Prevalence of valvular heart disease in cardiac amyloidosis and impact on survival.

BACKGROUND: Limited data exists on the prognostic impact of valvular heart disease in cardiac amyloidosis (CA). We therefore sought to define the prevalence of valvular disease in patients with CA and assess the effects of significant valve disease on survival. METHODS: This multi-center retrospective cohort study included consecutive patients with confirmed transthyretin (TTR) or light chain (AL) amyloidosis. Echocardiographic data closest to the date of amyloid diagnosis was reviewed, and severity was graded according to ASE guidelines. Kaplan-Meier survival analysis was performed to compare survival between patients with moderate or greater valve disease against those with mild or less disease. RESULTS: We included 345 patients (median age 76 years; 73 % men; 110 AL, 235TTR). The median survival for the total patient cohort with cardiac amyloidosis was 2.92 years, with 30 % of patients surviving at five years after their diagnosis. Median survival comparing AL vs ATTR was 2.58 years vs 2.82 years (p = 0.67) The most common valvular abnormalities in the total cohort were mitral (62 %) and tricuspid (66 %).regurgitation There was a statistically significant difference in median survival between patients with no or mild MR compared to those with moderate or severe MR (2.92 years vs 3.35 years, p = 0.0047) (Fig. 5). There was a statistically significant difference in median survival in patients with no or mild TR compared to those with moderate or severe TR (3.35 years vs 2.3 years, p = 0.015). CONCLUSION: Our study demonstrates a significant prevalence of mitral and tricuspid regurgitation in CA, with patients with moderate to severe MR and TR having a poorer prognosis.

Limitations of Apical Sparing Pattern in Cardiac Amyloidosis: A Multicenter Echocardiographic Study.

BACKGROUND: Although impaired left ventricular (LV) global longitudinal strain (GLS) with apical sparing is a feature of cardiac amyloidosis (CA), its diagnostic accuracy has varied across studies. We aimed to determine the ability of apical sparing ratio (ASR) and most common echocardiographic parameters to differentiate patients with confirmed CA from those with clinical and/or echocardiographic suspicion of CA, but with this diagnosis ruled out. METHODS: We identified 544 patients with confirmed CA and 200 controls as defined above (CTRL Patients). Measurements from transthoracic echocardiograms (TTE) were performed using artificial intelligence software (Us2.AI, Singapore) and audited by an experienced echocardiographer. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic performance and optimal cutoffs for the differentiation of CA patients from CTRL Patients. Additionally, a group of 174 healthy subjects (Healthy CTRL) was included to provide insight on how Patients and Healthy controls differed echocardiographically. RESULTS: LV GLS was more impaired (-13.9 ± 4.6% vs -15.9 ± 2.7%, p < 0.0005) and ASR was higher (2.4 ± 1.2 vs 1.7 ± 0.9, p < 0.0005) in the CA group vs. CTRL Patients. Relative wall thickness and ASR were the most accurate parameters for differentiating CA from CTRL Patients (AUC: 0.77 and 0.74, respectively). However, even with the optimal cutoff of 1.67, ASR was only 72% sensitive and 66% specific for CA, indicating presence of apical sparing in 32% of CTRL Patients and even in 6% Healthy CTRLs. CONCLUSIONS: Apical sparing did not prove to be a CA-specific biomarker for accurate identification of CA, when compared to clinically similar controls with no CA.

Temporal trends and procedural safety of transcatheter mitral valve repair with mitraclip in patients with hypertrophic cardiomyopathy: Insights from the national inpatient sample.

Data on utilization and safety of mitral Transcatheter Edge-to-Edge Repair (TEER) among hypertrophic cardiomyopathy (HCM) patients is limited. Our study aimed to assess the national utilization, safety, and clinical outcomes of TEER procedures among HCM patients using a nationwide real-world cohort. HCM patients undergoing TEER hospitalizations between 2015-2020 were identified using ICD-10 (International Classification of Diseases, (ICD-10-CM/PCS). HCM-TEER and HCM No-TEER formed the two comparison groups. Demographic characteristics, baseline comorbidities, procedural complications, inpatient mortality, length of stay (LOS), and cost of hospitalization were compared between the propensity-matched cohorts. Numeric values of 10 or less were not reported per NIS data use agreements. A total of 39,625 weighted cases of TEER were identified from 2015-2020. Of the included patients, 335 patients had the HCM diagnosis. The median age of the HCM-TEER group was 74 (70-79) vs. 79 (72-85) for the no-TEER cohort. The TEER procedure was more frequently performed among Caucasians (86.57%) and females (53.73%). The TEER procedure among HCM patients had similar in-hospital mortality (Adjusted odds ratio: aOR 1.50, 95% CI [0.68-3.29]; p = 0.30) and net adverse cardiac events (NACE) (aOR 1.16, 95% CI [0.73-1.85]; p = 0.51). TEER among HCM was associated with higher odds of gastrointestinal/hematological (aOR 2.33, 95% CI [1.29-4.19]; p = 0.003) complications. However, the odds of cardiac complications (aOR 0.57, 95% CI [0.33-0.96]; p = 0.03) were not higher. The median length of stay was similar in both the groups (median: 2 vs. 2, p = 0.74), although TEER among HCM was associated with higher costs of hospitalization ($44729.36 vs. $40513.82, p < 0.01). TEER is a minimally invasive procedure and could be a safe option for symptomatic HCM patients with significant MR who are poor surgical candidates. Mitral TEER among HCM has been increasingly utilized in recent years in the United States more commonly in obstructive HCM and is associated with no difference in mortality and net adverse cardiac events but higher odds for gastrointestinal/hematological complications than non-HCM patients.

A systematic review and meta-analysis of left atrial strain in hypertrophic cardiomyopathy and its prognostic utility.

Despite advances in noninvasive imaging modalities to identify atrial fibrillation (AF) risk in Hypertrophic Cardiomyopathy (HCM), there is a paucity of evidence concerning the impact of low Left Atrial strain (LAS) on AF and major adverse cardiac events (MACE) incidence in these patients. This study investigated the diagnostic and prognostic significance of LAS in predicting AF and MACE in HCM. Findings revealed lower LA reservoir (MD: -11.79, 95% CI -14.83, -8.74; p<0.00001), booster (MD: -4.10, 95% CI -6.29, -1.91; p=0.0002), and conduit (MD: -7.52, 95% CI -9.39, -5.65; p<0.00001) strains in HCM patients versus healthy controls, and also indicated a significant association between low LA reservoir/conduit/booster strain and the development of new AF as well as MACE prevalence in HCM patients. The results from this study suggest the valuable role of LA strain in HCM and its utility in predicting the development of new AF and cardiac events in HCM patients.

5-Year Prospective Evaluation of Mitral Valve-in-Valve, Valve-in-Ring, and Valve-in-MAC Outcomes: MITRAL Trial Final Results.

BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective trial to evaluate the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with failed surgical bioprostheses or annuloplasty rings and severe mitral annular calcification treated with mitral valve-in-valve (MViV), valve-in-ring (MViR), or valve-in-mitral annular calcification (ViMAC). OBJECTIVES: The aim of this study was to evaluate 5-year outcomes among these patients. METHODS: A multicenter prospective study was conducted among patients at high surgical risk at 13 U.S. sites. Patients underwent MViV (n = 30), MViR (n = 30), or ViMAC (n = 31) and were followed annually for 5 years. Kansas City Cardiomyopathy Questionnaire scores were obtained at baseline and follow-up visits. Echocardiograms were analyzed at independent core laboratories. RESULTS: A total of 91 patients underwent transcatheter mitral valve replacement (February 2015 to December 2017). The mean age was 74.3 ± 8.9 years. At 5-year follow-up, the lowest all-cause mortality was observed in the MViV group (21.4%), 94.7% of patients were in NYHA functional class I or II, and the mean mitral gradient was 6.6 ± 2.5 mm Hg. The MViR and ViMAC groups had higher all-cause mortality (65.5% and 67.9%), most survivors were in NYHA functional classes I and II (50% and 55.6%), and mean mitral gradients remained stable (5.8 ± 0.1 and 6.7 ± 2.5 mm Hg). Significant improvements in Kansas City Cardiomyopathy Questionnaire scores were observed when all 3 arms were pooled. CONCLUSIONS: MViV, MViR, and ViMAC procedures were associated with sustained improvement of heart failure symptoms and quality of life among survivors at 5 years. Transcatheter heart valve function remained stable in all 3 groups. Patients treated with MViV had excellent survival at 5 years, whereas survival was lower in the MViR and ViMAC groups, consistent with underlying disease severity. Patients with more residual mitral regurgitation had higher mortality.

2-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Annular Calcification, Rings, and Bioprostheses.

BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study for valve-in-mitral annular calcification (ViMAC), mitral valve-in-ring (MViR), and mitral valve-in-valve (MViV) using balloon-expandable aortic transcatheter heart valves. Procedural outcomes beyond 1 year are not well described. OBJECTIVES: This study evaluated 2-year outcomes in ViMAC, MViR, and MViV in the MITRAL trial. METHODS: This multicenter prospective study enrolled patients with severe MAC, prior failed mitral annuloplasty ring repair, or prior failed bioprosthetic MV replacement who were at high surgical risk at 13 U.S. sites. RESULTS: Between February 1, 2015, and December 31, 2017, 91 patients were enrolled (31 with ViMAC, 30 with MViR, and 30 with MViV). In the ViMAC group, 2-year all-cause mortality was 39.3%, 66.7% were New York Heart Association (NYHA) functional class I-II, and mean MV gradient was 5.6 ± 2.0 mm Hg. In the MViR group, 2-year all-cause mortality was 50%, 65% were NYHA functional class I-II, and mean MV gradient was 6.5 ± 2.7 mm Hg. In the MViV group, 2-year all-cause mortality was 6.7%, 85% were NYHA functional class I-II, and mean MV gradient was 6.9 ± 2.4 mm Hg. At 2 years, all patients had ≤mild mitral regurgitation and survivors in all 3 arms showed sustained improvement in Kansas City Cardiomyopathy Questionnaire scores compared to baseline. CONCLUSIONS: Use of balloon-expandable aortic transcatheter heart valves in selected patients with severe MAC, failed annuloplasty ring, and bioprosthetic MV dysfunction is associated with improvements in symptoms, quality of life, and stable prosthesis function at 2-year follow-up. Between 1 and 2 years, the MViR group experienced higher mortality rates than the MViV and ViMAC groups.

A case series of desmoplakin cardiomyopathy: a mimic of viral myocarditis.

Background: Clinical features and imaging presentation of myocarditis can overlap with other inflammatory or arrhythmogenic cardiomyopathies. Desmoplakin (DSP) is an important structural cardiac protein. Mutations in the DSP gene are associated with a variant of arrhythmogenic right ventricular cardiomyopathy (ARVC). Interestingly, this distinct genetic cardiomyopathy can also present with a myocardial inflammation and fibrosis pattern that may mimic other forms of myocarditis including viral myocarditis, which can raise a clinical challenge. We report two cases of DSP cardiomyopathy, which were initially thought to represent coronavirus disease of 2019 (COVID-19) myocarditis. Case summary: First patient is a 21-your-old woman with no past medical history but family history of presumed 'viral myocarditis' and ventricular tachycardia in her brother. She presented with acute chest pain and elevated cardiac enzymes. She tested positive for COVID-19 and given the suspicion for possible COVID-19 related acute myocarditis, cardiac magnetic resonance imaging obtained and revealed regional wall motion abnormalities, several areas of subepicardial and pericardial late gadolinium enhancement (LGE). Ambulatory cardiac monitoring showed runs of non-sustained ventricular tachycardia and considering her family history of arrhythmogenic myocarditis, genetic testing was performed that was positive for a likely pathogenic heterozygous mutation of DSP gene. She declined the recommended implantable cardioverter defibrillator (ICD).Second patient is a 34-year-old physician with no significant past medical history who works at a COVID-19 unit and presented with syncope and was found to have ventricular tachycardia. Echocardiogram revealed severely dilated left ventricle and globally depressed systolic function with left ventricular ejection fraction of 20%. Coronary computed tomography angiography showed no evidence of coronary atherosclerosis. Cardiac magnetic resonance imaging revealed several areas of mid myocardial and pericardial LGE. Subcutaneous ICD was implanted and an endomyocardial biopsy had evidence of lymphocytic myocarditis and adipose tissue infiltration of the myocardium. Genetic testing revealed pathogenic heterozygous DSP mutation. He underwent epicardial ablation for the episodes of ventricular tachycardia despite medical therapy. He was able to return to work and has not had any further episodes of arrhythmia. Conclusion: Mutations in the DSP gene are associated with left dominant arrhythmogenic cardiomyopathy, which is a variant of ARVC. Beside left ventricular systolic dysfunction and ventricular tachyarrhythmias, carriers of these mutations may present with episodes of chest pain associated with elevated cardiac enzymes and cardiac imaging findings indistinguishable from other forms of acute myocarditis including viral myocarditis. Currently, there are no guidelines for diagnosis and treatment of this entity.

Management of Patients With Severe Mitral Annular Calcification: JACC State-of-the-Art Review.

Mitral annular calcification (MAC) is a common and challenging pathologic condition, especially in the context of an aging society. Surgical mitral valve intervention in patients with MAC is difficult, with varying approaches to the calcified annular anatomy, and the advent of transcatheter valve interventions has provided additional treatment options. Advanced imaging provides the foundation for heart team discussions and management decisions concerning individual patients. This review focuses on the prognosis of, preoperative planning for, and management strategies for patients with MAC.

Impact of Tafamidis on Survival in a Real-World Community-Based Cohort.

Tafamidis is the only therapy shown to improve survival in transthyretin cardiac amyloidosis (ATTR) based on randomized controlled trial data. We sought to evaluate the impact of tafamidis on survival in a real-world community-based cohort. This was a prospective observational cohort study that included consecutive patients with confirmed ATTR based on biopsy or TcPYP imaging. Baseline characteristics were compared between patients taking tafamidis vs not, and Kaplan-Meier survival analysis was performed to compare survival between these groups. We examined the reasons that ATTR patients were not on tafamidis. Of 107 ATTR patients, median age was 83.9 years, 79% were men, and 63 (59%) of them were on tafamidis. Demographics and baseline cardiovascular risk factors did not differ significantly between those on vs off tafamidis, although there was a higher proportion of NYHA Class III or IV heart failure in those off tafamidis (76% vs 57%, P < 0.01). The most common reasons patients were not on tafamidis included delays in obtaining the drug or financial barriers (59%) and NYHA Class IV heart failure (19.5%). Patients taking tafamidis had a significantly higher median survival compared to those not on tafamidis (median survival 6.70 vs 1.43 years, P < 0.0001). Our study demonstrates significantly improved survival in ATTR patients taking tafamidis. Barriers exist to tafamidis initiation including delayed access and affordability, and efforts should be made to improve patient access.

Prognostic Value of Venous Thromboembolism Risk Assessment Models in Patients with Severe COVID-19.

Introduction Severe novel corona virus disease 2019 (COVID-19) causes dysregulation of the coagulation system with arterial and venous thromboembolism (VTE). We hypothesize that validated VTE risk scores would have prognostic ability in this population. Methods Retrospective observational cohort with severe COVID-19 performed in NorthShore University Health System. Patients were >18 years of age and met criteria for inpatient or intensive care unit (ICU) care. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) and Caprini scores were calculated and patients were stratified. Results This study includes 184 patients, mostly men (63.6%), Caucasian (54.3%), 63 years old (interquartile range [IQR]: 24-101), and 57.1% of them required ICU care. Twenty-seven (14.7%) thrombotic events occurred: 12 (6.5%) cases of disseminated intravascular coagulation (DIC), 9 (4.9%) of pulmonary embolism, 5 (2.7%) of deep vein thrombosis, and 1 (0.5%) stroke. Among them, 86 patients (46.7%) died, 95 (51.6%) were discharged, and 3 (1.6%) were still hospitalized. "Moderate risk for VTE" and "High risk for VTE" by IMPROVE score had significant mortality association: (hazard ratio [HR]: 5.68; 95% confidence interval [CI]: 2.93-11.03; p < 0.001) and (HR = 6.22; 95% CI: 3.04-12.71; p < 0.001), respectively, with 87% sensitivity and 63% specificity (area under the curve [AUC] = 0.752, p < 0.001). "High Risk for VTE" by Caprini score had significant mortality association (HR = 17.6; 95% CI: 5.56-55.96; p < 0.001) with 96% sensitivity and 55% specificity (AUC = 0.843, p < 0.001). Both scores were associated with thrombotic events when classified as "High risk for VTE" by IMPROVE (HR = 6.50; 95% CI: 2.72-15.53; p < 0.001) and Caprini scores (HR = 11.507; 95% CI: 2.697-49.104; p = 0.001). Conclusion The IMPROVE and Caprini risk scores were independent predictors of mortality and thrombotic events in severe COVID-19. With larger validation, this can be useful prognostic information.

Prospective Study of TMVR Using Balloon-Expandable Aortic Transcatheter Valves in MAC: MITRAL Trial 1-Year Outcomes.

OBJECTIVES: The aim of this study was to evaluate 1-year outcomes of valve-in-mitral annular calcification (ViMAC) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial. BACKGROUND: The MITRAL trial is the first prospective study evaluating the feasibility of ViMAC using balloon-expandable aortic transcatheter heart valves. METHODS: A multicenter prospective study was conducted, enrolling high-risk surgical patients with severe mitral annular calcification and symptomatic severe mitral valve dysfunction at 13 U.S. sites. RESULTS: Between February 2015 and December 2017, 31 patients were enrolled (median age 74.5 years [interquartile range (IQR): 71.3 to 81.0 years], 71% women, median Society of Thoracic Surgeons score 6.3% [IQR: 5.0% to 8.8%], 87.1% in New York Heart Association functional class III or IV). Access was transatrial (48.4%), transseptal (48.4%), or transapical (3.2%). Technical success was 74.2%. Left ventricular outflow tract obstruction (LVOTO) with hemodynamic compromise occurred in 3 patients (transatrial, n = 1; transseptal, n = 1; transapical, n = 1). After LVOTO occurred in the first 2 patients, pre-emptive alcohol septal ablation was implemented to decrease risk in high-risk patients. No intraprocedural deaths or conversions to open heart surgery occurred during the index procedures. All-cause mortality at 30 days was 16.7% (transatrial, 21.4%; transseptal, 6.7%; transapical, 100% [n = 1]; p = 0.33) and at 1 year was 34.5% (transatrial, 38.5%; transseptal, 26.7%; p = 0.69). At 1-year follow-up, 83.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.1 mm Hg (IQR: 5.6 to 7.1 mm Hg), and all patients had ≤1+ mitral regurgitation. CONCLUSIONS: At 1 year, ViMAC was associated with symptom improvement and stable transcatheter heart valve performance. Pre-emptive alcohol septal ablation may prevent transcatheter mitral valve replacement-induced LVOTO in patients at risk. Thirty-day mortality of patients treated via transseptal access was lower than predicted by the Society of Thoracic Surgeons score. Further studies are needed to evaluate safety and efficacy of ViMAC.

Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes.

OBJECTIVES: The aim of this study was to assess 1-year clinical outcomes among high-risk patients with failed surgical mitral bioprostheses who underwent transseptal mitral valve-in-valve (MViV) with the SAPIEN 3 aortic transcatheter heart valve (THV) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial. BACKGROUND: The MITRAL trial is the first prospective study evaluating transseptal MViV with the SAPIEN 3 aortic THV in high-risk patients with failed surgical mitral bioprostheses. METHODS: High-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis due to failed surgical mitral bioprostheses were prospectively enrolled. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year). RESULTS: Thirty patients were enrolled between July 2016 and October 2017 (median age 77.5 years [interquartile range (IQR): 70.3 to 82.8 years], 63.3% women, median Society of Thoracic Surgeons score 9.4% [IQR: 5.8% to 12.0%], 80% in New York Heart Association functional class III or IV). The technical success rate was 100%. The primary performance endpoint in survivors was achieved in 96.6% (28 of 29) at 30 days and 82.8% (24 of 29) at 1 year. Thirty-day all-cause mortality was 3.3% and was unchanged at 1 year. The only death was due to airway obstruction after swallowing several pills simultaneously 29 days post-MViV. At 1-year follow-up, 89.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.6 mm Hg (interquartile range: 5.5 to 8.9 mm Hg), and all patients had MR grade ≤1+. CONCLUSIONS: Transseptal MViV in high-risk patients was associated with 100% technical success, low procedural complication rates, and very low mortality at 1 year. The vast majority of patients experienced significant symptom alleviation, and THV performance remained stable at 1 year.

Prospective Evaluation of TMVR for Failed Surgical Annuloplasty Rings: MITRAL Trial Valve-in-Ring Arm 1-Year Outcomes.

OBJECTIVES: The authors report 1-year outcomes of high-risk patients with failed surgical annuloplasty rings undergoing transseptal mitral valve-in-ring (MViR) with the SAPIEN 3 aortic transcatheter heart valve (THV). BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study evaluating transseptal MViR with the SAPIEN 3 aortic THV in high-risk patients with failed surgical annuloplasty rings. METHODS: Prospective enrollment of high-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis and failed annuloplasty rings at 13 U.S. sites. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year). RESULTS: Thirty patients were enrolled between January 2016 and October 2017 (median age 71.5 years [interquartile range: 67.0 to 76.8 years], 36.7% women, median Society of Thoracic Surgeons score 7.6% [interquartile range: 5.1% to 11.8%], 76.7% in New York Heart Association functional class III or IV). Technical success was 66.7% (driven primarily by need for a second valve in 6 patients). There was no intraprocedural mortality or conversion to surgery. The primary performance endpoint was achieved in 85.7% of survivors at 30 days (24 of 28) and 89.5% of patients alive at 1 year with echocardiographic data available (17 of 19). All-cause mortality at 30 days was 6.7% and at 1 year was 23.3%. Among survivors at 1-year follow-up, 84.2% were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.0 mm Hg (interquartile range: 4.7 to 7.3 mm Hg), and all had ≤1+ MR. CONCLUSIONS: Transseptal MViR was associated with a 30-day mortality rate lower than predicted by the Society of Thoracic Surgeons score. At 1 year, transseptal MViR was associated with symptom improvement and stable THV performance.

Cost-effectiveness Analysis of Anatomic vs Functional Index Testing in Patients With Low-Risk Stable Chest Pain.

Importance: Both noninvasive anatomic and functional testing strategies are now routinely used as initial workup in patients with low-risk stable chest pain (SCP). Objective: To determine whether anatomic approaches (ie, coronary computed tomography angiography [CTA] and coronary CTA supplemented with noninvasive fractional flow reserve [FFRCT], performed in patients with 30% to 69% stenosis) are cost-effective compared with functional testing for the assessment of low-risk SCP. Design, Setting, and Participants: This cost-effectiveness analysis used an individual-based Markov microsimulation model for low-risk SCP. The model was developed using patient data from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. The model was validated by comparing model outcomes with outcomes observed in the PROMISE trial for anatomic (coronary CTA) and functional (stress testing) strategies, including diagnostic test results, referral to invasive coronary angiography (ICA), coronary revascularization, incident major adverse cardiovascular event (MACE), and costs during 60 days and 2 years. The validated model was used to determine whether anatomic approaches are cost-effective over a lifetime compared with functional testing. Exposure: Choice of index test for evaluation of low-risk SCP. Main Outcomes and Measures: Downstream ICA and coronary revascularization, MACE (death, nonfatal myocardial infarction), cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of competing strategies. Results: The model cohort included 10 003 individual patients (median [interquartile range] age, 60.0 [54.4-65.9] years; 5270 [52.7%] women; 7693 [77.4%] White individuals), who entered the model 100 times. The Markov model accurately estimated the test assignment, results of anatomic and functional index testing, referral to ICA, revascularization, MACE, and costs at 60 days and 2 years compared with observed data in PROMISE (eg, coronary CTA: ICA, 12.2% [95% CI, 10.9%-13.5%] vs 12.3% [95% CI, 12.2%-12.4%]; revascularization, 6.2% [95% CI, 5.5%-6.9%] vs 6.4% [95% CI, 6.3%-6.5%]; functional strategy: ICA, 8.1% [95% CI, 7.4%-8.9%] vs 8.2% [95% CI, 8.1%-8.3%]; revascularization, 3.2% [95% CI, 2.7%-3.7%] vs 3.3% [95% CI, 3.2%-3.4%]; 2-year MACE rates: coronary CTA, 2.1% [95% CI, 1.7%-2.5%] vs 2.3% [95% CI, 2.2%-2.4%]; functional strategy, 2.2% [95% CI, 1.8%-2.6%] vs 2.4% [95% CI, 2.3%-2.4%]). Anatomic approaches led to higher ICA and revascularization rates at 60 days, 2 years, and 5 years compared with functional testing but were more effective in patient selection for ICA (eg, 60-day revascularization-to-ICA ratio, CTA: 53.7% [95% CI, 53.3%-54.0%]; CTA with FFRCT: 59.5% [95% CI, 59.2%-59.8%]; functional testing: 40.7% [95% CI, 40.4%-50.0%]). Over a lifetime, anatomic approaches gained an additional 6 months in perfect health compared with functional testing (CTA, 25.16 [95% CI, 25.14-25.19] QALYs; CTA with FFRCT, 25.14 [95% CI, 25.12-25.17] QALYs; functional testing, 24.68 [95% CI, 24.66-24.70] QALYs). Anatomic strategies were less costly and more effective; thus, CTA with FFRCT dominated and CTA alone was cost-effective (ICERs ranged from $1912/QALY for women and $3,559/QALY for men) compared with functional testing. In probabilistic sensitivity analyses, anatomic approaches were cost-effective in more than 65% of scenarios, assuming a willingness-to-pay threshold of $100 000/QALY. Conclusions and Relevance: The results of this study suggest that anatomic strategies may present a more favorable initial diagnostic option in the evaluation of low-risk SCP compared with functional testing.

Guideline-Based Statin Eligibility, Coronary Artery Stenosis and Cardiovascular Events in Patients with Stable Chest Pain: A Secondary Analysis of the PROMISE Randomized Clinical Trial.

BACKGROUND: Recommendations for preventive statin treatment in patients with stable chest pain may be difficult as symptoms can be unspecific. It is unclear if coronary CT angiography (CTA)-detected coronary artery disease (CAD) can optimize statin prescription. METHODS: In stable chest pain patients randomized to CTA in the PROMISE trial, statin eligibility was defined per 2018 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Primary outcome was a composite of death, myocardial infarction or unstable angina over 26 months median follow-up. Hazard ratios (HR) of non-obstructive (1-69% stenosis) and obstructive (≥70% stenosis) CAD for events were determined using Cox proportional hazard models. Calculated HR were then incorporated into the ACC/AHA pooled cohort equation (PCE) to revised ASCVD risk and assess re-classification of statin eligibility. RESULTS: Among 3986 patients (60.5 ± 8.2 years; 51% female), 72.9% (2904/3986) were statin eligible. Event rates in statin-eligible vs. ineligible patients were 3.3% vs. 2.3% (HR = 1.4 (95% CI 0.9-2.2), p = 0.142). Although the proportion of statin-eligible patients increased with CAD severity, 54% without CAD were statin eligible. Incorporating information on CAD into PCE reclassified 12.7% of patients (1.3% towards statin, 11.4% towards no statin). Similar results were found in stratified analysis of statin naïve patients (reclassification of 13.9%, 1.0% towards statin, and 12.9% towards no statin). As a result, revised ASCVD risk improved model discrimination in all patients (c-statistic: 0.59 (95 %CI 0.55-0.62) vs. 0.52 (95 %CI 0.49-0.56); p 0.001), while reducing statin use by 10.1% (62.7% vs. 72.9% statin eligible, p 0.001). CONCLUSION: In stable chest pain patients, integration of CAD into guideline recommendations was associated with greater accuracy to reclassify those at increased risk for incident events and a more efficient use of statins.