Unveiling Cardiac Amyloidosis, its Characteristics, and Outcomes Among Patients With MR Undergoing Transcatheter Edge-to-Edge MV Repair.

BACKGROUND: Mitral regurgitation (MR) and cardiac amyloidosis (CA) both primarily affect older patients. Data on coexistence and prognostic implications of MR and CA are currently lacking. OBJECTIVES: This study sought to identify the prevalence, clinical characteristics, and outcomes of MR CA compared with lone MR. METHODS: Consecutive patients undergoing transcatheter edge-to-edge repair (TEER) for MR at 2 sites were screened for concomitant CA using a multiparametric approach including core laboratory 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy and echocardiography and immunoglobulin light chain assessment. Transthyretin CA (ATTR) was diagnosed by 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (Perugini grade 1: early infiltration; grades 2/3: clinical CA) and the absence of monoclonal protein, and light chain (AL) CA via tissue biopsy. All-cause mortality and hospitalization for heart failure (HHF) served as the endpoints. RESULTS: A total of 120 patients (age 76.9 ± 8.1 years, 55.8% male) were recruited. Clinical CA was diagnosed in 14 patients (11.7%; 12 ATTR, 1 AL, and 1 combined ATTR/AL) and early amyloid infiltration in 9 patients (7.5%). Independent predictors of MR CA were increased posterior wall thickness and the presence of a left anterior fascicular block on electrocardiography. Procedural success and periprocedural complications of TEER were similar in MR CA and lone MR (P for all = NS). After a median of 1.7 years, 25.8% had experienced death and/or HHF. MR CA had worse outcomes compared with lone MR (HR: 2.2; 95% CI: 1.0-4.7; P = 0.034), driven by a 2.5-fold higher risk for HHF (HR: 2.5; 95% CI: 1.1-5.9), but comparable mortality (HR: 1.6; 95% CI: 0.4-6.1). CONCLUSIONS: Dual pathology of MR CA is common in elderly patients with MR undergoing TEER and has worse postinterventional outcomes compared with lone MR.

Reverse Remodeling Following Valve Replacement in Coexisting Aortic Stenosis and Transthyretin Cardiac Amyloidosis.

BACKGROUND: Dual pathology of severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR) is increasingly recognized. Evolution of symptoms, biomarkers, and myocardial mechanics in AS-ATTR following valve replacement is unknown. We aimed to characterize reverse remodeling in AS-ATTR and compared with lone AS. METHODS: Consecutive patients referred for transcatheter aortic valve replacement (TAVR) underwent ATTR screening by blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) before intervention. ATTR was diagnosed by DPD and absence of monoclonal protein. Reverse remodeling was assessed by comprehensive evaluation before TAVR and at 1 year. RESULTS: One hundred twenty patients (81.8±6.3 years, 51.7% male, 95 lone AS, 25 AS-ATTR) with complete follow-up were studied. At 12 months (interquartile range, 7-17) after TAVR, both groups experienced significant symptomatic improvement by New York Heart Association functional class (both P<0.001). Yet, AS-ATTR remained more symptomatic (New York Heart Association ≥III: 36.0% versus 13.8; P=0.01) with higher residual NT-proBNP (N-terminal pro-brain natriuretic peptide) levels (P<0.001). Remodeling by echocardiography showed left ventricular mass regression only for lone AS (P=0.002) but not AS-ATTR (P=0.5). Global longitudinal strains improved similarly in both groups. Conversely, improvement of regional longitudinal strain showed a base-to-apex gradient in AS-ATTR, whereas all but apical segments improved in lone AS. This led to the development of an apical sparing pattern in AS-ATTR only after TAVR. CONCLUSIONS: Patterns of reverse remodeling differ from lone AS to AS-ATTR, with both groups experiencing symptomatic improvement by TAVR. After AS treatment, AS-ATTR transfers into a lone ATTR cardiomyopathy phenotype.

Prevalence and Outcomes of Cardiac Amyloidosis in All-Comer Referrals for Bone Scintigraphy.

The prevalence of cardiac amyloidosis (CA) in the general population and associated prognostic implications remain poorly understood. We aimed to identify CA prevalence and outcomes in bone scintigraphy referrals. Methods: Consecutive all-comers undergoing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic-acid (99mTc-DPD) bone scintigraphy between 2010 and 2020 were included. Perugini grade 1 was defined as low-grade uptake and grade 2 or 3 as confirmed CA. All-cause mortality, cardiovascular death, and heart failure hospitalization (HHF) served as endpoints. Results: In total, 17,387 scans from 11,527 subjects (age, 61 ± 16 y; 63.0% women, 73.6% cancer) were analyzed. Prevalence of 99mTc-DPD positivity was 3.3% (n = 376/11,527; grade 1: 1.8%, grade 2 or 3: 1.5%), and was higher among cardiac than noncardiac referrals (18.2% vs. 1.7%). In individuals with more than 1 scan, progression from grade 1 to grade 2 or 3 was observed. Among patients with biopsy-proven CA, the portion of light-chain (AL)-CA was significantly higher in grade 1 than grade 2 or 3 (73.3% vs. 15.4%). After a median of 6 y, clinical event rates were: 29.4% mortality, 2.6% cardiovascular death, and 1.5% HHF, all independently predicted by positive 99mTc-DPD. Overall, adverse outcomes were driven by confirmed CA (vs. grade 0, mortality: adjusted hazard ratio [AHR] 1.46 [95% CI 1.12-1.90]; cardiovascular death: AHR 2.34 [95% CI 1.49-3.68]; HHF: AHR 2.25 [95% CI 1.51-3.37]). One-year mortality was substantially higher in cancer than noncancer patients. Among noncancer patients, also grade 1 had worse outcomes than grade 0 (HHF/death: AHR 1.45 [95% CI 1.01-2.09]), presumably because of longer observation and higher prognostic impact of early infiltration. Conclusion: Positive 99mTc-DPD was identified in a substantial number of consecutive 99mTc-DPD referrals and associated with adverse outcomes.

Heart failure with preserved ejection fraction after left-sided valve surgery: prevalent and relevant.

AIMS: To investigate the epidemiological and prognostic relationship between heart failure with preserved ejection fraction (HFpEF) and left-sided valve surgery using all-cause mortality as a primary endpoint. METHODS AND RESULTS: We studied a total of 973 patients, of whom 673 had undergone left-sided valve surgery (time from surgery to enrolment 50 ± 30 months after valve surgery) and 300 patients with HFpEF without prior surgery served as control group. Among patients after surgery, 67.4% fulfilled all criteria of HFpEF according to current guideline recommendations, 20.6% had no heart failure (HF), and 12.0% had HF with mid-range or reduced ejection fraction (HFmrEF/HFrEF). During 83 ± 39 months of follow-up, a total of 335 (34.4%) patients died. Compared to surgical patients with no subsequent HF, patients with HFpEF and HFmrEF/HFrEF after surgery showed significantly higher all-cause mortality rates [hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.25-2.57, P = 0.001; and HR 1.86, 95% CI 1.16-2.98, P = 0.010, respectively]. This increased mortality rate was similar to the control HFpEF group without surgery (HR 2.05, 95% CI 1.38-3.02, P < 0.001). Results remained consistent after adjustment for clinical and imaging risk factors and when using the established HFA-PEFF risk score for HFpEF diagnosis. Notably, only 12.5% of HFpEF patients after surgery were diagnosed with HF despite regular follow-up visits by board-certified cardiologists. In contrast, 92.1% of HFmrEF/HFrEF patients after surgery were diagnosed correctly. CONCLUSIONS: Heart failure with preserved ejection fraction following left-sided valve surgery is highly prevalent, associated with unfavourable outcomes, but rarely recognized.