Dose-Blinded Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Outcomes Through 32 Weeks.

BACKGROUND: Septal reduction therapy (SRT) in patients with intractable symptoms from obstructive hypertrophic cardiomyopathy (oHCM) is associated with variable morbidity and mortality. The VALOR-HCM trial (A Study to Evaluate Mavacamten in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) examined the effect of mavacamten on the need for SRT through week 32 in oHCM. METHODS: A double-blind randomized placebo-controlled multicenter trial at 19 US sites included patients with oHCM on maximal tolerated medical therapy referred for SRT with left ventricular outflow tract gradient ≥50 mm Hg at rest or provocation (enrollment, July 2020-October 2021). The group initially randomized to mavacamten continued the drug for 32 weeks, and the placebo group crossed over to dose-blinded mavacamten from week 16 to week 32. Dose titrations were based on investigator-blinded echocardiographic assessment of left ventricular outflow tract gradient and left ventricular ejection fraction. The principal end point was the proportion of patients proceeding with SRT or remaining guideline eligible at 32 weeks in both treatment groups. RESULTS: From the 112 randomized patients with oHCM, 108 (mean age, 60.3 years; 50% men; 94% in New York Heart Association class III/IV) qualified for week 32 evaluation (56 in the original mavacamten group and 52 in the placebo cross-over group). After 32 weeks, 6 of 56 patients (10.7%) in the original mavacamten group and 7 of 52 patients (13.5%) in the placebo cross-over group met SRT guideline criteria or elected to undergo SRT. After 32 weeks, a sustained reduction in resting left ventricular outflow tract gradient (-33.0 mm Hg [95% CI, -41.1 to -24.9]) and Valsalva left ventricular outflow tract gradient (-43.0 mm Hg [95% CI, -52.1 to -33.9]) was observed in the original mavacamten group. A similar reduction in resting (-33.7 mm Hg [95% CI, -42.2 to -25.2]) and Valsalva (-52.9 mm Hg [95% CI, -63.2 to -42.6]) gradients was quantified in the cross-over group after 16 weeks of mavacamten. After 32 weeks, improvement by ≥1 New York Heart Association class was observed in 48 of 53 patients (90.6%) in the original mavacamten group and 35 of 50 patients (70%) after 16 weeks in the cross-over group. CONCLUSIONS: In severely symptomatic patients with oHCM, 32 weeks of mavacamten treatment showed sustained reduction in the proportion proceeding to SRT or remaining guideline eligible, with similar effects observed in patients who crossed over from placebo after 16 weeks. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04349072.

Evaluation and Management of Mechanical Heart Valve Dysfunction and Thrombosis.

PURPOSE OF REVIEW: Dysfunction and thrombosis of mechanical heart valves, although uncommon, represents a challenge that requires multidisciplinary expertise for diagnosis and management. The aim of this review is to summarize strengths and weaknesses of diagnostic methods and therapeutic strategies for this uncommon but potentially life-threatening pathology. RECENT FINDINGS: Expeditious diagnosis of mechanical valve thrombosis and exclusion of other diagnostic considerations, often with incorporation of multimodality imaging, can inform the best treatment strategy. Presentation of mechanical valve thrombosis can be asymptomatic or can include heart failure, life-threatening embolic events, or cardiogenic shock. Echocardiography, fluoroscopy and computed tomography are important in the evaluation of mechanical valve dysfunction. Therapeutic strategies for thrombosis include anticoagulation, systemic thrombolysis, and surgery. Choice of treatment depends on multiple factors including thrombus size, degree of valve dysfunction, clinical presentation, and available surgical expertise.

Anticoagulation after pulmonary vein isolation for atrial fibrillation: Associations with CHA2DS2-VASc score, sex, and rhythm.

Guidelines recommend using the CHA2DS2-VASc score to determine anticoagulation decisions in atrial fibrillation (AF) patients, including those who undergo pulmonary vein isolation (PVI), however this may not consistently occur in the real-world setting because of other clinical factors. We sought to evaluate the anticoagulation prescription rates patterns in AF patients 1 year PVI at our institution. Consecutive AF patients undergoing PVI in our prospective registry during 2014-2018 who were alive at 1-year post-PVI were studied. Anticoagulation prescription rates at this time-point were adjudicated, and correlated to CHA2DS2-VASc score, sex, and heart rhythm status at 1 year. Amongst 4596 patients undergoing PVI, mean age was 64.2 ± 10.0 years, 1328 (28.9%) were female, and based on CHA2DS2-VASc score anticoagulation was not indicated, can be considered and indicated in 872 (19.0%), 1183 (25.7%), and 2541 (55.3%) patients, respectively. At 1-year after PVI, 3504 (76.2%) patients were on anticoagulation, and 792 (17.2%) had recurrence of AF. Anticoagulation was continued in over half of AF patients without classic CHA2DS2-VASc indication particularly in those with AF recurrence and women, while they were mildly under-prescribed in those with indication, especially for those without AF recurrence and men. In a large real world cohort of patients after PVI, anticoagulation prescription is not solely depending on the CHA2DS2-VASc score and sex, but also heart rhythm status and other clinical or imaging factors.

Utility of positron emission tomography myocardial perfusion imaging for identifying ischemia and guiding treatment in patients with anomalous coronary arteries.

BACKGROUND: The assessment of anomalous coronary arteries (AAOCA) remains controversial without an optimal stress modality for ischemia. We evaluated the value of PET-CT myocardial perfusion imaging in these patients and subsequent management. METHODS AND RESULTS: AAOCA patients (n = 82) undergoing PET-CT from 2015 to 2021 were retrospectively chart reviewed. Multivariable analyses performed to assess relevant clinical and imaging factors associated with ischemia on PET and AAOCA surgery. Key characteristics include mean age 45 ± 20 years, 30 (37%) female, 45 (55%) with chest pain, 19 (23%) anomalous left main coronary artery, 58 (71%) anomalous right coronary artery, 26 (32%) with objective ischemia on PET-CT, and 37 (45%) who underwent AAOCA surgery. Adverse outcomes over mean follow-up of 2.2 ± 1.8 years included one death and two myocardial infarctions. Anomalous left main was independently associated with ischemia on PET-CT, odds ratio (95% confidence intervals) 4.15 (1.31-13.1), P = .006. Chest pain and ischemia on PET-CT were independently associated with and provided incremental prognostic value for surgery, odds ratio 9.73 (2.78-34.0), P < .001 and 6.79 (1.99-23.2), P = .002, respectively. CONCLUSION: Ischemia on PET-CT occurred in a third of our cohort, identifying patients who may benefit from surgery. Larger studies are needed to evaluate the interplay between AAOCA, ischemia by PET and surgery.

Optimal left ventricular ejection fraction in risk stratification of patients with cardiac sarcoidosis.

AIMS: Identifying patients with cardiac sarcoidosis (CS) who are at an increased risk of sudden cardiac death (SCD) poses a clinical challenge. We sought to identify the optimal cutoff for left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmia (VA) and all-cause mortality and to identify clinical and imaging risk factors in patients with known CS. METHODS AND RESULTS: This retrospective cohort included 273 patients with well-established CS. The primary endpoint was a composite of VA and all-cause mortality. A modified receiver operating curve analysis was utilized to identify the optimal cutoff for LVEF in predicting the primary composite endpoint. Cox proportional hazard regression analysis was used to identify independent risk factors of the outcomes. At median follow-up of 7.9 years, the rate of the primary endpoint was 38% (83 VAs and 32 all-cause deaths). The 5-year overall survival rate was 97%. The optimal cutoff LVEF for the primary composite endpoint was 42% in the entire cohort and in subjects without a history of VA. Younger age, history of VA, lower LVEF, and any presence of scar by cardiac magnetic resonance (CMR) imaging and/or positron emission tomography (PET) were found to be independent risk factors for the primary endpoint and for VA, whereas lower LVEF, baseline NT-proBNP, and any presence of scar were independent risk factor of all-cause mortality. CONCLUSION: Among patients with CS, a mild reduction in LVEF of 42% was identified as the optimal cutoff for predicting VA and all-cause mortality. Prior VA and scar by CMR or PET are strong risk factors for future VA and all-cause mortality.

Value of Routine Troponin Measurement in Open Abdominal Aortic Aneurysm Repair.

BACKGROUND: Cardiovascular complications are a major cause of morbidity and mortality in the postoperative period after major vascular surgery. Depending on the study population, up to 25% of patients have troponin elevation after noncardiac surgery, yet many do not meet the diagnosis of myocardial infarction (MI). Although outcomes of routine troponin elevation in patients undergoing mixed major vascular surgery have been evaluated, this has not been studied exclusively in elective, open abdominal aortic aneurysm repair (oAAA), especially regarding perioperative and overall mortality. METHODS: We conducted a single-center, retrospective review of routine troponin surveillance for consecutive, oAAA from 2014 to 2019. A total of 319 patients were identified and analyzed for management patterns and interventions. The cohort was stratified into groups for comparison based on those in whom troponin was routinely checked (RC) as part of a care strategy during the study period, not routinely checked (NRC), elevated troponin (ET) >0.001 ng/mL, and not elevated. The median follow-up was 21.5 ± 23.8 months. Groups were compared on demographic data, cardiac comorbidities, 30-day and 3-year outcomes for MI and death using two-sample t-tests, Wilcoxon rank sum tests, Pearson chi-square tests, and Fisher exact tests when appropriate. RESULTS: Troponin was measured in 83.7% (267/319) of patients who underwent elective oAAA repair. Routine troponin checks were obtained in 79.9% (255/319) of patients. ET was identified in 16.5% of those with RC (42/255) and 4.7% of those with NRC (3/64). Of patients with ET, 37.8% (17/45) had a cardiology consultation, 4.4% (2/45) had a percutaneous coronary intervention (PCI), and 4.4% (2/45) had another cardiac intervention. All 4 patients undergoing PCI or other cardiac intervention had received routine troponin checks. Patients with ET were older (71.2 vs. 68.6; P = 0.04), more likely to receive intraoperative blood products (P = 0.003), had longer operative times (P = 0.011), higher length of stay (9 vs. 7 days; P < 0.01), and higher 30-day MI rate (3 vs. 0; P = 0.04). They had neither longer aortic clamp times nor worse preoperative cardiac function, and the proximal clamp position during oAAA repair did not impact troponin detection. Additionally, 3-year overall mortality was increased in patients who had ET but there was not a significant difference in 3-year mortality between groups receiving routine troponin checks versus not. CONCLUSIONS: ET, identified after elective oAAA repair, was associated with a higher risk of 30-day MI and lower overall survival. However, it was not demonstrated that routine assessment of troponin levels postoperatively leads to decreased 3-year mortality in this setting.

The Association of Cardiac Biomarkers, the Intensity of Tc99 Pyrophosphate Uptake, and Survival in Patients Evaluated for Transthyretin Cardiac Amyloidosis in the Early Therapeutics Era.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure. Given the expansion of noninvasive diagnosis with 99mTc-pyrophosphate (99mTc-PYP) scanning, and clinical use of the transthyretin stabilizer, tafamidis, we sought to examine the interplay of planar imaging heart-to-contralateral lung (H/CL) ratio, cardiac biomarkers, and survival probability in a contemporary cohort of patients referred for noninvasive evaluation of ATTR-CM. METHODS: This single-center retrospective cohort study included 351 consecutive patients who underwent a standardized imaging protocol with 99mTc-PYP scanning for the evaluation of ATTR-CM from January 1, 2018, to January 1, 2020. After the exclusion of light chain amyloidosis, patients were characterized as scan consistent with ATTR (+ATTR-CM) or scan not consistent with ATTR (-ATTR-CM) using current guidelines. Linear regression was used to examine the relationship between biomarkers and H/CL and univariate Cox proportional hazards models were used to assess the probability of transplant-free survival. RESULTS: We included 318 patients in the analysis (n = 86 patients +ATTR-CM; n = 232 patients -ATTR-CM). The median follow-up time was 20.1 months. During the study period, 67% of +ATTR-CM patients received tafamidis (median treatment duration, 17 months). The median H/CL ratio was 1.58 (interquartile range, 1.40-1.75). An H/CL ratio of more than 1.6 or less than 1.6 did not seem to have an impact on survival probability in +ATTR-CM patients (P = .30; hazard ratio, 0.65; 95% confidence interval, 0.31-1.41). Cardiac biomarkers were poorly correlated with H/CL (troponin T, R2 = 0.024; N-terminal pro-B-type natriuretic peptide, R2 =0.023). The Gillmore staging system predicted survival probability in +ATTR-CM as well as in the entire cohort referred for scanning. There was a trend toward longer survival among those who were -ATTR-CM compared with +ATTR-CM (P = .051; hazard ratio, 0.64; 95% confidence interval, 0.40-1.00). CONCLUSIONS: At a large referral center, the intensity of 99mTc-PYP uptake (H/CL ratio) has neither correlation with cardiac biomarker concentrations nor prognostic usefulness in an analysis of intermediate term outcomes in the early therapeutics era. The H/CL ratio has diagnostic value, but offers little prognostic value in patients with ATTR-CM. Established staging schema were predictive of survival in this contemporary cohort, re-emphasizing the importance of cardiac biomarkers and renal function in assessing disease severity and prognosis.

Initial experience regarding the safety and yield of rest-stress myocardial perfusion imaging in emergency department patients with mildly abnormal high-sensitivity cardiac troponins.

BACKGROUND: With high-sensitivity troponin testing, approximately a third of patients presenting to emergency departments (EDs) with suspected acute coronary syndromes will have mildly abnormal values. However, data regarding rest-stress myocardial perfusion imaging (MPI) in these patients are limited. We hypothesize that stress testing is safe and that the yield for detecting myocardial ischemia is associated with risk stratification by the HEART score. METHODS AND RESULTS: We conducted a retrospective cohort study of consecutive patients referred for rest-stress MPI with mildly abnormal high-sensitivity troponin T (hs-cTn) values. Outcomes were adverse events related to stress MPI, defined as myocardial infarction or ventricular tachyarrhythmia, and the presence of ischemia, defined as a reversible perfusion defect. Among 213 patients, the median age was 67, most were male (61.5%, n = 131), and prior CAD was common (53.5%, n = 114). Myocardial ischemia was present in 13.6% (n = 29), and there were no adverse events attributable to stress MPI. A higher HEART score was associated with myocardial ischemia (Odds Ratio [OR] 1.50, 95% Confidence Interval [CI] 1.08 to 2.08, P = .002). CONCLUSION: Rest-stress MPI appears safe in patients with mildly abnormal hs-cTn values, and the yield for detecting ischemia is associated with the HEART score, though further validation studies are needed.

Novel dietary protocol prior to 18F-fluorodeoxyglucose positron emission tomography to evaluate for cardiac sarcoidosis.

The diagnosis of cardiac sarcoidosis (CS) is challenging. Recently, guidelines incorporated cardiac positron emission tomography (PET) with 18F-Fluorodeoxyglucose (F18-FDG) as a non-invasive diagnostic modality for the detection and follow-up of CS. However, this technique is dependent of patient dietary preparation to suppress physiological myocardial F18-FDG uptake. We present a case of possible CS which highlights a novel preparation protocol that facilitated appropriate myocardial suppression.

Initial experience with regadenoson stress positron emission tomography in patients with left bundle branch block: Low prevalence of septal defects and high accuracy for obstructive coronary artery disease.

BACKGROUND: Assessing for coronary artery disease (CAD) in patients with left bundle branch block (LBBB) is difficult with noninvasive cardiac imaging. Few studies report the prevalence of LBBB associated septal-apical perfusion defects using regadenoson stress on Positron Electron Tomography (PET) imaging. METHODS AND RESULTS: We identified 101 consecutive patients with baseline LBBB, and without known CAD, who underwent rest-stress regadenoson PET. Investigators have the ability to prospectively identify studies, whose quality is limited by LBBB artifact. With the infusion of regadenoson, resting to peak stress heart rate rose from a median of 78 to 93 BPM. Despite this, LBBB perfusion artifacts were not identified in any studies. 10 individuals had both regadenoson SPECT and PET within 1 year. 3 of the 10 SPECT studies had LBBB artifacts, all of which were not seen on subsequent PET. 21 patients with PET had subsequent coronary angiography. Of these, 9 PETs were without significant inducible ischemia, and angiogram was without flow-limiting disease. 3 PETs identified inducible ischemia, but did not have flow-limiting disease on angiogram. 9 PETs identified inducible ischemia and had flow-limiting disease on angiogram. CONCLUSIONS: In patients with LBBB undergoing regadenoson PET stress imaging, artifactual septal perfusion defects are rare.

Incorporating coronary calcification by computed tomography into CHA2DS2-VASc score: impact on cardiovascular outcomes in patients with atrial fibrillation.

AIMS: CHA2DS2-VASc score is widely utilized for risk stratification and guiding anticoagulation in patients with atrial fibrillation (AF). Cardiac computed tomography (CCT) routinely performed for pulmonary vein isolation (PVI) can also identify coronary artery calcifications (CAC). We evaluated the frequency and outcomes of incorporating CAC into the CHA2DS2-VASc score in AF patients undergoing PVI. METHODS AND RESULTS: Consecutive patients in a prospective PVI registry during 2014-18 having CCT within 1 year of PVI were studied. Reclassification of CHA2DS2-VASc score and associations between CAC as a binary variable detected on CCT with clinical characteristics, stroke as primary endpoint, death, myocardial infarction, and major adverse cardiovascular events (MACE) were analysed. Amongst 3604 AF patients, 2238 (62.1%) had CAC detected on CCT and was associated with most traditional cardiovascular risk factors. Coronary artery calcification was independently associated with all pre-specified endpoints adjusting for clinical parameters in multivariable analysis. Adjusting for CHA2DS2-VASc score, CAC was associated with stroke (hazards ratio 3.64, 95% confidence interval 1.25-10.6, P = 0.018), death (2.26, 1.29-3.98, P = 0.006), and MACE (2.08, 1.36-3.16, P = 0.001) during 2.8 ± 1.6-year follow-up. Incorporating CAC as a vascular disease parameter of CHA2DS2-VASc score, anticoagulation decision-making would be revised in 723 (20.1%) patients, including an additional 488 (13.5%) patients where anticoagulation would be now indicated. CONCLUSION: Coronary artery calcification is prevalent in AF patients undergoing PVI and independently associated stroke, death and MACE even when adjusted for traditional CHA2DS2-VASc score. Adding CAC as vascular component to the CHA2DS2-VASc score requires further research as it potentially modified the anticoagulation management in 20% of our AF cohort.

Pericardial Diseases in COVID19: a Contemporary Review.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID19) involves the heart, including pericardium. This article reviews the possible pathophysiological mechanisms in pericardial involvement in COVID19 and pericardial manifestations of COVID19. It also summarizes the patients with pericarditis secondary to COVID19 and outlines the contemporary treatment strategies in this patient population. RECENT FINDINGS: A high degree of suspicion is required to identify the pericardial involvement in COVID19 patients. It is proposed that an underlying hyperinflammatory reaction in COVID19 leads to pericardial inflammation. Acute pericarditis with or without myocardial involvement is diagnosed on clinical presentation, serum inflammatory markers, electrocardiogram, and echocardiogram. Multimodality imaging may also have an additional diagnostic value. Patients are usually managed medically, but some patients develop a life-threatening pericardial tamponade necessitating pericardial drainage. Pericardial involvement is an important clinical manifestation of COVID19 requiring a proper workup. Timely diagnosis and a specific management plan based on the presentation and concomitant organ involvement usually lead to a complete recovery.

SARS-CoV-2 Myocarditis: Insights Into Incidence, Prognosis, and Therapeutic Implications.

PURPOSE OF REVIEW: In coronavirus disease 2019 (COVID-19), myocardial injury occurs frequently in severe or critically ill hospitalized patients, yet myocarditis is much less common. In this context, revisiting the definition of myocarditis is appropriate with a specific focus on diagnostic and management considerations in patients infected with SARS-CoV-2. RECENT FINDINGS: Pathologic cardiac specimens from patients with COVID-19 suggest a mixed inflammatory response involving lymphocytes and macrophages, and importantly, cellular injury occurs predominantly at the level of pericytes and endothelial cells, less often involving direct myocyte necrosis. In COVID-19, the diagnosis of myocarditis has understandably been based predominantly on clinical criteria, and the number of patients with clinically suspected myocarditis who would meet diagnostic histological criteria is unclear. Echocardiography and cardiac magnetic resonance are important diagnostic tools, although the prognostic implications of abnormalities are still being defined. Importantly, SARS-CoV2 myocarditis should be diagnosed within an appropriate clinical context and should not be based on isolated imaging findings. Therapies in COVID-19 have focused on the major clinical manifestation of pneumonia, but the promotion of viral clearance early in the disease could prevent the development of myocarditis, and further study of immunosuppressive therapies once myocarditis has developed are indicated. A strict and uniform approach is needed to diagnose myocarditis due to SARS-CoV-2 to better understand the natural history of this disease and to facilitate evaluation of potential therapeutic interventions. A methodological approach will also better inform the incidence of COVID-19 associated myocarditis and potential long-term health effects.

Prosthetic Valve Endocarditis After TAVR and SAVR: Insights From the PARTNER Trials.

BACKGROUND: Prosthetic valve endocarditis (PVE) is a rare but critical mechanism of valve failure and death after transcatheter and surgical aortic valve replacement (TAVR, SAVR) warranting further analysis in modern aortic valve replacement experience. We characterize the incidence, risk factors, microbiological profile and outcomes of PVE from the PARTNER trials and registries (Placement of Aortic Transcatheter Valve). METHODS: We analyzed a pooled cohort of all patients in PARTNER 1 and PARTNER 2 trials and registries. Patients had severe aortic stenosis, were treated with TAVR or SAVR, and were analyzed with respect to development of PVE. PVE adjudication by a clinical events committee was based on modified Duke Criteria. The incidence, infection timing, organism, and association between PVE and all-cause mortality were analyzed. RESULTS: 8530 patients were included. PVE occurred in 107 cases (5.06 PVE events per 1000 person-years over a mean follow-up of 2.69±1.55 years [95% CI, 4.19-6.12]). The incidence of TAVR-PVE (5.21 PVE per 1000 person-years [95% CI, 4.26-6.38]) was not significantly different from SAVR-PVE (4.10 per 1000 person-years [95% CI, 2.33-7.22]; incident rate ratio, 1.27 [95% CI, 0.70-2.32]; P=0.44). Temporal risk of PVE was similar for TAVR and SAVR, even after adjusting for competing risk of death (hazard ratio, 1.15 [95% CI, 0.58-2.28]; P=0.69). Through multivariable analysis, PVE was associated with baseline cirrhosis (incident rate ratio, 2.86 [95% CI, 1.33-6.16]; P=0.007), pulmonary disease (incident rate ratio, 1.70 [95% CI, 1.16-2.48]; P=0.006), and renal insufficiency (incident rate ratio, 1.71 [95% CI, 1.03-2.83]; P=0.04). Timing of PVE was similar between TAVR and SAVR (<30 days: 4.2% vs 8.3%; 31 days to 1 year: 52.6% vs 66.7%; >1 year: 43.2% vs 25.0%; P=0.28). Staphylococcus occurred more commonly after SAVR (58.3% vs 28.4% in TAVR; P=0.04). PVE was strongly associated with all-cause mortality after endocarditis diagnosis (hazard ratio, 4.4 [95% CI, 3.42-5.72]; P<0.0001). CONCLUSIONS: The widespread adoption of TAVR and application to lower-risk patients makes understanding mechanisms of valve failure increasingly important. PVE is an established mechanism of prosthetic valve failure post-SAVR and TAVR with unclear differences between approaches. We herein demonstrate in the largest trials and registries of TAVR that PVE remains rare, but often fatal, in modern AVR experience and that there is no difference in incidence, predictors, or risk of PVE between TAVR and SAVR. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifiers: NCT00530894 (PARTNER 1), NCT01314313 (PARTNER 1IA), NCT02184442 (PARTNER 1IB), NCT03222141 (PII S3HR), NCT03222128 (PII S3i).

The incidence and prognostic implications of worsening right ventricular function after surgical or transcatheter aortic valve replacement: insights from PARTNER IIA.

Aims: In patients randomized to transcatheter or surgical aortic valve replacement (TAVR, SAVR), we sought to determine whether SAVR is associated with worsening right ventricular (RV) function and whether RV deterioration is associated with mortality. Methods and results: In 1376 patients from PARTNERIIA with paired baseline and 30-day core lab echocardiograms, worsening RV function was defined as decline by at least one grade from baseline to 30 days. Our primary outcome was all-cause mortality from 30 days to 2 years. Among 744 patients with TAVR, 62 (8.3%) had worsening RV function, compared with 156 of 632 patients with SAVR (24.7%) (P < 0.0001). In a multivariable model, SAVR [odds ratio (OR) 4.05, 95% confidence interval (CI) 2.55-6.44], a dilated RV (OR 2.38, 95% CI 1.37-4.14), and more than mild tricuspid regurgitation (TR) (OR 2.58, 95% CI 1.25-5.33) were associated with worsening RV function. There were 169 deaths, and patients with worsening RV function had higher all-cause mortality [hazard ratio (HR) 1.98, 95% CI 1.40-2.79]. This association remained robust after adjusting for clinical and echocardiographic variables. Among patients with worsening RV function, there was no mortality difference between TAVR and SAVR (HR 1.16, 95% CI 0.61-2.18). The development of moderate or severe RV dysfunction from baseline normal RV function conferred the worst prognosis (HR 2.87, 95% CI 1.40-5.89). Conclusion: After aortic valve replacement, worsening RV function is more common in patients with baseline RV dilation, more than mild TR, and in patients treated with SAVR. Worsening RV function and the magnitude of deterioration have important prognostic implications.

Artificial neural network-based model enhances risk stratification and reduces non-invasive cardiac stress imaging compared to Diamond-Forrester and Morise risk assessment models: A prospective study.

BACKGROUND: Coronary artery disease (CAD) accounts for more than half of all cardiovascular events. Stress testing remains the cornerstone for non-invasive assessment of patients with possible or known CAD. Clinical utilization reviews show that most patients presenting for evaluation of stable CAD by stress testing are categorized as low risk prior to the test. Attempts to enhance risk stratification of individuals who are sent for stress testing seem to be more in need today. The present study compares artificial neural networks (ANN)-based prediction models to the other risk models being used in practice (the Diamond-Forrester and the Morise models). METHODS: In our study, we prospectively recruited patients who were 19 years of age or older, and were being evaluated for coronary artery disease with imaging-based stress tests. For ANN, the network architecture employed a systematic method, where the number of neurons is changed incrementally, and bootstrapping was performed to evaluate the accuracy of the models. RESULTS: We prospectively enrolled 486 patients. The mean age of patients undergoing stress test was 55.2 ± 11.2 years, 35% were women, and 12% had a positive stress test for ischemic heart disease. When compared to Diamond-Forrester and Morise risk models, the ANN model for predicting ischemia provided higher discriminatory power (DP)(1.61), had a negative predictive value of 98%, Sensitivity 91% [81%-97%], Specificity 65% [60%-79%], positive predictive value 26%, and a potential 59% reduction of non-invasive imaging. CONCLUSION: The ANN models improved risk stratification when compared to the other risk scores (Diamond-Forrester and Morise) with a 98% negative predictive value and a significant potential reduction in non-invasive imaging tests.

Reliability of updated left ventricular diastolic function recommendations in predicting elevated left ventricular filling pressure and prognosis.

An updated 2016 echocardiographic algorithm for diagnosing left ventricular (LV) diastolic dysfunction (DD) was recently proposed. We aimed to assess the reliability of the 2016 echocardiographic LVDD grading algorithm in predicting elevated LV filling pressure and clinical outcomes compared to the 2009 version. METHODS: We retrospectively identified 460 consecutive patients without atrial fibrillation or significant mitral valve disease who underwent transthoracic echocardiography within 24 hours of elective heart catheterization. LV end-diastolic pressure (LVEDP) and the time constant of isovolumic pressure decay (Tau) were determined. The association between DD grading by 2009 LVDD Recommendations and 2016 Recommendations with hemodynamic parameters and all-cause mortality were compared. RESULTS: The 2009 LVDD Recommendations classified 55 patients (12%) as having normal, 132 (29%) as grade 1, 156 (34%) as grade 2, and 117 (25%) as grade 3 DD. Based on 2016 Recommendations, 177 patients (38%) were normal, 50 (11%) were indeterminate, 124 (27%) patients were grade 1, 75 (16%) were grade 2, 26 (6%) were grade 3 DD, and 8 (2%) were cannot determine. The 2016 Recommendations had superior discriminatory accuracy in predicting LVEDP (P<.001) but were not superior in predicting Tau. During median follow-up of 416 days (interquartile range: 5 to 2004 days), 54 patients (12%) died. Significant DD by 2016 Recommendations was associated with higher risk of mortality (P=.039, subdistribution HR1.85 [95% CI, 1.03-3.33]) in multivariable competing risk regression. CONCLUSIONS: The grading algorithm proposed by the 2016 LV diastolic dysfunction Recommendations detects elevated LVEDP and poor prognosis better than the 2009 Recommendations.

New Insights into Pericarditis: Mechanisms of Injury and Therapeutic Targets.

PURPOSE OF REVIEW: This review article aims to provide a contemporary insight into the pathophysiological mechanisms of and therapeutic targets for pericarditis, drawing distinction between autoinflammatory and autoimmune pericarditis. RECENT FINDINGS: Recent research has focused on the distinction between autoinflammatory and autoimmune pericarditis. In autoinflammatory pericarditis, viruses can activate the sensor molecule of the inflammasome, which results in downstream release of cytokines, such as interleukin-1, that recruit neutrophils and macrophages to the site of injury. Conversely, in autoimmune pericarditis, a type I interferon signature predominates, and pericardial manifestations coincide with the severity of the underlying systemic autoimmune disease. In addition, autoimmune pericarditis can also develop after cardiac injury syndromes. With either type of pericarditis, imaging can help stage the inflammatory state. Prominent pericardial delayed hyperenhancement on magnetic resonance imaging suggests ongoing inflammation whereas calcium on computed tomography suggests a completed inflammatory cascade. In patients with ongoing pericarditis, treatments that converge on the inflammasome, such as colchicine and anakinra, have proved effective in recurrent autoinflammatory pericarditis, though further clinical trials with anakinra are warranted. An improved understanding of the pathophysiological mechanisms of pericarditis helps unravel effective therapeutic targets for this condition.