Showing papers by "Marco Canepa published in 2020"
TL;DR: The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to identify cardiac involvement across a wider spectrum of TTR mutations.
Abstract: Objectives The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation. Background Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations. Methods A total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)–diphosphonate (DPD) or 99mTc–hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini’s method. Results Among 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings. Conclusions The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.
74 citations
TL;DR: Evolving HCM populations include progressively greater representation of older patients with sporadic disease, mild phenotypes, and genotype-negative status, which suggests a prominent role of imaging over genetic testing in promoting HCM diagnoses and urges efforts to understand genotypes-negative disease eluding the classic monogenic paradigm.
Abstract: Background: Over the last 50 years, the epidemiology of hypertrophic cardiomyopathy (HCM) has changed because of increased awareness and availability of advanced diagnostic tools. We aim to describ...
34 citations
TL;DR: Half of non-severe COVID-19 survivors show functional capacity limitation mainly explained by muscular impairment, albeit cardiopulmonary causes are possible, and these findings call for future research to identify patients at higher risk of long-term effects, that may benefit from careful surveillance and targeted rehabilitation.
Abstract: Introduction Long-term effects of Coronavirus Disease of 2019 (COVID-19) and their sustainability in a large number of patients are of the utmost relevance. We aimed to determine: 1)functional capacity of non-severe COVID-19 survivors by cardiopulmonary exercise testing (CPET); 2)those characteristics associated with worse CPET performance. Methods We prospectively enrolled the first 150 consecutive subjects with laboratory-confirmed COVID-19 infection discharged alive from March to April 2020 at Azienda Sanitaria Locale (ASL)3, Genoa, Italy. At 3-month from hospital discharge, complete clinical evaluation, trans-thoracic echocardiography, cardiopulmonary exercise testing (CPET), pulmonary function test (PFT), and dominant leg extension (DLE) maximal strength evaluation were performed. Results Excluding severe and incomplete/missing cases, 110 patients were analyzed. Median percent predicted peak oxygen uptake (%pVO2) was 90.9(79.2-109.0)%. Thirty-eight(34.5%) patients had %pVO2 below, whereas 72(65.5%) above the 85% predicted value (indicating normality). Median PFT parameters were within normal limits. Eight(21.1%) patients had a mainly respiratory, 9(23.7%) a mainly cardiac, 3(7.9%) a mixed-cardiopulmonary, and 18(47.4%) a non-cardiopulmonary limitation of exercise. Eighty-one(73.6%) patients experimented at least one symptom, without relationship with %pVO2 (p>0.05). Multivariate linear regression analysis showed age (β=0.46, p=0.020), percent weight loss (β=-0.77, p=0.029), active smoke status (β=-7.07, p=0.019), length of hospital stay (β=-0.20, p=0.042), and DLE maximal strength (β=1.65, p=0.039) independently associated with %pVO2. Conclusions Half of non-severe COVID-19 survivors show functional capacity limitation mainly explained by muscular impairment, albeit cardiopulmonary causes are possible. These findings call for future research to identify patients at higher risk of long-term effects, that may benefit from careful surveillance and targeted rehabilitation. Take-home messages at 3-month cardiopulmonary exercise testing 38/110(34.5%) non-severe COVID-19 survivors had percent predicted peak oxygen uptake (%pVO2)
23 citations
TL;DR: The role of syncope in predicting subsequent malignant arrhythmias in BrS is evaluated through systematic literature review and it is found that syncope can be a positive predictive factor in the diagnosis of cancer in Brugada syndrome.
Abstract: Introduction Distinguishing syncope due to malignant arrhythmias from an incidental benign form in Brugada syndrome (BrS) is often difficult. Through systematic literature review, we evaluated the role of syncope in predicting subsequent malignant arrhythmias in BrS. Methods A comprehensive literature search was performed on PubMed (MeSH search terms "Brugada syndrome" and "syncope"). Overall, 9 studies for a total of 1347 patients were included. Patients were stratified as affected by suspected arrhythmic syncope (SAS), undefined syncope (US) or neurally-mediated syncope (NMS). Results Overall, 15.7% of the 279 patients with SAS had malignant arrhythmic events during a mean follow-up of 67 months, corresponding to 2.8 events per 100/person year. At the same time, 7% of the 527 patients affected by US had malignant arrhythmias during a mean follow-up of 39 months, corresponding 2.2 events per 100/person year. Conversely, 0.7% of 541 patients with NMS had malignant arrhythmic events at follow-up, corresponding to 0.13 events per 100/person year (p = .0001 NMS versus SAS and US pooled). Conclusion In BrS population, the risk of arrhythmic events in the follow-up may be stratified according to the clinical evaluation. The "relatively" low predictive value of the clinical diagnosis of SAS warrants for a more accurate multi-parametric assessment, to restrict the number of candidates for implantable cardioverter-defibrillator therapy.
22 citations
TL;DR: There is increasing recognition that heart failure (HF) and cancer are conditions with a number of shared characteristics.
Abstract: Background: There is increasing recognition that heart failure (HF) and cancer are conditions with a number of shared characteristics. Objectives: To explore the association between tumour biomarkers and HF outcomes. Methods: In 2,079 patients of BIOSTAT-CHF cohort, we measured six established tumour biomarkers: CA125, CA15-3, CA19-9, CEA, CYFRA 21-1 and AFP. Results: During a median follow-up of 21 months, 555 (27%) patients reached the primary end-point of all-cause mortality. CA125, CYFRA 21-1, CEA and CA19-9 levels were positively correlated with NT-proBNP quartiles (all P < 0.001, P for trend < 0.001) and were, respectively, associated with a hazard ratio of 1.17 (95% CI 1.12–1.23; P < 0.0001), 1.45 (95% CI 1.30–1.61; P < 0.0001), 1.19 (95% CI 1.09–1.30; P = 0.006) and 1.10 (95% CI 1.05–1.16; P < 0.001) for all-cause mortality after correction for BIOSTAT risk model (age, BUN, NT-proBNP, haemoglobin and beta blocker). All tumour biomarkers (except AFP) had significant associations with secondary end-points (composite of all-cause mortality and HF hospitalization, HF hospitalization, cardiovascular (CV) mortality and non-CV mortality). ROC curves showed the AUC of CYFRA 21-1 (0.64) had a noninferior AUC compared with NT-proBNP (0.68) for all-cause mortality (P = 0.08). A combination of CYFRA 21-1 and NT-proBNP (AUC = 0.71) improved the predictive value of the model for all-cause mortality (P = 0.0002 compared with NT-proBNP). Conclusions: Several established tumour biomarkers showed independent associations with indices of severity of HF and independent prognostic value for HF outcomes. This demonstrates that pathophysiological pathways sensed by these tumour biomarkers are also dysregulated in HF.
22 citations
TL;DR: Cancer is a major, yet overlooked cause of noncardiovascular death in heart failure with reduced ejection fraction, which has become more prominent with cardiovascular mortality decline, and meta‐regression did not reveal significant sources of heterogeneity.
Abstract: Background The burden of cancer in heart failure with reduced ejection fraction is apparently growing. Randomized controlled trials (RCTs) may help understanding this observation, since they span d...
19 citations
TL;DR: Important differences between HF patients hospitalized in CA vs. IM are demonstrated, and the need for a greater interaction between these two medical specialties for a better care of HF patients is demonstrated.
Abstract: The majority of patients hospitalized for heart failure (HF) are admitted to internal medicine (IM) rather than to cardiology (CA) units, but to date few studies have analyzed the characteristics of these two populations. In this snapshot survey, we compared consecutive patients admitted for HF in six IM units vs. one non-intensive CA unit. During the 6-month survey period, 467 patients were enrolled (127 in CA, 27.2% vs. 340 in IM, 72.8%). IM patients were almost 10 years older (CA 75 ± 10, IM 82 ± 8 years; p < 0.001), more frequently female (CA 39%, IM 55%; p = 0.002) and living at home alone (CA 12%, IM 21%; p = 0.017). The leading cause of hospitalization in both groups was acute worsening of HF (CA 42%, IM 53%; p = 0.031), followed by atrial fibrillation (CA 29%, IM 12%; p < 0.001) and infections (CA 24%, IM 27%; p = 0.563). Ischemic (CA 43%, IM 30%; p = 0.008) and dilated cardiomyopathy patients (CA 21%, IM 12%; p < 0.001) were primarily admitted to CA unit, whereas those with hypertensive heart disease to IM (CA 3%, IM 39%; p < 0.001). Left ventricular ejection fraction (LVEF) was available in 96% of CA patients, but only in 60% of IM patients (p = 0.001). Among patients with LVEF measured, those with LVEF < 40% were predominantly admitted to CA (CA 60%, IM 14%; p < 0.001), whereas those with LVEF ≥ 50% were admitted to IM (CA 21%, IM 33%; p = 0.019); 26% of IM patients were discharged without a known LVEF. Medical treatments also significantly differed, according to patients’ clinical and instrumental characteristics in each unit. This study demonstrates important differences between HF patients hospitalized in CA vs. IM, and the need for a greater interaction between these two medical specialties for a better care of HF patients.
18 citations
TL;DR: Very short DAPT reduces haemorrhagic events and, followed by a P2Y12 inhibitor monotherapy, may be preferred in order to pursue a trade-off between major bleeding and ischemia.
Abstract: Aims To compare safety and efficacy of very short (≤3 months), short (6 months), standard (12 months) and extended (>12 months) DAPT, and subsequent monotherapies, after DES. Methods and results Twenty-two RCT (n = 110059 patients/year) were selected and included in a Bayesian network meta-analysis. The primary efficacy endpoint (PEP) was a composite of cardiac death, myocardial infarction (MI) and stent thrombosis (ST), the primary safety endpoint was major bleeding. Compared to standard, we found lower rate of MI (OR 0.56, 95% CI 0.44-0.77) in extended DAPT; lower rate of major bleeding (OR 0.61, 95% CI 0.39-0.87) in very short and lower rate of any bleeding (OR 0.61, 95% CI 0.38-0.90) in short DAPT. All DAPT durations were comparable regarding the secondary efficacy endpoints. Very short followed by P2Y12 inhibition was the treatment of choice to reduce both major bleeding and myocardial infarction. In the ACS subgroup, extended (as compared to standard DAPT) reduced PEP and ST (but not MI). Conclusion The efficacy of short and very short is comparable with that of standard DAPT after DES implantation, whereas extended DAPT reduces MI rate. Very short DAPT reduces haemorrhagic events and, followed by a P2Y12 inhibitor monotherapy, may be preferred in order to pursue a trade-off between major bleeding and ischemia.
15 citations
TL;DR: In this article, the authors present recommendations for a safe and feasible pre-symptomatic genetic testing protocol in hereditary transthyretin amyloidosis (ATTRv) in the era of emerging treatments, taking also into account Italian patients' characteristics and healthcare system rules.
Abstract: Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington’s disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients’ characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.
12 citations
TL;DR: Even when considered not aggressive, concomitant cancer worsens HF prognosis and the inverse relationship between HF severity and cancer death in the absence of prior tumor warrants further study.
Abstract: BACKGROUND Cancer complicating heart failure (HF) is an emerging issue. We investigated it in the GISSI-HF trial, which uniquely included patients with malignancies if deemed likely to allow follow-up. METHODS AND RESULTS At enrolment, 256 of 6913 participants in GISSI-HF (3.7%) had a tumour diagnosis, which was malignant (cancer) in 145 (2.1%). Patients with cancer were older and more often former smokers, had lower body mass index, lower left ventricular ejection fraction (LVEF), less implanted devices, lower glucose and haemoglobin and higher uric acid levels than those without cancer. During a median 4-year follow-up, cardiovascular (CV), non-CV non-cancer and cancer death occurred in 1477, 272 and 220 subjects (75%, 13.8% and 11.2% of total mortality, respectively). Cancer at trial entry portended an increased risk of all-cause mortality after accounting for age and confounders (HR 1.33, 95%CI 1.02-1.73), which was attributable to cancer-specific mortality. Among the 6657 patients without any tumour at enrolment, 1879 subsequently died. CV, non-CV non-cancer and cancer causes accounted for 1422 (75.7%), 261 (13.9%) and 196 (10.4%) of these deaths, respectively, median time to specific death being 22, 25 and 30 months (P < .0001). Patients facing cancer vs CV death had lower NYHA class, slower heart rate, higher blood pressure, higher LVEF, shorter HF history, less diuretic use, lower creatinine and uric acid and higher haemoglobin and cholesterol. CONCLUSIONS Even when considered not aggressive, concomitant cancer worsens HF prognosis. The inverse relationship between HF severity and cancer death in the absence of prior tumour warrants further study.
7 citations
TL;DR: This review attempts to 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.
Abstract: 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.
TL;DR: The findings support the use of longitudinal data to improve prognostication in patients with HFrEF, and warrant validation in external cohorts and creation of new prognostic tools.
TL;DR: The Hypertrophic Cardiomyopathy Outpatient Clinic at the Ospedale Policlinico San Martino, Genova, regularly follows patients affected by HCM and cardiac amyloidosis and each patient with a scheduled visit in the forthcoming weeks was contacted by a medical trainee to assess urgency related to her/his medical evaluation.
Abstract: Methods The Hypertrophic Cardiomyopathy (HCM) Outpatient Clinic at the Ospedale Policlinico San Martino, Genova, regularly follows patients affected by HCM and cardiac amyloidosis. At the beginning of the COVID-19 lockdown an already operating service for patients’ communications (via telephone and E-mail) was implemented, and each patient with a scheduled visit in the forthcoming weeks (up to 15 May 2020) was contacted by a medical trainee to assess urgency related to her/his medical evaluation. According to information collected via the telemedical contact, patients were divided into ‘stable’ (group-A) and ‘potentially unstable’ (group-B). Patients were deemed as ‘potentially unstable’ if one or more of the following were present: signs and/or symptoms of heart failure, in particular if worsening relatively to the precontact condition; known end-stage HCM; heart failure hospitalization(s) and/or more than three outpatients evaluations in the prior 6 months. Those in group-B received weekly telemedical contact to monitor their conditions.
Journal Article•
TL;DR: In this paper, the safety and efficacy of the Orsiro sirolimus-eluting stent (Biotronik) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI) was evaluated.
Abstract: Objectives To evaluate the safety and efficacy of the Orsiro sirolimus-eluting stent (Biotronik) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Specific drug-eluting stent (DES) platforms might influence pPCI success rate in the mid-to-long term. Orsiro, a hybrid sirolimus DES with thin struts and a biodegradable polymer, may potentially cause less stent malapposition, stent-induced inflammation, and mechanical damage, improving clinical outcomes. Methods We retrospectively enrolled all patients who received 1 or more Orsiro DES in the target vessel of pPCI at 9 Italian centers from January 2012 to March 2016. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, any myocardial infarction clearly attributable to the intervention culprit vessel (TVMI), and ischemic-driven target-lesion revascularization (ID-TLR) at 1-year follow-up. Secondary endpoints were: (1) DOCE at 6-month and 3-year follow-up; (2) any definite/probable stent thrombosis; and (3) any major bleeding. Results The study cohort comprised 353 patients. At 1-year follow-up, we observed a 3.7% cumulative incidence of DOCE, consisting of 11 cardiac deaths (3.1%), 2 TVMIs (0.6%), and 2 ID-TLRs (0.6%). There was only 1 definite stent thrombosis (0.3%) and 8 bleedings (2.4%). Kaplan-Meier analysis showed DOCE-free survival rates of 96.6% at 6 months, 96.3% at 1 year, and 93.8% at 3 years. Conclusions Our findings support the real-world safety and efficacy of the Orsiro stent for pPCI.