High prevalence of cardiac post-acute sequelae in patients recovered from Covid-19. Results from the ARCA post-COVID study.

Background: Many data were published about Long-Covid prevalence, very few about the findings of new cardiac alterations (NCA) in COVID-19-recovered people. ARCA-post-COVID is an observational study designed to investigate the prevalence of NCA in patients recovered from Covid-19.Methods: from June 2020 to December 2022, we enrolled 502 patients with a positive nasopharyngeal swab for SARS-CoV2 and a subsequent negative one. We performed anamnesis, lab-test, and routine cardiological tests (ECG, Holter, TTE). Results: The median age was 56 years (IQR 44-67); women were 52.19%; in the acute phase 24.1% of patients were treated in a medical department, 7.2% in the ICU and the others at home. At the visit, 389 patients (77.49%) complained of a broad range of symptoms. We reported patients' characteristics according to the course of the disease and the persistence of symptoms. NCA were found in 138 patients (27.49%): among them 60 cases (11.95%) of pericardial effusion. Patients with NCA were older (median 60y, IQR: 47-72, vs median 56y, IQR 42-65), had a higher prevalence of smokers (27% vs 17%; p0.014), CAD (11% vs 6%; p0.048) and stroke/TIA (3.6% vs 0.3%; p0.002) and a lower prevalence of hypercholesterolemia (18% vs 30%; p0.007). The prevalence of NCA seems constant with different subtypes of the virus. Conclusion: the prevalence of NCA in patients who recovered from COVID-19 is high and constant since the beginning of the pandemic; it is predictable based on hospitalization and long-lasting symptoms (9.64%-42.52%). Patients with one of these characteristics should undergo cardiological screening.

Clinical outcomes of newly diagnosed, stable angina patients managed according to current guidelines. The ARCA (Arca Registry for Chronic Angina) Registry: A prospective, observational, nationwide study.

BACKGROUND: Clinical outcomes of stable angina patients treated according to guidelines recommendations (medical therapy first, selective revascularization in high risk or unresponsive patients) are not fully known. METHODS AND RESULTS: Eight hundred thirty-three patients with newly diagnosed, stable angina were enrolled in a prospective, observational, nationwide registry and followed for 1 year. Symptoms and quality of life were evaluated with the CCS angina grading, with a self-assessment scale and with the SAQ-7. A composite end-point of MACEs (all-cause death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina) at 1 year was considered. Upon enrollment, all patients were prescribed guidelines directed medical therapy. After one month of therapy, angina relieved or improved in 47% of the overall population. Patients in CCS class I significantly increased from 28.4% at enrollment to 67.1% at 12 months, and the SAQ-7 score from 58.4 ± 20 to 85.9 ± 14. The rate of MACEs was low (2.9%) in the overall population. After one month of medical therapy, 40.6% of patients were referred for coronary angiography and revascularization for resistant symptoms (invasive strategy). Among these, 38.2% had normal coronary arteries and 47% actually underwent revascularization. No difference between invasive and medical groups was found at 12 months in symptoms, quality of life and MACEs, except for a greater improvement in self-assessed symptoms in the invasive group. Combined medical and invasive strategies left 28.5% of patients still symptomatic at the end of the study. CONCLUSIONS: The study confirms the efficacy and safety of a tailored approach to stable angina, as recommended by guidelines, with medical therapy first followed by selective revascularization when needed.

Factors for heterogeneous outcomes of angina and myocardial ischemia without obstructive coronary atherosclerosis.

BACKGROUND AND OBJECTIVES: The absence of obstructive coronary artery disease (CAD) in patients with angina is common, but its prognosis is debated. We investigated outcomes of such patients to identify predictors of cardiovascular events. METHODS: We selected 1014 patients with angina, evidence of myocardial ischemia at the electrocardiogram (ECG) exercise test or imaging stress tests, and nonobstructive CAD (absence of lumen diameter reduction ≥50%) at coronary angiography between 1999 and 2015. Note that, 1905 age- and risk factors-matched asymptomatic subjects served as "real-world" comparators. The primary endpoint was the occurrence of all-cause death or myocardial infarction. RESULTS: At 6-years median follow-up (interquartile range, 3-9 years), the primary endpoint occurred in 53 patients (5.5%, 0.92/100 person-years). Besides similar event rates compared with asymptomatic subjects (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.62-1.15, p = 0.28), the index population showed a very heterogeneous prognosis. Patients with nonobstructive CAD (HR 1.85, 95% CI 1.02-3.37, p = 0.04, compared with "normal" coronary arteries) and ischemia at imaging tests (HR 2.11, 95% CI 1.07-4.14, p = 0.03, compared with ischemia detected only at the ECG exercise test) were at higher risk and those with both these components showing even >10-fold event rates as compared with the absence of both. Three-hundred and twenty-five patients (34%) continued to experience angina, 69 (7.2%) underwent repeat coronary angiography, and 14 (1.5%) had consequent coronary revascularization for atherosclerosis progression. CONCLUSION: Apart from the impaired quality of life, angina without obstructive CAD has an overall benign but very heterogeneous prognosis. Nonobstructive CAD and myocardial ischemia at imaging tests both confer a higher risk.

Stable ischemic heart disease: re-appraisal of coronary revascularization criteria in the light of contemporary evidence.

The term "stable ischemic heart disease" includes a variety of clinical and pathophysiological situations resulting in different presentation modalities, often with complex referral patterns, and with multiple potential therapeutical options. Multifactorial pathogenesis and multiform expressivity are poorly captured by the traditional vision of ischemic heart disease (IHD) as the clogged pipes disease. The availability of different technologies for studying patients with symptoms suggestive of IHD, has shed a new light on the pathophysiology of the disease, but has also allowed appropriate follow-up of patients allocated to different therapeutical options. Though coronary revascularization has been one primary treatment option for obstructive coronary artery disease (CAD), the evidence for its efficacy in patients without acute presentation is far from optimal. A number of studies and meta-analyses strongly support the need for a personalized and optimized medical approach (including functional assessment and therapy) before the tailored option of revascularization in selected patients, in order to optimize its effects on symptoms and outcome. Most recent data have expanded the need for a more personalised approach to this complex situation, which should be patient-centered and not focused on technologies. In this review, we discuss the major pathophysiological factors and the most recent clinical data and guidelines suggestions, needed for a critical re-appraisal of the clinical decision-making to perform revascularization in patients with stable IHD. Moreover we aimed at suggesting the potential role for future studies to fill the existing knowledge gaps but also to counteract a reductive, hydraulic view of chronic IHD, which seems to be still alive and kicking, both in clinical and research communities, despite multiple evidences and recommendations.

High sensitivity cardiac troponins: Can they help in diagnosing myocardial ischaemia?

BACKGROUND: Cardiac troponin is the most sensitive marker of myocardial injury, but controversy still exists about its role in detecting ischaemia. METHODS: To investigate the role of troponin as a marker of stress-induced ischaemia, circulating high sensitivity cardiac troponin T (hs-cTnT) was measured and compared with the MB fraction of creatine kinase (CK-MB) in 125 patients undergoing a stress test (53 electrocardiogram/echo exercise, 42 echo dipyridamole and 30 echo dobutamine tests). RESULTS: Plasma concentrations of hs-cTnT increased after the tests in 90/125 patients, while an increase of CK-MB was seen in 31/125 patients ( p<0.0001). Overall, hs-cTnT significantly increased from 17.5±16.9 ng/l to 25.5±27.9 ng/l ( p<0.0001), without significant changes of CK-MB. Significant increments in hs-cTnT were documented after exercise test (from 15.9±11.9 ng/l to 19.5±13.6 ng/l, p<0.0001) and dobutamine test (from 20.6±20.8 ng/l to 37.8±31.1 ng/l, p=0.0006), in absence of changes in CK-MB according to each stressor. Among the 125 tests, 84 were diagnosed as negative and 41 as positive for myocardial ischaemia. Significant increments in hs-cTnT were detected after both negative (from 18.6±19.2 ng/l to 27.1±32.1 ng/l, p=0.0018) and positive test (from 15.2±10.8 ng/l to 22.3±16.2 ng/l, p=0.0005), without significant changes of CK-MB according to the test result. Despite a positive correlation between stress-induced increase of hs-cTnT and obstructive coronary artery disease, the release of troponin was observed also in a significant proportion of patients without coronary stenoses. Left ventricular hypertrophy markedly enhanced myocardial release of troponin. CONCLUSIONS: Circulating troponin increases in most patients undergoing a stress test, irrespective of the test result and of coronary artery disease. Plasma release of troponin depends on multiple pathogenetic mechanisms, making the biomarker a not reliable tool in detecting transient ischaemia.

Interactions Between Reciprocal ST-Segment Downsloping During ST-Elevated Myocardial Infarction and Global Cardiac Perfusion and Functional Abnormalities.

Reciprocal ST-segment downsloping on electrocardiogram is a frequent finding during ST-elevated myocardial infarction (STEMI), but its etiology is still disputed. We sought to evaluate the relation between reciprocal ST-segment downsloping during STEMI and major cardiac perfusion and functional parameters. One hundred eighty-five patients with STEMI underwent emergency coronary angiography. The presence of reciprocal ST-segment downsloping was assessed. At coronary angiography, the corrected TIMI frame count (cTFC) was computed both on culprit and remote vessels and the occurrence of "no/slow reflow" phenomenon after percutaneous coronary intervention (PCI) identified. The left ventricular wall motion score index ratio (discharge/admission values) at echocardiography and the slope of high-sensitivity troponin elimination were computed as measures of effective myocardial reperfusion. Reciprocal ST-segment downsloping was revealed in 91 patients (49%). They presented higher cTFC values on remote vessels than patients without reciprocal electrocardiographic abnormalities (44 ± 18 vs 37 ± 15 cineframes × second-1, p = 0.004). The presence of remote ST-segment downsloping was also associated with a higher prevalence of "no/slow reflow" phenomenon (59% vs 40%, p = 0.013) as well as more abnormal values of wall motion score index ratio (p = 0.042) and high-sensitivity troponin slope (p = 0.012). At multivariate analyses, a higher cTFC on remote vessels predicted the occurrence of reciprocal ST-segment changes (p = 0.018) and the development of "no/slow reflow" phenomenon after PCI (p = 0.005). In conclusion, the presence of reciprocal ST-segment downsloping during STEMI clusters with significant perfusion and cardiac functional abnormalities, predicting the development of "no reflow" phenomenon after PCI.

Stress Testing After Complete and Successful Coronary Revascularization.

BACKGROUND: Noninvasive stress tests play a determinant role in the initial management of patients with chronic angina. Nonetheless, their use in the same patient population is considered inappropriate within 2 years after percutaneous coronary intervention (PCI). Indeed, early abnormal results correlate less well with angiographic control and are attributed to a number of confounding factors. We prospectively assessed prevalence and impact on the quality of life of abnormal stress test results in a highly selected patient population. METHODS: Patients with no cardiac comorbidities who underwent successful and complete PCI with stenting for typical angina and had an abnormal exercise stress test (EST) under guideline-directed medical treatment were administered the Seattle Angina Questionnaire (SAQ). Clinical evaluation, EST, and the SAQ were repeated at 1, 6, and 12 months after the index PCI. RESULTS: One hundred ninety-eight patients qualified and were included in the study (mean age, 64 years; 79% men). Although the majority had normal EST results or an increased threshold to angina, at 1 month after the index PCI, 29% of patients still had an abnormal result. At 6 and 12 months, 31% and 29% of patients had abnormal results, respectively. Quality-of-life assessment by the SAQ showed consistent results, with persistent angina in one third of patients. Control angiography documented a critical lesion, attributable to in-stent coronary restenosis, in only 8% of patients. CONCLUSIONS: When stress testing is systematically performed after PCI, the prevalence of abnormal results is high and is associated with impaired quality of life. Prognostic significance along with the underlying pathophysiological mechanisms of such findings should be investigated.

Indications, Utility and Appropriateness of Echocardiography in Outpatient Cardiology.

OBJECTIVE: Respect of "appropriateness" is considered an essential requirement, both on the clinical and the economic profile, and also as it helps to shorten the waiting list. However, only a few studies have dealt with the control of appropriateness in clinical practice, and most of them have focused only on hospital admissions and invasive procedures. MATERIALS AND METHODS: INDICARD-out is a prospective, multicenter study carried out by A.R.C.A. (Associazioni Regionali Cardiologi Ambulatoriali) cardiologists from 13 Italian Regions, providing information on indications, utility and appropriateness of echocardiography in outpatient cardiology. RESULTS: A total of 2110 prescriptions for echocardiogram were evaluated. Hypertension (23%) and the screening of asymptomatic subjects (17%) by far were the most frequent indications to echocardiography. Overall, 54% of the tests resulted appropriate, 30% were of uncertain appropriateness and 16% were inappropriate. Besides, 31% of the echocardiograms were not useful, and 28% were non pertinent for patient management. The vast majority of prescriptions (72%) came from non-cardiologist physicians (54% from general practitioners). The echocardiograms prescribed by cardiologists were significantly more appropriate, more useful and more pertinent than the tests prescribed by non-cardiologists. CONCLUSIONS: The appropriateness, utility and pertinence of the echocardiography are still suboptimal in practice cardiology, especially when indicated by non-cardiologists. The cardiologist, from mere executor of tests prescribed and managed by other physicians, should gain the role of the clinician who takes care of all the cardiologic needs of the patient community.

Association of furosemide dose with clinical status, left ventricular dysfunction, natriuretic peptides, and outcome in clinically stable patients with chronic systolic heart failure.

In chronic heart failure (HF), high daily doses of furosemide have been associated with increased mortality. The authors sought to evaluate the relationships between orally administered furosemide doses, clinical status, left ventricular (LV) dysfunction, N-terminal proBNP (NT-proBNP), and outcome in 400 outpatients with chronic HF and LV ejection fraction (EF) ≤ 45%. Clinical status, NT-proBNP levels, and estimated glomerular filtration rate (eGFR) were evaluated. Median follow-up duration was 32 months. The median values of daily-dose furosemide and of furosemide dose normalized to body surface area were 25 mg (12.5-62.5 mg) and 15 mg/m(2) (13-34 mg/m(2)), respectively. A total of 32% of patients had decompensated HF according to Framingham score and criteria for congestion. In clinically stable patients, a multivariable Cox model, which included clinical and echocardiographic parameters plus NT-proBNP, hemoglobin, and eGFR, showed that normalized furosemide dose (P=.017), anemia (P=.060), age (P=.080), and New York Heart Association class (P=.080) were predictors of all cause-mortality. In patients with decompensated HF, LV end-systolic volume index (P=.018), NT-proBNP (P=.060), and reduced eGFR (P=.070) were independently related to the outcome. Normalized furosemide dose was a major determinant of prognosis in patients with chronic HF but without ongoing signs and symptoms, and this suggests a possible negative interaction of this drug in clinically stable patients.

Right ventricular dysfunction is associated with chronic kidney disease and predicts survival in patients with chronic systolic heart failure.

AIMS: Chronic kidney disease (CKD) and right ventricular (RV) dysfunction are important predictors of prognosis in heart failure (HF). We investigated the relationship between RV dysfunction and CKD in outpatients with chronic systolic HF, an association which remains poorly defined. METHODS AND RESULTS: Outpatients (n = 373) with chronic HF and left ventricular ejection fraction (LVEF) ≤45% underwent clinical and echo-Doppler evaluations and were followed up for 31 ± 24 months. Tricuspid annular plane systolic excursion (TAPSE) assessed RV dysfunction. The estimated glomerular filtration rate (GFR) was measured by the simplified Modification of Diet in Renal Disease (MDRD) formula. Correlation analysis was used to characterize the association between TAPSE and estimated GFR. Odds ratios (ORs) for CKD and hazard ratios (HRs) for all-cause mortality were assessed using multivariable logistic or proportional hazards regression models. TAPSE and estimated GFR were significantly correlated (r = 0.38, P < 0.0001). TAPSE ≤14 mm was associated with elevated estimated right atrial pressure and N-terminal pro brain natriuretic peptide levels. TAPSE ≤14 mm increased the odds of estimated GFR <60 mL/min/1.73 m(2), OR [95% confidence interval (CI)] = 2.51(1.44-4.39), P < 0.0001 and predicted all-cause mortality, HR (95% CI) = 1.80 (1.20-2.71) after multivariable adjustment. CONCLUSIONS: Right ventricular dysfunction is cross-sectionally associated with CKD and prospectively predicts survival in outpatients with chronic systolic HF. These data suggest RV dysfunction to be one of the possible mechanistic links between HF and CKD.

Matching pathophysiology and evidence-based medicine for optimal management of ischemic heart disease.

In recent years, our understanding of the pathophysiology of ischemic heart disease has evolved greatly. Atherosclerosis, traditionally considered a focal cholesterol storage disease, is now viewed as a widespread inflammatory process, responsible for the development, evolution and complications of arterial lesions. It is now recognized that most atherosclerotic lesions grow outward; thus, a substantial burden of atherosclerosis can exist in the absence of stenosis. Moreover, intravascular ultrasound and autopsy studies have indicated that vulnerable plaques are usually represented by mildly obstructive lesions. In the pathophysiology of ischemic heart disease, particular attention has been focused on endothelial and microvascular function. Structural or functional alterations of coronary microcirculation have been documented in several clinical conditions, such as stable and unstable angina. In this clinical setting, microvascular dysfunction acts not only as an independent risk marker, but can also contribute to the precipitation or maintenance of myocardial ischemia, even in the absence of coronary atherosclerosis. These observations challenge the traditional hemodynamic approach to the treatment of ischemic heart disease based on the degree of arterial stenosis. Isolated revascularization of a coronary artery can relieve angina and ischemia caused by a flow-limiting stenosis, but is often unable to protect against future atherothrombotic events or to modify the natural history of disease. Recent randomized trials have confirmed these pathophysiological findings, revealing no advantage of a routine over a selective invasive strategy in the treatment of stable angina. Global management of ischemic heart disease should aim to combine primary and secondary prevention measures directed at long-term risk reduction, with optimal revascularization therapies.

[Appropriateness of prescription of exercise stress test, echocardiography, Holter monitoring and vascular echography]. / L'appropriatezza dei test cardiologici non invasivi. studio osservazionale sull'appropriatezza della prescrizione del test da sforzo, dell'ecocardiogramma, dell'ECG dinamico e dell'ecografia vascolare.

BACKGROUND: The aim of this study was to evaluate the appropriateness of prescription of non-invasive cardiological tests (exercise stress test, echocardiography, Holter monitoring and vascular echography), consecutively performed in our outpatient laboratory during 4 weeks. METHODS: We collected the following data: the appropriateness of prescription (according to the Italian Federation of Cardiology guidelines); test indications; the prescribing physician (cardiologist/non-cardiologist); type of prescription (elective/urgent); clinical utility (useful/useless) and result (normal/abnormal) of each test. RESULTS: We evaluated 960 prescriptions (320 exercise tests; 282 echocardiograms; 158 Holter tests; 200 vascular echographies). Test indications were appropriate (class I) in 37%, doubtfully appropriate (class II) in 39% and inappropriate (class III) in 24% of the cases. The appropriateness was slightly better for vascular echography and echocardiography (class I: 44% and 43%, respectively), markedly worse for exercise test (class I: 27%). The tests were considered useful in 46% and abnormal in 39% of the cases. Cardiologist-prescribed exams resulted more often appropriate (class I: 53 vs 30%; class II: 41 vs 38%; class III: 6 vs. 32%; p = 0.0001), more often useful (74 vs. 34%; p = 0.0001) and more frequently abnormal (43 vs. 37%; p = 0.05), when compared to non-cardiologist-prescribed exams. No differences in appropriateness, utility and test result have been detected between elective and urgent exams. Exercise test, echocardiogram and Holter monitoring resulted more often appropriate and useful when prescribed by cardiologists. CONCLUSIONS: This study confirms that only one third of prescriptions for non-invasive cardiological tests are appropriate. Cardiologist-prescribed exams are more often appropriate, useful and abnormal.

A computer protocol to evaluate subjects with chest pain in the emergency department: a multicenter study.

OBJECTIVE: Chest pain is a frequent cause of medical admission to the emergency department and the main differential diagnosis is between coronary and non-coronary chest pain. We elaborated a computer protocol for the management of patients with chest pain. METHODS: The computer protocol was made of three sections according to clinical, electrocardiographic and biochemical data. Each section was coded by a letter indicating the probability of coronary chest pain for each section. The combination of the three letters formed a score string used to assign patients to four subgroups of overall probability of coronary chest pain (low, medium-low, medium-high, and high). Low-probability patients were discharged from the emergency department, whereas high-probability patients were admitted to the coronary care unit. The medium-probability patients underwent further evaluation by means of a stress test and were re-classified as having a final low probability (negative test) or high probability (positive test). RESULTS: We evaluated 472 patients (mean age 64 years, range 18-97 years; 47% female). The incidence of coronary events in patients with low, medium-low, medium-high and high overall probability was 1.9, 12.8,13.5 and 68.0%, respectively (P < 0.05). The positive and negative predictive values of the protocol were 64.7 and 97.1%, respectively. CONCLUSIONS: Our computer protocol represents a reliable method for the management of patients with chest pain and a non-diagnostic electrocardiogram.

[Feasibility and accuracy of a rapid evaluation of the abdominal aorta during routine transthoracic echocardiography]. / Fattibilità ed accuratezza di una rapida valutazione dell'aorta addominale durante l'esame ecocardiografico transtoracico.

BACKGROUND: Mass screening for occult abdominal aortic aneurysm is not realistic for the low prevalence of this condition in the general population. Screening in a high-risk population, especially during standard echocardiographic examination, could be more cost-effective than a separate screening program. The aim of this study was to evaluate the feasibility and accuracy of a rapid evaluation (examination arbitrary time-limit of 2 min) of the abdominal aorta at the end of a routine transthoracic echocardiographic examination. METHODS: One hundred and eighty-one male patients (average age 61 years, range 45-79 years) were studied. A subgroup of 83 patients was also blindly examined by a radiologist for diagnostic accuracy evaluation. RESULTS: Abdominal aortic aneurysm was defined as an aortic diameter enlargement > or = 3.0 cm. Sixteen patients were excluded due to suboptimal aortic wall imaging or to examination lasting > 2 min (feasibility 91%). An occult aneurysm was found in 7 patients (3.8%). As regards the presence/absence of aneurysms in the subgroup of patients undergoing double examination, sensitivity and specificity were 80 and 100% respectively. CONCLUSIONS: Rapid evaluation of the abdominal aorta for aortic screening during routine echocardiography is highly feasible and accurate without any significant prolongation of the examination time and should therefore be routinely performed during standard examination.

[Evaluation of the appropriateness of prescribing exercise tests]. / La valutazione dell'appropriatezza della prescrizione del test da sforzo.

BACKGROUND: We evaluated the appropriateness of the indications to exercise testing for ambulatory patients performed during 4 weeks in 21 laboratories in Tuscany and Umbria, Italy. METHODS: We collected the following data: the appropriateness of the prescription (according to the guidelines of the Italian Federation of Cardiology), the prescribing physician (cardiologist vs non-cardiologist), the synthetic result (normal vs abnormal) and the clinical utility (useful vs useless) of each exam. RESULTS: We evaluated 1158 prescriptions (population: 822 males, 336 females; mean age 60 years, range 16-82 years). Prescriptions were of class I (appropriate) in 38.9%, of class II (of doubtful appropriateness) in 52.5% and of class III (inappropriate) in 8.6% of the cases. In 14.2% of the cases the exam was abnormal: it was abnormal in 35.5% of class I, in 26.6% of class II and in 23% of class III exams (p < 0.05). The exam was useful in 51.6% of the cases; it was useful in 62.4% of class I, in 50.2% of class II and in 13% of class III exams (p < 0.05). Cardiologists required 596/1158 tests (51.5%). Their indications were included in class I in 45.6%, in class II in 49.7% and in class III in 4.7% of the cases vs 31.7, 55.5 e 12.8% of non-cardiologists' prescriptions (p < 0.05). The test was abnormal in 35.7% of cardiologist vs 23.5% of non-cardiologist-prescribed examinations (odds ratio 1.81, 95% confidence interval 1.4-2.34; p < 0.05); the test was useful in 64.4% of cardiologist vs 38.2% of non-cardiologist-prescribed exams (odds ratio 2.92, 95% confidence interval 2.3-3.71; p < 0.05). CONCLUSIONS: In Tuscany and Umbria, Italy, less than half of exercise testing procedures are appropriate; appropriately-prescribed exams are more often abnormal and useful; cardiologist-prescribed exams are significantly more appropriate, abnormal and useful.