FMR (0-4). Time-to-event Kaplan-Meier estimations of freedom from death or reoperation were performed using the log-rank test. Cox proportional hazards models evaluated all-cause mortality and reported in hazards ratios (HR) and 95% confidence intervals (CI). Patients were categorized by postoperative recurrent FMR: 45% (91/201) of patients had grade 0, 29% (58/201) grade 1, 20% (40/201) grade 2, 2% (4/201) grade 3%, and 4% (8/201) grade 4. The cumulative incidence of reoperation with death as a competing risk was higher in patients with grades ≥3 recurrent FMR compared to grades ≤2 (44.6% vs 14.6%, subhazard ratio 3.69 [95% CI, 1.17-11.6]; P = 0.026). Overall freedom from death or reoperation was superior for recurrent FMR grades ≤2 compared to grades ≥3 (log-rank P < 0.001). Increasing recurrent FMR grade was independently associated with mortality (HR 1.30 [95% CI, 1.07-1.59] P = 0.009). Reduced postoperative FMR grade resulted in an incrementally lower risk of death or reoperation after MVr. These results suggest that achieving a durable reduction in FMR burden improves long-term survival.

Integrated Infectious Disease and Substance Use Disorder Care for the Treatment of Injection Drug Use-Associated Infections: A Prospective Cohort Study With Historical Control.

Background: To address the infectious disease (ID) and substance use disorder (SUD) syndemic, we developed an integrated ID/SUD clinical team rooted in harm reduction at a county hospital in Miami, Florida. The Severe Injection-Related Infection (SIRI) team treats people who inject drugs (PWID) and provides medical care, SUD treatment, and patient navigation during hospitalization and after hospital discharge. We assessed the impact of the SIRI team on ID and SUD treatment and healthcare utilization outcomes. Methods: We prospectively collected data on patients seen by the SIRI team. A diagnostic code algorithm confirmed by chart review was used to identify a historical control group of patients with SIRI hospitalizations in the year preceding implementation of the SIRI team. The primary outcome was death or readmission within 90 days post-hospital discharge. Secondary outcomes included initiation of medications for opioid use disorder (MOUD) and antibiotic course completion. Results: There were 129 patients included in the study: 59 in the SIRI team intervention and 70 in the pre-SIRI team control group. SIRI team patients had a 45% risk reduction (aRR, 0.55 [95% confidence interval CI, .32-.95]; 24% vs 44%) of being readmitted in 90 days or dying compared to pre-SIRI historical controls. SIRI team patients were more likely to initiate MOUD in the hospital (93% vs 33%, P < .01), complete antibiotic treatment (90% vs 60%, P < .01), and less likely to have patient-directed discharge (17% vs 37%, P = .02). Conclusions: An integrated ID/SUD team was associated with improvements in healthcare utilization, MOUD initiation, and antibiotic completion for PWID with infections.

Patient and Surgeon Predictors of Mitral and Tricuspid Valve Repair for Infective Endocarditis.

Mitral repair (MVr) is superior to replacement for degenerative disease; however, its benefit is less established for endocarditis. We report outcomes of repair or replacement for mitral/tricuspid endocarditis and identify predictors of MVr. Patients undergoing first-time surgery for mitral (n = 260) or tricuspid (n = 71) endocarditis between 1992 to 2018 were identified. Patients with aortic endocarditis were excluded. Primary outcome was all-cause mortality and secondary outcome was MVr. Patients were stratified into active and treated endocarditis separately for mitral and tricuspid groups. Predictors of MVr were assessed through multivariable logistic regression and adjusted likelihood of MVr through marginal effects estimates. A mitral specialist was defined by performing ≥25 annual degenerative MVr. Among 331 patients, 70% (181/260) of those with mitral valve endocarditis and 52% (37/71) of those with tricuspid endocarditis underwent repair. The MVr group compared with replacement had a higher proportion of elective acuity and less diabetes, hypertension, active endocarditis, cardiogenic shock, and dialysis. Estimated 5-year survival did not differ between repair versus replacement for active mitral (68 ± 14% vs 60 ± 14%, P = 0.34) or tricuspid endocarditis (60 ± 17% vs 61 ± 19%, P = 0.67), but was superior after repair for treated mitral endocarditis (86 ± 7% vs 51 ± 24%, P = 0.014). Independent predictors of mortality included dialysis for active and treated mitral endocarditis, and mitral replacement (vs MVr) for treated mitral endocarditis. The likelihood of MVr was 82 ± 5% for mitral specialists and 47 ± 9% for non-specialists (P < 0.001). MVr for endocarditis should be pursued, if feasible. Importantly, achieving MVr was driven not only by patient factors, but also surgeon experience.

Ultrasonic Emulsification of Severe Mitral Annular Calcification During Mitral Valve Replacement.

PURPOSE: Severe mitral annular calcification (MAC) increases surgical complexity and is independently associated with increased operative mortality for mitral valve replacement (MVR). Recently we adopted ultrasonic emulsification/aspiration for annular decalcification to address these risks and describe our early experience with this new technology. DESCRIPTION: Excluding previous mitral valve surgery or endocarditis, 179 patients with MAC underwent MVR at a single institution between January 2015 and March 2020. Of these, 15 consecutive patients with severe MAC (≥50% of the annulus) underwent annular decalcification with ultrasonic emulsification/aspiration as an adjunct treatment during MVR from April 2019 to March 2020. EVALUATION: Mean patient age was 68 ± 12 years, and 72% (n = 128) were female. Mean preoperative left ventricular ejection fraction was 60% ± 11%, and mean mitral valve gradient was 9.1 ± 4.4 mm Hg. Concomitant procedures included antiarrhythmia (n = 52), aortic valve replacement (n = 32), and coronary artery bypass grafting (n = 20). There were no operative deaths or strokes in the group undergoing ultrasonic emulsification and aspiration. CONCLUSIONS: The use of ultrasonic emulsification and aspiration in severe MAC patients may help mitigate the risks of MVR and facilitate operative success in this challenging, high-risk population.

Rheumatic mitral valve repair or replacement in the valve-in-valve era.

OBJECTIVE: For degenerative mitral disease, repair is superior to replacement; however, the best operative strategy for rheumatic mitral disease remains unclear. We evaluated the association between decision-making in choosing repair versus replacement and outcomes across 2 decades of rheumatic mitral surgery. METHODS: Patients undergoing isolated, first-time rheumatic mitral surgery were identified. Era 1 (1997-2008) and Era 2 (2009-2018) were distinguished by intraoperative assessment of anterior leaflet mobility/calcification (Era 2) in deciding between mitral repair versus replacement. Primary outcome was a composite of death, reoperation, and severe valve dysfunction. RESULTS: Among 180 patients, age was 59 ± 14 years, and ejection fraction was 58% ± 10%. A higher proportion in Era 1 (n = 56) compared with Era 2 (n = 124) had preoperative atrial fibrillation (68% vs 46%; P = .006); the groups were otherwise similar. Primary indication was mitral stenosis in 69% (124 out of 180; pure = 35, mixed = 89) and did not differ by era (P = .67). During Era 1, 70% (39 out of 56) underwent repair, compared with 33% (41 out of 124) during Era 2 (P < .001). Freedom from death, reoperation, or severe valve dysfunction at 5 years was higher in Era 2 (72% ± 9%) than Era 1 (54% ± 13%; P = .04). Five-year survival was higher in Era 2 than Era 1, but did not differ between repair versus replacement. Five-year cumulative incidence of reoperation with death as a competing risk did not differ by era, but was higher after repair than replacement. CONCLUSIONS: Careful assessment of anterior leaflet mobility/calcification to determine mitral repair or replacement was associated with improved outcomes. This decision-making strategy may alter the threshold for rheumatic mitral replacement in the current valve-in-valve era.

Surgical strategy and outcomes for atrial functional mitral regurgitation: All functional mitral regurgitation is not the same!

OBJECTIVE: Functional mitral regurgitation (FMR) is a cardiac pathology that causes the mitral valve to malfunction, leading to mitral regurgitation (MR). The optimal strategy for FMR remains unclear, and FMR outcomes are poor. All etiologies of FMR might not be the same, and subdividing patients with FMR caused by atrial (AFMR) versus ventricular FMR pathology might be important. Herein, we present outcomes of patients with AFMR to define this "new" population. METHODS: Data of patients who underwent mitral valve repair for MR from 2000 to 2020 were reviewed. Patients with degenerative/myxomatous disease, ejection fraction <50% (ventricular FMR), and miscellaneous etiologies including endocarditis and rheumatic disease were excluded to isolate a population of "pure" AFMR patients. Descriptive characteristics and outcomes data were analyzed. RESULTS: Among 123 total AFMR patients, mean preoperative left atrial dimensions were enlarged to 4.9 (95% CI, 4.7-5.0) cm, whereas mean preoperative left ventricular diastolic dimensions remained near normal at 5.0 (95% CI, 4.9-5.2) cm. Preoperative atrial fibrillation was noted in 61% (74/123). Echocardiogram was performed in 58% (71/123) of patients at a median of 569 (interquartile range, 75-1782) days after surgery. Of those, 72% (51/71) had trivial or no MR, 22% (16/71) mild, and only 6% (4/71) moderate or greater MR. Only 1.6% (2/123) required redo mitral valve reoperation. Estimated 5-year survival was 74%. CONCLUSIONS: Patients with AFMR do well after mitral valve repair using an annuloplasty ring, with low rates of reoperation, mortality, and recurrence of MR. Mitral annuloplasty should be considered the surgical therapy of choice for AFMR.

Anterior versus posterior leaflet mitral valve repair: A propensity-matched analysis.

OBJECTIVE: Mitral valve repair is superior to replacement for degenerative disease, but long-term outcomes of anterior versus posterior leaflet repair remain poorly defined. We propensity matched anterior and posterior repairs to compare long-term outcomes. METHODS: Patients undergoing first-time degenerative mitral repair between 1992 and 2018 were identified. Primary outcome was overall survival. Secondary outcomes were postprocedural residual mitral regurgitation and reoperation. From 1025 patients, 1:1 propensity score matching was performed, yielding 309 anterior (isolated anterior = 85, bileaflet = 224) and 309 isolated posterior repairs. RESULTS: Age was 58 ± 15 years, ejection fraction was 57% ± 10%, and matched groups were well balanced. Anterior repairs had longer bypass (122 ± 53 vs 109 ± 43 minutes, P = .001) and crossclamp (94 ± 44 vs 85 ± 62 minutes, P = .033) times. Mean residual mitral regurgitation grade was 0.44 (95% confidence interval, 0.24-0.65) for anterior repair and 0.30 (95% confidence interval, 0.13-0.47) for posterior repair (P = .31). Overall, 92% (569/618) of matched patients had no residual mitral regurgitation, with no differences in mitral regurgitation grade between groups (P = .77). Survival did not differ between anterior (10 years: 72% ± 7%; 15 years: 63% ± 7%) and posterior (10 years: 74% ± 7%; 15 years: 60% ± 8%) groups (log-rank P = .93). Linearized incidence of reoperation was 0.62% per patient-year, including 0.74% for anterior and 0.48% for posterior repairs. Cumulative incidence of reoperation at 15 years was 7.5% after anterior repair and 4.9% after posterior repair (Gray's test P = .26). CONCLUSIONS: No long-term survival or reoperation difference was found between posterior and anterior repair. On the basis of these findings, surgeons at centers of excellence should aim for repair of both anterior and posterior leaflet pathology with the same decision-making threshold over valve replacement for degenerative mitral disease.

Economic Analysis and Long-term Follow-up of Distant Referral for Degenerative Mitral Valve Repair.

BACKGROUND: Despite the superiority of mitral valve repair (MVr) over replacement for degenerative disease, repair rates vary widely across centers. Traveling to a mitral reference center (MRC) is 1 way to increase the odds of MVr. This study assessed the economic value (quality/cost) and long-term outcomes of distant referral to an MRC. METHODS: Among 746 mitral surgery patients between January 2011 and June 2013, low-risk patients with an ejection fraction greater than 40% undergoing isolated degenerative MVr were identified and included 26 out-of-state (DISTANT) and 104 in-state patients (LOCAL). Short- and long-term outcomes and institutional financial data (including travel expenses) were used to compare groups. National average and MRC-specific MVr rates, clinical outcomes, and marginal value of quality-adjusted life-years collected from The Society of Thoracic Surgeons database and Medicare estimates were used to perform a nationally representative cost-benefit analysis for distant referral. RESULTS: Age, ejection fraction, operative time, blood transfusions, and annuloplasty ring size did not differ between groups. Median charges were $76,022 for LOCAL and $74,171 for DISTANT (P = .35), whereas median payments (including travel expenses) were $57,795 for LOCAL and $58,477 for DISTANT (P = .70). Short- and long-term outcomes were similar between groups and median follow-up was 7.1 years. Estimated 5-year survival was 97% (96% for LOCAL and 100% for DISTANT; P = .24). Cost-benefit analysis showed a net benefit through distant referral to an MRC ranging from $436 to $6078 to the payer and $22,163 to $30,067 to the patient, combining for an estimated $22,599 to $32,528 societal benefit. CONCLUSIONS: These data suggest that distant referral to an MRC is achievable and reasonable.

Inflammatory and Antioxidant Gene Transcripts: A Novel Profile in Postoperative Atrial Fibrillation.

Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; however, antiarrhythmic strategies have not lowered the rate of POAF. This study aimed to identify specific gene transcripts of atrial inflammation, inflammatory handling, and oxidative stress associated with POAF. Left atrial tissue was obtained from 50 patients undergoing intended degenerative mitral repair who did not have any of the following risk factors for POAF: history of atrial fibrillation or other arrhythmia, left atrial diameter greater than 6.0 cm, or left ventricular ejection fraction less than 40%. Postoperative outcomes and left atrial tissue messenger ribonucleuc acid (mRNA) levels were recorded. Parametric 2-sample t-tests and chi-square tests were used to evaluate for statistical significance in comparing POAF and non-POAF groups. Within 30 days of surgery, 19 of 50 of patients (38%) developed POAF. There were no significant preoperative, intraoperative, or postoperative differences between POAF and non-POAF patients. In the tissue transcriptome analysis, POAF patients were found to have a worse preoperative inflammatory state with higher levels of tumor necrosis factor alpha, Interleukin-6, and nuclear factor of kappa light polypeptide gene enhancer in B-cells mRNA, worse inflammatory handling capacity with lower levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor mRNA, and reduced antioxidant defenses with lower levels of glutathione synthetase, glutathione reductase, and mitochondrial superoxide dismutase 2 mRNA. This study found POAF patients to have preoperative left atrial tissue profiles suggestive of more inflammation, worse inflammatory handling, and reduced antioxidant defenses against oxidative stress. Investigation of therapies targeted to the tissue-specific inflammatory transcriptome of POAF patients is warranted.

CCR2 Mediates Chronic LPS-Induced Pulmonary Inflammation and Hypoalveolarization in a Murine Model of Bronchopulmonary Dysplasia.

The histopathology of bronchopulmonary dysplasia (BPD) includes hypoalveolarization and interstitial thickening due to abnormal myofibroblast accumulation. Chorioamnionitis and sepsis are major risk factors for BPD development. The cellular mechanisms leading to these lung structural abnormalities are poorly understood. We used an animal model with repeated lipopolysaccharide (LPS) administration into the airways of immature mice to simulate prolonged airway exposure to gram-negative bacteria, focusing on the role of C-C chemokine receptor type 2-positive (CCR2+) exudative macrophages (ExMf). Repetitive LPS exposure of immature mice induced persistent hypoalveolarization observed at 4 and 18 days after the last LPS administration. LPS upregulated the expression of lung pro-inflammatory cytokines (TNF-α, IL-17a, IL-6, IL-1ß) and chemokines (CCL2, CCL7, CXCL1, and CXCL2), while the expression of genes involved in lung alveolar and mesenchymal cell development (PDGFR-α, FGF7, FGF10, and SPRY1) was decreased. LPS induced recruitment of ExMf, including CCR2+ ExMf, as well as other myeloid cells like DCs and neutrophils. Lungs of LPS-exposed CCR2-/- mice showed preserved alveolar structure and normal patterns of α-actin and PDGFRα expression at the tips of the secondary alveolar crests. Compared to wild type mice, a significantly lower number of ExMf, including TNF-α+ ExMf were recruited to the lungs of CCR2-/- mice following repetitive LPS exposure. Further, pharmacological inhibition of TLR4 with TAK-242 also blocked the effect of LPS on alveolarization, α-SMA and PDGFRα expression. TNF-α and IL-17a induced α-smooth muscle actin expression in the distal airspaces of E16 fetal mouse lung explants. In human preterm lung mesenchymal stromal cells, TNF-α reduced mRNA and protein expression of PDGFR-α and decreased mRNA expression of WNT2, FOXF2, and SPRY1. Collectively, our findings demonstrate that in immature mice repetitive LPS exposure, through TLR4 signaling increases lung inflammation and impairs lung alveolar growth in a CCR2-dependent manner.

Outcomes of Guideline-Directed Concomitant Annuloplasty for Functional Tricuspid Regurgitation.

BACKGROUND: Despite guideline recommendations, rates of concomitant tricuspid valve repair are suboptimal, possibly due to fear of complications. We reviewed morbidity, mortality, recurrent tricuspid regurgitation, and right ventricular remodeling after guideline-directed concomitant tricuspid valve repair. METHODS: We performed guideline-directed concomitant tricuspid valve repair on 171 consecutive patients who underwent left-sided valve surgery (degenerative mitral surgery or aortic valve replacement) between May 2012 and March 2016. Exclusion criteria included functional mitral regurgitation, rheumatic disease, active endocarditis, and concomitant coronary artery bypass grafting or complex aortic surgery. RESULTS: Mean age was 68 ± 12 years, and 47% (81 of 171) were women. Preoperative atrial fibrillation was present in 57% (98 of 171), and preoperative tricuspid regurgitation was moderate or higher in 64% (108 of 171). The rate of de novo pacemaker placement was 4.1% (7 of 171), and the 30-day mortality rate was 0.6% (1 of 171). Estimated survival was 95% ± 4% at 1 year and 92% ± 5% at 5 years. Freedom from moderate or worse residual/recurrent tricuspid regurgitation was 93% ± 6% at 6 months and 89% ± 8% at 3 years. Quantitative echocardiography found no significant increase in right ventricular dimensions or area at 1 year in subgroup analysis. Mean echocardiographic follow-up was 14.1 months, and mean clinical follow-up was 33.9 months. CONCLUSIONS: Guideline-directed concomitant tricuspid valve repair resulted in excellent safety end points and survival. At 14 months, freedom from moderate or worse tricuspid regurgitation was high, right ventricular performance did not worsen, and the pacemaker rate was comparable to rates after isolated mitral repair. Given these findings, adherence to current guidelines regarding functional tricuspid regurgitation should be encouraged.