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The 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.

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.

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.

Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by left or biventricular systolic impairment. Historically, most of the clinical attention has been devoted to the evaluation of left ventricular function and morphology, while right ventricle (RV) has been for many years the forgotten chamber. Recently, progresses in cardiac imaging gave clinicians precious tools for the evaluation of RV, raising the awareness of the importance of biventricular assessment in DCM. Indeed, RV involvement is far from being uncommon in DCM, and the presence of right ventricular dysfunction (RVD) is one of the major negative prognostic determinants in DCM patients. However, some aspects such as the possible role of specific genetic mutations in determining the biventricular phenotype in DCM, or the lack of specific treatments able to primarily counteract RVD, still need research. In this review, we summarized the current knowledge on RV involvement in DCM, giving an overview on the epidemiology and pathogenetic mechanisms implicated in determining RVD. Furthermore, we discussed the imaging techniques to evaluate RV function and the role of RV failure in advanced heart failure.

Right ventricular (RV) dysfunction (RVD) is associated with worse outcome in coronavirus disease 2019 (COVID-19). Pulmonary hypertension (PH) is a cause of RVD in COVID-19 respiratory failure and is associated with negative prognosis. Major pulmonary embolism, alveolar and endothelial injury, and thrombotic microangiopathy are potential triggers for new-onset PH in the acute phase. Persistent RV involvement has been reported in patients recovered from COVID-19. However, the association between persistent RV impairment and new-onset PH remains unexplored. We evaluated the prevalence of PH and RVD in patients recovered from COVID-19.

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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 &ge, 10 points associated with a decrease &ge, 10% in indexed LV end-diastolic diameter, LARR was defined as a decrease &gt, 15% in the left atrium end-systolic volume. We analyzed 77 patients (65 &plusmn, 11 years old, 78% males, 40% ischemic etiology) with 76 (28&ndash, 165) months since HFrEF diagnosis. After a median follow-up of 9 (interquartile range 6&ndash, 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 &minus, 8.3 &plusmn, 4% to &minus, 12 &plusmn, 4.7% (p &lt, 0.001), total left atrial emptying fraction (TLAEF) from 28.2 &plusmn, 14.4% to 32.6 &plusmn, 13.7% (p = 0.01) and peak atrial longitudinal strain (PALS) from 10.3 &plusmn, 6.9% to 13.7 &plusmn, 7.6% (p &lt, 0.001). In HFrEF patients, despite a long history of the disease, the introduction of sacubitril/valsartan provides a rapid global (i.e., LV and LA) RR in &gt, 25% of cases, both at standard and advanced echocardiographic evaluations.

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 ≥ 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 ± 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.