Conservative, surgical, and percutaneous treatment for mitral regurgitation shortly after acute myocardial infarction.

AIMS: Severe mitral regurgitation (MR) following acute myocardial infarction (MI) is associated with high mortality rates and has inconclusive recommendations in clinical guidelines. We aimed to report the international experience of patients with secondary MR following acute MI and compare the outcomes of those treated conservatively, surgically, and percutaneously. METHODS AND RESULTS: Retrospective international registry of consecutive patients with at least moderate-to-severe MR following MI treated in 21 centres in North America, Europe, and the Middle East. The registry included patients treated conservatively and those having surgical mitral valve repair or replacement (SMVR) or percutaneous mitral valve repair (PMVR) using edge-to-edge repair. The primary endpoint was in-hospital mortality. A total of 471 patients were included (43% female, age 73 ± 11 years): 205 underwent interventions, of whom 106 were SMVR and 99 PMVR. Patients who underwent mitral valve intervention were in a worse clinical state (Killip class ≥3 in 60% vs. 43%, P < 0.01), but yet had lower in-hospital and 1-year mortality compared with those treated conservatively [11% vs. 27%, P < 0.01 and 16% vs. 35%, P < 0.01; adjusted hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.18-0.46, P < 0.01]. Surgical mitral valve repair or replacement was performed earlier than PMVR [median of 12 days from MI date (interquartile range 5-19) vs. 19 days (10-40), P < 0.01]. The immediate procedural success did not differ between SMVR and PMVR (92% vs. 93%, P = 0.53). However, in-hospital and 1-year mortality rates were significantly higher in SMVR than in PMVR (16% vs. 6%, P = 0.03 and 31% vs. 17%, P = 0.04; adjusted HR 3.75, 95% CI 1.55-9.07, P < 0.01). CONCLUSIONS: Early intervention may mitigate the poor prognosis associated with conservative therapy in patients with post-MI MR. Percutaneous mitral valve repair can serve as an alternative for surgery in reducing MR for high-risk patients.

Transcatheter mitral valve repair for inotrope dependent cardiogenic shock - Design and rationale of the CAPITAL MINOS trial.

BACKGROUND: Functional mitral regurgitation (MR) is an important clinical consideration in patients with heart failure. Transcatheter edge-to-edge repair (TEER) has emerged as a useful therapeutic tool for patients with chronic heart failure, however the role of TEER in patients with cardiogenic shock (CS) and MR has not yet been studied in a randomized trial. The Transcatheter Mitral Valve Repair for Inotrope Dependent Cardiogenic Shock (CAPITAL MINOS) trial was therefore designed to determine if TEER improves clinical outcomes in the CS population. METHODS AND DESIGN: The CAPITAL MINOS trial is an open-label, multi-center randomized clinical trial comparing TEER to medical therapy in patients with CS and MR. A total of 144 patients with Society for Cardiovascular Angiography and Interventions (SCAI) class C or D CS and at least 3+ MR will be randomized in a 1:1 ratio to TEER or medical therapy alone. The primary outcome will be a composite of in-hospital all-cause mortality, cardiac transplantation, implantation of durable left ventricular assist device, or discharge on palliative inotropic therapy. Patients will be followed for the duration of their index hospitalization for the primary outcome. Secondary outcomes include 6 month mortality. IMPLICATIONS: The CAPITAL MINOS trial will determine whether TEER improves outcomes in patients with CS and MR and will be an important step in optimizing treatment for this high-risk patient population.

Use of MitraClip for mitral valve repair in patients with acute mitral regurgitation following acute myocardial infarction: Effect of cardiogenic shock on outcomes (IREMMI Registry).

OBJECTIVES: To assess outcomes in patients with acute mitral regurgitation (MR) following acute myocardial infarction (AMI) who received percutaneous mitral valve repair (PMVR) with the MitraClip device and to compare outcomes of patients who developed cardiogenic shock (CS) to those who did not (non-CS). BACKGROUND: Acute MR after AMI may lead to CS and is associated with high mortality. METHODS: This registry analyzed patients with MR after AMI who were treated with MitraClip at 18 centers within eight countries between January 2016 and February 2020. Patients were stratified into CS and non-CS groups. Primary outcomes were mortality and rehospitalization due to heart failure. Secondary outcomes were acute procedural success, functional improvement, and MR reduction. Multivariable Cox regression analysis evaluated association of CS with clinical outcomes. RESULTS: Among 93 patients analyzed (age 70.3 ± 10.2 years), 50 patients (53.8%) experienced CS before PMVR. Mortality at 30 days (10% CS vs. 2.3% non-CS; p = .212) did not differ between groups. After median follow-up of 7 months (IQR 2.5-17 months), the combined event mortality/re-hospitalization was similar (28% CS vs. 25.6% non-CS; p = .793). Likewise, immediate procedural success (90% CS vs. 93% non-CS; p = .793) and need for reintervention (CS 6% vs. non-CS 2.3%, p = .621) or re-admission due to HF (CS 13% vs. NCS 23%, p = .253) at 3 months did not differ. CS was not independently associated with the combined end-point (hazard ratio 1.1; 95% CI, 0.3-4.6; p = .889). CONCLUSIONS: Patients found to have significant MR during their index hospitalization for AMI had similar clinical outcomes with PMVR whether they presented in or out of cardiogenic shock, provided initial hemodynamic stabilization was first achieved before PMVR.

Association between transitional care factors and hospital readmission after transcatheter aortic valve replacement: a retrospective observational cohort study.

BACKGROUND: Studies have shown that patients who undergo trans-catheter aortic valve replacement (TAVR) have high rates of hospital readmission. Our objectives were to identify the causes of readmission after TAVR, determine whether transitional care factors were associated with a reduction in readmission and to identify other predictors that could be used to target quality improvement efforts. METHODS: We conducted a chart abstraction study that included all patients who underwent TAVR in Ontario, Canada between 2007 and 2013 and survived to hospital discharge. These data were linked to provincial administrative databases. The association between transitional care factors (home care, rehabilitation, family physician and cardiologist follow-up) and 1-year hospital readmission was examined using a time-to-event analysis. Cause-specific hazards models were used to account for the competing risk of death. RESULTS: There were 937 patients in the cohort and the rate of readmission at 1-year was 49%. The most common causes of readmission were heart failure and bleeding. Rehabilitation (HR 1.34, 95% CI 1.11-1.62; p = 0.002) and cardiologist follow-up (HR 1.41, 95% CI 1.14-1.75; p = 0.002) were both associated with higher readmission rates. While, home care (HR 1.18, 95% CI 0.96-1.44; p = 0.12) and family physician follow-up (HR 1.04, 95% CI 0.85-1.28; p = 0.71) were not associated with readmission. CONCLUSION: Readmission post TAVR is common; however, we did not identify any transitional care factors associated with reductions in hospital readmission. This suggests ongoing research is required to identify targets for improvement in post-procedural care.

Trends in the incidence and outcomes of patients with aortic stenosis hospitalization.

BACKGROUND: Although the burden of aortic stenosis (AS) on our health care system is expected to rise, little is known regarding its epidemiology at the population level. Our primary objective was to evaluate trends in AS hospitalization, treatment and outcomes. METHODS: We performed a population-based observational study including 37,970 patients newly hospitalized with AS from 2004 and 2013 in Ontario, Canada. We calculated age- and sex-standardized rate of AS hospitalization through direct standardization. The independent association between year of the hospitalization, and 30-day and 1-year mortality rate was evaluated using logistic regression models to account for temporal changes in patient characteristics. RESULTS: The overall age- and sex-standardized AS hospitalization rate increased slightly from 36 per 100,000 in 2004 to 39 per 100,000 in 2013. A substantial increase was seen in patients ≥85years, where hospitalization rates increased 29% from 400 to 516 per 100,000 from 2004 to 2013 (P<.001). In this study period, 36.2% of patients received aortic valve interventions within 30days of hospitalization. Among treated patients, an improving mortality trend was observed in which the adjusted odds ratio (OR) was significantly lower in 2013 as compared to 2004 (OR 0.55 for 30-day mortality, 0.74 for 1-year morality). In contrast, no significant temporal change in mortality was seen among patients without aortic valve intervention. CONCLUSION: AS hospitalizations in the elderly increased significantly beyond that was expected from population growth. Many AS patients did not receive aortic valve intervention after hospitalization. Mortality among the treated patients improved significantly over time.

Clinical outcomes after trans-catheter aortic valve replacement in men and women in Ontario, Canada.

OBJECTIVE: Our objective was to evaluate sex-differences in outcomes after trans-catheter aortic valve replacement (TAVR) in a population-based cohort from Ontario, Canada. BACKGROUND: Prior studies comparing outcomes in men and women after TAVR have yielded divergent results. Some studies have suggested that women have better survival than men while others have not corroborated this finding. METHODS: A retrospective observational cohort study was conducted using chart abstraction data on all TAVR procedures performed between 2007 and 2013 in Ontario, Canada. Patients who had emergency TAVR procedures were excluded. The primary outcome was all-cause mortality at 30-days and 1-year. Secondary outcomes included mortality at last follow-up, cause-specific, and all-cause hospital readmission. Inverse probability of treatment weighting (IPTW) using propensity score was used to adjust for baseline differences between men and women. RESULTS: The final study cohort consisted of 453 women and 546 men with a mean follow-up of 3.5 years. Women were generally older and more frail but had less comorbid conditions. Women had lower unadjusted mean EuroScores (7% ± 5% vs 8% ± 7%; P = 0.008), but underwent significantly more trans-apical procedures (26.5% vs 19.2%; P = 0.006) than men. After IPTW, the groups were well balanced. Although mortality was numerically higher for women at 30-days (7.2% vs 5.4%), this was not statistically significant (P = 0.34). At 1-year, there was no difference in mortality (18.2% vs 19.2%; P = 0.85). There were no significant differences in all-cause readmission. CONCLUSION: In this population-based cohort including all patients undergoing TAVR, mortality or all-cause readmission were not significantly different between men and women. © 2017 Wiley Periodicals, Inc.

Association of prior ß-blocker use and the outcomes of patients with out-of-hospital cardiac arrest.

UNLABELLED: ß-Blocker therapy is one of the most commonly prescribed treatments for patients with cardiac conditions. In patients with out-of-hospital cardiac arrest (OHCA), however, recent data suggest that prior treatment with ß-blockers could be harmful by lowering the incidence of a shockable presenting rhythm. The main objective of our study was to determine the association between prior ß-blocker use and mortality in OHCA patients. METHODS: An observational study was conducted using the Toronto Rescu Epistry database that captured consecutive OHCA patients from 2005 to 2010. Patients older than 65 years with nontraumatic cardiac arrest and attempted resuscitation were included. Patients prescribed ß-blockers within 90 days of the arrest were compared with those without such therapy. The primary outcome was all-cause mortality at 30 days. Potential confounders were accounted for by inverse probability of treatment weighting using the propensity score. RESULTS: The median age of 8,266 OHCA patients was 79 years, 41% were women, and 2,911 (35.2%) were prescribed a ß-blocker prior to cardiac arrest. Patients prescribed ß-blockers were more likely to have existing cardiac risk factors and cardiovascular conditions. In the propensity-weighted cohort, there were no differences in the presenting rhythm, with 18.4% of patients in the ß-blocker group having a shockable rhythm vs 17.5% in the no ß-blocker group (standardized difference .023). In addition, 30-day mortality was not significantly different between patients prescribed ß-blockers and no ß-blockers (95.6% vs 95.1%, P = .36). CONCLUSION: ß-Blocker use was not associated with lower rates of shockable rhythms or mortality among older patients with OHCA.

Factors associated with physician follow-up among patients with chest pain discharged from the emergency department.

BACKGROUND: Many patients with chest pain do not receive follow-up from a physician after discharge from the emergency department despite significant survival benefit associated with follow-up care. Our objective was to evaluate factors associated with physician follow-up to understand this gap in practice. METHODS: We conducted an observational study involving patients at high risk who were assessed for chest pain and discharged from an emergency department in Ontario between April 2004 and March 2010. We used multivariable logistic regression to determine the association of clinical and nonclinical characteristics with physician follow-up. RESULTS: We identified 56 767 patients, of whom 25.1% did not receive any follow-up by a physician, 69.0% were seen by their primary care physician, and 17.3% were seen by a cardiologist within 30 days. Patients who had medical comorbidities and cardiac conditions such as myocardial infarction or heart failure were less likely to have follow-up. In contrast, a previous visit to a primary care physician was associated with the highest odds of having physician follow-up (odds ratio [OR] 6.44, 95% confidence interval [CI] 5.91-7.01). Similarly, a previous visit to a cardiologist was strongly associated with follow-up by a cardiologist (OR 3.01, 95% CI 2.85-3.17). Patients evaluated in emergency departments with the highest tertile of chest pain volume were more likely to receive follow-up from any physician (OR 1.52, 95% CI 1.31-1.77) and from a cardiologist (OR 2.04, 95% CI 1.61-2.57). INTERPRETATION: Nonclinical factors are strongly associated with physician follow-up for patients with chest pain after discharge from the emergency department. However, patients with comorbidities and at higher risk for future adverse events are less likely to receive follow-up care.

Association between physician follow-up and outcomes of care after chest pain assessment in high-risk patients.

BACKGROUND: Assessment of chest pain is one of the most common reasons for emergency department visits in developed countries. Although guidelines recommend primary care physician (PCP) follow-up for patients who are subsequently discharged, little is known about the relationship between physician follow-up and clinical outcomes. METHODS AND RESULTS: An observational study was conducted on patients with higher baseline risk, defined as having diabetes mellitus or established cardiovascular disease, who were evaluated for chest pain, discharged, and without adverse clinical outcomes for 30 days in Ontario from 2004 to 2010. Multivariable proportional hazard models were constructed to adjust for potential confounding between physician groups (cardiologist, PCP, or none). Among 56767 included patients, 17% were evaluated by cardiologists, 58% were evaluated by PCPs alone, and 25% had no physician follow-up. The mean age was 66±15 years, and 53% were male. The highest rates of diagnostic testing, medical therapy, and coronary revascularization were seen among patients treated by cardiologists. At 1 year, the rate of death or MI was 5.5% (95% confidence interval, 5.0-5.9) in the cardiology group, 7.7% (95% confidence interval, 7.4-7.9) in the PCP group, and 8.6% (95% confidence interval, 8.2-9.1) in the no-physician group. After adjustment, cardiologist follow-up was associated with significantly lower adjusted hazard ratio of death or MI compared with PCP (hazard ratio, 0.85; 95% confidence interval, 0.78-0.92) and no physician (hazard ratio, 0.79; 95% confidence interval, 0.71-0.88) follow-up. CONCLUSIONS: Among patients with higher baseline cardiovascular risk who were discharged from the emergency department after evaluation for chest pain in Ontario, follow-up with a cardiologist was associated with a decreased risk of all-cause mortality or hospitalization for MI at 1 year compared with follow-up with a PCP or no physician follow-up.

The role of primary care physician and cardiologist follow-up for low-risk patients with chest pain after emergency department assessment.

BACKGROUND: Chest pain is one of the most common reasons for presentation to the emergency department (ED); however, there is a paucity of data evaluating the impact of physician follow-up and subsequent management. To evaluate the impact of physician follow-up for low-risk chest pain patients after ED assessment. METHODS: We performed a retrospective observational study of low-risk chest pain patients who were assessed and discharged home from an Ontario ED. Low risk was defined as ≥50 years of age and no diabetes or preexisting cardiovascular disease. Follow-up within 30 days was stratified as (a) no physician, (b) primary care physician (PCP) alone, (c) PCP with cardiologist, and (d) cardiologist alone. The primary outcome was death or myocardial infarction (MI) at 1 year. RESULTS: Among 216,527 patients, 29% had no-physician, 60% had PCP-alone, 8% had PCP with cardiologist, and 4% had cardiologist-alone follow-up after ED discharge. The mean age of the study cohort was 64.2 years, and 42% of the patients were male. After adjusting for important differences in baseline characteristics between physician follow-up groups, the adjusted hazard ratios for death or MI were 1.07 (95% CI 1.00-1.14) for the PCP group, 0.81 (95% CI 0.72-0.91) for the PCP with cardiologist group, and 0.87 (95% CI 0.74-1.02) for the cardiologist alone group, as compared with patients who had no follow-up. CONCLUSION: In this cohort of low-risk patients who presented to an ED with chest pain, follow-up with a PCP and cardiologist was associated with significantly reduced risk of death or MI at 1 year.

Transcatheter edge-to-edge repair in papillary muscle injury complicating acute myocardial infarction.

AIMS: Acute mitral regurgitation (MR) in the setting of myocardial infarction (MI) may be the result of papillary muscle rupture (PMR). This condition is associated with high morbidity and mortality. We aim to evaluate the feasibility of transcatheter edge-to-edge mitral valve repair (TEER) in this acute setting. METHODS AND RESULTS: We analysed data from the International Registry of MitraClip in Acute Mitral Regurgitation following acute Myocardial Infarction (IREMMI) of 30 centres in Europe, North America, and the middle east. We included patients with post-MI PMR treated with TEER as a salvage procedure, and we evaluated immediate and 30-day outcomes. Twenty-three patients were included in this analysis (9 patients suffered complete papillary muscle rupture, 9 partial and 5 chordal rupture). The patients' mean age was 68 ± 14 years. Patients were at high surgical risk with median EuroSCORE II 27% (IQR 16, 28) and 20 out of 23 (87% were in cardiogenic shock). All patients were treated with vasopressors, and 17 out of 23 patients required mechanical support. TEER procedure was performed on the median 6 days after the index MI date IQR (3, 11). Procedural success was achieved in 87% of patients. The grade of MR was significantly decreased after the procedure. MR reduction to 0 or 1 + was achieved in 13 patients (57%), to 2 + in 7 patients (30%), P < 0.01. V-Wave was reduced from 49 ± 8 mmHg to 26 ± 10 mmHg post-procedure, P < 0.01. Sixteen out of 23 patients (70%) were discharged from hospital and 5 of them required reintervention with surgical mitral valve replacement. No additional death at 1 year was documented. CONCLUSIONS: TEER is a feasible therapy in critically ill patients with PMR due to a recent MI. TEER may have a role as salvage treatment or bridge to surgery in this population.

Relationship of Neighbourhood Social Deprivation and Ethnicity on Access to Transcatheter and Surgical Aortic Valve Replacement: A Population-Level Study.

BACKGROUND: Wide geographic variation in access to transcatheter (TAVR) and surgical (SAVR) aortic valve replacement exists, but the impact of socioethnic factors on the geographic variation of AS management in Ontario, Canada, is unknown. METHODS: Neighbourhood rates of AS admissions, as a proxy for AS burden, and downstream TAVR and SAVR referrals and procedures were estimated for the 76 subregions in Ontario. To determine if the socioethnic geographic variations in referrals and procedures were concordant or discordant with AS burden, we calculated Pearson correlation coefficients to determine the relationship between AS burden and each of TAVR referrals, TAVR procedures, SAVR referrals, or SAVR procedures. We developed generalised linear models to determine the association between social deprivation indices captured in the Ontario Marginalization index and the rates of AS burden as well as TAVR/SAVR referral and procedures. RESULTS: There was wide geographic variation that was concordant between AS burden and the referral and procedure rates for TAVR and SAVR (correlation coefficients 0.86-0.96). Increased dependency was associated with higher rates of both TAVR/SAVR referrals and procedures (rate ratios 1.63-2.22). Neighbourhoods with a higher concentration of ethnic minorities were associated with lower AS burden as well as lower rates of both SAVR and TAVR referrals and procedures (rate ratios 0.57-0.85). CONCLUSIONS: An important ethnic gradient exists in AS burden and in both referral and completion of TAVR and SAVR in Ontario. Further research is necessary to understand if this gradient is appropriate or requires mitigation.

Transcatheter Edge-to-Edge Mitral Valve Repair in Patients With Severe Mitral Regurgitation and Cardiogenic Shock.

BACKGROUND: Data on the efficacy of transcatheter edge-to-edge repair (TEER) in patients with cardiogenic shock (CS) are limited. OBJECTIVES: This study investigated the characteristics and outcomes of consecutive patients with significant mitral regurgitation (MR) and CS who underwent TEER. METHODS: The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was assessed from November 22, 2013, to December 31, 2021. CS was defined as the coding of: 1) CS; 2) inotrope use; or 3) mechanical circulatory support before TEER. Device success was defined as MR reduction of ≥1 grade and a final MR grade ≤2+. The primary outcome was the impact of device success on 1-year mortality or heart failure (HF) readmissions. Cox proportional hazards models were used to report the risk-adjusted association between device success and 1-year outcomes. RESULTS: A total of 3,797 patients met the inclusion criteria. Mean age was 73.0 ± 11.9 years, and 59.5% were male. Mean Society of Thoracic Surgery score (MV repair) was 14.9% ± 15.3%. MR etiology was degenerative (53.4%) and functional (27.5%). Device success was achieved in 3,249 (85.6%) patients given successful achievement of final MR grade ≤2+ (88.2%) and MR reduction ≥1 absolute grade (91.4%). At 1 year after TEER, device success was associated with significantly lower all-cause mortality (34.6% vs 55.5%; adjusted HR: 0.49; 95% CI: 0.41-0.59; P < 0.001) and a composite of mortality or HF admissions (29.6% vs 45.2%; adjusted HR: 0.51; 95% CI: 0.42-0.62; P < 0.001). CONCLUSIONS: Successful MR reduction is achievable in most patients with CS and is associated with significantly lower mortality and HF hospitalization at 1 year. Randomized trials assessing TEER in CS are needed to establish this potential therapeutic approach.

Impact of Transcatheter Mitral Valve Repair on Preprocedural and Postprocedural Hospitalization Rates.

OBJECTIVES: The objective of this study was to determine the effect of transcatheter mitral valve repair (TMVr) on hospitalization rates by assessing pre- and postprocedural hospitalization patterns. BACKGROUND: TMVr has emerged as the treatment of choice for selected patients with mitral regurgitation, but the impact of these procedures on hospital utilization remains unclear. METHODS: All patients who underwent TMVr in Ontario, Canada, between 2011 and 2017 were included in this observational study using population-based data. Hospitalization person-year rates were assessed in the years before and after TMVr and 4 predefined intervals: 1 to 30, 31 to 90, 91 to 182, and 183 to 365 days. Main outcomes of interest were all-cause and heart failure (HF) hospitalizations. Poisson regression models were used to compare incidence rates across all time periods. RESULTS: The study cohort included 523 patients. In the year preceding TMVr, 66.2% of patients were hospitalized compared with 47.4% in the year following. There were stepwise increases in both all-cause and HF hospitalization rates in the periods preceding the index procedure, and all postprocedural periods had significantly lower hospitalization rates. The adjusted rate ratios for all-cause and HF-related hospitalization in the year after TMVr were 0.65 (95% CI: 0.56-0.76) and 0.38 (95% CI: 0.29-0.51), respectively. All time periods had significant reductions in all-cause and HF hospitalization in the adjusted analysis. CONCLUSIONS: In this population-based study, significant reductions were observed in both all-cause and HF-related hospitalizations in all time periods after TMVr compared with the year prior. This suggests that TMVr has a sustained effect on hospitalization rates despite a high-risk population.

Safety and Feasibility of MitraClip Implantation in Patients with Acute Mitral Regurgitation after Recent Myocardial Infarction and Severe Left Ventricle Dysfunction.

Patients with severe mitral regurgitation (MR) after myocardial infarction (MI) have an increased risk of mortality. Transcatheter mitral valve repair may therefore be a suitable therapy. However, data on clinical outcomes of patients in an acute setting are scarce, especially those with reduced left ventricle (LV) dysfunction. We conducted a multinational, collaborative data analysis from 21 centers for patients who were, within 90 days of acute MI, treated with MitraClip due to severe MR. The cohort was divided according to median left ventricle ejection fraction (LVEF)-35%. Included in the study were 105 patients. The mean age was 71 ± 10 years. Patients in the LVEF < 35% group were younger but with comparable Euroscore II, multivessel coronary artery disease, prior MI and coronary artery bypass graft surgery. Procedure time was comparable and acute success rate was high in both groups (94% vs. 90%, p = 0.728). MR grade was significantly reduced in both groups along with an immediate reduction in left atrial V-wave, pulmonary artery pressure and improvement in New York Heart Association (NYHA) class. In-hospital and 1-year mortality rates were not significantly different between the two groups (11% vs. 7%, p = 0.51 and 19% vs. 12%, p = 0.49) and neither was the 3-month re-hospitalization rate. In conclusion, MitraClip intervention in patients with acute severe functional mitral regurgitation (FMR) due to a recent MI in an acute setting is safe and feasible. Even patients with severe LV dysfunction may benefit from transcatheter mitral valve intervention and should not be excluded.

The utility of tissue Doppler imaging for the noninvasive determination of left ventricular filling pressures in patients with septic shock.

BACKGROUND: Pulmonary artery wedge pressure (PAWP) is an important indicator of volume status in septic patients. Although it requires invasive pulmonary artery catheterization (PAC), a noninvasive method to assess PAWP would be clinically useful in this select patient population. Diastolic indices using transthoracic echocardiography (TTE) may provide an accurate estimate of PAWP. OBJECTIVE: To determine whether echocardiographic Doppler assessment is accurate in estimating PAWP in patients with septic shock. METHODS: A retrospective chart review was performed of 320 patients admitted with a diagnosis of septic shock from 2007-2008. Of the total patient population, 40 patients fulfilled the inclusion criteria, having undergone both TTE and PAC within 4 hours. Spectral Doppler indices including peak early (E) and late (A) transmitral velocities, E/A ratio, and E-wave deceleration time were measured. Tissue Doppler indices including S', E' and A' velocities were determined. Pulmonary artery wedge pressure values measured invasively were compared to the dimensionless index of E/E' in each patient. RESULTS: The mean age was 68 +/- 12 years with 28 males (70%). On echo assessment, 28% of patients had evidence of mild left ventricular diastolic dysfunction while 17% of patients had moderate diastolic dysfunction. Pulmonary artery wedge pressures ranged from 7 to 31 mm Hg with a mean of 18 +/- 5 mm Hg. The mean E/E' was 11 +/- 8. Linear regression analysis between PAWP and E/E7apos; demonstrated a strong correlation (r = .84, P < .05). CONCLUSION: Tissue Doppler indices using TTE is a feasible and strong predictor of PAWP in patients with septic shock.

Comparison of 1-Year Pre- and Post-Transcatheter Aortic Valve Replacement Hospitalization Rates: A Population-Based Cohort Study.

BACKGROUND: Rehospitalization rates post-transcatheter aortic valve replacement (TAVR) are high; however, it is not known how these compare with pre-TAVR hospitalization rates. Our objective was to determine the association between the index TAVR and hospitalization rates pre- and postprocedure. METHODS: A retrospective observational study was performed including all TAVR procedures performed in Ontario, Canada, between 2013 and 2017. Patients who died during the index hospitalization were excluded. The primary outcome was all-cause hospitalization within 1 year of TAVR discharge. Hospitalization rates per person-year were calculated and compared for each of the following analogous time periods pre- and post-index TAVR: 1 to 30, 31 to 90, 91 to 365, and 1 to 365 days. Poisson regression models were used to generate rate ratios to compare hospitalization rates. RESULTS: The final study cohort included 2547 patients. In the year before TAVR, 60.2% of patients were hospitalized, compared with 45.9% in the year following the procedure. The rate ratio (RR) for the year post-TAVR compared with pre-TAVR was 0.82 (95% confidence interval [CI], 0.77- 0.88). When comparing each parallel time period post- vs pre-TAVR, all intervals were associated with significant reductions in hospitalization after TAVR, except the 30-day periprocedural period. The largest change in hospitalization rates occurred in the 31 to 90 days post- vs the corresponding period pre-TAVR (RR: 0.57; 95% CI, 0.50-0.64) CONCLUSION: TAVR is associated with a significant and sustained reduction in all-cause hospitalization in the year following the procedure compared with the preprocedural period.

High-throughput continuous-flow microfluidic electroporation of mRNA into primary human T cells for applications in cellular therapy manufacturing.

Implementation of gene editing technologies such as CRISPR/Cas9 in the manufacture of novel cell-based therapeutics has the potential to enable highly-targeted, stable, and persistent genome modifications without the use of viral vectors. Electroporation has emerged as a preferred method for delivering gene-editing machinery to target cells, but a major challenge remaining is that most commercial electroporation machines are built for research and process development rather than for large-scale, automated cellular therapy manufacturing. Here we present a microfluidic continuous-flow electrotransfection device designed for precise, consistent, and high-throughput genetic modification of target cells in cellular therapy manufacturing applications. We optimized our device for delivery of mRNA into primary human T cells and demonstrated up to 95% transfection efficiency with minimum impact on cell viability and expansion potential. We additionally demonstrated processing of samples comprising up to 500 million T cells at a rate of 20 million cells/min. We anticipate that our device will help to streamline the production of autologous therapies requiring on the order of 10[Formula: see text]-10[Formula: see text] cells, and that it is well-suited to scale for production of trillions of cells to support emerging allogeneic therapies.

Transcatheter Mitral Valve Edge-to-Edge Repair with the New MitraClip XTR System for Acute Mitral Regurgitation Caused by Papillary Muscle Rupture.

Treatment of patients presenting with cardiogenic shock due to acute mitral regurgitation related to papillary muscle rupture poses significant challenges, owing to the high risk associated with conventional surgery. We hereby report successful transcatheter mitral valve edge-to-edge repair with the new Mitraclip XTR device (Abbott Vascular, Santa Clara, CA) in a patient with acute myocardial infarction and cardiogenic shock. Although surgical intervention remains the standard of care, the new MitraClip XTR system offers a novel treatment option for patients with papillary muscle rupture by overcoming the anatomic challenges often seen in this pathology.

Association Between Hospital Teaching Status and Outcomes After Out-of-Hospital Cardiac Arrest.

BACKGROUND: Controversy exists about how best to organize systems of care for patients with out-of-hospital cardiac arrest (OHCA), as little evidence exists to guide policy-makers. In Canada, teaching hospitals are mainly cardiac referral centers that are potentially well suited towards treating patients with OHCA. Our objective was to determine whether patients with OHCA are more likely to survive if they present to teaching hospitals. METHODS AND RESULTS: We conducted a retrospective observational cohort study by linking several population-based administrative databases in Ontario, Canada. All patients >20 years old who arrived alive to hospital after OHCA between April 1, 2007, and March 31, 2014, were eligible for inclusion. Patients with ST-segment-elevation myocardial infarction were excluded. The primary outcome was survival at 30 days. To determine the association between teaching status and 30-day survival, logistic regression models were used to adjust for baseline differences in patient characteristics. Prespecified analysis was performed stratified by age: ≤65, 66 to 80, and >80 years old. A total of 25 346 patients were included: 5413 at teaching and 19 933 at nonteaching hospitals. Survival at 30 days was 13.9% in teaching and 11.0% (P<0.001) in nonteaching hospitals. Hospital teaching status was associated with a significantly higher adjusted odds of 30-day survival (odds ratio, 1.38 [95% CI, 1.14-1.67]). This improvement in survival was observed in younger patients (≤65 years: odds ratio, 1.41 [95% CI, 1.14-1.74]; 66 to 80 years: odds ratio,1.37 [95% CI, 1.13-1.67]), but there was no significant difference in the elderly (>80 years: odds ratio, 1.07 [95% CI, 0.79-1.44]). CONCLUSIONS: Patients with OHCA treated at teaching hospitals were more likely to survive to 30 days. These findings support current recommendations suggesting that treatment of these patients should be provided at specialized hospitals.