bluuebunny/crossref_metadata_2025 huggingface dataset:
3 year outcomes of permanent pacemaker implantation after alcoholic septal ablation
Authors: Grazina A , Ferreira V , Cardoso I , Garcia Bras P , Viegas J M , Aguiar Rosa S , Fiarresga A , Ramos R , Castelo A , Teixeira A R , Teixeira B , Jacinto S , Martins Oliveira M , Cacela D , Cruz Ferreira R
Published: October 2022

Introduction

Patients with hypertrophic obstructive cardiomyopathy (HOCM) that remain symptomatic despite optimized medical therapy are often submitted to alcohol septal ablation (ASA). One of the most frequent complications is the complete hear block (CHB), requiring permanent pacemaker (PPM) in variable rates, up to 20% of the patients. The long-term impact of PPM implantation in these patients remains unclear.

Objectives

This study aims to evaluate the long-term clinical outcomes in patients who implant PPM after ASA.

Methods

In a tertiary center, patients who underwent ASA were consecutively enrolled prospectively. Patients with previous PPM or implantable cardio-defibrillator were from this analysis. The groups with and without PPM implantation after ASA were compared regarding baseline characteristics, procedure data and 3-year primary and secondary endpoints.

Results

Between 2009 and 2020, 109 patients underwent ASA. 97 patients were included in this analysis (68% female, mean age 65.2 years-old). 16 patients (16.5%) required PPM implantation for CHB. In those, no vascular access, pacemaker pocket or pulmonary parenchyma complications were noted. The baseline characteristics regarding comorbidities, symptoms, echocardiographic and electrocardiographic findings were identical in the two groups, with statistically significant differences in the mean age (70.6y/o in the PPM group versus 64.1y/o) and in the beta-blocker therapy rates previously to the intervention (56% in the PPM group versus 84%). Procedure-related data showed higher creatine kinase (CK) peaks in the PPM group (1692U/L versus 1243U/L, p0.05), without significant differences in the alcohol dose (2.1ml in both groups, p0.33). At 3 years after ASA procedure, the primary endpoint (composite of all-cause mortality and all-cause re-hospitalization) showed a statistical tendency to a lower event rate in the group who implanted PPM (p-value 0.097, Graphic 1). The secondary endpoint (composite of all-cause mortality and cardiac cause re-hospitalization) did not show any significant statistical difference between the two groups (p-value 0.216, Graphic 2).

Conclusions

The long-term endpoint analysis suggests that the outcomes in patients who implant PPM after ASA are non-inferior to those who do not, with a tendency to a lower rate of the endpoint composite of all-cause mortality and all cause re-hospitalizations.

Funding Acknowledgement

Type of funding sources: None.
Change in left atrial function and volume predicts heart failure with preserved and reduced ejection fraction: the multi-ethnic study of atherosclerosis
Authors: Lim D , Varadarajan V , Quinaglia T , Pezel T , Wu C , Noda C , Heckbert S , Bluemke D , Ambale-Venkatesh B , Lima J
Published: October 2022

Aims

This study used cardiac magnetic resonance (CMR) imaging to investigate the relationship between longitudinal change in left atrial (LA) function and incident heart failure (HF), in a multi-ethnic population free of known cardiovascular disease at baseline.

Methods and results

In the Multi-Ethnic Study of Atherosclerosis (MESA), 2470 participants (60±9 years, 47% males), free at baseline of clinically recognized cardiovascular disease, had LA volume and function assessed with CMR imaging at baseline (2000–02) and 9.4±0.6 years later. Seventy three (3%) participants developed incident HF over 7.1±2.1 years; of these, 39 participants had preserved ejection fraction (HFpEF) and 34 participants had reduced ejection fraction (HFrEF). An annual decrease of 1-SD unit in peak LA strain (ΔLASmax) was most strongly associated with the risk of HFpEF (subdistribution HR=2.56, 95% confidence interval (CI) [1.34–4.90], P=0.004) and improved model reclassification and discrimination in predicting HFpEF (c-statistic=0.84, 95% CI [0.79–0.90]; NRI=0.34, P=0.01; IDI=0.02, P=0.02; x2=4.25, P=0.89) adjusting for event-specific risk factors and baseline LA parameters. An annual decrease of 1ml/m2 of pre-atrial LA volume index (ΔLAVipreA) was most strongly associated with the risk of HFrEF (subdistribution HR=1.88, 95% CI [1.44–2.45], P<0.001) and improved model reclassification and discrimination in predicting HFrEF (c-statistic=0.81, 95% CI (0.72–0.90); NRI=0.31, P=0.03; IDI=0.01, P=0.50; x2=15.4, P=0.08), adjusting for event-specific risk factors and baseline LA measures (Table 1).

Conclusion

In this multi-ethnic population free of clinical cardiovascular disease at baseline, ΔLASmax and ΔLAVipreA were associated with, and incrementally predictive of HFpEF and HFrEF respectively, after adjusting for event-specific risk factors and baseline LA measures.

Disclaimer

The views expressed in this abstract are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): National Heart, Lung and Blood InstituteNational Center for Advancing Translational Sciences
Representativeness of EXPLORER-HCM trial and prevalence of eligibility criteria for Mavacamten in a nationwide cohort
Authors: Brandao M , Goncalves Almeida J , Fonseca P , Faria R , Sousa O , Fonseca C , Fontes-Carvalho R
Published: October 2022

Introduction

The EXPLORER-HCM trial evaluated the safety and efficacy of Mavacamten, a cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy (HCM). Mavacamten improved symptoms, exercise capacity and left ventricular outflow tract (LVOT) obstruction. However, the proportion of patients eligible for this therapy in real practice remains unclear.

Purpose

To determine the prevalence of eligibility criteria for Mavacamten and to describe the profile of patients complying with EXPLORER-HCM criteria in a nationwide cohort.

Methods

Cross-sectional study including all HCM patients enrolled in a European country-based nationwide registry. Presence of EXPLORER-HCM inclusion [≥18 years, obstructive HCM (LVOT gradient ≥50 mmHg), left ventricular ejection fraction (LVEF) ≥55%, New York Heart Association (NYHA) class II–III] and exclusion criteria [syncope or sustained ventricular tachycardia with exercise] were analyzed.

Results

Of 1042 patients included in this analysis (57.8% male, mean age at diagnosis 52 years, 39.6% obstructive HCM), 45 met the EXPLORER-HCM inclusion criteria and, after applying exclusion criteria, 30 patients were eligible for therapy with Mavacamten.

Eligible patients were all Caucasian, mostly female (63.3%), with a mean age at diagnosis of 58±14 years. All patients presented with heart failure symptoms, and were mostly in NYHA class II (83.3%); 4 patients (13.3%) presented with atrial fibrillation. In the baseline echocardiogram, mean LVEF was 68±9%; mean interventricular septum thickness was 20±4 mm; most patients presented with systolic anterior motion of the mitral valve (96.7%) and mitral regurgitation (96.7%). In cardiac magnetic resonance imaging evaluation, maximal wall thickness was 22±4 mm and 76.9% had late gadolinium enhancement. A pathogenic or likely pathogenic HCM gene variant was identified in 5 patients (MYH7 and MYBPC3 gene mutations).

In this group, 86.2% of patients were treated with beta-blockers and 34.5% with calcium channel antagonists. Only 1 patient was on Disopyramide. Septal reduction techniques were used in 43.3% of patients: alcohol septal ablation and septal myectomy were performed in 7 (23.3%) and 6 (20.0%) patients, respectively. Cardioverter-defibrillators were implanted in 2 patients for primary prevention of sudden cardiac death, and 6 patients received a pacemaker for bradycardia indications.

Conclusion

Specific therapies remain an unmet need in HCM. In this large nationwide cohort, only 2.9% of patients were eligible for therapy with Mavacamten according to EXPLORER-HCM criteria. Among patients complying with the study criteria, invasive septal reduction therapies were offered to a high proportion of patients. Further real-world data are warranted to estimate the proportion of HCM patients that will benefit from Mavacamten.

Funding Acknowledgement

Type of funding sources: None.
Temporal trends, characteristics and comorbidities of patients with hypertrophic cardiomyopathy in Denmark from 2005 to 2018: a nationwide cohort study
Authors: Zoerner C R , Pallisgaard J L , Schjerning A M , Toennesen J , Jensen M K , Gislason G , Hansen M L
Published: October 2022

Background

The majority of patients with Hypertrophic cardiomyopathy (HCM) are mildly symptomatic or unaware of their condition, but some develop serious complications such as heart failure, atrial fibrillation (AF) as well as sudden cardiac death. Previous studies have suggested that HCM detection-rates in women are significantly lower than in men. This leads to diagnosis often being delayed to later stages of the disease in women, where symptoms are more severe. Further characterization of HCM patients to improve early detection of adverse outcomes and warning signs might improve long-term outcomes.

Purpose

To describe the characteristics of Danish patients diagnosed with HCM between 2005–2018 and determine trends and changes in these factors over time.

Methods

All patients aged 16 years or older with a diagnosis of HCM between the 1st of January 2005 and the 31st of December 2018 were identified in Danish nationwide administrative registers and included in the study.

Time trends were calculated, and differences analyzed using the Cochran-Armitage trend test and linear regression.

Results

A total of 3856 patients were diagnosed with HCM in the study period and included in the study. The median age at diagnosis was 68 years (IQR 56 and 78 years), 53% were male, and 44% were diagnosed with obstructive HCM, while the number of patients diagnosed with HCM each year overall increased. At the time of diagnosis, 22,3% patients were previously diagnosed with ischemic heart disease, 17% with AF, 7,5% with ischemic stroke, 13,6% with heart failure. Median age and gender distribution remained stable over time, while the proportion of obstructive HCM among the newly diagnosed decreased (p = <0.001) (Figure1). During the study period, there was a significant decrease in the prevalence of heart failure (p = <0.001), ischemic heart disease (p = <0.001), and chronic obstructive pulmonary syndrome (p = <0.001), while the prevalence of AF, hypertension and ischemic stroke remained stable (Figure 2).

Conclusion

Despite previous studies describing a gender gap in patients diagnosed with HCM, gender distribution was near equal in this cohort. The number of patients diagnosed with non-obstructive HCM is increasing and the prevalence of comorbidities such as heart failure, ischemic heart disease, and COPD decreased over time.

Whether these findings are the result of improved early detection of HCM warrants further research and examination.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Herlev-Gentofte Hospital, Denmark
Outcomes in hypertrophic obstructive cardiomyopathy patients undergoing non-cardiac surgery-a nationwide analysis
Authors: Victor V , Abumoawad A , Ibrahim F , Barssoum K
Published: October 2022

Introduction

Patients with hypertrophic obstructive cardiomyopathy (HOCM) have a unique pathophysiological profile that increases their chances of having adverse events in the postoperative period following surgical procedures. Owing to the rarity of the disease, few studies are available for assessing readmission risk in HOCM patients undergoing noncardiac surgical procedures.

Purpose

Our study aimed to assess 30-day readmission rates and causes for readmissions among HOCM patients who had undergone noncardiac surgeries in hospitals across the United States (US).

Methods

We used appropriate International Classification of Diseases Code, 10th Revision Clinical Modification (ICD-10-CM) codes to identify patients who had been admitted for non-cardiac surgeries between January 2016 and December 2019 based on data from the National Readmissions Database (NRD). The NRD is a publicly available all-payer in-patient database sponsored by the Agency for Healthcare Research and Quality, containing discharge data from approximately 18 million discharges each year, accounting for 61.8% of the total US resident population. Patients were subdivided into two sub-groups based on the presence or absence of HOCM. 30-day readmission rates and causes of readmissions were compared between both groups. STATA version 17 (College Station,TX: StataCorp LLC) was used for statistical analyses.

Results

A total of 5,497,134 patients out of whom 2,089 had HOCM were identified and included for analysis. Patients with HOCM had statistically significant higher rates of readmissions for central nervous system related complications such as stroke or transient ischemic attack (TIA), cardiogenic shock, acute heart failure, unspecified iatrogenic cardiac complications, acute kidney injury, sepsis in addition to higher rates of post op respiratory failure, acute myocardial infarction and major adverse cardiovascular and cerebrovascular events (MACCE) during the index admission when compared to the other subgroup.

Conclusion

Our study, despite being retrospective in nature, is one of the largest to date assessing readmission risk in HOCM patients undergoing noncardiac surgeries. Similar to previous studies, HOCM patients have higher rates of readmissions and MACCE in the 30-day period following noncardiac surgical procedures. In light of these findings, shared medical decision making and appropriate counseling regarding complications in the postoperative period will be necessary for HOCM patients who undergo noncardiac surgical procedures.

Funding Acknowledgement

Type of funding sources: None.
Influence of novel risk markers on defibrillator implantation in hypertrophic cardiomyopathy
Authors: Procter W T C , Husselbury T , Michailidou S , Dhinoja M B , Petersen S E , O'Mahony C , Mohiddin S A , Malcolmson J W
Published: October 2022

Background/Introduction

To guide implantable defibrillator (ICD) use in hypertrophic cardiomyopathy (HCM), European Society of Cardiology (ESC) guidelines recommend using individualised sudden death (SCD) risk scores based on quantitative clinical data. Newly published American guidelines are based on the accumulation of binary risk markers, which include imaging-based novel risk markers (NRMs) that were absent from the development of the ESC's algorithm. These NRMs are ejection fraction <50%, apical aneurysm, and extensive late gadolinium enhancement on cardiac magnetic resonance (CMR) imaging.

Purpose

To assess how NRMs may have altered ICD prescription across ESC-based SCD risk status prior to publication of current American guidance.

Methods

We examined electronic records (2013–2020) of a subset of HCM patients with contemporaneous (within 12 months) CMR and echocardiography data for NRMs, ESC risk status, and ICD prescription. Differences in categorical data were assessed by Fisher's exact test.

Results

We studied 334 HCM patients (74% male; age: 58±14 years), of whom 83 (25%) were referred for ICD. ESC risk status was considered low, medium (4–6% 5-year SCD risk), or high in 264, 26, and 20 patients, for whom ICDs were recommended in 40 (15%), 20 (77%), and 18 (90%) patients, respectively. In patients with low SCD risk status, rate of ICD recommendation was significantly higher when ≥1 NRMs were present (34/126 – 27% vs. 0 NRMs: 6/138 – 4%; p<0.0001). NRMs did not appear to influence ICD recommendation in patients with medium (≥1 NRMs: 14/17 – 82% vs. 0 NRMs: 6/9 – 67%; p=0.6) or high (≥1 NRMs: 14/15 – 93% vs. 0 NRMs: 4/5 – 80%; p=0.4) SCD risk status (Figure 1). NRMs were less frequent in low risk patients than in high risk patients (126/264 – 48% vs. 15/20 – 75%; p<0.05), suggesting interaction between ESC status and NRMs (Figure 2).

Conclusion

NRMs have disproportionate influence on ICD prescription in low ESC risk HCM patients. However, NRMs are not independent of ESC risk status, suggesting iterative development of the ESC's algorithmic approach will be the most effective way of predicting SCD.

Funding Acknowledgement

Type of funding sources: None.
Association between obesity and hypertrophic cardiomyopathy phenotype, validation in a latin american cohort
Authors: Quiroga A , Zonis L , Veron L F , Casabe J H , Moukarzel J A , Banchio Dal Bo J , Fanilla M , Cutine P , Litwak N , Fernandez A
Published: October 2022

Objectives

Hypertrophic Cardiomyopathy (HCM) is the most common genetic cardiomyopathy. The influence of obesity on the disease phenotype is not well established. A recent publication sought to answer this gap. Our objective is to assess the relationship of a obesity on the phenotype of our cohort and compare it to the published literature.

Methods

We performed a retrospective observational study of consecutive patients diagnosed with HCM at a single center in Argentina. We included 1331 patients between March 1993 and December 2021. We excluded patients <18 years of age, metabolic diseases & syndromes and patients who were lost on follow up. We defined Obesity as a body mass index ≥30 kg/m2.

Results

1168 patients had available data for analysis. 54 (10.4%) patients were obese. Mean age was 54±28 years and 33 (61%) were male. Average maximal left ventricular wall thickness (LVWT) in this group was 20 mm ± 5 mm. When comparing obese vs non-obese patients we found no statistically significant differences for gender, age, family history of HCM, family history of sudden death (SD), previous VF/VT/NSVT, ESC low, intermediate or high risk for SD groups, fibrosis, apical aneurism, LV diameter, maximum LVWT, high risk genetic mutation, abnormal BP response to exercise, device implant, septal alcohol ablation, reduced EF on follow up, nor death/HF/Stroke/AICD appropriate therapy/AF development. We did find that obese patients had less unexplained syncope (6% vs 13%, OR 0.43, p=0.03), had more frequently an NYHA > III/IV (15.3% vs 8.9%, OR 1.8, p=0,03), a trend to having less frequently a LVWT >30 mm (3.5% vs 8.1%, OR 0.41, p=0.07) but more frequently had systolic anterior motion of the mitral valve on echocardiography (45% vs 34%, OR 1.58, p=0.04). We noted a trend to being more frequently indicated LV myectomy (9.2% vs 5%, OR 1.9, p=0,07) and significantly having elevated ultrasensitive troponin I (7.8% vs 3.7%, OR 2.2, p=0,04).

Conclusions

We found that obese patients from our cohort, as described in other series, had more advanced symptoms. In our set of obese patients they were more frequently sent to myectomy rather than alcohol septal ablation as described in other series. AF was not more prevalent among our obese patients and maximum wall thickness and fibrosis were not higher either. We did find that obese patients had more frequently elevated biomarkers. As HCM is so frequent it is important to characterize cohorts and compare data.

Funding Acknowledgement

Type of funding sources: None.
Natural history and clinical parameters of chemotherapy-induced dilated cardiomyopathy
Authors: Lalario A , Del Mestre E , Lo Casto M , Nuzzi V , Manca P , Bromage D , Barbati G , Merlo M , Sinagra G , Cannata A
Published: October 2022

Background

Chemotherapy-induced dilated cardiomyopathy (CI-DCM) is a well-recognized phenotype of non-ischemic dilated cardiomyopathy (DCM), characterized by poor outcomes. However, a detailed comparison between idiopathic DCM (iDCM) and CI-DCM is still lacking.

Methods

All consecutive DCM patients enrolled in the Trieste Muscle Heart Disease Registry were analyzed. CI-DCM and iDCM were defined according to current recommendations. The primary study outcome measure was all-mortality death and secondary outcomes were a) a composite of cardiovascular death/heart-transplantation/ventricular-assist-device implantation, and b) major ventricular arrhythmias.

Results

The study included 551 patients (499 iDCM and 52 CI-DCM). At enrolment, compared to iDCM, CI-DCM patients were older (51±14 years vs 58±3 years respectively, p<0.001) and had a higher left ventricular ejection fraction (35%±10 vs 32%±9, p=0.03). Over a median follow-up of 90 months (IQR 54–140 months), CI-DCM patients had a higher incidence of all-cause mortality compared to iDCM (36.5% vs 8.4% in CI-DCM and iDCM respectively, p<0.001), while the incidence of major ventricular arrhythmias was higher in the iDCM group compared to CI-DCM (4% vs 0%, in CI-DCM and iDCM respectively, p=0.03). The risk of the composite outcome was comparable between the two groups (p=0.91). At Cox multivariable analysis, the diagnosis of CI-DCM emerged as independently associated to primary outcome (HR 6.42, 95% CI 2.52–16.31, p<0.001).

Conclusions

In a well-selected DCM cohort, patients with a chemotherapy-induced aetiology had a higher incidence of all-cause mortality compared to iDCM. Conversely, the incidence of life-threatening ventricular arrhythmic events was higher among patients with iDCM.

Funding Acknowledgement

Type of funding sources: None.
The joint role of collagen turn-over biomarkers and late gadolinium enhancement to predict cardiovascular outcome in nonischemic dilated cardiomyopathy
Authors: Zlibut A , Agoston R , Orzan R I , Muresan I D , Horvat D , Agoston-Coldea L
Published: October 2022

Background

Myocardial scarring is a primary pathogenetic process in nonischemic dilated cardiomyopathy (NIDCM) which is responsible for progressive cardiac remodeling and heart failure, severely impacting the survival of these patients. Although several collagens turn-over biomarkers have been associated with myocardial fibrosis, their clinical utility is still limited. Late gadolinium enhancement (LGE) determined by cardiac magnetic resonance imaging (CMR) has become a feasible method to detect myocardial replacement fibrosis.

Purpose

We sought to evaluate the association between collagen turn-over biomarkers and replacement myocardial scarring by CMR and, also, to test their ability to predict outcome in conjunction with LGE in patients with NIDCM.

Method

We conducted a prospective study on 194 patients (48.7±14.3 years of age; 74% male gender) with NIDCM. CMR was used to determine the presence and extent of LGE. Several collagen turn-over biomarkers were determined at the diagnosis, comprising galectin-3 (Gal3), procollagen type I carboxy-terminal pro-peptide (PICP) and N-terminal pro-peptide of procollagen type III (PIIINP). A composite outcome (all-cause mortality, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. Of all, 17% (n=33) of patients reached the outcome: all-cause mortality (n=6), malignant ventricular tachyarrhythmia (n=14) and HF hospitalization (n=13).

Results

Gal3, PICP and PIIINP were considerably increased in those with LGE+ (p<0.001), being also directly correlated with LGE mass (r2=0.42; r2=0.44; r2=0.31; all p<0.001). Receiver operating characteristic (ROC) analysis revealed significant ability to diagnose LGE, with area under the ROC: 0.816 for Gal3, 0.705 for PICP, and 0.757 for PIIINP (all p<0.0001). Kaplan-Meier analysis showed that at a threshold of >13.8 ng/dL for Gal3 and >97 ng/dL for PICP, they significantly predicted the outcome (HR=2.66, p<0.001; HR=1.93, p<0.002). Moreover, for a combined model of LGE+/Gal3+/PICP+, time-to-event analysis demonstrated the highest ability to predict composite outcome, as compared to any other models (p=0.004). Nevertheless, in multivariate analysis, after adjustment for covariates, only LGE+ and Gal3+ remained independent predictors for outcome (p=0.008; p=0.04).

Conclusion

In patients with NIDCM, serum collagen turn-over biomarkers such as Gal3, PICP and PIIINP are closely related to the presence and extent of LGE and can significantly predict cardiovascular outcome. The joint use of LGE with Gal3 and PICP significantly improved outcome prediction.

Funding Acknowledgement

Type of funding sources: None.
Different prognosis of ARVC patients between DSG2 and PKP2 variant carriers
Authors: Sonoda K , Nagase S , Aiba T , Kato K , Shiga T , Kusano K , Horie M , Ohno S
Published: October 2022

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy mainly caused by desmosomal gene variants. In Europe and North America, pathogenic variants in PKP2 were identified in most of the ARVC patients. On the other hand, we have reported that the genetic backgrounds of ARVC in Japanese were different from those in European; pathogenic variants in DSG2 were predominant in Japanese. Genotype-phenotype correlations, however, have not been clarified yet.

Purpose

In this study, we aimed to examine whether the genotype affect the phenotype and outcome in Japanese ARVC patients.

Methods and results

This study included 167 Japanese ARVC patients who received genetic testing (128 males [77%]). Their median age at diagnosis was 44 [24–55] years old and median follow-up duration was 10 [4–21] years. We found 90 patients with pathogenic variants: 52 in DSG2 (31%), 30 in PKP2 (18%), 3 in DSP (1.8%), 1 in DSC (0.6%), 1 in JUP (0.6%) and 3 in DES (1.8%). The age of the first sustained ventricular arrhythmia (SVT) were older in the patients with DSG2 than those with PKP2 variants (48±15 years vs. 35±15 years, P=0.008) but younger in DSG2 variant carriers at the first hospitalization for heart failure (41 [22–61] years vs. 67 [61–74] years, P=0.03). The left ventricular ejection fractions of DSG2 variant carriers were significantly lower at diagnosis than that of PKP2 (52 [41–60] % vs. 61 [56–66] %, P=0.002). Kaplan-Meier survival curve for lethal arrhythmic events including SVT, ventricular fibrillation and sudden death revealed that the event rate of DSG2 variant carriers was significantly lower than that of PKP2 (log-rank test, P=0.02) (Fig. 1).

Among 11 patients who had both SVT and hospitalizations for HF, 7 PKP2 variant carriers had SVT first, then, hospitalized for HF (48 [35–53] years and 67 [55–71] years, P=0.02). Contrary, the clinical course of 4 DSG2 variants carriers were different from those with PKP2 (54 [40–68] years for SVT and 65 [56–70, P=0.1] years for HF) (Fig. 2).

Conclusion

The patients with DSG2, which is the major causative gene for ARVC in Japanese, show different phenotype and outcome from those with PKP2. We should examine the effect of variants on the prognosis of ARVC patients in more large population including various ethnics.

Funding Acknowledgement

Type of funding sources: None.
Global longitudinal strain and quantitative sensory testing in pre-symptomatic patients with mutation for transthyretin amyloidosis
Authors: Canciello G , Tozza S , Lombardi R , Nolano M , Todde G , Severi D , Borrelli F , Acampa W , Esposito G , Manganelli F , Losi M A
Published: October 2022

Background

Hereditary transthyretin (ATTRv) amyloidosis is a rare, autosomal dominant, and devastating disease. If untreated, the disease is fatal within 4–15 years from onset.

Thus, diagnosis in the early stages of ATTRv amyloidosis is crucial to start treatment and to prevent or delay disease progression. However, the diagnosis of symptomatic ATTRv amyloidosis in TTR gene mutation carriers may be challenging.

Purpose

We aimed identifying early indexes of cardiac and/or neurological involvement in pre-symptomatic subjects (carriers) harboring a TTR gene mutation.

Methods

Eight TTR-mutation carriers (mean age 51±9 years, 5 males) constituted the study populations. Mutations identified were: Val30Met in 4, and Phe64Leu in the remaining 4 patients. Patients underwent tactile and thermal quantitative sensory testing (QST), 99mTc-labeled bisphosphonate (HMDP) scintigraphy with the evaluation of Perugini score, and comprehensive echocardiogram with evaluation of global longitudinal strain (GLS).

Results

Table 1 reports results in overall patients. PADO indicates predicted age of disease onset. MWT indicates maximal wall thickness at echocardiography.

There was a strong and inverse correlation between the °C degree at HPT and GLS (r=−0.790; p=0.02, demonstrating that a worse HPT corresponded a better GLS (Figure 1).

Conclusion

GLS and QST findings support an early involvement of heart and small nerve fibers even many years before the PADO. Interestingly, cardiac impairment seems to not parallel that of small nerve fibers. An inhomogeneous accumulation of fibrils, as well possible different pathophysiological mechanisms in heart and nerve fibers, might result in a variable organ impairment at least in the earliest stage of disease.

Our observation needs to be tested in a wider population with such a rare disease.

Funding Acknowledgement

Type of funding sources: None.
Two-dimensional speckle-tracking echocardiography in tafamidis-treated patients with transthyretin amyloid cardiomyopathy: a glimmer of hope for viable therapy monitoring?
Authors: Rettl R , Duca F , Binder C , Dachs T , Cherouny B , Camuz Ligios L , Mann C , Schrutka L , Dalos D , Charwat-Resl S , Badr Eslam R , Kastner J , Bonderman D
Published: October 2022

Background

Treatment with Tafamidis in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) has been shown to have beneficial effects on the left ventricle (LV), as assessed by cardiac magnetic resonance (CMR) imaging. Although CMR represents the gold standard among imaging modalities, its limited availability in clinical practice makes it unfeasible for routine therapy monitoring.

Purpose

We aimed to determine Tafamidis-induced changes using two-dimensional (2D) speckle-tracking echocardiography and to identify echocardiographic imaging parameters that could be used for specific therapy monitoring.

Methods

We subjected a series of ATTR-CM patients to transthoracic echocardiography (TTE) at baseline and follow-up and compared patients treated with Tafamidis 61mg once daily (QD) to a historical control cohort treated with Tafamidis 20mg QD, as well as to a historical treatment-naïve control cohort reflecting the natural course of the disease.

Results

Patients receiving Tafamidis 61mg (n=62) or 20mg (n=21) QD showed stable measurements at follow-up [61mg: 8.5 months, 20mg: 7.0 months] in LV global longitudinal strain (GLS) (61mg: −11.75% vs. −11.58%, p=0.534; 20mg: −10.61% vs. −10.12%, p=0.309), right ventricular (RV) GLS (61mg: −14.18% vs. −13.72%, p=0.377; 20mg: −14.53% vs. −13.99%, p=0.452) and left atrial (LA) reservoir strain (LASr; 61mg: 8.80% vs. 9.42%, p=0.283; 20mg: 8.23% vs. 8.67%, p=0.589), whereas treatment-naïve ATTR-CM patients (n=54) had clear signs of disease progression at the end of the observation period [10.5 months; LV-GLS: −11.71% vs. −10.59%, p=0.001; RV-GLS: −14.36% vs. −12.99%, p=0.038; LASr: 10.67% vs. 8.41%, p=0.005]. Between-group comparison at follow-up revealed beneficial effects of Tafamidis 61mg on LASr (p=0.003), LV-GLS (p=0.030) and interventricular septum (IVS) thickness (p=0.006), resulting in clinical benefits (six-minute walk distance (6-MWD): p=0.006, NT-proBNP: p≤0.001), while patients treated with Tafamidis 20mg QD showed positive effects on LASr (p=0.039) but no differences in LV-GLS (p=0.274), IVS thickness (p=0.068) and clinical status (6-MWD: p=0.124, NT-proBNP: p=0.053) compared to the natural course.

Conclusion

Treatment with Tafamidis 61mg in ATTR-CM patients delays the increase in IVS thickness and the deterioration of LA and LV longitudinal function, resulting in significant clinical benefits compared with natural history. Serial TTE with 2D speckle-tracking imaging may be appropriate for disease-specific therapy monitoring.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): This work was supported by the Pfizer Inc. However, Pfizer Inc. did not have influence on study design, data processing, or statistical analysis.
Prevalence of amyloid transthyretin cardiomyopathy in elderly subjects from the general population: first results from the CATCH study
Authors: Aimo A , Vergaro G , Moscardini S , Puccianti D , Castiglione V , Gentile F , Fabiani I , Barison A , Agazio A , Picerni A , Poggianti E , Taddei C , Arzilli C , Passino C , Emdin M
Published: October 2022

Background

Amyloid transthyretin cardiomyopathy (ATTR-CM) has become treatable. Wild-type ATTR-CM is an age-related disorder. Establishing the exact prevalence of ATTR-CM in elderly subjects from the general population may be useful for healthcare providers and policy makers alike.

Methods

The Characterizing the burden of Amyloid Transthyretin CardiomyopatHy in the elderly (CATCH) study is a population screening on all subjects aged ≥65 years followed by general practitioners working in a part of Tuscany (Italy) where there is no cluster of variant ATTR. The study started on March 12, 2021 and is ongoing. The first step of the evaluation includes clinical history and physical examination, electrocardiogram, transthoracic echocardiogram, and blood sampling with measurement of N-terminal pro-B-type natriuretic peptide and high-sensitivity (hs) troponin T. The following elements are searched: 1) any clinical red flag of amyloidosis (history of carpal tunnel syndrome, lumbar spine stenosis, etc.), 2) interventricular septal thickness ≥12 mm or other echocardiographic red flags, 3) hs-troponin T higher than the upper reference limit (14 ng/L). Patients with any of these elements are referred to a second step including diphosphonate scintigraphy and the search for a monoclonal protein in the serum and urine. The standard diagnostic workup for CA is then followed until the diagnosis is confirmed or discarded.

Results

As of October 13, 2021, 514 subjects ≥65 years have been evaluated for possible participation. Among them, 135 (26%) could not be contacted, were reluctant to enter the study, died before being contacted, or were bedridden. Out of the other 379 subjects, 329 (87%) have already undergone the first step. Forty percent of individuals (n=132) have been referred to the second step. Thirteen subjects have declined (10%); 69 patients have undergone diphosphonate scintigraphy and the search for a monoclonal protein (while the other 50 are awaiting these exams). Two subjects showed an intense myocardial uptake of the diphosphonate tracer (Perugini score 2–3) and no monoclonal protein, and were then diagnosed with ATTR-CM. They were both women, aged 83 and 78 years, both mildly symptomatic for dyspnea (New York Heart Association II) and with unexplained hypertrophy. The search for TTR gene mutation was negative in the first case and is still ongoing in the second. Based on these preliminary data, the prevalence of ATTR-CM in the elderly population can be calculated as 2/266=0.8% (Figure 1).

Conclusions

The CATCH study is expected to enroll at least 1,000 subjects and will provide the first data on the epidemiology of ATTR-CM in elderly subjects. Based on an interim analysis, almost 1 in 100 individuals ≥65 years has ATTR-CM.

Funding Acknowledgement

Type of funding sources: None.
Multi-imaging characterisation of cardiac phenotype in different types of amyloidosis
Authors: Ioannou A , Patel R K , Razvi Y , Porcari A , Knight D , Martinez-Naharro A , Kotecha T , Venneri L , Chacko L , Hawkins P N , Gillmore J D , Fontana M
Published: October 2022

Background

Bone scintigraphy is extremely valuable when assessing patients with suspected cardiac amyloidosis (CA), but the clinical significance and associated phenotype of different degrees of myocardial tracer uptake across different types of amyloidosis is yet to be defined.

Purpose

We sought to define the phenotypes of patients with varying degrees of cardiac uptake on bone scintigraphy, across multiple types of systemic amyloidosis using extensive characterisation comprising of biomarkers, echocardiographic and cardiac magnetic resonance (CMR) imaging.

Methods

A total of 296 patients (117 immunoglobulin light-chain [AL] amyloidosis, 165 transthyretin [ATTR] amyloidosis, 7 apolipoprotein-A1-amyloidosis [AApoAI],and 7 apolipoprotein-A4-amyloidosis [AApoA4]) underwent deep characterisation of their cardiac phenotype.

Results

AL-amyloidosis patients with grade 0 myocardial radiotracer uptake spanned the spectrum of CMR findings from no evidence of CA to characteristic features of CA, while AL-amyloidosis patients with grade 1–3 always produced characteristic CMR features. In ATTR-amyloidosis the CA burden strongly correlated with myocardial tracer uptake (correlation between bone scintigraphy cardiac uptake and CMR derived extracellular volume: R=0.88, 95% CI [0.84–0.91], P<0.001), except in patients with the Ser77Tyr variant. AApoAI-amyloidosis presented with grade 0–1 myocardial tracer uptake, and unique features of disproportionate right sided involvement such as disproportionate right ventricular (RV) and right atrial uptake on bone scintigraphy, RV free wall thickening, and tricuspid valve thickening and dysfunction. Within our cohort, AApoAIV-amyloidosis always presented with grade 0 myocardial tracer uptake, and characteristic features of CA on CMR. All AL-amyloidosis patients with grade 1 myocardial tracer uptake had characteristic CMR features of CA (n=48, 100%), while only ATTR-amyloidosis grade 1 patients with the Ser77Tyr variant had characteristic features of CA on CMR (n=5, 11.4%). Following the exclusion of Ser77Tyr and AApoAI, a CMR showing characteristic features of CA or an extracellular volume >0.40 in a patient with grade 1 myocardial tracer uptake had a sensitivity and specificity of 100% for diagnosing AL-amyloidosis.

Conclusion

Deep characterisation of the cardiac phenotype in different types of amyloidosis, across a range of bone scintigraphy cardiac uptake grades has identified clear differences between each amyloidosis type. The distinctive characteristics in each cohort has allowed the development of a diagnostic pathway to help define the diagnostic differentials and the clinical phenotype in each individual patient, following comprehensive assessment with bone scintigraphy and CMR.

Funding Acknowledgement

Type of funding sources: None.
Unveiling cardiac amyloidosis, its characteristics and outcomes among patients with mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair
Authors: Nitsche C , Dona C D , Heitzinger G , Mascherbauer K M , Kammerlander A K , Dannenberg V D , Halavina K H , Traub-Weidinger T T W , Puchiner J P , Lamm G L , Hengstenberg C H , Fontana M F , Goliasch G G , Mascherbauer J M
Published: October 2022

Background

Mitral regurgitation (MR) and cardiac amyloidosis (CA) both primarily affect older patients. Data on co-existence and prognostic implications of MR and CA are currently lacking.

Purpose

We aimed to identify prevalence, clinical characteristics and outcomes of MR-CA compared to lone MR.

Methods

Consecutive patients undergoing transcatheter edge-to-edge repair (TEER) for MR were screened for concomitant CA at two Austrian centers using a multi-parametric approach including core-lab 99mTc-DPD bone scintigraphy and echocardiography, and immunoglobulin light-chain assessment. Transthyretin-CA (ATTR) was diagnosed by DPD (Perugini Grade-1: early infiltration; Grades-2/3: clinical CA) and absence of monoclonal protein, and light-chain-(AL)-CA via tissue biopsy. Mass spectroscopy was performed in case of conflicting immunohistochemical results. All-cause mortality and hospitalization for heart failure (HHF) served as composite endpoint.

Results

In total, 120 patients (76.9±8.1 years, 55.8% male) were recruited. Clinical CA was diagnosed in n=14 (11.7%; 12 ATTR, 1 AL, 1 combined ATTR/AL), and early amyloid infiltration in n=9 (7.5%). MR-CA had higher troponin levels, thicker left ventricular walls, and a higher prevalence of carpal tunnel syndrome and left anterior fascicular block compared to lone MR (all p<0.05). Independent predictors of MR-CA were increased posterior wall thickness, and presence of left anterior fascicular block on ECG. Procedural success (MR reduction ≥1 grade) and periprocedural complications of TEER were similar in MR-CA and lone MR (p for all=n.s.).

After a median of 1.7 years, 25.8% had experienced death and/or HHF. MR-CA had worse outcomes compared to lone MR with regard to the composite endpoint (HR 2.2, 95% confidence interval [95% CI] 1.0–4.7, p=0.039), 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; Graphical abstract).

Conclusions

Dual pathology of MR-CA is common in elderly MR patients undergoing TEER, and has worse post-interventional outcomes compared to lone MR. Given technical feasibility of TEER in MR-CA, valvular repair should be considered as an option to improve forward volume in a state with typically low output. Future studies should evaluate the prognostic benefits of TEER and CA-specific treatment in MR-CA.

Funding Acknowledgement

Type of funding sources: None.
Transthyretin amyloid cardiomyopathy: a 2-year single-centre experience
Authors: Rocha B , Amador R , Maltes S , Marques M , Oliveira C , Lopes P , Cunha G , Paiva M , Strong C , Abreu F , Pintao S , Aguiar C , Mendes M
Published: October 2022

Background

Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is an under-diagnosed condition often presenting with Heart Failure (HF). We aimed to assess a cohort of patients with ATTR-CM and HF, focusing on the centre strategies to identify new cases, prognosticate and tailor treatment.

Methods

We conducted an all-comers single-centre prospective registry of consecutive patients with HF due to ATTR-CM followed in our centre from November 2019 to 2021. As per site protocol, diagnosis is established according to the algorithm by Gilmore et al. and all patients are assessed in our HF outpatient clinic at least twice yearly with systematic electronic chart data collection. We evaluated disease-modifying treatment and compliance with the current European Guidelines and CHAD-STOP management. A summary of this program is presented in the central figure.

Results

Overall, 60 patients were included (mean age 83±7 years; 80% male). ATTR-CM was confirmed by the non-invasive algorithm in all but 8 patients, in whom endomyocardial biopsy was positive. Of those undergoing genetic testing (n=30), 7 (23%) presented with the hereditary form of ATTR-CM (4 Val50Met and 3 Val142Ile mutations). The initial presentation was most often HF (n=43), atrial fibrillation (n=9), or “incidental” myocardial uptake on 99mTc-HMDP bone scintigraphy (grade 2) performed for cancer staging (n=5). Beta-blockers were reduced or stopped in 40 (67%) patients, all of whom improved in NYHA class and/or NT-proBNP (>30% reduction) at 1–3 months. Tafamidis 61mg was started in 22 patients and 15 more currently await approval. Those initiated on or referred to tafamidis 61mg (n=37) had less severe HF, as per NYHA (class I-II – 94 vs. 50%, p=0.033) and performance status (e.g. Karnofsky score 80–100 – 79 vs. 21%, p=0.010). Of those already on tafamidis (n=22), NYHA class remained stable or improved in all but 1 patient. In the year following vs. preceding treatment there was 2 vs. 3 total HF hospitalizations. No drug-related severe adverse events were reported. Over a 2-year follow-up, 14 (23.3%) patients died, of whom 1 was on tafamidis (compassionate use for 19 months).

Conclusions

ATTR-CM recognition is improving in our dedicated rare disease program, possibly due to the implementation of several alert pathways. The identification of the disease at an earlier stage allows targeted treatment, compliant with the recommendations. Nonetheless, the rarity of this disease and the required expertise for its optimal management argues in favour of a national strategic plan based on referral centres for ATTR-CM.

Funding Acknowledgement

Type of funding sources: None.
Coronary flow reserve by PET 13N-ammonia in patients with hereditary transthyretin amyloidosis with and without cardiac involvement
Authors: Alencar Neto A C , Cafezeiro C R F , Bueno B V K , Ribeiro De Souza F , Henrique Rissato J H S , Souza Borges T , Freitas Carvalhal S , Santos Lima M , Alberto Buchpiguel C , Azem Chalela W , Alvarez Ramires F J , Shcolnik Szor R , Kalil Filho R , Rochitte C E , Fernandes F
Published: October 2022

Background

Transthyretin Cardiac amyloidosis (ATTR) presents with diffuse deposition of amyloid fibrils in the heart. Biomarkers of cardiac involvement such as troponins are often elevated even in early disease stages, reflecting direct cardiomyocyte damage and coronary microvascular dysfunction by amyloid deposits.

Objectives

Evaluate global and segmental coronary flow reserve (CFR) by PET 13N-ammonia in patients with hereditary Transtirretina Amyloidosis with and without cardiac involvement.

Methodology

Thirty-eight ATTR mutation carrier patients (18 with cardiac amyloidosis and 20 without cardiac amyloidosis underwent CFR study by PET 13N-ammonia. Cardiac involvement was defined by means of echocardiography, with an end-diastolic interventricular septal wall thickness ≥12 mm or positive endomyocardial biopsy or grade II or III nuclear scintigraphy using bone avid radiotracers. The Mann-Whitney test was used to compare the values of coronary flow reserve between the groups. The effect size was calculated using the Wilcox method and 95% confidence intervals, obtained by bootstrapping. A multivariate linear regression model was applied to identify the main determinants of global coronary flow reserve.

Results

Compared with patients without cardiac involvement, patients with cardiac involvement were older (69±8 vs. 41±11 years old; p<0,001), had worse NYHA functional classification, higher left ventricular mass index (198±51 g/m2 x 75±19 g/m2; p<0,001), thicker interventricular septum (17,9±3,4 mm vs. 8,7 ± mm; p<0,001]. Coronary flow reserve values were significantly lower in the cardiac amyloidosis group globally (1,8±0,4 vs. 2,9±0,7; p<0,001) and in all analyzed segments (p<0.01). The apical segments were also affected when comparing group with and without cardiac involvement (2,0±1 vs. 3,0±0,7; P=0,002), suggesting absence of microvascular apical preservation. In multivariable linear regression analyses, age and BNP were the main factors associated to coronary reserve flow. The reduction in global CRF was 0,25, 0,08 and 0,17 points, on average, for each decade of life, for each 100 mg/dl of serum BNP and for each 0,1 heart to contralateral lung ratio uptake in 3-hour caption on TcPYP scintigraphy respectively.

Conclusion

Patients with cardiac amyloidosis present lower coronary flow reserve both globally and segmental compared to mutation carrier without cardiac amyloidosis. The evaluation of Coronary flow reserve by PET 13N-ammonia may be a worthwhile tool in cardiac involvement in TTR patients.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer