Characteristics of patients with recurrent acute myocardial infarction after MINOCA.

BACKGROUND: Myocardial infarction (MI) with non-obstructed coronary arteries (MINOCA) is an increasingly recognized condition with challenging management. Some MINOCA patients ultimately experience recurrent acute MI (re-AMI) during follow-up; however, clinical and angiographic factors predisposing to re-AMI are still poorly defined. METHODS: In this retrospective multicenter cohort study we enrolled consecutive patients fulfilling diagnostic criteria of MINOCA according to the IV universal definition of myocardial infarction; characteristics of patients experiencing re-AMI during the follow-up were compared to a group of MINOCA patients without re-AMI. RESULTS: 54 patients (mean age 66 ± 13) experienced a subsequent re-AMI after MINOCA and follow-up was available in 44 (81%). Compared to MINOCA patients without re-AMI (n = 695), on first invasive coronary angiography (ICA) MINOCA patients with re-AMI showed less frequent angiographically normal coronaries (37 versus 53%, p = 0.032) and had a higher prevalence of atherosclerosis involving 3 vessels or left main stem (17% versus 8%, p = 0.049). Twenty-four patients (44%) with re-AMI underwent a new ICA: 25% had normal coronary arteries, 12.5% had mild luminal irregularities (<30%), 20.8% had moderate coronary atherosclerosis (30-49%), and 41.7% showed obstructive coronary atherosclerosis (≥50% stenosis). Among patients undergoing new ICA, atherosclerosis progression was observed in 11 (45.8%), 37.5% received revascularization, only 4.5% had low-density lipoprotein cholesterol (LDL_C) under 55 mg/dL and 33% experienced a new cardiovascular disease (CVD) event (death, AMI, heart failure, stroke) at subsequent follow-up. CONCLUSIONS: In the present study, only a minority of MINOCA patients with re-AMI underwent a repeated ICA, nearly one out of two showed atherosclerosis progression, often requiring revascularization. Recommended LDL-C levels were achieved only in a minority of the cases, indicating a possible underestimation of CVD risk in this population.

Beyond VO2: the complex cardiopulmonary exercise test.

Cardiopulmonary exercise test (CPET) is a valuable diagnostic tool with a specific application in heart failure (HF) thanks to the strong prognostic value of its parameters. The most important value provided by CPET is the peak oxygen uptake (peak VO2), the maximum rate of oxygen consumption attainable during physical exertion. According to the Fick principle, VO2 equals cardiac output (Qc) times the arteriovenous content difference [C(a-v)O2], where Ca is the arterial oxygen and Cv is the mixed venous oxygen content, respectively; therefore, VO2 can be reduced both by impaired O2 delivery (reduced Qc) or extraction (reduced arteriovenous O2 content). However, standard CPET is not capable of discriminating between these different impairments, leading to the need for 'complex' CPET technologies. Among non-invasive methods for Qc measurement during CPET, inert gas rebreathing and thoracic impedance cardiography are the most used techniques, both validated in healthy subjects and patients with HF, at rest and during exercise. On the other hand, the non-invasive assessment of peripheral muscle perfusion is possible with the application of near-infrared spectroscopy, capable of measuring tissue oxygenation. Measuring Qc allows, by having haemoglobin values available, to discriminate how much any VO2 deficit depends on the muscle, anaemia or heart.

Heart failure patients with improved ejection fraction: Insights from the MECKI score database.

AIMS: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). METHODS AND RESULTS: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis. CONCLUSIONS: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Prognostic value of cardiopulmonary exercise testing repetition during follow-up of clinically stable patients with severe dilated cardiomyopathy. A preliminary study.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a recognized tool for prognostic stratification in patients with dilated cardiomyopathy (DCM). Given the lack of data currently available, the aim of this study was to test the prognostic value of repeating CPET during the follow-up of patients with DCM. METHODS: This multicenter, retrospective study, analyzed DCM patients who consecutively performed two echocardiographies and CPETs during clinical stability. The study end-point was a composite of death from all causes, heart transplantation, left ventricular assist device implantation, life-threatening ventricular arrhythmias or hospitalization for heart failure. RESULTS: 216 DCM patients were enrolled (52 years, 78% male, NYHA I-II 82%, LVEF 32%, 94% on ACE inhibitors/ARNI, 95% on beta-blockers). The interval between CPETs was 15 months. During a median follow-up of 38 months from the second CPET, 102 (47%) patients experienced the study end-point. Among them, there was stability of echocardiographic values but a significant worsening of functional capacity. Among the 173 patients (80%) who did not show echocardiographic left ventricular reverse remodeling (LVRR), the 1-year prevalence of the study-end point was higher in patients who worsened vs patients who maintained stable their functional capacity at CPET (38 vs. 15% respectively, p-value: 0.001). These results were consistent also when excluding life-threatening ventricular arrhythmias from the composite end-point. CONCLUSION: In clinically stable DCM patients with important depression of LVEF, the repetition of combined echocardiography and CPET might be recommended. When LVRR fails, 1-year repetition of CPET could identify higher-risk patients.

The importance of re-evaluating the risk score in heart failure patients: An analysis from the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database.

BACKGROUND: The role of risk scores in heart failure (HF) management has been highlighted by international guidelines. In contrast with HF, which is intrinsically a dynamic and unstable syndrome, all its prognostic studies have been based on a single evaluation. We investigated whether time-related changes of a well-recognized risk score, the MECKI score, added prognostic value. MECKI score is based on peak VO2, VE/VCO2 slope, Na+, LVEF, MDRD and Hb. METHODS: A multi-centre retrospective study was conducted involving 660 patients who performed MECKI re-evaluation at least 6 months apart. Based on the difference between II and I evaluation of MECKI values (MECKI II - MECKI I = ∆ MECKI) the study population was divided in 2 groups: those presenting a score reduction (∆ MECKI <0, i.e. clinical improvement), vs. patients presenting an increase (∆ MECKI >0, clinical deterioration). RESULTS: The prognostic value of MECKI score is confirmed also when re-assessed during follow-up. The group with improved MECKI (366 patients) showed a better prognosis compared to patients with worsened MECKI (294 patients) (p < 0.0001). At 1st evaluation, the two groups differentiated by LVEF, VE/VCO2 slope and blood Na+ concentration, while at 2nd evaluation they differentiated in all 6 parameters considered in the score. The patients who improved MECKI score, improved in all components of the score but hemoglobin, while patients who worsened the score, worsened all parameters. CONCLUSIONS: This study shows that re-assessment of MECKI score identifies HF subjects at higher risk and that score improvement or deterioration regards several MECKI score generating parameters confirming the holistic background of HF.

Does moderate hyperkalemia influence survival in HF? Insights from the MECKI score data base.

BACKGROUND: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin-angiotensin-aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. OBJECTIVES: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. METHODS AND RESULTS: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9-7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1-14.1%] and 7.3% [IQR 3.4-15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. CONCLUSIONS: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

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 Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy.

BACKGROUND: Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption. OBJECTIVES: This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. METHODS: Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries. RESULTS: A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; P = 0.001), absence of hypertension (OR: 2.28; 95% CI: 1.67-3.13; P < 0.001), and absence of left bundle branch block (OR: 3.58; 95% CI: 2.57-5.01; P < 0.001). A score containing these factors predicted a G+ result, ranging from 3% when all predictors were absent to 79% when ≥4 predictors were present. Internal validation provided a C-statistic of 0.74 (95% CI: 0.71-0.77) and a calibration slope of 0.94 (95% CI: 0.80-1.10). The C-statistic in the external validation cohort was 0.74 (95% CI: 0.71-0.78). CONCLUSIONS: The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD.

Role of the electrocardiogram in differentiating genetically determined dilated cardiomyopathy from athlete's heart.

BACKGROUND: Physiological cardiac remodelling in highly trained athletes may overlap with dilated cardiomyopathy (DCM). OBJECTIVES: The aim of this study was to investigate the role of the electrocardiogram (ECG) in differentiating between physiological and pathological remodelling. METHODS: The study population consisted of 30 patients with DCM who revealed a pathogenic variant at genetic testing and 30 elite athletes with significant cardiac remodelling defined by a left ventricular (LV) end-diastolic diameter >62 mm and/or LV ejection fraction between 45% and 50%. RESULTS: The ECG was abnormal in 22 (73%) patients with DCM. The most common abnormalities were low voltages (n = 14, 47%), lateral T-wave inversion (TWI) (n = 6, 20%), ventricular ectopic beats (n = 5, 17%) and anterior TWI (n = 4, 13). Two athletes revealed an abnormal ECG: complete left bundle branch block (LBBB) in one case and atrial flutter in the other. The sensitivity, specificity and accuracy of the ECG in differentiating DCM from physiological adaptation to exercise in athletes was 73% (confidence interval [CI]: 54%-88%), 93% (CI: 78%-99%) and 0.83 (CI: 0.71-0.92) respectively. CONCLUSIONS: While the ECG is usually normal in athletes exhibiting significant LV dilatation and/or systolic dysfunction, this test is often abnormal in patients with DCM harbouring a pathogenic variant. Low voltages in the limb leads and lateral TWI are the most common abnormalities.

Pick Your Threshold: A Comparison Among Different Methods of Anaerobic Threshold Evaluation in Heart Failure Prognostic Assessment.

BACKGROUND: In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. RESEARCH QUESTION: What is the prognostic power of these different ways to report AT? STUDY DESIGN AND METHODS: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. RESULTS: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305 mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O2 < 12 mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. INTERPRETATION: In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

The double anaerobic threshold in heart failure: MECKI score database overview.

AIMS: In heart failure (HF), anaerobic threshold (AT) may be indeterminable but its value held a relevant prognostic role. AT is evaluated joining three methods: V-slope, ventilatory equivalent, and end-tidal methods. The possible non-concordance between the V-slope (met AT) and the other two methods (vent AT) has been highlighted in healthy individuals and named double threshold (DT). METHODS AND RESULTS: We reanalysed 1075 cardiopulmonary exercise tests of HF patients recruited in the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score database. We identified DT in 43% of cases. Met AT precedes vent AT being met-ventΔVO2 221 (interquartile range: 129-319) mL/min. Peak VO2 , 1307 ± 485 vs. 1343 ± 446 mL/min (63 ± 17 vs. 63 ± 17 percentage of predicted), was similar between DT+ and DT- patients. Differently, DT+ showed a lower ventilatory vs. carbon dioxide production (VE/VCO2 ) slope (29.6 ± 6.1 vs. 31.0 ± 6.3), a lower peak exercise end-tidal oxygen tension (PetO2 ) 115.3 (111.5-118.9) vs. 116.4 (112.4-120.2) mmHg, and a higher carbon dioxide tension (PetCO2 ) 34.2 (30.9-37.1) vs. 32.4 (28.7-35.5) mmHg. Vent AT showed a significant higher VO2 , 957 ± 318 vs. 719 ± 252 mL/min, VCO2 , 939 ± 319 vs. 627 ± 226 mL/min, ventilation, 31.0 ± 8.3 vs. 22.5 ± 6.3 L/min, respiratory exchange ratio, 0.98 ± 0.08 vs. 0.87 ± 0.07, PetO2 , 108 (104-112) vs. 105 (101-109) mmHg, PetCO2 , 37 (34-40) vs. 36 (33-39) mmHg, and VE/VO2 ratio, 33.5 ± 6.7 vs. 32.6 ± 6.9, but lower VE/VCO2 ratio, 33 (30-37) vs. 36 (32-41), compared with met AT. At 2 year survival by Kaplan-Meier analysis, even adjusted for confounders, DT resulted not associated with survival. CONCLUSIONS: Double threshold is frequently observed in HF patients. DT+ is associated to a decreased ventilatory response during exercise.

Exercise oxygen pulse kinetics in patients with hypertrophic cardiomyopathy.

OBJECTIVES: Reduced cardiac output (CO) has been considered crucial in symptoms' genesis in hypertrophic cardiomyopathy (HCM). Absolute value and temporal behaviour of O2-pulse (oxygen uptake/heart rate (VO2/HR)), and the VO2/work relationship during exercise reflect closely stroke volume (SV) and CO changes, respectively. We hypothesise that adding O2-pulse absolute value and kinetics, and VO2/work relationship to standard cardiopulmonary exercise testing (CPET) could help identify more exercise-limited patients with HCM. METHODS: CPETs were performed in 3 HCM dedicated clinical units. We retrospectively enrolled non-end-stage consecutive patients with HCM, grouped according to left ventricle outflow tract obstruction (LVOTO) at rest or during Valsalva manoeuvre (72% of patients with LVOTO <30; 10% between 30 and 49 and 18% ≥50 mm Hg). We evaluated the CPET response in HCM focusing on parameters strongly associated with SV and CO, such as O2-pulse and VO2, respectively, considering their absolute values and temporal behaviour during exercise. RESULTS: We included 312 patients (70% males, age 49±18 years). Peak VO2 (percentage of predicted), O2-pulse and ventilation to carbon dioxide production (VE/VCO2) slope did not change across LVOTO groups. Ninety-six (31%) patients with HCM presented an abnormal O2-pulse temporal behaviour, irrespective of LVOTO values. These patients showed lower peak systolic pressure, workload (106±45 vs 130±49 W), VO2 (21.3±6.6 vs 24.1±7.7 mL/min/kg; 74%±17% vs 80%±20%) and O2-pulse (12 (9-14) vs 14 (11-17) mL/beat), with higher VE/VCO2 slope (28 (25-31) vs 27 (24-31)) (p<0.005 for all). Only 2 patients had an abnormal VO2/work slope. CONCLUSION: None of the frequently used CPET parameters, either as absolute values or dynamic relationships, were associated with LVOTO. Differently, an abnormal temporal behaviour of O2-pulse during exercise, which is strongly related to inadequate SV increase, correlates with reduced functional capacity (peak and anaerobic threshold VO2 and workload) and increased VE/VCO2 slope, identifying more advanced disease irrespectively of LVOTO.

Supraventricular Tachycardia Causing Left Ventricular Dysfunction.

There is limited evidence on characterization and natural history of supraventricular tachycardia (SVT)-induced left ventricular (LV) dysfunction. The aim of this work was to characterize clinical features and long-term evolution of SVT-induced LV dysfunction. Patients consecutively admitted with sustained SVT and heart rate >100 bpm as the only known cause of a new onset LV systolic dysfunction (i.e., LV ejection fraction [EF] <50%) were analyzed. Patients were then revaluated periodically. Recovered LVEF (i.e., ≥50%) and a composite of death, heart transplant or first episode of major ventricular arrhythmias were evaluated as study end-points. We enrolled 83 patients. After SVT therapy, 56 (67%) showed a recovered LVEF at the last follow-up of median 54 (interquartile range 36 to 87) months. Seventeen (30%) of those patients had a temporary new drop in LVEF during follow-up associated to high-rate SVT relapse. At presentation, patients with recovered LVEF were younger (52 vs 67 years respectively, p <0.001) and had higher LVEF (34% vs 27% respectively, p = 0.005) compared to non-recovered LVEF patients. Finally, 4% of recovered LVEF patients vs 26% of nonrecovered LVEF patients experienced death/heart transplant/major ventricular arrhythmias during follow-up (p = 0.004). In conclusion, after almost 5 years of follow-up, two-thirds of patients with high-rate SVT causing a newly diagnosed LV systolic dysfunction recovered and maintained normal LV function after SVT control, with a subsequent benign outcome. Long term individual surveillance is required in those patients, as arrhythmic recurrences and new drops in LVEF are common in the long term.

Pharmacological therapy for the prevention of cardiovascular events in patients with myocardial infarction with non-obstructed coronary arteries (MINOCA): Insights from a multicentre national registry.

AIMS: To assess the effect of pharmacological therapy on long-term prognosis of patients with MINOCA. METHODS AND RESULTS: In this retrospective multicentre cohort study involving 9 Hub Hospitals across Italy we enrolled consecutive patients 18 years and older with diagnosis of MINOCA discharged from 1st March 2012 to 31st March 2018. Data on baseline characteristics and pharmacological therapy at discharge (ACEI/ARB, angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists; ASA, acetylsalicylic acid; beta-blockers; CCB, calcium-channel blockers; DAPT, dual anti-platelet therapy; statins), were collected systematically. The primary endpoint (PE) of the study was a composite of all cause death or acute myocardial infarction or acute coronary syndrome or heart failure leading to hospitalization or stroke. A total of 621 patients were included (mean [SD] age 65.1 [13.9] years; 344 [55.4%] female), of whom 106 (17.1%) experienced PE, including 27 patients (4.3%) who died. Multivariable analysis, after correction for all baseline differences, showed a significant association between pharmacological therapy at discharge and an increased risk of PE for aspirin (HR[95%CI] = 2.47[1.05-5.78], adjusted p = 0.04), whereas beta-blockers were associated with a significant benefit (HR[95%CI] = 0.49 [0.31-0.79], adjusted p = 0.02). CONCLUSION: The use of beta-blockers was significantly associated to a less frequent occurrence of adverse outcomes at long-term follow-up among patients with MINOCA, whereas ASA displayed a potentially harmful impact on prognosis. The findings in the study may be relevant for the design of future studies which should take into account possible heterogeneity among MINOCA patients.

Risk stratification in cardiomyopathy.

Prognostic stratification of cardiomyopathies represents a cornerstone for the appropriate management of patients and is focused mainly on arrhythmic events and heart failure. Cardiopulmonary exercise testing provides additional prognostic information, particularly in the setting of heart failure. Cardiopulmonary exercise testing data, integrated in scores such as the Metabolism Exercise Cardiac Kidney Index score have been shown to improve the risk stratification of these patients. Cardiopulmonary exercise testing has been analysed as a potential supplier of prognostic parameters in the context of hypertrophic cardiomyopathy, for which it has been shown that a reduced oxygen consumption peak, an increased ventilation/carbon dioxide production slope and chronotropic incompetence correlate with a worse prognosis. To a lesser extent, in dilated cardiomyopathy, it has been shown that the percentage of oxygen consumption peak, not the pure value, and the ventilation/carbon dioxide production slope are associated with a greater cardiovascular risk. Few data are available about other cardiomyopathies (arrhythmogenic and restrictive). Cardiomyopathy patients should be early and routinely referred to heart failure advanced centres in order to perform a comprehensive risk stratification which should include a cardiopulmonary exercise test, with variables and cut-offs shown to improve their risk stratification.

Management of nonischemic-dilated cardiomyopathies in clinical practice: a position paper of the working group on myocardial and pericardial diseases of Italian Society of Cardiology.

: Nonischemic-dilated cardiomyopathy (NIDCM) is an entity that gathers extremely heterogeneous diseases. This awareness, although leading to continuous improvement in survival, has increased the complexity of NIDCM patients' management. Even though the endorsed 'red-flags' approach helps clinicians in pursuing an accurate etiological definition in clinical practice, it is not clear when and how peripheral centers should interact with referral centers with specific expertise in challenging scenarios (e.g. postmyocarditis and genetically determined dilated cardiomyopathy) and with easier access to second-line diagnostic tools and therapies. This position paper will summarize each step in NIDCM management, highlighting the multiple interactions between peripheral and referral centers, from first-line diagnostic workup and therapy to advanced heart failure management and long-term follow-up.

ECG in dilated cardiomyopathy: specific findings and long-term prognostic significance.

OBJECTIVE: The objective was to provide an exhaustive characterization of ECG features in a large cohort of dilated cardiomyopathies (DCMs) and then investigate their possible prognostic role in the long term. BACKGROUND: ECG is an accessible, reproducible, low-cost diagnostic and prognostic tool. However, an extensive description of ECG features and their long-term prognostic role in a large cohort of DCM is lacking. METHODS: All available baseline ECGs of DCM patients enrolled from 1992 to 2013 were systematically analysed. Patients underwent to a complete clinical-laboratory evaluation. The study outcome measures were death or heart transplant (D/HT) and sudden death or malignant ventricular arrhythmias (SD/MVA). RESULTS: Four hundred and fourteen DCM patients were enrolled. During a median follow-up of 125 months, 55 and 57 patients experienced D/HT and SD/MVA, respectively. At multivariate analysis, left ventricular hypertrophy (P = 0.017), heart rate (HR, P = 0.005) and anterolateral T-wave inversion (P = 0.041) predicted D/HT. Regarding SD/MVA, S wave amplitude in V2 (P = 0.008), R wave amplitude in DIII (P = 0.007), anterolateral T-wave inversion (P = 0.017) emerged as predictors. At receiver-operating curve analyses, the addition of ECG models to the clinical-laboratory evaluation significantly increased the area under the curve both for D/HT (from 0.68 to 0.74, P = 0.042) and SD/MVA (from 0.70 to 0.77, P = 0.048). CONCLUSION: The exhaustive systematic evaluation of ECG has an incremental impact in the prognostication of a large cohort of DCM patients, also regarding the arrhythmic stratification.