Sex differences in natural history of cardiovascular magnetic resonance- and biopsy-proven lymphocytic myocarditis

Aims: the role of sex in determining the profile and the outcomes of patients with myocarditis is largely unexplored. We evaluated the impact of sex as a modifier factor in the clinical characterization and natural history of patients with definite diagnosis of myocarditis. Methods and results: we retrospectively analysed a single-centre cohort of consecutive patients with definite diagnosis of myocarditis (i.e. endomyocardial biopsy or cardiac magnetic resonance proven). Specific sub-analyses were performed in cohorts of patients with chest pain, ventricular arrhythmias, and heart failure as different main symptoms at presentation. The primary outcome measure was a composite of all-cause mortality or heart transplantation (HTx). We included 312 patients, of which 211, 68% of the whole population, were males. Despite no clinically relevant differences found at baseline presentation, males had a higher indexed left ventricular end-diastolic volume (62 ± 23 mL/m2 vs. 52 ± 20 mL/m2, P = 0.011 in males vs. females, respectively) at follow-up evaluation. At a median follow-up of 72 months, 36 (17%) males vs. 8 (8%) females experienced death or HTx (P = 0.033). Male sex emerged as predictors of all-cause mortality or HTx in every combination of covariates (HR 2.600; 1.163–5.809; P = 0.020). Results were agreeable regardless of the main symptom of presentation. Conclusions: in a large cohort of patients with definite diagnosis of myocarditis, females experienced a more favourable long-term prognosis than males, despite a similar clinical profile at presentation

Acute inflammatory cardiomyopathy: apparent neutral prognostic impact of immunosuppressive therapy

N/

Prognostic Prediction of Genotype vs Phenotype in Genetic Cardiomyopathies

Background: Diverse genetic backgrounds often lead to phenotypic heterogeneity in cardiomyopathies (CMPs). Previous genotype-phenotype studies have primarily focused on the analysis of a single phenotype, and the diagnostic and prognostic features of the CMP genotype across different phenotypic expressions remain poorly understood. Objectives: We sought to define differences in outcome prediction when stratifying patients based on phenotype at presentation compared with genotype in a large cohort of patients with CMPs and positive genetic testing. Methods: Dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, and biventricular arrhythmogenic cardiomyopathy were examined in this study. A total of 281 patients (80% DCM) with pathogenic or likely pathogenic variants were included. The primary and secondary outcomes were: 1) all-cause mortality (D)/heart transplant (HT); 2) sudden cardiac death/major ventricular arrhythmias (SCD/MVA); and 3) heart failure-related death (DHF)/HT/left ventricular assist device implantation (LVAD). Results: Survival analysis revealed that SCD/MVA events occurred more frequently in patients without a DCM phenotype and in carriers of DSP, PKP2, LMNA, and FLNC variants. However, after adjustment for age and sex, genotype-based classification, but not phenotype-based classification, was predictive of SCD/MVA. LMNA showed the worst trends in terms of D/HT and DHF/HT/LVAD. Conclusions: Genotypes were associated with significant phenotypic heterogeneity in genetic cardiomyopathies. Nevertheless, in our study, genotypic-based classification showed higher precision in predicting the outcome of patients with CMP than phenotype-based classification. These findings add to our current understanding of inherited CMPs and contribute to the risk stratification of patients with positive genetic testing

Clinical impact of myocardial fibrosis in severe aortic stenosis

8The pressure overload due to the progressive narrowing of the valve area determines the development of the left ventricular hypertrophy which characterizes aortic stenosis (AS). The onset of myocardial fibrosis marks the inexorable decline of an initially compensatory response towards heart failure. However, myocardial fibrosis does not yet represent a key element in the prognostic and therapeutic framework of AS. In this context, cardiac magnetic resonance imaging plays a major role by highlighting both the focal irreversible fibrotic replacement, using the late gadolinium enhancement (LGE) technique, and the earlier diffuse reversible interstitial fibrosis, using the T1 mapping techniques. For this reason, the presence of myocardial fibrosis would be useful to identify a subgroup of patients at greater risk of events among the subjects with severe AS. Actually, more and more evidences seem to identify the presence of LGE as a powerful prognostic factor to be used to optimize the timing of prosthetic valve replacement. Randomized clinical trials, such as the EVoLVeD trial currently underway, will be needed to better define the importance of myocardial fibrosis assessment in the management of patients with AS.openopenCastrichini, Matteo; Vitrella, Giancarlo; De Luca, Antonio; Altinier, Alessandro; Korcova, Renata; Pagura, Linda; Radesich, Cinzia; Sinagra, GianfrancoCastrichini, Matteo; Vitrella, Giancarlo; De Luca, Antonio; Altinier, Alessandro; Korcova, Renata; Pagura, Linda; Radesich, Cinzia; Sinagra, Gianfranc

Sacubitril/Valsartan Induces Global Cardiac Reverse Remodeling in Long-Lasting Heart Failure with Reduced Ejection Fraction: Standard and Advanced Echocardiographic Evidences

Sacubitril/valsartan reduces mortality in heart failure with reduced ejection fraction (HFrEF) patients, partially due to cardiac reverse remodeling (RR). Little is known about the RR rate in long-lasting HFrEF and the evolution of advanced echocardiographic parameters, despite their known prognostic impact in this setting. We sought to evaluate the rates of left ventricle (LV) and left atrial (LA) RR through standard and advanced echocardiographic imaging in a cohort of HFrEF patients, after the introduction of sacubitril/valsartan. A multi-parametric standard and advanced echocardiographic evaluation was performed at the moment of introduction of sacubitril/valsartan and at 3 to 18 months subsequent follow-up. LVRR was defined as an increase in the LV ejection fraction 6510 points associated with a decrease 6510% in indexed LV end-diastolic diameter; LARR was defined as a decrease >15% in the left atrium end-systolic volume. We analyzed 77 patients (65 \ub1 11 years old, 78% males, 40% ischemic etiology) with 76 (28-165) months since HFrEF diagnosis. After a median follow-up of 9 (interquartile range 6-14) months from the beginning of sacubitril/valsartan, LVRR occurred in 20 patients (26%) and LARR in 33 patients (43%). Moreover, left ventricular global longitudinal strain (LVGLS) improved from -8.3 \ub1 4% to -12 \ub1 4.7% (p 25% of cases, both at standard and advanced echocardiographic evaluations

Lyme Carditis: From Pathophysiology to Clinical Management

Cardiac involvement is a rare but relevant manifestation of Lyme disease that frequently presents as atrioventricular block (AVB). Immune-mediated injury has been implicated in the pathogenesis of Lyme carditis due to possible cross-reaction between Borrelia burgdorferi antigens and cardiac epitopes. The degree of the AVB can fluctuate rapidly, with two-thirds of patients progressing to complete AVB. Thus, continuous heart rhythm monitoring is essential, and a temporary pacemaker may be necessary. Routinely permanent pacemaker implantation, however, is contraindicated because of the frequent transient nature of the condition. Antibiotic therapy should be initiated as soon as the clinical suspicion of Lyme carditis arises to reduce the duration of the disease and minimize the risk of complications. Diagnosis is challenging and is based on geographical epidemiology, clinical history, signs and symptoms, serological testing, ECG and echocardiographic findings, and exclusion of other pathologies. This paper aims to explain the pathophysiological basis of Lyme carditis, describe its clinical features, and delineate the treatment principles

Cardiac Tumors: Diagnosis, Prognosis, and Treatment

Cardiac masses frequently present significant diagnostic and therapeutic clinical challenges and encompass a broad set of lesions that can be either neoplastic or non-neoplastic. We sought to provide an overview of cardiac tumors using a cardiac chamber prevalence approach and providing epidemiology, imaging, histopathology, diagnostic workup, treatment, and prognoses of cardiac tumors

Modifications of medical treatment and outcome after percutaneous correction of secondary mitral regurgitation

Aims: The optimization of guideline-directed medical therapy (GDMT) in reduced ejection fraction heart failure (HFrEF) is associated with improved survival and can reduce the severity of secondary mitral regurgitation (SMR). Highest tolerated doses should be achieved before percutaneous mitral valve repair (pMVR) and drugs titration further pursued after procedure. The degree of GDMT titration in patients with HFrEF and SMR treated with pMVR remains unexplored. We sought to evaluate the adherence to GDMT in HFrEF in patients undergoing pMVR and to explore the association between changes in GDMT post-pMVR and prognosis. Methods and results: We included all the patients with HFrEF and SMR 65 3 + treated with pMVR between 2012 and 2019 and with available follow-up. GDMT, comprehensive of dosages, was systematically recorded. The study endpoint was a composite of death and heart transplantation. Among 133 patients successfully treated, 121 were included (67 \ub1 12 years old, 77% male patients). Treatment rates of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitor (ACEIs/ARBs/ARNI), beta-blockers, and mineralcorticoid receptor antagonist at baseline and follow-up were 73% and 79%, 85% and 84%, 70% and 70%, respectively. At baseline, 33% and 32% of patients were using >50% of the target dose of ACEI/ARB/ARNI and beta-blockers. At follow-up (median time 4 months), 33% of patients unchanged, 34% uptitrated, and 33% of patients downtitrated GDMT. Downtitration of GDMT was independently associated with higher risk of death/heart transplantation (hazard ratio: 2.542, 95%confidence interval: 1.377-4.694, P = 0.003). Conclusions: Guideline-directed medical therapy is frequently underdosed in HFrEF patients with SMR undergoing pMVR. Downtitration of medications after procedure is associated with poor prognosis

Autonomic function in Takotsubo syndrome long after the acute phase

Objectives Although it is well documented that an exaggerated sympathetic stimulation plays a role in the development of Takotsubo Syndrome (TS) during the acute phase, only few studies have focused on autonomic adaptations in stress-induced cardiomyopathy long after the acute phase. Aim of the study was to investigate whether an impairment of the autonomic function is still present long after a TS event. This was done by comparing the response to a maximal exercise test in TS patients after apparent recovery (> 1-year after the acute event) with that obtained in healthy subjects and in post-myocardial infarction (post-MI) patients. Methods To assess heart rate recovery (HRR) and chronotropic response (CR), 24 TS patients, 25 healthy subjects and 22 post-MI patients underwent maximal exercise test, after at least 3 days of β-blockers wash-out. Results HRR in TS patients (19.2 ± 9.7 bpm) was lower than in healthy subjects (27.7 ± 8.3, p = 0.003), and similar to post-MI patients (19.3 ± 8.4; p = 0.99). A decreasing CR trend (p=0.06), higher in healthy subjects (72±13%) than in TS (65±22%) and post-MI (57±21%) patients, was also found. Conclusion Compared to healthy subjects, TS patients showed a blunted parasympathetic reactivation after exercise, similar to that observed in post-MI patients, thereby suggesting that vagal control of heart rate after exercise is abnormal long after the acute presentation of TS

Prevalence and predictors of persistent sinus rhythm after elective electrical cardioversion for atrial fibrillation

Aims: To evaluate the prevalence and predictors of persistent sinus rhythm in a recent cohort of unselected patients undergoing electrical cardioversion for atrial fibrillation. Methods: We enrolled all consecutive patients undergoing elective electrical cardioversion for atrial fibrillation between January 2017 and December 2018. We analysed baseline clinical and echocardiographic data as well as pharmacological antiarrhythmic therapy. Primary endpoint was the maintenance of sinus rhythm at 12 months after electrical cardioversion. Results: Of the 300 patients enrolled, 270 (90%) had successful electrical cardioversion and among them, 201 patients have 12-month follow-up data (mean age 70 \ub1 10 years; 74% men). At 12 months, only 45.7% were in sinus rhythm. Patients without sinus rhythm compared with persistent sinus rhythm at 12 months had a lower baseline left ventricle ejection fraction (LVEF) (49.1 \ub1 16 vs. 59.7 \ub1 9%, P = 0.02) and had more frequently a history of atrial fibrillation more than 12 months (55 vs. 34% P = 0.003). At the multivariate analysis, only the duration of the disease beyond 12 months (OR 0.26, 95% CI: 0.08-0.88, P = 0.032), LVEF (OR 1.06, 95% CI: 1.01-1.12, P = 0.012) and the presence of sinus rhythm at 1-month follow-up (OR 18.28, 95% CI: 3.3-100, P = 0.001) were associated with the probability of maintaining sinus rhythm at 12 months. Conclusion: In unselected patients with atrial fibrillation undergoing elective electrical cardioversion, only 45.7% were in sinus rhythm at 12 months. The presence of sinus rhythm at 1-month follow-up emerged as an independent predictor of maintenance of sinus rhythm. This highlights that early re-evaluation of these patients appears useful for assessing longer term outcomes also from the perspective of a possible selective approach to ablation strategies