Echocardiographic heart ageing patterns predict cardiovascular and non-cardiovascular events and reflect biological age: the SardiNIA study.

AIMS: Age is a crucial risk factor for cardiovascular (CV) and non-CV diseases. As people age at different rates, the concept of biological age has been introduced as a personalized measure of functional deterioration. Associations of age with echocardiographic quantitative traits were analysed to assess different heart ageing rates and their ability to predict outcomes and reflect biological age. METHODS AND RESULTS: Associations of age with left ventricular mass, geometry, diastolic function, left atrial volume, and aortic root size were measured in 2614 healthy subjects. Based on the 95% two-sided tolerance intervals of each correlation, three discrete ageing trajectories were identified and categorized as 'slow', 'normal', and 'accelerated' heart ageing patterns. The primary endpoint included fatal and non-fatal CV events, and the secondary endpoint was a composite of CV and non-CV events and all-cause death. The phenotypic age of the heart (HeartPhAge) was estimated as a proxy of biological age. The slow ageing pattern was found in 8.7% of healthy participants, the normal pattern in 76.9%, and the accelerated pattern in 14.4%. Kaplan-Meier curves of the heart ageing patterns diverged significantly (P = 0.0001) for both primary and secondary endpoints, with the event rate being lowest in the slow, intermediate in the normal, and highest in the accelerated pattern. In the Cox proportional hazards model, heart ageing patterns predicted both primary (P = 0.01) and secondary (P = 0.03 to <0.0001) endpoints, independent of chronological age and risk factors. Compared with chronological age, HeartPhAge was 9 years younger in slow, 4 years older in accelerated (both P < 0.0001), and overlapping in normal ageing patterns. CONCLUSION: Standard Doppler echocardiography detects slow, normal, and accelerated heart ageing patterns. They predict CV and non-CV events, reflect biological age, and provide a new tool to calibrate prevention timing and intensity.

Age is the main risk factor for cardiovascular (CV) disease. Since people age and develop diseases at very different rates, biological age has been proposed as a more accurate measure of the body's functional decline. This study aimed to investigate the ageing rates of the heart and to assess their impact on CV events. The phenotypic age of the heart was also estimated as a proxy for biological age. Associations of age with Doppler echocardiographic parameters were analysed in a subgroup of 2614 clinically healthy subjects, part of a larger cohort of 3817 adults of both sexes.Three patterns of slow, normal, and accelerated ageing rates of the heart were detected. They predicted both CV and non-CV events, with different and progressively increasing event rates from the slow to the accelerated pattern. Compared with chronological age, the phenotypic (biological) age of the heart was 9 years younger in the slow pattern, 4 years older in the accelerated pattern, and comparable in the normal pattern.A standard Doppler echocardiogram is therefore able to detect three distinct heart ageing patterns, which reflect different biological susceptibilities to age-dependent diseases and provide a new tool for personalizing timeliness and intensity of prevention.

Platelet inhibition with orodispersible ticagrelor in acute coronary syndromes according to morphine use: the TASTER study final results.

AIM: To date, it is still unknown whether orodispersible tablet (ODT) ticagrelor might represent a suitable way to reach a proper antiaggregation in acute coronary syndrome (ACS) patients receiving morphine. Aim of the present study was to evaluate platelet inhibition with 180 mg ticagrelor loading dose (LD) administered as ODT compared with standard coated tablet ticagrelor formulation in ACS patients undergoing percutaneous coronary intervention (PCI) according to morphine use. METHODS AND RESULTS: One-hundred and 30 patients presenting with STEMI or very high-risk NSTE-ACS were randomly assigned to receive ODT or standard ticagrelor LD. Potential morphine-ticagrelor interaction was assessed by stratified randomization according to morphine use. Platelet reactivity was evaluated by Platelet Reactivity Units (PRU) VerifyNow™ 1, 2, 4, and 6 h after ticagrelor LD. The primary endpoint was residual platelet reactivity 1 h after LD across the two ticagrelor formulation and according to morphine use. Safety endpoints were major bleedings and other in-hospital ticagrelor administration-related adverse events. One hour after LD, PRU median value was higher in morphine-treated patients (N = 32) as compared with patients not receiving morphine (N = 98; PRU = 187 [70-217]) vs. 73 [7-187]; P = 0.012). In patients with morphine, 1-h PRU values were similar between study groups (192 [114-236] vs. 173 [16-215] in ODT and standard tablet ticagrelor, respectively). Similarly, in patients without morphine, 1-h PRU values were not significantly different between study groups (69 [8-152] vs. 110 [6-193] in ODT and standard tablet ticagrelor, respectively). Platelet reactivity appeared similar in the 2 study arms at 2, 4, and 6 h after LD. No significant difference was observed among patients with or without morphine regarding in-hospital adverse events or drug side-effects, even if a reinfarction due to acute stent thrombosis was observed in a patient treated with morphine. CONCLUSIONS: There was no difference between ODT and standard ticagrelor tablets in terms of post-LD residual platelet reactivity, percentage of platelet inhibition or safety regardless to morphine use.

Prevalence and clinical significance of electrocardiographic signs of atrial myopathy in rheumatoid arthritis: results from the EDRA study.

OBJECTIVES: We sought to determine whether the increased risk of atrial fibrillation and stroke in rheumatoid arthritis (RA) can be accounted for by an increased prevalence of electrocardiographic markers of atrial myopathy. METHODS: We retrospectively evaluated clinical and electrocardiographic data of 218 RA patients prospectively enrolled in the Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis study (EDRA study ClinicalTrials.gov: NCT02341066) and 109 controls matched by age and gender. The prevalence of interatrial blocks (IAB, partial - pIAB or advanced - aIAB), abnormal P-wave terminal force in lead V1 (aPtfV1) and atrial myopathy (electrocardiographically defined as the presence of 1) aIAB, or 2) pIAB plus abnormal aPtfV1) was assessed in each group. RA patients were followed-up for 5 years for incident atrial fibrillation and cardiovascular events. RESULTS: Barring the prevalence of hyperlipidaemia and obesity, the demographic characteristics and cardiovascular risk profile of RA patients and controls were comparable. All subjects enrolled in the study were free from previous cardiovascular disease and atrial fibrillation. Compared to controls, RA patients had longer P-wave duration (118±12 vs. 112±10 ms, p<0.001) and higher prevalence of pIAB (43% vs. 21%, p<0.001) and abnormal PtfV1 (27% vs. 10%, p<0.001). Accordingly, atrial myopathy was significantly more prevalent (15% vs 4%, p=0.003) in RA patients. In multiple regression, male gender (OR [95% CI] = 3.09 [1.48-6.47], p=0.003) and RA (OR [95% CI] = 4.83 [1.58-14.73], p=0.006) were independently associated with atrial myopathy. Atrial myopathy was not significantly associated with incident atrial fibrillation or cardiovascular events in RA patients after 5 years of follow-up. CONCLUSIONS: Electrocardiographic markers of atrial myopathy are independently associated with RA. Further studies with larger sample size and longer follow-up are needed to determine whether the increased prevalence of atrial myopathy contributes to the increased risk of atrial fibrillation and stroke in this group.

Dual Antiplatelet Therapy with 3rd Generation P2Y12 Inhibitors in STEMI Patients: Impact of Body Mass Index on Loading Dose-Response.

PURPOSE: This study aims to assess the association between body mass index (BMI) and platelet reactivity in STEMI patients treated with oral 3rd generation P2Y12 inhibitors. METHODS: Overall, 429 STEMI patients were enrolled in this study. Patients were divided into two groups according to BMI (BMI < 25 vs ≥ 25 kg/m2). A propensity score matching (1:1) was performed to balance potential confounders in patient baseline characteristics. Platelet reactivity was assessed by VerifyNow at baseline and after 3rd generation P2Y12 inhibitor (ticagrelor or prasugrel) loading dose (LD). Blood samples were obtained at baseline (T0), 1 h (T1), 2 h (T2), 4-6 h (T3), and 8-12 h (T4) after the LD. High on-treatment platelet reactivity (HTPR) was defined as a platelet reactivity unit value ≥ 208 units. RESULTS: After propensity score matching, patients with BMI ≥ 25 had similar values of baseline platelet reactivity, while they had higher level of platelet reactivity at 1 and 2 h after the LD and higher rate of HRPT. Furthermore, multivariate analysis demonstrated that BMI ≥ 25 was an independent predictor of HTPR at 2 h (OR 2.01, p = .009). Conversely, starting from 4 h after the LD, platelet reactivity values and HRPT rates were comparable among the two study groups. CONCLUSIONS: A BMI ≥ 25 kg/m2 is associated with delayed pharmacodynamic response to oral 3rd generation P2Y12 inhibitor LD, and it is a strong predictor of HTPR in STEMI patients treated by dual antiplatelet therapy with ticagrelor or prasugrel.

The Electrocardiogram in the Diagnosis and Management of Patients With Left Ventricular Non-Compaction.

PURPOSE OF THE REVIEW: Left ventricular non-compaction (LVNC) is characterised by prominent left ventricular trabeculae and deep inter-trabecular recesses. Although considered a distinct cardiomyopathy, prominent trabeculations may also be found in other cardiomyopathies, in athletes or during pregnancy. Clinical presentation includes heart failure symptoms, systemic embolic events, arrhythmias and sudden cardiac death. Currently, LVNC diagnosis relies on imaging criteria, and clinicians face several challenges in the assessment of patients with prominent trabeculations. In this review, we summarise the available information on the role of the ECG in the diagnosis and management of LVNC. RECENT FINDINGS: ECG abnormalities have been reported in 75-94% of adults and children with LVNC. The lack of specificity of these ECG abnormalities does not allow (in isolation) to diagnose the condition. However, when considered in a set of diagnostic criteria including family history, clinical information, and imaging features, the ECG may differentiate between physiological and pathological findings or may provide clues raising the possibility of specific underlying conditions. Finally, some ECG features in LVNC constitute ominous signs that require a stricter patient surveillance or specific therapeutic measures. The ECG remains a cornerstone in the diagnosis and management of patients with cardiomyopathies, including LVNC.

Left atrial remodeling in heart failure: the role of sphericity index (the SPHERICAT-HF study).

Left atrial sphericity index (LASI) is an echocardiographic index easily obtained; its use in patients with heart failure (HF) has never been investigated so far. This single-centre study aimed to investigate the usefulness of LASI in an unselected cohort of patients hospitalized for acute HF, and its potential correlation with the amino-terminal portion of pro-B-type natriuretic peptide (NT-proBNP) levels and with New York Heart Association (NYHA) functional class. Ninety-four consecutive HF patients underwent a transthoracic echocardiogram with a detailed study of the left atrium (LA) including LASI (calculated from the apical four-chamber view as the ratio between the transverse and longitudinal diameters), and blood tests (including NT-proBNP) on the same day. Median age was 75.5 (interquartile range-IQR 62-82) years and 55% were males, 58.5% had a NYHA class III-IV, and median NT-proBNP was 3284 (IQR 1215-7055) pg/ml. The LA was dilated in 94%, and median biplane LA volume index was 62 ml/m2. Patients with advanced NYHA class showed more advanced LA remodeling. Mean LASI was 0.78 ± 0.09 and did not correlate with NT-proBNP levels (r 0.03; p 0.75) or with patient NYHA class (R2 0.011; p 0.287). None of the echocardiographic indices of LA structural and functional remodeling proved to be independently associated with a high NYHA class on multivariate regression analysis. In conclusion, LA remodeling is almost invariably present in patients with HF. LASI does not correlate with NT-proBNP levels or with NYHA functional class. Further studies are needed to describe the complex patterns of atrial remodeling in HF.

Relationship between electrocardiographic interatrial blocks and echocardiographic indices of left atrial function in acute heart failure.

The presence of an interatrial block (IAB) on surface ECG should be considered as a hallmark of atrial electrical remodelling. This is often accompanied by morphological abnormalities. We aimed to investigate the frequency of IAB and its relationship with the echocardiographic indices of left atrial (LA) remodelling in patients hospitalised with acute HF. Ninety-four consecutive HF patients underwent 12-lead ECG, transthoracic echocardiogram including a detailed study of the LA, and blood tests (including NT-proBNP) on the same day. Thirty-six patients were excluded from the analysis because of atrial fibrillation or rhythms other than sinus. Twenty-eight over 58 (48%) were males. Median age was 72 (IQR 60-82) years. The majority of patients (72%) were diagnosed as having an HF with reduced ejection fraction. Overall, 27 (46%) patients presented with an advanced III or IV NYHA functional class. Median plasma NT-proBNP was 3046 (IQR 1066-5460) pg/ml. Nearly, all the enrolled patients (90%) showed LA dilation. Nineteen patients (33%) presented with advanced IAB. There was a trend toward a more advanced age in patients with advanced IAB (median age 79 vs 68, p = 0.051). Moreover, they were more frequently treated with anticoagulants (42% vs 13%, p = 0.01), and they exhibited greater LA structural and functional remodelling documented by larger area (28 vs 26 cm2, p = 0.04) and greater minimum LA volume index-LAVi (43 ± 16 vs 36 ± 10, p = 0.04). Advanced IAB resulted to be an independent determinant of LA area (Beta 3.49 (0.37-6.60), p = 0.03) and minimum LAVi (Beta 7.22 (0.15-14.30), p = 0.045), and vice versa. LA electrical and structural remodelling is highly prevalent in a non-selected cohort of patients with acute HF. Advanced IAB on surface ECG is present in a high percentage of cases. Patients with advanced IAB tend to be older, and they exhibit higher degrees of LA structural and functional remodelling.

Not-high before-treatment platelet reactivity in patients with STEMI: prevalence, clinical characteristics, response to therapy and outcomes.

Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. Patients with not-high before-treatment platelet reactivity (NHPR) have been poorly studied so far. The aim of this study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI.We analyzed the data from 358 STEMI patients with assessment of PR by VerifyNow before P2Y12 inhibitor loading dose (LD). Blood samples were obtained at baseline, and after 1 hour, 2 hours, 4-6 hours and 8-12 hours after LD. High platelet reactivity (HPR) was defined as Platelet Reactivity Unit values ≥208, while patients with values <208 at baseline were defined as having NHPR.Overall, 20% patients had NHPR. Age and male gender both resulted independent predictors of NHPR, even after propensity score adjustment. The percentage of inhibition of PR after ticagrelor or prasugrel LD was similar between HPR and NHPR patients at each time point. However, patients with HPR showed worse in-hospital clinical outcomes, and the composite adverse outcome endpoint of death, reinfarction, stroke, acute kidney injury or heart failure was significantly higher (10.0% vs 1.4%; p = .017) as compared with the NHPR group.In conclusion, a significant proportion of patients presenting with STEMI has a baseline NHPR that is associated with better in-hospital outcomes as compared with patients with HPR. Further studies are needed to better elucidate the potential therapeutic implications of NHPR in terms of secondary prevention.

Prevalence, clinical and instrumental features of left bundle branch block-induced cardiomyopathy: the CLIMB registry.

AIMS: Although increasingly recognized as a distinct pathological entity, left bundle branch block-induced cardiomyopathy (LBBB-ICMP) is not included among the possible aetiologies of acquired dilated cardiomyopathies (DCM). While diagnostic criteria have been proposed, its recognition remains principally retrospective, in the presence of clinical and instrumental red flags. We aimed to assess the prevalence and clinical and instrumental features of LBBB-ICMP in a large cohort of patients with DCM. METHODS AND RESULTS: We analysed a cohort of 242 DCM patients from a two-centre registry. Inclusion criteria were age > 18, non-ischaemic or non-valvular DCM, and LBBB on electrocardiogram. LBBB-ICMP was defined according to previously proposed diagnostic criteria: (i) neither family history nor clinically identifiable potential causes for DCM; (ii) negative genetic testing; (iii) echocardiographic features including non-severe chamber dilation, normal absolute and relative wall thickness, marked dyssynchrony, and normal right ventricular function; and (iv) absence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). From the entire cohort, we identified 30 subjects (similar in terms of New York Heart Association class I or II in 80% vs. 75%, P = 0.56; QRS width of 150 ± 22 vs. 151 ± 24 ms, P = 0.82; and cardiac remodelling of baseline end-diastolic diameter 66 ± 8 vs. 65 ± 10 mm, P = 0.53) with a comprehensive dataset including CMR and genetic testing, required to verify the presence of the diagnostic criteria proposed for LBBB-ICMP. The main characteristics of this subgroup were 73% males, age 45 ± 13 years, left ventricular ejection fraction (LVEF) 30 ± 10%, LGE in 38% of patients, and QRS complex of 150 ± 22 ms. Patients were under guideline-directed medical therapy, and 57% of them were treated with cardiac resynchronization therapy (CRT). Two patients (6.67%, 50% males, age 53 ± 13 years) fulfilled the diagnostic criteria proposed for LBBB-ICMP. After a follow-up of 44 (12-76) months, LVEF was normal and QRS width significantly reduced (from 154 ± 25 to 116 ± 52 ms) in patients with LBBB-ICMP. Both patients were under optimal medical treatment, and one was implanted with CRT-D. Neither of the two patients experienced death, malignant ventricular arrhythmia, or heart failure hospitalization at follow-up. CONCLUSIONS: Left bundle branch block-induced cardiomyopathy emerges as a distinct pathological entity, promptly identifiable in a minority but not negligible proportion of patients with newly diagnosed DCM and LBBB, using a series of diagnostic criteria including CMR and genetic testing. Further studies are needed to better elucidate the clinical course of LBBB-ICMP.

Echocardiographic Longitudinal Strain Analysis in Heart Failure: Real Usefulness for Clinical Management Beyond Diagnostic Value and Prognostic Correlations? A Comprehensive Review.

Heart failure (HF) is a highly prevalent clinical syndrome characterized by considerable phenotypic heterogeneity. The traditional classification based on left ventricular ejection fraction (LVEF) is widely accepted by the guidelines and represents the grounds for patient enrollment in clinical trials, even though it shows several limitations. Ejection fraction (EF) is affected by preload, afterload, and contractility, it being problematic to express LV function in several conditions, such as HF with preserved EF (HFpEF), valvular heart disease, and subclinical HF, and in athletes. Over the last two decades, developments in diagnostic techniques have provided useful tools to overcome EF limitations. Strain imaging analysis (particularly global longitudinal strain (GLS)) has emerged as a useful echocardiographic technique in patients with HF, as it is able to simultaneously supply information on both systolic and diastolic functions, depending on cardiac anatomy and physiology/pathophysiology. The use of GLS has proved helpful in terms of diagnostic performance and prognostic value in several HF studies. Universally accepted cutoff values and variability across vendors remain an area to be fully explored, hence limiting routine application of this technique in clinical practice. In the present review, the current role of GLS in the diagnosis and management of patients with HF will be discussed. We describe, by critical analysis of the pros and cons, various clinical settings in HF, and how the appropriate use and interpretation of GLS can provide important clues.

Impact of glucose-6-phosphate dehydrogenase deficiency on the severity of coronary atherosclerosis in patients with acute coronary syndromes.

AIMS: The impact of glucose-6-phosphate dehydrogenase (G6PD) deficiency on coronary atherosclerosis has not been clearly investigated so far. We aimed to assess the effects of G6PD deficiency on the extent and complexity of coronary atherosclerosis in a large unselected cohort of consecutive patients with acute coronary syndromes (ACS). METHODS: We studied 623 consecutive patients presenting with ACS and undergoing coronary angiography and percutaneous coronary intervention (PCI). G6PD activity was quantitatively measured in all individuals using a biochemical assay based on the G6PD/6GPD ratio in erythrocytes. Individuals were defined as deficient when the ratio was less than 0.80. The severity and complexity of coronary atherosclerosis were assessed by SYNTAX score at baseline angiography. RESULTS: Fifty-six patients (9%) showed G6PD deficiency. Severe (i.e. enzymatic activity < 0.10) G6PD deficiency was detected in 33 (5.3%) individuals, mainly of male sex (n = 32). Overall, the cardiovascular risk profile was similar between patients with G6PD deficiency and controls. Patients with G6PD deficiency showed similar severity and complexity of coronary atherosclerosis as compared to control patients; accordingly, the SYNTAX score (15 vs. 14.5, P = 0.90, respectively, in G6PD-deficent patients and controls), and all its components were similar between deficient individuals and controls. The only independent predictor of a SYNTAX score of more than 22 was patients' age (odds ratio 1.035, 95% confidence interval 1.018-1.051; P < 0.001). CONCLUSION: G6PD deficiency does not impact on the extent and complexity of coronary atherosclerosis assessed by coronary angiography in patents presenting with ACS.

Outcomes of single­lead VDD pacemakers in atrioventricular blocks: The OSCAR study.

BACKGROUND: VDD pacemakers are regarded as a second choice in patients with atrio-ventricular blocks mainly due to the potential failure of atrial sensing, leading to a loss of atrio-ventricular synchrony. This single-centre study aimed to evaluate the prevalence of loss of atrial sensing and its potential determinants in patients with VDD pacemakers. METHOD: 142 patients with an implanted VDD device underwent long-term follow-up with clinical evaluation, electrocardiogram, device interrogation and echocardiogram. RESULTS: Over a long follow-up period [median 110 (68-156) months], 17 patients (12%) in sinus rhythm presented loss of atrial sensing. This was most often intermittent, but three patients required a permanent switch to VVI mode. ECG showed higher prevalence of interatrial blocks (50% vs 26.6%, p = 0.057) and longer P wave duration (116 ± 19 vs 105 ± 15 ms, p = 0.019) in patients with loss of atrial sensing. Echocardiography revealed larger left atrial (LA) volumes (p < 0.05) in patients with loss of atrial sensing, and lower LA ejection fraction (0.40 vs 0.47, p = 0.0037) and expansion index (0.63 ± 0.26 vs 0.90 ± 0.31, p = 0.003). P wave duration on ECG proved to be independently associated with loss of atrial sensing on multivariable analysis (OR 1.062, 95% CI 1.015-1.110; p = 0.008). The prevalence of atrial fibrillation and subsequent switch to VVI mode was high (16%). CONCLUSIONS: In the long-term follow-up, the loss of atrial sensing is present in 12% of patients with implanted VDD pacemakers. ECG and echocardiographic parameters may serve as screening tools for the detection of atrial myopathy which is associated with the loss of atrial sensing.