Publications by authors named "Maria Beatrice Musumeci"

43 Publications

Insights from Cardiopulmonary Exercise Testing in Pediatric Patients with Hypertrophic Cardiomyopathy.

Biomolecules 2021 Mar 2;11(3). Epub 2021 Mar 2.

Department of Clinical and Molecular Medicine, Sapienza University, 00189 Rome, Italy.

The usefulness of cardiopulmonary exercise test (CPET) in adult hypertrophic cardiomyopathy (HCM) patients is well-known, whereas its role in pediatric HCM patients has not yet been explored. The present study investigates possible insights from a CPET assessment in a cohort of pediatric HCM outpatients in terms of functional and prognostic assessment. Sixty consecutive pediatric HCM outpatients aged <18 years old were enrolled, each of them undergoing a full clinical assessment including a CPET; a group of 60 healthy subjects served as controls. A unique composite end-point of heart failure (HF) related and sudden cardiac death (SCD) or SCD-equivalent events was also explored. During a median follow-up of 53 months (25th-75th: 13-84 months), a total of 13 HF- and 7 SCD-related first events were collected. Compared to controls, HCM patients showed an impaired functional capacity with most of them showing peak oxygen uptake (pVO) values of <80% of the predicted, clearly discrepant with functional New York Heart Association class assessment. The composite end-point occurred more frequently in patients with the worst CPETs' profiles. At the univariate analysis, pVO% was the variable with the strongest association with adverse events at follow-up (C-index = 0.72, = 0.025) and a cut-off value equal to 60% was the most accurate in identifying those patients at the highest risk. In a pediatric HCM subset, the CPET assessment allows a true functional capacity estimation and it might be helpful in identifying early those patients at high risk of events.
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http://dx.doi.org/10.3390/biom11030376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999553PMC
March 2021

TNNI3 and KCNQ1 co-inherited variants in a family with hypertrophic cardiomyopathy and long QT phenotypes: A case report.

Mol Genet Metab Rep 2021 Jun 18;27:100743. Epub 2021 Mar 18.

Department of Clinical and Molecular Medicine, School of Medicine and Psychology, "Sapienza" University of Rome, Rome 00189, Italy.

QTc prolongation is reported in patients with hypertrophic cardiomyopathy (HCM). However, the causes of the QTc interval increase remain unclear. The main contribution to QTc prolongation in HCM is attributed to the myocardial hypertrophy and related structural damage. In a 24-year-old male proband, affected by HCM and long QTc, we identified by Next Generation Sequencing a pathogenic variant in gene co-inherited with a damaging variant in gene. This evidence suggests the possibility that QTc interval prolongation and its dispersion in HCM could be associated not only to the severity of left ventricular hypertrophy but also to the co-inheritance of pathogenic variants related to both long QT Syndrome (LQTS) and HCM. Although the simultaneous presence of pathogenic variants in genes related to different heart diseases is extremely rare, counseling and genetic testing appear crucial for the clinical diagnosis. Screening of LQTS genes should be considered in HCM patients to clarify the origin of long QTc, to provide more information about the clinical presentation and to evaluate the incidence of the co-existence of LQTS/HCM gene variants that could occur more frequently than so far reported.
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http://dx.doi.org/10.1016/j.ymgmr.2021.100743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985525PMC
June 2021

The natural history of hypertrophic cardiomyopathy.

Eur Heart J Suppl 2020 Nov 18;22(Suppl L):L11-L14. Epub 2020 Nov 18.

Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.

In the early years of the disease recognition, hypertrophic cardiomyopathy (HCM) was viewed as an ominous disease with unfavourable prognosis and with an annual mortality between 4% and 6%. At that time, 73% of the patients reported in the literature came from only two referral centres. With the introduction of echocardiography, our understanding of HCM has improved and non-selected patient populations were assembled in several centres. A more benign prognostic profile was documented with an annual mortality rate of 1.5% or less. In the 2000s, important therapeutic interventions further improved the prognosis of patients with HCM: implantable-cardioverter defibrillator for prevention of sudden death, heart transplantation for treatment of severe refractory heart failure, and an extensive treatment with myectomy for relief of left ventricular outflow tract gradient. The natural history of HCM has changed substantially with contemporary treatment achieving an annual mortality rate less than 1% with extended longevity and a greatly improved quality of life.
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http://dx.doi.org/10.1093/eurheartj/suaa125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904071PMC
November 2020

Reply to the letter "Takotsubo syndrome: Any more covariates of its recurrence?"

Int J Cardiol 2021 Feb 26. Epub 2021 Feb 26.

Cardiology, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1016/j.ijcard.2021.02.063DOI Listing
February 2021

Clinical characteristics of patients with takotsubo syndrome recurrence: An observational study with long-term follow-up.

Int J Cardiol 2021 Apr 24;329:23-27. Epub 2020 Dec 24.

Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

Background: Research investigating takotsubo syndrome (TTS) recurrence yielded conflicting results. Aim of the present study is to describe clinical characteristics of patients with TTS recurrence in a cohort with available long-term follow-up.

Methods: The study population included 234 TTS patients enrolled in a prospective multicenter registry, median follow-up of 1328 (407, 2526) days. To investigate factors associated with TTS recurrence, we analyzed patients with recurrence (Group A) in comparison with a subgroup of TTS patients within the whole population (group B) who had similar age, sex and median follow-up length (Group A 2280 days vs Group B 2361 days).

Results: We observed 9 TTS recurrences affecting 8 patients, all women, with a rate of 0.9% patients/year. Median time to first recurrence was 1593 days (interquartile range: 950, 2516). We detected no significant differences between patients with and without recurrences regarding cardiovascular risk factors, symptoms, ECG and echocardiographic findings at presentation, discharge therapy. Physical trigger and chronic obstructive pulmonary disease (COPD) were more prevalent in patients who experienced a recurrence (75% vs 27% and 50% vs 14% with p = 0.01 and p = 0.022 respectively). Univariable Cox regression analysis identified physical trigger and history of COPD to be both associated with TTS recurrence [hazard ratio (HR) 11.4, 95% confidence interval (CI) 2.29-56.8, p = 0.003 and HR 4.94, 95% CI 1.16-20.99 p = 0.031 respectively].

Conclusion: TTS recurrence is relatively uncommon. Association with physical trigger and COPD would suggest a closer follow-up in this subgroup of patients.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.047DOI Listing
April 2021

Incidence and determinants of high-sensitivity troponin and natriuretic peptides elevation at admission in hospitalized COVID-19 pneumonia patients.

Intern Emerg Med 2020 Nov 28;15(8):1467-1476. Epub 2020 Sep 28.

Heart Failure Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Covid Unit, Sapienza University of Rome, Rome, Italy.

Background: Myocardial involvement in the course of coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. The aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia.

Methods: In this multicenter observational study, we analyzed data from n = 111 patients. Cardiac biomarkers subgroups were identified according to values beyond reference range.

Results: Increased hs-Troponin and NP were found in 38 and 56% of the cases, respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and had more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03, respectively). Both hs-Troponin and NP were higher in patients with in-hospital mortality (p = 0.001 and p = 0.002, respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B = - 0.212, p = 0.013; and B = 0.179, p = 0.037, respectively) and of NP with age and previous CVD (B = 0.480, p < 0.001; and B = 0.253, p = 0.001, respectively).

Conclusions: Myocardial involvement at admission is common in COVID-19 pneumonia. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point toward existing different mechanisms leading to their elevation in this setting.
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http://dx.doi.org/10.1007/s11739-020-02498-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520380PMC
November 2020

Arterial thrombo-embolic events in cardiac amyloidosis: a look beyond atrial fibrillation.

Amyloid 2021 Mar 28;28(1):12-18. Epub 2020 Sep 28.

Cardiology, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy.

Background: Intracardiac thrombosis is reported to occur frequently in cardiac amyloidosis (CA). However, data regarding arterial thrombo-embolic events (AEs) in CA are limited. We aimed at assessing prevalence, clinical characteristics and predictors of AEs in a large multicentric CA cohort.

Methods And Results: Four-hundred-six consecutive CA patients (134 AL, 73 ATTRm and 199 ATTRwt) from 5 Italian referral centres were retrospectively evaluated and followed-up for a median time of 19 months. Thirty-one patients (7.6%) suffered from an AE, of whom 10 (32.2%) were in sinus rhythm and had no history of AF. There were no significant differences in terms of age, gender and type of CA between patients with or without AEs. Fourteen (7.6%) of 185 patients on anticoagulation had an AE despite therapy. Anticoagulation therapy did not appear to fully protect from the risk of events (HR 1.23, 95%CI 0.52-2.92,  = .64). The only predictor of AEs, in particular among CA patients in sinus rhythm, was a CHA2DS2-VASC score ≥ 3 (HR 2.84, 95%CI 1.02-7.92,  = .05 in overall population; HR 10.13, 95%CI 1.12-91.19,  = .04 in patients in sinus rhythm).

Conclusions: In our large, multicentric, real-world cohort, prevalence and incidence rate of AEs was high. A consistent proportion of events occurred despite anticoagulation therapy or in patients in sinus rhythm. A higher CHA2DS2-VASc score might identify patients at risk of AEs also among those in sinus rhythm.
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http://dx.doi.org/10.1080/13506129.2020.1798922DOI Listing
March 2021

Incidence, determinants and prognostic relevance of dyspnea at admission in patients with Takotsubo syndrome: results from the international multicenter GEIST registry.

Sci Rep 2020 08 12;10(1):13603. Epub 2020 Aug 12.

Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto n.1, 71122, Foggia, Italy.

Clinical presentation of Takotsubo syndrome (TTS) may range from acute chest pain to dyspnea: the prognostic role of clinical onset is still controversial. Aim of this study was therefore to investigate the prognostic relevance of dyspnea at presentation in patients with TTS. We analyzed 1,071 TTS patients (median age 72 years, 90% female) enrolled in the international multicenter GEIST registry. Patients were divided according to the presence or absence of dyspnea at hospital admission, as clinically assessed by the accepting physician. The primary endpoint was occurrence of in-hospital complications defined as a composite of pulmonary edema, cardiogenic shock and death. Overall, 316 (30%) patients presented with dyspnea at hospital admission. Diabetes, lower left ventricular ejection fraction and presence of pulmonary disease or atrial fibrillation were independently associated with dyspnea. In-hospital pulmonary edema, cardiogenic shock and death (17% vs. 3%, p < 0.001; 12% vs. 7%, p = 0.009; 5% vs. 2%, p = 0.004 respectively) and long-term overall mortality (22% vs. 11%, p < 0.001) occurred more frequently in patients with dyspnea than in those without. At multivariable analysis, dyspnea at presentation remained independently associated to both the composite primary endpoint [odds ratio 2.98 (95% confidence interval (CI) 1.95-4.59, p < 0.001] and all-cause mortality [hazard ratio 2.03 (95% CI 1.37-2.99), p < 0.001]. Dyspnea at presentation is common in TTS and is independently associated with in-hospital complications and impaired long-term prognosis. Thorough symptom assessment including dyspnea therefore represents a valuable tool to potentially optimize risk-stratification models for TTS patients.
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http://dx.doi.org/10.1038/s41598-020-70445-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424520PMC
August 2020

Transcatheter aortic valve replacement for aortic regurgitation after septal myectomy in patients with obstructive hypertrophic cardiomyopathy.

Cardiovasc Revasc Med 2020 Jun 15. Epub 2020 Jun 15.

Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1016/j.carrev.2020.06.010DOI Listing
June 2020

A systematic review on focal takotsubo syndrome: a not-so-small matter.

Heart Fail Rev 2020 Jun 13. Epub 2020 Jun 13.

Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Via Di Grottarossa 1035/1039, 00189, Rome, Italy.

A focal contraction pattern in takotsubo syndrome (TTS) is considered rare. Due to its peculiar presentation, which includes segmental left ventricular (LV) regional wall motion abnormalities (RWMA), the focal TTS pattern may be hardly differentiable from other entities, such as myocarditis or myocardial infarction. We performed a comprehensive systematic literature review researching for works in English published in Journals indexed in Embase, available online for consultation, using the following keywords (in Title and/or Abstract): ("takotsubo" OR "broken heart" OR "apical ballooning" OR "stress cardiomyopathy") AND ("focal" OR "atypical" OR "variant" OR "segments"). Thirty-three papers were retrieved: 17 case reports, 6 case series, and 10 population studies-with a total of 166 focal TTS patients. Prevalence of focal TTS ranged between 0.1% and 14% (pooled mean: 2.8%). Mean age of onset (58 years), gender distribution (80% of females), and type of triggers appeared similar to those reported in typical TTS. RWMA more frequently involved the interventricular septum and the anterolateral LV segments, with often preserved LV ejection fraction. In the majority of focal TTS reports that included adequate ECG information (n = 13), abnormalities were localized and not diffuse, always matching RWMA, and in 3 cases, reciprocal changes were observed. No in-hospital nor long-term deaths were reported. The focal TTS contraction pattern may be more prevalent than currently reported. Though possibly presenting with similar demographic background compared with typical TTS, the focal variant might be characterized by peculiar ECG modifications and better prognosis.
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http://dx.doi.org/10.1007/s10741-020-09988-yDOI Listing
June 2020

Clinical outcomes in adult athletes with hypertrophic cardiomyopathy: a 7-year follow-up study.

Br J Sports Med 2020 Aug 12;54(16):1008-1012. Epub 2020 Jun 12.

Departement of Medicine, Azienda Ospedaliera Sant Andrea, Roma, Lazio, Italy.

Objective: Current guidelines recommend precautionary disqualification from competitive sports in patients with hypertrophic cardiomyopathy (HCM). We assessed the incidence of cardiovascular events in a cohort of patients with HCM engaged in long-term exercise programmes and competitive sport.

Methods: We reviewed data on 88 consecutive athletes diagnosed with HCM, from 1997 to 2017; 92% male, 98% Caucasian, median age 31 (IQR: 19-44) years. All participated in regular exercise programmes and competitive sport at study entry.We performed follow-up evaluation after 7±5 (1-21) years. 61 (69%) of the athletes had substantially reduced or stopped exercise and sport (ie, HCM-detrained), and 27 had continued with regular training and sport competitions (HCM-trained). At baseline evaluation, both groups were similar for age, gender balance, symptoms, ECG abnormalities, extent of left ventricular hypertrophy, arrhythmias and risk profile for sudden cardiac death/arrest.

Results: During the follow-up period, two participants suffered sudden cardiac arrest or death (0.3% per year) both outside of sport participation. In addition, 19 (22%) reported symptoms (syncope in 3, palpitations in 10, chest pain in 4 and dyspnoea in 2). The Kaplan-Meier analyses of freedom from combined sudden cardiac arrest/death and symptoms (log-rank test p=0.264) showed no differences between HCM-trained and detrained patients.

Conclusion: In this adult cohort of low-risk HCM athletes, voluntary decision to pursue in participation in competitive sport events was not associated with increased risk for major cardiac events or clinical worsening compared with decision to reduce or withdraw from exercise programmes and sport. Similar results may not be seen in younger or racially diverse athlete populations, or in patients with more severe HCM phenotypes.
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http://dx.doi.org/10.1136/bjsports-2019-100890DOI Listing
August 2020

The neglected issue of cardiac amyloidosis in trials on heart failure with preserved ejection fraction in the elderly.

Eur J Heart Fail 2020 09 3;22(9):1740-1741. Epub 2020 Apr 3.

Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1002/ejhf.1766DOI Listing
September 2020

Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis.

JACC Cardiovasc Imaging 2020 06 18;13(6):1314-1321. Epub 2019 Dec 18.

Cardiology, Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater University of Bologna, Bologna, Italy.

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.
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http://dx.doi.org/10.1016/j.jcmg.2019.10.015DOI Listing
June 2020

Prognostic relevance of GRACE risk score in Takotsubo syndrome.

Eur Heart J Acute Cardiovasc Care 2020 Oct 23;9(7):721-728. Epub 2019 Oct 23.

Clinical and Interventional Cardiology, Sassari University Hospital, Italy.

Background: Takotsubo syndrome is an increasingly recognised cardiac condition that clinically mimics an acute coronary syndrome, but data regarding its prognosis remain controversial. It is currently unknown whether acute coronary syndrome risk scores could effectively be applied to Takotsubo syndrome patients. This study aims to assess whether the Global Registry of Acute Coronary Events (GRACE) score can predict clinical outcome in Takotsubo syndrome and to compare the prognosis with matched acute coronary syndrome patients.

Methods: A total of 561 Takotsubo syndrome patients was included in this prospective registry. According to the GRACE score, the population was divided into quartiles. The primary endpoint was all-cause mortality and the secondary endpoints were cardiocerebrovascular events (a composite of all-cause mortality, cardiovascular death, recurrence of Takotsubo syndrome and stroke).

Results: The median GRACE risk score was 139±27. Takotsubo syndrome patients with a higher GRACE risk score mostly have a higher rate of physical triggers and lower left ventricular ejection fraction on admission. During long-term follow-up, all-cause mortality rates were 5%, 11%, 12% and 22%, respectively, in the first, second, third and fourth quartile (<0.001). After multivariate analysis, the GRACE risk score was found to be a strong predictor of all-cause mortality (odds ratio (OR) 1.68, 95% confidence interval (CI) 1.28-2.20; =0.001) and cardiocerebrovascular events (OR 1.63, 95% CI 1.26-2.11; =0.001). Moreover, all-cause mortality in Takotsubo syndrome patients was comparable with the matched acute coronary syndrome cohort.

Conclusion: In Takotsubo syndrome, the GRACE risk score allows us to predict all-cause mortality and cardiocerebrovascular events at long-term follow-up.
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http://dx.doi.org/10.1177/2048872619882363DOI Listing
October 2020

Safety and efficacy of anti-tachycardia pacing in patients with hypertrophic cardiomyopathy implanted with an ICD.

Pacing Clin Electrophysiol 2019 06 5;42(6):610-616. Epub 2019 Apr 5.

Division of Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome, Italy.

Background: In hypertrophic cardiomyopathy (HCM) patients implanted with an implantable cardioverter defibrillator (ICD), clinical outcomes of antitachycardia pacing (ATP) have been poorly explored. In a retrospective analysis of a cohort of consecutive HCM patients implanted with an ICD, we aimed to assess the efficacy, safety, and clinical value of ATP.

Methods: The cohort of HCM patients implanted with a transvenous ICD and followed in our center was assessed for device intervention from implantation to last clinical follow-up.

Results: Overall 77 patients (45 males; mean age: 46 ± 16 years) were analyzed. After 67 ± 41 months, 24 patients had 49 ventricular tachycardia/fibrillation (VT/VF) appropriately treated (5.8% per year). Among 39 monomorphic VTs, ATP was effective in 27 (success rate: 69%). Mean time from VT onset to ATP delivery was 9.1 ± 4.9 s. The only clinical variable improving ATP success was use of beta-blockers (81% vs 50%; P = .04). Out of 12 ineffectively treated VTs, one was immediately shocked, four self-terminated after 18 ± 12 s, and seven (18%) were accelerated to a new VT. ATP was also delivered for 27 of 42 inappropriately detected episodes and induced two de novo VTs (7%). In the per patient analysis, 14 out 77 (18%) patients had one or more appropriate and effective ATP (3.4% per year), and only six (8%; 1.4% per year) received more than one ATP.

Conclusion: ATP is moderately effective for the treatment of monomorphic VTs in HCM patients. However, the rate of appropriate ATP therapies is low, ATP is often prematurely delivered, and ATP-induced arrhythmia degeneration is of concern.
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http://dx.doi.org/10.1111/pace.13665DOI Listing
June 2019

24-Hour ambulatory blood pressure levels and control in a large cohort of adult outpatients with different classes of obesity.

J Hum Hypertens 2019 04 12;33(4):298-307. Epub 2018 Nov 12.

Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.

Effective and sustained blood pressure (BP) control in hypertensive patients with moderate-to-severe obesity is often difficult to achieve. We evaluated clinic, 24h, day-time and night-time systolic/diastolic BP levels and control in a large cohort of adult outpatients with different classes of obesity. A single center, prospective, cohort study was conducted at Hypertension Unit, Division of Cardiology, Sant'Andrea Hospital, Rome Italy. All BP measurements were performed and BP thresholds were set according to guidelines. Study population was stratified according to BMI. We included 4,766 individuals (women 48.6%, age 60.3 ± 11.6 years, clinic BP 143.8 ± 18.2/90.9 ± 12.3 mmHg, 24h BP 130.2 ± 13.3/79.1 ± 9.5 mmHg), among whom 36.0% had normal weight, 43.5% were overweight, 15.7% had class I, and 4.8% class II/III obesity. Obese outpatients had higher prevalence of risk factors, and were treated more frequently and with more antihypertensive drugs than those with normal body weight. Obese outpatients showed higher systolic BP levels at all BP measurements, mostly 24h and night-time periods, than those observed in normal weight outpatients. BMI resulted significantly related with clinic (r = 0.053; P < 0.001), 24h (r = 0.098; P < 0.001) and night-time systolic BP (r = 0.126; P < 0.001), and left ventricular mass indexed by height^2.7 (r = 0.311; P < 0.001). BMI was also negatively and independently associated with predefined BP goals at all types of BP measurements. Obesity was associated with higher systolic BP levels during the entire 24h period and increased left ventricular mass. These effects were independently observed, even after correction for major cardiovascular risk factors and comorbidities, as well as the number and type of antihypertensive drug classes.
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http://dx.doi.org/10.1038/s41371-018-0132-4DOI Listing
April 2019

Long-Term Left Ventricular Remodeling of Patients With Hypertrophic Cardiomyopathy.

Am J Cardiol 2018 12 8;122(11):1924-1931. Epub 2018 Sep 8.

Cardiology Unit, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. Electronic address:

In hypertrophic cardiomyopathy (HC), a process of left ventricular (LV) remodeling carrying an adverse prognosis has been described. Conversely, a gradual and benign LV wall thinning has been suggested but never investigated. Therefore, we studied a HC cohort over a long period of time to evaluate the occurrence of a LV remodeling with a benign clinical course. Data of HC patients aged 18 to 65 years and without any condition known to influence LV remodeling were analyzed over a mean follow-up of 7.6 ± 5.7 years. Of 231 HC patients (65% males, mean age 46 ± 12 years), 47 (20%) developed LV remodeling, of whom 23 (10%) had a thinning ≥15% of LV maximal wall thickness from baseline without systolic dysfunction (MWT thinning); 13 (6%) progressed to a LV ejection fraction <50% (end-stage HC) and 11 (5%) developed an apical aneurysm. Follow-up length (odds ratio 1.07, 95% confidence interval 1.00 to 1.15, p = 0.06) and maximal LV wall thickness at baseline (odds ratio 1.14, 95% confidence interval 1.04 to 1.25, p = 0.004) were the main predictors of MWT thinning. Compared with patients with end-stage HC and apical aneurysm, those with MWT thinning showed lower HC-related morbidity (92% and 36% vs 22%, p = 0.003) and mortality (31% and 27% vs 4%, p = 0.02). Furthermore, they showed a combined HC-related morbidity and mortality similar to patients without LV remodeling (incidence 29/1000 vs 26/1000 patient-year, p = 0.77). In conclusion, a process of LV wall thinning with a benign outcome can occur over the long term in patients with HC. The prognostic importance of LV remodeling varies in relation to the different changes in LV morphology and function.
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http://dx.doi.org/10.1016/j.amjcard.2018.08.041DOI Listing
December 2018

Admission heart rate and in-hospital course of patients with Takotsubo syndrome.

Int J Cardiol 2018 Dec 2;273:15-21. Epub 2018 Aug 2.

Cardiology, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

Background: In-hospital course of patients with Takotsubo syndrome (TS) is quite heterogeneous and life-threatening complications are not uncommon in the acute phase. The role of heart rate (HR) as a predictor of prognosis has not been sufficiently investigated in this setting. The study aims to assess the impact of HR at presentation on in-hospital course of patients with TS.

Methods: The study population included 221 patients with TS enrolled in a multicentric registry. HR at admission was evaluated on the first electrocardiogram. According to tertile distribution of HR at presentation, 3 groups were identified: Group A (HR ≤ 76 beats per minute (bpm), n = 76), Group B (HR 77-95 bpm, n = 74) and Group C (HR > 95 bpm, n = 71). Acute in-hospital complications were defined as occurrence of severe pump failure and major arrhythmias.

Results: 32 (14.4%) patients experienced complicated in-hospital course. HR on admission was significantly higher (108 bpm vs. 85 bpm; p < 0.001) and ejection fraction (EF) lower (35% vs. 40%; p = 0.009) in patients with complications than in those without. Patients in Group C experienced a 5-fold higher rate of complications compared to group A and B. After multivariate analysis, higher HR (odds ratio 1.34 per 10 bpm increase, 95% confidence interval (CI) 1.12-1.59; p = 0.001) and lower EF (odds ratio 1.24 per 5% decrease, 95% CI 1.01-1.54; p = 0.049) remained independently associated with a worse outcome.

Conclusion: In a large population with TS, high HR on admission independently predicted complicated in-hospital course.
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http://dx.doi.org/10.1016/j.ijcard.2018.07.145DOI Listing
December 2018

Therapeutic Approach to Hypertension Urgencies and Emergencies During Acute Coronary Syndrome.

High Blood Press Cardiovasc Prev 2018 Sep 31;25(3):253-259. Epub 2018 Jul 31.

Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy.

Uncontrolled hypertension is one of the most common determinant for the persistently high burden of cardiovascular (CV) disease, mostly including coronary artery disease (CAD) and hospital admissions due to acute coronary events. Markedly high blood pressure (BP) levels are also frequently observed during the acute phase of coronary syndromes (both ST-segment and non-ST-segment elevation myocardial infarction and unstable angina). In particular, a sustained raise of BP levels above 180/110 mmHg associated with acute cardiac organ damage, i.e. myocardial ischemia, represents a condition of hypertension emergency and requires rapid hospital admission, prompt pharmacological therapies and non-pharmacological interventions, aimed at restoring coronary flow and preserve vital myocardium. Diagnosis of CAD in hypertensive patients may often be complicated by the concomitant presence of electrocardiographic abnormalities, such as ST-segment depression (at rest or during exercise), which may occur even in the absence of coronary atherosclerosis. Thus, proper identification of CAD may result difficult to perform in the setting of clinical practice, mostly in the presence of left ventricular hypertrophy. In this review, we will briefly discuss diagnostic protocols and pharmacological strategies that can be applied in a setting of hypertension emergency with acute cardiac organ damage in the light of the currently available evidence and recommendations from recent guidelines on hypertension management and control.
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http://dx.doi.org/10.1007/s40292-018-0275-yDOI Listing
September 2018

Nocturnal blood pressure patterns and cardiovascular outcomes in patients with masked hypertension.

J Clin Hypertens (Greenwich) 2018 09 29;20(9):1238-1246. Epub 2018 Jul 29.

Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy.

Masked hypertension (MHT) is characterized by normal clinic and above normal 24-hour ambulatory blood pressure (BP) levels. We evaluated clinical characteristics and CV outcomes of different nocturnal patterns of MHT. We analyzed data derived from a large cohort of adult individuals, who consecutively underwent home, clinic, and ambulatory BP monitoring at our Hypertension Unit between January 2007 and December 2016. MHT was defined as clinic BP <140/90 mm Hg and 24-hour BP ≥ 130/80 mm Hg, and stratified into three groups according to dipping status: (a) dippers, (b) nondippers, and (c) reverse dippers. From an overall sample of 6695 individuals, we selected 2628 (46.2%) adult untreated individuals, among whom 153 (5.0%) had MHT. In this group, 67 (43.8%) were nondippers, 65 (42.5%) dippers, and 21 (13.7%) reverse dippers. No significant differences were found among groups regarding demographics, clinical characteristics, and prevalence of risk factors, excluding older age in reverse dippers compared to other groups (P < 0.001). Systolic BP levels were significantly higher in reverse dippers than in other groups at both 24-hour (135.6 ± 8.5 vs 130.4 ± 6.0 vs 128.2 ± 6.8 mm Hg, respectively; P < 0.001) and nighttime periods (138.2 ± 9.1 vs 125.0 ± 6.3 vs 114.5 ± 7.7 mm Hg; P < 0.001). Reverse dipping was associated with a significantly higher risk of stroke, even after correction for age, gender, BMI, dyslipidemia, and diabetes (OR 18.660; 95% IC [1.056-33.813]; P = 0.046). MHT with reverse dipping status was associated with higher burden of BP and relatively high risk of stroke compared to both dipping and nondipping profiles, although a limited number of CV outcomes have been recorded during the follow-up.
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http://dx.doi.org/10.1111/jch.13361DOI Listing
September 2018

[A unique case of secondary takotsubo syndrome].

G Ital Cardiol (Rome) 2018 Apr;19(4):239-241

Cattedra di Cardiologia, Dipartimento di Medicina Clinica e Molecolare, Facoltà di Medicina e Psicologia, Sapienza Università di Roma.

Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by transient systolic left ventricular dysfunction frequently preceded by stressful events. It typically affects postmenopausal women without angiographic evidence of obstructive coronary artery disease. We report here an uncommon occurrence of secondary TTS in a male with coronary artery disease after exogenous catecholamine administration and pacemaker implantation. This unexpected case suggests that, in such clinical scenario, a TTS diagnosis might be considered even in unsuspected individuals.
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http://dx.doi.org/10.1714/2898.29218DOI Listing
April 2018

Effects of different statin types and dosages on systolic/diastolic blood pressure: Retrospective analysis of 24-hour ambulatory blood pressure database.

J Clin Hypertens (Greenwich) 2018 05 23;20(5):967-975. Epub 2018 Apr 23.

Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome Sapienza, Rome, Italy.

We previously demonstrated lower diastolic blood pressure (BP) levels under statin therapy in adult individuals who consecutively underwent 24-hour ambulatory BP monitoring and compared their levels to untreated outpatients. Here we evaluated systolic/diastolic BP levels according to different statin types and dosages. 987 patients (47.5% female, age 66.0 ± 10.1 years, BMI 27.7 ± 4.6 kg/m , clinic BP 146.9 ± 19.4/86.1 ± 12.1 mm Hg, 24-hour BP 129.2 ± 14.4/74.9 ± 9.2 mm Hg) were stratified into 4 groups: 291 (29.5%) on simvastatin 10-80 mg/d, 341 (34.5%) on atorvastatin 10-80 mg/d, 187 (18.9%) on rosuvastatin 5-40 mg/d, and 168 (17.0%) on other statins. There were no significant BP differences among patients treated by various statin types and dosages, except in lower clinic (P = .007) and daytime (P = .013) diastolic BP in patients treated with simvastatin and atorvastatin compared to other statins. Favorable effects of statins on systolic/diastolic BP levels seem to be independent of types or dosages, thus suggesting a potential class effect of these drugs.
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http://dx.doi.org/10.1111/jch.13283DOI Listing
May 2018

Pulmonary hypertension and clinical correlates in hypertrophic cardiomyopathy.

Int J Cardiol 2017 Dec 14;248:326-332. Epub 2017 Jul 14.

Cardiology Division, Clinical and Molecular Medicine Department, Sapienza University of Rome, Rome, Italy.

Background: Pulmonary hypertension (PH) in patients with hypertrophic cardiomyopathy (HCM) has been investigated in a small number of studies. Purpose of this study was to assess the prevalence and its association with outcome in a population of consecutive HCM outpatients.

Methods: We retrospectively analyzed data of 361 consecutive HCM outpatients in whom echocardiographic measurements of pulmonary artery systolic pressure (PASP) were available at initial and most recent evaluation. Four different clinical groups were specifically investigated: patients without left ventricular outflow tract obstruction (group A, 165), with obstruction (group B, 126), patients diagnosed at the age≥65 (group C, 50) and patients with end stage (ES) HCM (group D, 20).

Results: PH was identified in 41 (11.4%) of the 361 patients at initial evaluation while it has been recognized in 25 (7,8% [1.1%/year]) during a median follow-up of 3.4years. Analysis of subgroups showed that prevalence of PH increased from patient group A to D (8%, group A, 19%, group B, 28% group C, 70%, group D, respectively, p<0,01). During follow-up, patients with PH showed a significant higher HCM-related mortality (p=0.01) and morbidity (p<0.001) as compared with those without PH, but in multivariable analysis, PH resulted an independent risk factor only for HCM-related morbidity (HR=2.50, 95% CI 1.08-5.79, p=0.03).

Conclusion: PH affects a significant proportion of patients with HCM. Its prevalence varies according to different clinical profiles. It is associated with an unfavorable clinical outcome and is an independent predictor of morbidity.
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http://dx.doi.org/10.1016/j.ijcard.2017.07.010DOI Listing
December 2017

Attitudes and preferences for the clinical management of hypertension and hypertension-related cerebrovascular disease in the general practice: results of the Italian hypertension and brain survey.

Clin Hypertens 2017 15;23:10. Epub 2017 May 15.

Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Via di Grottarossa 1035, Rome, 00189 Italy.

Background: The aim of this survey was to evaluate attitudes and preferences for the clinical management of hypertension and hypertension-related cerebrovascular diseases (CVD) in Italy.

Methods: A predefined 16-item survey questionnaire was anonymously administered to a large community sample of general practitioners (GPs), trained by specialized physicians (SPs), who have been included in an educational program between January and November 2015.

Results: A total of 591 physicians, among whom 48 (8%) training SPs and 543 (92%) trained GPs, provided 12,258 valid answers to the survey questionnaire. Left ventricular hypertrophy was considered the most frequent marker of hypertension-related organ damage, whereas atrial fibrillation and carotid atherosclerosis were considered relatively not frequent (10-20%). The most appropriate blood pressure (BP) targets to be achieved in hypertensive patients with CVD were <140/90 mmHg for SPs and <135/85 mmHg for GPs. To achieve these goals, ACE inhibitors were considered the most effective strategies by GPs, whereas SPs expressed a preference for ARBs, both in monotherapies and in combination therapies with beta-blockers.

Conclusions: This survey demonstrates that Italian physicians considered left ventricular hypertrophy frequently associated to CVD and that drugs inhibiting the renin-angiotensin system the most appropriate therapy to manage hypertension and hypertension-related CVD.
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http://dx.doi.org/10.1186/s40885-017-0066-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430606PMC
May 2017

QT spatial dispersion and sudden cardiac death in hypertrophic cardiomyopathy: Time for reappraisal.

J Cardiol 2017 Oct 22;70(4):310-315. Epub 2017 Mar 22.

Department of Clinical and Molecular Medicine, "Sapienza" University, Rome, Italy.

Background: The 12-lead surface electrocardiographic (ECG) analysis is able to provide independent predictors of prognosis in several cardiovascular settings, including hypertrophic cardiomyopathy (HCM). The present single-center study investigated the possible ability of several ECG-derived variables in stratifying sudden cardiac death (SCD) risk and, possibly, in improving the accuracy of the 2014 European Society of Cardiology guidelines.

Methods: A total of 221 consecutive HCM outpatients were recruited and prospectively followed. All of them underwent a full clinical and instrumental examination, including a 12-lead surface ECG to calculate the dispersion for the following intervals: QRS, Q-Tend (QT), Q-Tpeak (QTp), Tpeak-Tend (TpTe), J-Tpeak (JTp), and J-Tend (JT). The study composite end-point was SCD, aborted SCD, and appropriate implantable cardioverter defibrillator (ICD) interventions.

Results: During a median follow-up of 4.4 years (25th-75th interquartile range: 2.4-9.4 years), 23 patients reached the end-point at 5-years (3 SCD, 3 aborted SCD, 17 appropriate ICD interventions). At multivariate analysis, the spatial QT dispersion corrected according to Bazett's formula (QTcd) remains independently associated to the study endpoint over the HCM Risk-SCD score (C-index 0.737). A QTcd cut-off value of 93ms showed the best accuracy in predicting the SCD endpoint within the entire HCM study cohort (sensitivity 56%, specificity 75%, positive predictive value 22%, negative predictive value 97%).

Conclusion: Our data suggest that the QTcd might be helpful in SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to the contemporary guidelines.
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http://dx.doi.org/10.1016/j.jjcc.2017.01.006DOI Listing
October 2017

Tortuosity, Recurrent Segments, and Bridging of the Epicardial Coronary Arteries in Patients With the Takotsubo Syndrome.

Am J Cardiol 2017 Jan 8;119(2):243-248. Epub 2016 Oct 8.

Cardiology Department, Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. Electronic address:

Myocardial bridging (MB) and a long recurrent wraparound left anterior descending artery (wrap-LAD) are coronary anatomic variants that have been recently suggested to be associated with takotsubo syndrome (TS). Until now, coronary artery tortuosity (CAT) has never been investigated in this setting. Our study sought to evaluate the prevalence of the aforementioned anatomic variants in a large population with TS. In this retrospective angiographic study, 109 patients with TS were compared with 109 age- and gender-matched subjects without coronary artery disease, valve heart disease, or cardiomyopathy. CAT was identified by ≥3 consecutive curvatures ≥90° (criteria 1) or by ≥2 consecutive curvatures ≥180° (criteria 2). Wrap-LAD was defined if any part of the vessel outreached the apex of the left ventricle and MB as the presence of a milking effect or a step-up and step-down phenomenon. An anatomic variant was found in 79 patients with TS (72%) and in 48 controls (44%) (p <0.001). CAT in at least 1 vessel (criteria 1: 49% vs 20%, p <0.001; criteria 2: 38% vs 13%, p <0.001), ≥2 vessels (criteria 2: 14% vs 3%, p = 0.005), and wrap-LAD (41% vs 27%, p = 0.02) were significantly more frequent in patients with TS than in controls. The prevalence of MB (9% vs 5%, p = 0.18) did not differ between groups. In conclusion, CAT and wrap-LAD have higher prevalence in patients with TS than in matched controls. These findings could support the hypothesis that anatomic variants might act as potential pathogenic substrates in TS.
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http://dx.doi.org/10.1016/j.amjcard.2016.09.055DOI Listing
January 2017