bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and prognostic value of significant mitral regurgitation development after pacemaker implantation
Authors: Nabeta T , Galloo X , Stassen J , Delgado V , Marsan N A , Bax J J
Published: November 2023

Background

Mitral regurgitation (MR) is one of the complications after pacemaker (PM) implantation. However, the underlying mechanism leading to MR progression after PM implantation is not yet fully understood. There is also a lack of information on the clinical impact of the development of MR after PM implantation.

Purpose

This study aims to evaluate the prevalence and mechanism of MR progression after PM implantation and to determine its prognostic value.

Methods

Patients who underwent de novo PM implantation at our university medical centre between 2010 and 2020 were included. Patients with previous mitral valve surgery, transcatheter edge-to-edge repair, or MR severity ≥ moderate before device implantation were excluded. The development of significant MR was defined as a worsening of MR severity ≥ moderate within five years after PM implantation. Clinical endpoints were defined as a composite of all-cause mortality or heart failure hospitalization.

Results

A total of 451 patients (mean age 69 ± 15 years, 61% male) were included. High-degree atrioventricular block (76%) was the main indication for PM implantation. Dual-chamber PM was implanted in 370 (82%) patients. The development of significant MR occurred in 131 (29%) patients at a median of 2.4 years [interquartile range (IQR): 1.0-3.8 years] after PM implantation. Multivariate logistic regression analysis demonstrated that implanted single-chamber PM, LV end-systolic volume index (LVESVI), and mild MR (vs no MR) at baseline were independently associated with the development of significant MR. Prespecified endpoints occurred in 143 patients (31.7%) during median follow-up of 5.4 years [IQR: 3.0-8.1 years] after PM implantation. The Kaplan-Meier analysis showed that patients with significant MR after PM implantation had a significantly higher incidence of endpoints than those without. (Figure) Multivariate Cox regression analysis demonstrated that the development of significant MR, age, male gender, and diabetes mellitus were independently associated with the occurrence of the combined endpoints. The development of significant MR had significant incremental prognostic value for the composite endpoints over the multivariate models including a decrease in LV ejection fraction of ≥ 10% (p = 0.008) or an increase in LVESVI of ≥ 20% (p = 0.016) after PM implantation.

Conclusions

The development of significant MR occurred in 131 patients after PM implantation. The development of significant MR was independently associated with cardiac events, and its prognostic value was also significant even when included in models including a decrease in LV ejection fraction or an increase in LVESVI after PM implantation.Figure:Kaplan-Meier Curve
Influence of device generations on alternations of mitral annulus after transcatheter edge-to-edge repair: a real-time three-dimensional transesophageal echocardiography study
Authors: Ohmori M , Hirasawa K , Izumo M , Ochida M , Satou Y , Kobayashi Y , Kuwata S , Okuyama K , Arima H , Akashi Y , Sasano T
Published: November 2023

Background

Alternation of the mitral annulus (MA) after transcatheter edge-to-edge mitral valve repair (TEER) is reported to be associated with a reduction of mitral regurgitation (MR). However, the influence of the new device system with 4 device size options (MitraClip G4) on MA geometry compared to the conventional device (G2) remains unknown.

Methods and results

A total of 129 patients (mean age 79±10 years, male 66%) including 38 primary MR and 91 secondary MR who underwent TEER guided with three-dimensional (3D) transesophageal echocardiography (TEE) were included. MA area, anterior-posterior (AP) diameter, inter-commissure (CC) diameter, and MA ellipticity before and after MitraClip implantation were measured using 3D TEE images assessed by dedicated software. MitraClip G4 was used in 54 cases (42%). In patients with secondary MR, greater changes in MA area, AP diameter, and MA ellipticity were observed in patients treated with G4 compared to G2 (P=0.001, 0.003, and 0.39, respectively). In contrast, patients with primary MR had no differences in the change of MA parameters between G2 and G4. Patients with significant residual MR had less increase of MA ellipticity after device implantation in secondary MR (P=0.014), but not in primary MR (P=0.062).

Conclusion

In patients with secondary MR, MitraClip G4 made greater changes in MAA, AP diameter, and MA ellipticity compared to MitraClip G2, but not in CC diameter. The change of ellipticity was associated with a reduction of MR after device implantation in secondary MR. These findings indicated that MitraClip G4 may lead favorable MA alternation than G2, especially in secondary MR.
Handgrip echocardiography improves risk stratification in patients with atrial functional mitral regurgitation
Authors: Spieker M , Sidabras J , Lagarden H , Fallack D , Christian L , Zweck E , Bejianriu A , Veulemans V , Akhyari A , Horn P , Westenfeld R , Kelm M , Rana O
Published: November 2023

Background

In the last years, cardiologist increasingly recognize "atrial functional mitral regurgitation" (AFMR) frequently associated with heart failure with persevered ejection fraction and atrial fibrillation. Exercise echocardiography is recommended by current guidelines in patients with secondary mitral regurgitation (MR) in several clinical scenarios. However, there are no data on the prognostic impact of exercise induced AFMR yet. We hypothesise that handgrip exercise during echocardiography unravels dynamic changes of MR severity that may impact further clinical decision making.

Purpose

We aimed to assess the prognostic impact of isometric exercise-induced changes in patients with AFMR.

Methods

Patients with atrial fibrillation and at least mild AFMR who underwent handgrip exercise echocardiography between January 2019 and September 2021 were included. Patients were followed-up for one year to assess clinical outcomes. The combined endpoint included all-cause mortality, heart failure hospitalisation and mitral valve surgery/intervention.

Results

We included 80 patients with AFMR (median age was 80 (77-83) years; 53.8%were female). Echocardiography at rest showed mild MR in half of the patients (53.8%), moderate MR in 20 patients (25.0%), and severe MR in 17 patients (21.2%). In nearly every fifth patient (17.5%) with non-severe MR at rest, the MR became severe during exercise. Median follow-up duration was 12 months (IQR: 4-17 months). Follow-up was completed in 78 of the 80 patients (97.5%). Thirty-five patients (44.9%) experienced adverse events. Kaplan-Meier survival analysis revealed adverse clinical outcomes more often in patients with severe MR during exercise (76.9%) compared to patients with non-severe MR during exercise (33.3%)(p<0.001). Addition of handgrip exercise testing to echocardiographic assessment at rest improved the global chi-square (from 21.2 to 30.2) and the Harrell’s c-index (from 0.69 to 0.78) for prediction of mitral valve surgery/interventions during follow-up.

Conclusions

Isometric handgrip exercise testing unmasks severe MR in a significant proportion of patients with non-severe MR at rest and improves further risk stratification in these patients.
3D atrial stiffness in chronic mitral regurgitation: impact of sex, regurgitation mechanism and valve geometry - the 3D-PRIME study
Authors: Cramariuc D , Berg-Hansen C E , Persson R M , Urheim S , Hung J
Published: November 2023

Background

Chronic mitral regurgitation (MR) is both a cause and a consequence of progressive left atrial (LA) remodeling. The degree of LA stiffness in relation to clinical risk factors as well as atrio-valvular remodeling has not been reported in patients with MR.

Aims

To assess the severity and determinants of 3D LA stiffness in chronic MR.

Methods

In the prospective 3D-PRIME (3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation) study, 100 patients with chronic MR (70±13years, 38% women, 55% with a history of atrial fibrillation (AF), 42% with severe MR) recruited at one heart valve center were investigated with 2D and 3D transthoracic and transesophageal echocardiography. MR severity was quantified by the regurgitant fraction and MR classified as primary (54%), atrial functional (26%) or ventricular functional (20%). 3D LA volume (LAV) was measured at end-diastole (min LAV) and end-systole (max LAV), and 3D LA function assessed in by the emptying fraction (EF) and the peak strain in the reservoir phase (LASr). LA stiffness was estimated from the ratio: mitral peak E-wave velocity divided by the mitral annular e’ velocity (E/e´) / LASr and classified as high for age if ≥ 0.55.

Results

High LA stiffness for age was present in 58% of patients and more often in those with a history of AF (73% vs. 45%) and in severe vs moderate MR (70% vs. 42%) (both p <0.01). Patients with high LA stiffness had larger LAVs with lower LA EF, lower right ventricular ejection fraction, increased mitral annulus area, and larger mitral valve leaflets (all p<0.05).

Men had considerably larger LAVs in all MR subgroups, and highly stiff LAs in atrial functional MR compared to women (p <0.05, Figure) despite similar MR severity (regurgitation fraction 50% vs 52%, respectively).

In multiple regression analysis, after stepwise removal of the following factors: MR severity, mitral leaflet to ring area ratio, and right ventricular ejection fraction, increased LA stiffness was independently associated with male sex, history of AF, lower LA EF and lower mitral intertrigonal diameter (R2 0.40, p <0.001, Table).

Conclusion

LA is stiff for age in over half of patients with chronic MR, excessively stiff in men with atrial functional MR, and associated with specific changes in mitral valve geometry and LA function. This gives mechanistic insights into the complex atrio-valvular interplay in chronic MR.Figure.Table.
Right heart remodeling and outcomes of patients with tricuspid regurgitation
Authors: Bombace S , Fortuni F , Viggiani G , Meucci M C , Esposito G , Condorelli G , Von Roeder M , Thiele H , Lurz P , Grayburn P A , Sannino A
Published: November 2023

Background

Albeit long neglected, significant (at least moderate, ≥ 2+) tricuspid regurgitation (TR) is currently known to be associated with increased mortality, and has thus become a relevant therapeutic target [1-3]. Recent and somewhat preliminary evidence has shown, however, that different subtypes of TR might respond differently to current therapeutic options [4-5]. In fact, secondary TR, rather than being a single entity, can develop because of either right ventricular (RV) remodelling (i.e functional TR) or tricuspid annulus (TA) dilation secondary to right atrial (RA) dilation (i.e isolated TR).

Purpose

The aim of this meta-analysis was to study the association between right heart remodeling and long-term all-cause mortality in a population of patients with significant TR, independent of the treatment option.

Methods

MEDLINE, ISI Web of Science, and SCOPUS databases were searched for studies published up to July 2022. Studies reporting data on at least one echocardiographic RV anatomic and/or functional parameter and outcome in patients with significant TR were included. This study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. The primary endpoint was long-term all-cause mortality.

Results

Out of 3152 studies, a total of 14 were included in the final analytic synthesis, enrolling 4394 subjects. The median follow-up was 33 [24–51] months. Overall, long-term all-cause mortality was 31% (95% confidence interval [CI]: 20-41%, p = <0.001; Figure 1); however, a significant difference was noted in the medical subgroup vs. the surgery subgroup (43% [32-53%] vs 11% [20-41%]). By means of a meta-regression analysis, a significant and inverse relation was found between tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV-FAC) and mortality (11 studies enrolling 3551 subjects, coefficient -0.063 [-0.111 to -0.014], p = 0.011; 9 studies, 2975 subjects, coefficient -0.044 [-0.059 to -0.029], p < 0.001, respectively; Figure 2A and 2B), whereas a significant and concordant relation was found between TA dimension, RA area and mortality (7 studies, 2986 subjects, coefficient 0.003 [0.002 to 0.005], p < 0.001; 6 studies, 1920 subjects, coefficient -0.019 [-0.025 to -0.013], p < 0.001, respectively; Figure 2C and 2D).

Conclusions

The higher mortality associated with right ventricular dysfunction and reduced mortality with increasing right atrial dilatation suggest a better prognostic outcome for isolated TR than functional TR. Careful assessment of right heart anatomy and function is warranted, as it might foster the identification of different subtypes of TR with unique prognoses.Forest plot all-cause mortalityResult of the meta-regression analysis
Left ventricular fibrosis influences the time to recovery in patients with arrhythmia-induced cardiomyopathy
Authors: Schach C , Lavall D , Vosshage N , Koertl T , Muehleck F , Baum P , Uecer E , Hamer O , Maier L , Wachter R , Sossalla S
Published: November 2023

Background

The hallmark of arrhythmia-induced cardiomyopathy (AIC) is reversibility of left ventricular systolic dysfunction (LVSD) following rhythm restoration. Atrial fibrillation and LVSD very frequently co-exist and hence AIC is likely to be under recognized in daily practice. We tested the hypothesis, that left ventricular fibrosis has an influence on the time to recovery (TTR) in patients with AIC.

Method

We prospectively screened patients hospitalized for newly diagnosed and otherwise unexplainable LVSD (i.e. left ventricular ejection fraction (LVEF) <50%) and coexisting tachyarrhythmia (atrial fibrillation/flutter + heart rate (HR) >100/min). Causes other than tachyarrhythmic for LVSD had to be excluded (e.g. valvular, ischaemic, inflammatory). Left ventricular function was assessed by echocardiography at presentation and at follow-up visits 2, 4, and 6 months after rhythm control. Left ventricular (LV) late gadolinium enhancement (LGE) was measured via magnetic resonance imaging after rhythm restoration. Patients were classified AIC, if LVEF significantly recovered after 6 months (increase by ≥15% or above 50% with an increase of ≥10%) and then correlated with LGE as an indicator for fibrosis.

Results

39 patients were included in the LGE analysis, 31 of them recovered and were classified AIC. Although we found no difference in LGE content in AIC vs. non-AIC patients (mean ± SEM 7.7 ± 0.9% vs. 6.5 ± 1.4%; p = 0.542) and contingency analysis of AIC/non-AIC vs. LGE-positive/LGE-negative patients revealed no difference between the groups (p = 0.682), there was a negative correlation of ΔLVEF (month 2 minus baseline) with LGE (Fig. 1) and a positive correlation of the TTR with LGE (Fig. 2) in LGE-positive patients, suggesting an influence of LV fibrosis on the speed of recovery.

Conclusion

Reliable criteria for recovery of LVEF in patients with newly diagnosed LVSD and coexisting arrhythmia are lacking. We found, that LV LGE correlated with the time to recovery of LVEF in patients with AIC. These results may help to estimate the recovery period and thereby optimize the diagnostic and therapeutic strategy for patients with AIC.Figures 1 and 2.
Comparing clinical outcomes in bicuspid versus trileaflet aortic valve endocarditis
Authors: Chatrath N , Dargan J , Hampal R , Kaza N , Bhatia R , Fyyaz S , Maclachlan H , Breathnatch A , Sharma S , Papadakis M , Tome Esteban M , Marciniak A
Published: November 2023

Background

The incidence of bicuspid aortic valve infective endocarditis (BAV-IE) has been reported at 2% in contemporary BAV cohorts with an estimated risk of developing BAV-IE 11 times that of the general population with a trileaflet aortic valve (TAV).

Purpose

To characterise BAV-IE from a clinical and microbiological perspective and compare clinical outcomes with a cohort of individuals with trileaflet aortic valve infective endocarditis (TAV-IE).

Methods

The clinical records of all patients (>16 years old) admitted to a large tertiary referral centre in the United Kingdom between 2015 and 2022 with a definitive diagnosis of native aortic valve IE by Duke’s criteria were included. Clinical, echocardiographic and microbiological data were obtained. The primary outcomes were death or surgical aortic valve intervention during the indexed hospital admission. Secondary outcomes included the incidence of cardiac complications (e.g. aortic root abscess or fistula formation, IE affecting another valve or high degree atrioventricular block requiring temporary or permanent pacing). Extra-cardiac complications included embolic phenomena and thrombotic events.

Results

83 patients were included (BAV-IE 34; TAV-IE 49). BAV-IE patients were significantly younger at presentation than TAV-IE patients (Table 1). There was no difference age-adjusted mortality rate between the two groups (mortality rate BAV-IE 0.20 (95% CI 0.08-0.54) versus TAV-IE 0.29 (95% CI 0.17-0.48). The rate of cardiac complications including aortic root abscess or fistula formation, and concomitant mitral valve endocarditis was greater in the BAV group, though not reaching statistical significance. Those in the BAV-IE group were more likely to develop at least moderate aortic regurgitation and have aortic valve intervention during the admission (70.6% (24/34) BAV-IE versus 46.9% (23/49) TAV-IE, p=0.03).

Conclusion

Despite an estimated prevalence of 1% in the general population, BAV accounted for 41% of all native AV IE cases at our institution. This study demonstrates that even in young, otherwise healthy individuals, BAV-IE has a poor prognosis with a high proportion developing structural complications. Age-adjusted mortality rates are similar to those with TAV-IE, who are often older with more co-morbidities. Though antibiotic prophylaxis is currently only recommended for those at the highest risk, these findings reinforce the importance of mitigating sources of infection in individuals with BAV. Prompt medical attention and treatment of suspected IE cases is of utmost importance as degeneration of a BAV and other cardiac complications, particularly aortic regurgitation, can rapidly develop.
Valvulitis: a new echocardiographic criterion for the diagnosis of prosthetic valve infective endocarditis
Authors: Zulet Fraile P , Olmos C , Pozo E , Carnero M , Saiz-Pardo M , Mahia P , Jeronimo A , Islas F , Gomez-Ramirez D , De Agustin A , San Roman J A , Vilacosta I
Published: November 2023

Background

Diffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been previously described in some patients with aortic bioprosthetic valve endocarditis (PVE). This echocardiographic finding has been termed valvulitis.

Objectives

Our aim was to estimate the prevalence of valvulitis, to precisely describe its echocardiographic characteristics, and to determine their clinical significance in patients with aortic bioprosthetic valve endocarditis.

Methods

From 2011 to 2022, 388 consecutive patients with IE admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with aortic bioprosthetic valve endocarditis (n=86) were selected, and their TEE images were thoroughly evaluated by three independent cardiologists to identify all potential cases of valvulitis. The diagnosis of valvulitis was considered to be present when all three were in complete agreement.

Results

Prevalence of isolated valvulitis in the total cohort was 12.8%, and 20.9% of patients had valvulitis accompanying other classical echocardiographic findings of IE.

A description of the main clinical and imaging findings of 11 patients with valvulitis and no other echocardiographic signs of IE is shown at the Table. Diagnosis status corresponds to the criteria for the diagnosis of IE according to the ESC 2015 IE guidelines, including 18F-FDG PET/CT.

TEE long-axis and short-axis views of a patient with bioprosthetic valvulitis (homogeneous and hypoechoic thickening of the aortic leaflets) resulting in severe aortic stenosis are shown at the Figure, Panel A. At Panel B, abnormal FDG uptake (white arrow) at the prosthetic valve is seen on PET/CT scan of the same patient. At Panel C, histology of the aortic bioprosthetic leaflet of the same patient with valvulitis is presented (hematoxylin and eosin stain of the aortic leaflet; granulation tissue is well demonstrated (red bracket) covering the aortic fibrosa (red asterisk)).

Moderate or severe valve stenosis was more common in those with valvulitis (81.8 vs 34.9%, p<0.001). Patients with isolated valvulitis tended to have a lower IE-related in-hospital mortality (9.1 vs 23.3%, p=0.219) and cardiac surgery was less frequently performed than in the other subjects with aortic PVE (27.3 vs 58.1%, p=0.17), but these results were not statistically significant.

Conclusions

Valvulitis can be the only echocardiographic finding in infected biological aortic prosthesis and needs to be recognized by imagers for early patient diagnosis. The identification of this sort of lesion is important since the clinical profile and management of these patients is different from that of patients with classical PVE.TableFigure
Exploring the complex spectrum of dominance and recessiveness in genetic cardiomyopathies
Authors: Lipov A , Jurgens S J , Mazzarotto F , Allouba M , Pirruccello J P , Aguib Y , Gennarelli M , Yacoub M , Ellinor P T , Bezzina C R , Walsh R
Published: November 2023

Background

Cardiomyopathies are a set of cardiac diseases which are typically thought to have an autosomal dominant mode of inheritance and usually present in adulthood. However, their genetic architecture is increasingly recognised to be more complex, characterised by incomplete penetrance, variable expressivity and high genetic heterogeneity. In addition, there has been a recent rapid rise in genes associated with cardiomyopathy via a recessive, rather than dominant, mode of inheritance. However, there is increasing evidence that the classical recessive/dominant dichotomy in many Mendelian-like diseases is an oversimplification, with reports of clinically relevant phenotypes, albeit milder, in heterozygous carriers of known recessive variants.

Purpose

Investigate the genetic landscape of recessive cardiomyopathy and explore the putative spectrum of dominance and recessiveness in cardiomyopathies.

Methods

Published genetic studies of cardiomyopathies caused by biallelic genotypes were systematically analysed. For established recessive cardiomyopathy genes, monoallelic associations with relevant cardiac phenotypes were investigated using the UK Biobank.

Results

After appraisal, we characterised 17 genes that are robustly associated with recessive cardiomyopathy based on exome or genome sequencing across multiple pedigrees. The recessive cases were characterised by early age of onset (mean (SD) 12.5±15.1 years), poor outcomes (42.8% reported deceased) and predominance of dilated cardiomyopathy (11/17 genes). Studies in understudied groups, particularly bottleneck populations and regions of high consanguinity, were particularly informative for novel gene discovery. For several of the recessive genes, monoallelic variants were associated with cardiac phenotypes in the UK BioBank, for example, ALPK3 and SLC30A5 with hypertrophic cardiomyopathy and LMOD2 with dilated cardiomyopathy, the latter two are novel monoallelic associations. Analysing individuals with biallelic variants in established dominant sarcomeric cardiomyopathy genes revealed an earlier age of onset compared to monoallelic carriers (median (IQR) 13.5 (1.0-30.0) vs 37.5 (23.6-49.8) years), although with variability between genes and variant classes.

Conclusions

Disease genes associated with recessive inheritance are becoming an increasingly important aspect of the genetic architecture of cardiomyopathies, but there is also evidence of the presence, and spectrum, of phenotypes in monoallelic carriers of variants for several of these same genes. These findings illustrate the complexities of genotype-phenotype associations in cardiomyopathy and the need for more comprehensive and informed clinical genetic testing, particularly for patients from diverse and understudied ancestries.Recessive cardiomyopathy cases
Cardiac Sarcoidosis treated with non-steroidal immunosuppressive therapy
Authors: Suwa K , Naruse Y , Nabeta T , Kitai T , Taniguchi T , Yoshioka K , Tanaka H , Okumura T , Baba Y , Matsue Y , Maekawa Y
Published: November 2023

Background

Non-steroidal immunosuppressive therapy is a potential treatment strategy for cardiac sarcoidosis. However, due to the lack of robust evidence, it is not recommended as an established treatment option in the guideline.

Purpose

The purpose of the study is to demonstrate the clinical outcome of the patients with cardiac sarcoidosis using non-steroidal immunosuppressive therapy in a retrospective registry entitled ILLUMINATE-CS (ILLUstration of the Management and prognosIs of JapaNese pATiEnts with Cardiac Sarcoidosis).

Methods

Of an entire cohort of 512 patients, 26 who received immunosuppressive therapy other than steroids were recruited for the analysis. The clinical outcome included all-cause death, fatal ventricular arrhythmic event (FVAE), and worsening heart failure with hospitalization.

Results

The reasons to use non-steroidal immunosuppressant were increased fluorodeoxyglucose (FDG) accumulation on the heart suggesting worsened inflammation (n = 13), side effects of steroid (n = 7), ventricular tachycardia or frequent ventricular premature contraction (n=4), complete atrioventricular block (n = 2), worsened symptom relating to non-cardiac sarcoidosis including neuro and pulmonary sarcoidosis (n = 2), and the other reason (n = 2), with some overlapping. Used non-steroidal immunosuppressants were comprised of methotrexate (n = 20, 6.9 ± 2.1 mg/week), cyclosporine (n =2, 75 or 100 mg/day), cyclophosphamide (n = 2, 25 or 50 mg/day), and azathioprine (n = 3, 100 mg/day in each). Side effects of non-steroidal immunosuppressant were observed in six cases and included one with methotrexate-related interstitial pneumonia, one with a methotrexate-associated lymphoproliferative disorder, one with septic coxitis with methotrexate, one with methotrexate-induced acute kidney injury, one with methotrexate-induced hepatic dysfunction, and one with azathioprine-induced anemia. After the addition of a non-steroidal immunosuppressant, steroids could be reduced in 14 cases of 26 cases with a median maintenance dose of 5 (interquartile range of 5–17) mg, although no cases stopped steroids. Of 13 cases who started non-steroidal immunosuppressant for the increased FDG uptake, decreased FDG uptake was observed in seven cases at the follow-up scan. Clinical outcome events were observed in 11 cases (42.3%). Detected events included all-cause death in five cases (19.2%), FVAE in four cases (15.4%), and worsening heart failure with hospitalization in five cases (19.2%), with some overlapping.

Conclusions

Non-steroidal immunosuppressive therapy may be a possible treatment option for patients who are not stabilized using sole steroid therapy or who suffer from the side effects of steroids.
Genetic testing in presumed cardiac sarcoidosis
Authors: Castrichini M , Agboola K , Siontis K C , Abou Ezzeddine O , Giudicessi J , Rosenbaum A , Pereira N
Published: November 2023

Background

Cardiac sarcoidosis (CS) is a difficult to diagnose inflammatory heart disease. Certain types of genetic cardiomyopathy have been reported to masquerade as inflammatory cardiomyopathy. The utility of genetic testing in the evaluation of inflammatory cardiomyopathy is not completely explored and data regarding the prevalence of genetic cardiomyopathies in patients with presumed CS is limited.

Methods

We retrospectively analyzed patients evaluated from May 2020 to October 2022 in our Cardiac Sarcoid Clinic diagnosed with presumed CS as inferred by either fluorodeoxyglucose positron emission tomography (FDG-PET) - computed tomography (CT) or cardiac magnetic resonance (CMR) or both. Pertinent demographic, genetic, electrocardiographic, and imaging data for these patients was extracted from the electronic medical record.

Results

Genetic testing was obtained in 47 (22%) of the 213 presumed CS patients, among whom 43 (91%) presented with suspected isolated CS, and 4 (9%) with possible cardiac involvement in the setting of systemic sarcoidosis. Among the patients who underwent genetic testing, 10 (21 %) had a pathogenic or likely pathogenic (P/LP) variant(s) in a genetic cardiomyopathy-susceptibility gene, including DSP (n=2), LMNA, FHL1, TPM1, MYBPC3, NRAS, MYH7 (n=2) and TTN (n= 2) genes. All P/LP patients had FDG uptake, and in those with CMR data, 100% had late gadolinium enhancement. The seven patients with P/LP who underwent endomyocardial biopsy had no evidence of granulomatous inflammation. Immunosuppression was initiated in 60% of the P/LP patients before knowledge of genetic results.

Conclusion

Patients suspected to have CS may have concomitant or primarily genetic cardiomyopathy that may masquerade as an inflammatory phenotype Genetic testing should be considered in these patients, not only to clarify the diagnosis and its prognostic and therapeutic implications, but also to offer cascade screening for the family of patients with P/LP variants who otherwise would not have been considered to have a heritable disease.
Incidence and risk factors of myocarditis in hospitalized patients with COVID-19 in Germany
Authors: Keller K , Sagoschen I , Konstantinides S , Gori T , Munzel T , Hobohm L
Published: November 2023

Background

In December 2019 first patient cases of pneumonia caused by a previously unknown virus was detected in China. This began the coronavirus disease 2019 (COVID-19)-pandemic with a never seen infectious disease burden and impact on the healthcare systems worldwide. The first severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections in Germany were reported on January 27th, 2020. From this initial cluster (in Bavaria), a sustained transmission of SARS-CoV-2 was followed by a substantial spread of COVID-19 in the German population.

Although COVID-19 is frequently accompanied by symptoms like fever, cough, sore throat, malaise, myalgias, and dyspnoea, and the infection affects the lungs primarily, COVID-19 might also lead to acute cardiac, kidney, and liver injury. Cardiac complications, particularly myocarditis, and pericarditis, were associated with SARS-CoV-2 infection. Viral infections are frequent causes of myocarditis, an inflammation of the myocardium, which may result in hospitalization and heart failure and can be followed by sudden cardiac death. Myocarditis as cardiac involvement in COVID-19 infection is well known. Real-world data about incidence in hospitalized COVID-19 patients and risk factors for myocarditis in COVID-19 patients are sparse.

Methods

We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19-diagnosis in Germany in 2020 and stratified them for myocarditis (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2020, own calculations).

Results

Overall, 176,137 hospitalizations (52.3%males, 53.6%aged≥70years) with confirmed COVID-19-infection were coded in Germany in 2020, and among them, 226 (0.01%) had myocarditis (incidence:1.28 per 1000 hospitalization cases). Absolute numbers of myocarditis increased, while relative numbers decreased with age. COVID-19 patients with myocarditis were younger (64.0 [IQR 43.0/78.0] vs.71.0 [56.0/82.0], P<0.001). In-hospital case fatality was 1.3-fold higher in COVID-19 patients with than without myocarditis (24.3% vs. 18.9%, P=0.012). Myocarditis was independently associated with increased case fatality (OR 1.89 [95%CI 1.33-2.67], P<0.001). Independent risk factors for myocarditis were age<70years (OR 2.36 [95%CI 1.72-3.24], P<0.001), male sex (1.68 [95%CI 1.28-2.23], P<0.001), pneumonia (OR 1.77 [95%CI 1.30-2.42], P<0.001) and multi-systemic inflammatory COVID-19-infection (OR 10.73 [95%CI 5.39-21.39], P<0.001).

Conclusion

The incidence of myocarditis in hospitalized COVID-19 patients in Germany was 1.28 cases per 1000 hospitalizations in 2020. Risk factors for myocarditis in COVID-19 were young age, male sex, pneumonia, and multi-systemic inflammatory COVID-19 infection. Myocarditis was independently associated with increased case fatality.
Mortality in hypertrophic cardiomyopathy is unrelated to genotype
Authors: Bonaventura J , Rowin E J , Chin M T , Puchnerova V , Polakova E , Macek Jr M , Koethe B , Veselka J , Maron B J , Maron M S
Published: November 2023

Background

Hypertrophic cardiomyopathy (HCM) patients with a pathogenic variant are presumed to have worse prognosis than patients without a pathogenic mutation. However, the genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and relationship between genotype status and outcomes have not been completely resolved.

Objective

We assessed a large international HCM cohort to define the natural history and clinical consequences of genotype status.

Methods

Consecutive patients (n=1468) with established clinical HCM diagnosis underwent genetic testing focused on HCM-related genes. Patients with pathogenic or likely pathogenic variants were considered genotype positive (G+), and those without definite disease-causing mutation or a variant of uncertain significance (VUS) were considered genotype negative (G-). Patients were followed for 9.6 ± 8.2 years for clinical outcomes.

Results

Of 1468 HCM patients, 1156 (79%) were G - and 312 (21%) were G+. Over the follow-up 116 (10%) G- patients died at 70 ± 14 years, including in 26 (2.2%) from HCM-related causes. HCM-related mortality was not significantly different in G- patients (0.3%/year) as compared to G+ patients (0.3%/year) when adjusted for age (HR 0.93, 95% CI 0.38-2.30, p=0.87). All-cause mortality was not different among these groups (0.7%/year G- vs. 0.6%/year G+) when adjusted for age (HR 0.62, 95% CI 0.3-1.2, p=0.14) or comorbidities (HR 0.78, 95% CI 0.46-1.31, p=0.35). Rate of progression to advanced heart failure NYHA class III/IV in nonobstructive patients was not different in G- (4%/ year) vs. G+ (3%/year, HR 1.20, 95% CI 0.63-2.26, p=0.58). Sudden death events (appropriate ICD shocks, aborted cardiac arrest and sudden death) were more frequent in G+ patients (1.7%/year) than in G- patients (0.5%/year), albeit of borderline statistical significance when adjusted for age and SD risk factors (HR 1.58, 95% CI 1.00-2.49, p=0.05).

Conclusions

In this large consecutive genotyped cohort, all-cause and HCM-related mortality was unrelated to genotype status. Substantial proportion of G- patients experienced progressive HF, at a similar rate when compared to G+ patients. Although G- patients had less frequently SD events, genotype negative status could not be considered benign.FiguresTable
Epigenetic study of the differential phenotypic expression of a hypertrophic cardiomyopathy-related pathological variant at MYBPC3 in a cohort of monozygotic twins
Authors: Penarroya A , Fraga M , Rodriguez Reguero J J , Gomez J , Moris C , Lorca R
Published: November 2023

Introduction

Hypertrophic cardiomyopathy (HCM) is a inherited cardiac disease with a variable penetrance and expressivity. Epigenetics orchestrates the interplay between the environment and the molecular changes that lead to the development of the pathological phenotype. It is of great interest to identify the changes that determine the magnitude of left ventricular hypertrophy (LVH) in patients carrying a given pathogenic variant.

Methods

In this work, we used peripheral blood samples from a cohort of three homozygous twin pairs carrying the p.Gly263Ter pathogenic variant at MYBPC3 gene to suppress the underlying genetic effect and isolate the role of DNA methylation in its divergent phenotypic expressivity.

Results

We found a poorer life-style and a more anxious personality among the more severely affected patients. Using a pair-matched model corrected by cell type proportions, a total of 2486 differentially methylated positions (DMP) were extracted with moderate but proportional methylation changes to the LVH of the patients. DMP were enriched in functional regions controlled by repressor histone marks (H3K27me3, H3K9me3) and tended to colocalise forming differentially methylated regions (DMR) across genes mainly related to homophilic surface adhesion molecules and Ca2+ transport. Strikingly, many affected genes were found to be involved in LVH development, such as PLSCR2, ELMO3, TRIM68, HOXA5, UCN3, PCDHGA3, PAX8-AS1, suggesting that the analysis of blood samples could be able to recapitulate alterations at cardiac tissue level. Furthermore, the relationship of the observed changes with the development of the pathology was successfully validated with an external cohort of peripheral blood samples from healthy patients. Further studies are needed to validate the observed changes at cardiac tissue and to verify their causal role.

Conclusions

In this cohort of monozygotic twins we were able to identify promising epigenetic peripheral blood changes that relate to the expressivity of the HCM. Anxious personalities and lifestyle divergences could lie behind our findings. DNA methylation changes tend to locate at key positions related to cell-to-cell communication and Ca2+ metabolism, as well as at other loci already described to regulate LVH and stress.
Association of left atrial strain with long-term cardiovascular mortality in hypertrophic cardiomyopathy
Authors: Kim J , Lee H J , Kim H K , Lee S C
Published: November 2023

Background

Hypertrophic cardiomyopathy (HCM) is a relatively common genetic cardiac disease affecting 1 in 200 people. Although sudden cardiac death (SCD) is considered the most devastating event in patients with HCM, cardiovascular death (CVD) is the leading cause of death in this population. Little is known about the predictors of cardiovascular mortality.

Purpose

The aim of this study was to investigate prognostic implication of left atrial (LA) strain on long-term cardiovascular mortality in patients with HCM.

Methods

Peak longitudinal LA strain was measured on echocardiography at initial evaluation using vendor-independent speckle-tracking software. Among a prospective cohort of 865 HCM patients collected at two large tertiary centers, 697 with adequate echocardiographic images to measure biplane LA strain were included in the analysis. The primary endpoint was CVD during 10 years after initial evaluation.

Results

The median age was 56.0 years and 74.6% were male. Among the 697 patients, 25 died due to cardiovascular cause for 10 years. Among clinical and echocardiographic variables, older age, female sex, previous myocardial infarction, previous stroke, higher SCD risk score by European Society of Cariology, presence of SCD risk factors by American College of Cardiology, obstructive HCM, larger LA diameter, and lower LA strain were associated with CVD. LA strain had the highest predictive power for CVD occurrence, with a c-statistic of 0.79 (Figure 1). In multivariable Cox analysis, LA strain remains an independent predictor of CVD (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.82–0.94). Patients with LA strain <19.4% (the lowest quartile), compared with those with LAS ≥19.4%, had a significantly higher risk of CVD (19.5% vs. 2.1%, HR 7.31, 95% CI 3.15–16.95), as well as death by any cause, SCD, and a composite of CVD, heart failure admission, and stroke (Figure 2).

Conclusions

In patients with HCM, LA strain is an independent predictor of long-term CVD.
Prognostic role of the progression of late gadolinium enhancement in hypertrophic cardiomyopathy
Authors: Todiere G , Aquaro G D , Barison A , Grigoratos C , Parisella M L , Amedei M , Grilli G , Faggioni L , Cioni D , Lencioni R , Neri E , Emdin M
Published: November 2023

Background

Late Gadolinium Enhancement (LGE) extent ≥15% of left ventricular (LV) mass is a widely accepted prognostic risk factor in hypertrophic cardiomyopathy (HCM). However, LGE extent increases over time and the clinical role of the progression of LGE (LGE-rate) was not prospectively evaluated in previous studies.

Purpose

We evaluated the clinical and prognostic role of LGE-rate in HCM.

Methods

105 patients with HCM underwent cardiac-MR at baseline (CMR-I) and after ≥2 years of follow-up (CMR-II). LGE extent was measured in both the examinations (LGE was defined using threshold validated method of ≥6 SD exceeding the mean of normal myocardium (1)).

LGE-rate was defined as the ratio between the increase of LGE extent (g) and the time interval (months) between CMR-I and CMR-II. A combined endpoint of sudden cardiac death (SCD), resuscitated cardiac arrest, appropriate ICD intervention and sustained ventricular tachycardia was used (hard events).

Results

The percentage of patients with LGE extent ≥15% increased from 9% to 20% at CMR-II (p=0.03), compared to CMR-I. During a median follow-up of 52 months, 25 hard events were recorded. The presence of LGE≥15% at CMR-II allowed a significant reclassification of the risk of patients than at LGE≥15% at CMR-I (NRI 0.21, p=0.046). At maximally selected rank statistical analysis the optimal prognostic cut-point for LGE-rate was >0.07 g/months. At Kaplan-Meier curve analysis patients with LGE-rate>0.07 had significant worse prognosis than those without (p<0.0001) (figure 1). LGE-rate>0.07 allowed a significant reclassification of the risk compared to LGE≥15% at CMR-I and at CMR-II (NRI 0.49, p=0.003) (figure 2). At Cox regression multivariable analysis, LGE-rate>0.07 was the best independent predictor of hard events.

Conclusions

LGE-rate is heterogenous among patients with HCM and a follow-up CMR should be performed after 2 years to reclassify the risk of SCD of those patients. High LGE-rate should be considered as a novel prognostic risk factor in HCM.Figure 1Figure 2
Assessment of Myocardial Work in sarcomere gene mutation carriers and overt hypertrophic cardiomyopathy
Authors: Marques Pires C , Triantafyllou M , Monteiro R P , Joy G , Ferreira A , Savvatis K , Lopes L R
Published: November 2023

Introduction

Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease defined by unexplained hypertrophy and often characterized by diastolic and systolic dysfunction. In recent studies, HCM patients were found to have impaired left ventricular (LV) myocardial work (MW), a more load-independent parameter compared to global longitudinal strain (GLS). MW was never studied in sarcomere mutation carriers.

Aim

To compare MW between sarcomere mutation carriers, healthy controls and overt HCM.

Methods

A single centre study with a case-control design. The study population comprised 3 groups: overt HCM patients with a likely pathogenic/pathogenic sarcomere gene variant (n=51), carriers (n=51) and age and sex matched (to the carriers) healthy controls (n=32). All participants (pts) underwent a transthoracic echocardiogram including myocardial deformation analysis to calculate global longitudinal strain (GLS) and MW. MW was calculated from same-day non-invasive blood pressure evaluation. Global work index (GWI), Global constructive work (GCW), Global work efficiency (GWE) and Global wasted work (GWW) were obtained.

Results

GWI (1695mmHg% vs 1869mmHg%, p=0.001) and GCW (1993mmHg% vs 2244mmHg%, p<0.001) were lower in sarcomere mutation carriers compared to controls. LVEF and GLS were similar between the two groups (p=0.233). HCM pts were older (p<0.001), less likely female (p=0.01) and had a higher prevalence of cardiovascular (Cv) comorbidities, including hypertension (p<0.001), compared with sarcomere gene mutation carriers. Global work index (GWI) (1209mmHg%vs1695mmHg%), global constructive work (1456mmHg% vs 1993mmHg%, p<0.001) and global work efficiency (GWE) (89% vs 95%, p<0.001) were significantly lower in overt HCM compared with sarcomere mutation carriers. GWW was higher (117mmHg% vs 95mmHg%, p=0.006) in overt HCM.

Conclusion

In this study, we show for the first time that MW indexes were significantly worse in sarcomere gene mutation carriers compared to controls. GLS and MW indexes were also significantly different between overt HCM and sarcomere gene mutation carriers. These data suggest that MW is more sensitive to early changes than GLS and could play a major role in the evaluation and follow-up of sarcomere mutation carriers.
Left atrial strain and long-term risk of atrial fibrillation in hypertrophic cardiomyopathy
Authors: Kim J , Lee H J , Kim H K , Lee S C
Published: November 2023

Background

The prevalence of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients is higher than in the general population, and it is associated with an increased risk of adverse outcomes, such as stroke, heart failure, and mortality. The left atrium (LA) plays an important role in maintaining normal cardiac function, and alterations in its structure and function can contribute to the development of AF. LA strain, a surrogate of LA remodeling, has been suggested a predictor of future AF.

Purpose

The aim of this study was to explore risk factors of new onset AF highlighting LA strain in patients with HCM.

Methods

Among a prospective cohort of 865 HCM patients collected at two large tertiary centers, 696 with adequate echocardiographic images to measure LA strain without a history of AF were included in the analysis. LA strain was measured on apical four-chamber view at initial evaluation using vendor-independent speckle-tracking software. The primary endpoint was new onset AF during 10 years after initial evaluation.

Results

The median age was 55.0 years and 74.3% were male. A median value of LA reservoir strain (LARS) was 26.2 % [interquartile range 20.4, 33.3]. Among the 696 patients, 66 had new onset AF 10 years, with a 10-year incidence of 15.8%. The unadjusted risk factors for new onset AF were previous stroke, non-apical HCM, family history of HCM, non-sustained ventricular tachycardia, obstructive HCM, extensive late gadolinium enhancement, larger LA diameter, larger LA volume, and lower LARS. LARS remained an independent predictor of new onset AF in multivariable analysis. The best cut-off value of LARS was 17.9% (hazard ratio 4.00, 95% confidence interval 2.44–6.55, p<0.001). Compared with LARS ≥17.9%, LARS <17.9% was significantly associated with a higher incidence of new onset AF, irrespective of presence of clinical risk factors (Figure 1) and LA enlargement (Figure 2).

Conclusions

In patients with HCM, low LA strain is an independent predictor of new onset AF.