Gennaro Provenza

Civil Hospital, Conegliano, Conegliano, Veneto, Italy

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Publications (27)96.08 Total impact

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    ABSTRACT: Molecular mechanisms protecting cardiomyocytes from stress-induced death, including tension stress, are essential for cardiac physiology and defects in these protective mechanisms can result in pathological alterations. Bcl2-associated athanogene 3 (BAG3) is expressed in cardiomyocytes and is a component of the chaperone-assisted autophagy pathway, essential for homeostasis of mechanically altered cells. BAG3 ablation in mice results in a lethal cardiomyopathy soon after birth and mutations of this gene have been associated with different cardiomyopathies including stress-induced Takotsubo cardiomyopathy (TTC). The pathogenic mechanism leading to TTC has not been defined, but it has been suggested that the heart can be damaged by excessive epinephrine (epi) spillover in the absence of a protective mechanism. The aim of this study was to provide more evidence for a role of BAG3 in the pathogenesis of TTC. Therefore, we sequenced BAG3 gene in 70 TTC patients and in 81 healthy donors with the absence of evaluable cardiovascular disease. Mutations and polymorphisms detected in the BAG3 gene included a frequent nucleotide change g2252c in the BAG3 3'-untranslated region (3'-UTR) of Takotsubo patients (P<0.05), resulting in loss of binding of microRNA-371a-5p (miR-371a-5p) as evidenced by dual-luciferase reporter assays and argonaute RNA-induced silencing complex catalytic component 2/pull-down assays. Moreover, we describe a novel signaling pathway in cardiomyocytes that leads to BAG3 upregulation on exposure to epi through an ERK-dependent upregulation of miR-371a-5p. In conclusion, the presence of a g2252c polymorphism in the BAG3 3'-UTR determines loss of miR-371a-5p binding and results in an altered response to epi, potentially representing a new molecular mechanism that contributes to TTC pathogenesis.
    Cell Death & Disease 10/2015; 6(10):e1948. DOI:10.1038/cddis.2015.280 · 5.01 Impact Factor

  • JACC. Cardiovascular imaging 09/2015; DOI:10.1016/j.jcmg.2015.06.005 · 7.19 Impact Factor
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    ABSTRACT: Objective: To assess left ventricular (LV) twist by three-dimensional speckle tracking imaging (3D-STI) in a pacing induced heart failure canine model with left bundle-branch block (LBBB) undergoing cardiac resynchronization therapy (CRT). Methods: After induction of left bundle branch block by radiofrequency ablation, rapid right ventricular pacing (RVP) at 200 beats/min was utilized in 22 adult beagle dogs for 6 weeks to induce heart failure. Then 15 dogs received CRT for 4 weeks and others were treated as control. Apical full-volume acquisition of the LV was obtained in conscious animals at baseline, the end of 6-week RVP and the end of 4-week CRT. Peak LV systolic twist (Ptw) and torsion (Ptor) along with peak apical and basal rotation were automatically calculated by Tom-Tec 4D LV Analysis 3.0 software to identify the ideal parameter in predicting treatment response of CRT. Results: After 4 weeks of CRT, LVEF increased [(31.97 ± 1.47) vs. (37.47 ± 3.60)%, p=0.002] and LVESV decreased [(24.13 ± 3.72) vs. (21.87 ± 3.15)ml, p=0.007] significantly in dogs with heart failure. By shortening the delay of basal rotation [(23.73 ± 9.98) vs. (17.87 ± 5.94)ms, p=0.009], CRT improved peak LV systolic twist [(6.88 ± 0.99) vs. (8.03 ± 0.63)°, p=0.008] and torsion [(1.21 ± 0.36) vs. (1.98 ± 0.39)°/cm, p=0.010] instead of peak apical [(5.97 ± 0.57) vs. (6.13 ± 0.61)°, p=0.103] and basal rotation [(2.08 ± 0.45) vs. (2.13 ± 0.46)°, p=0.469]. CRT treatment response, defined as improvement of LVESV≥15%, was observed in 9 dogs. Significant difference was found in Ptw [(7.43 ± 0.61) vs. (6.06 ± 0.89)°, p=0.016] and Ptor [(1.43 ± 0.45) vs. (0.67 ± 0.36)°/cm, p=0.042] between responders and nonresponders. The cut-off values derived from receiver-operating characteristic curve analysis were 6.73° for Ptw and 1.00°/cm for Ptor with satisfying sensitivity as 89% and 85%, specificity as 83% and 84%, respectively. Conclusions: CRT improved LV systolic twist and reversed LV remodeling by reconciling basal with apical rotation. Peak twist and torsion evaluated by 3D-STI demonstrated potential prediction value for treatment response of CRT.
    European Heart Journal – Cardiovascular Imaging 12/2014; 15 Suppl 2(suppl 2):ii20-ii22. DOI:10.1093/ehjci/jeu242 · 2.65 Impact Factor

  • International journal of cardiology 03/2014; DOI:10.1016/j.ijcard.2013.12.239 · 4.04 Impact Factor
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    ABSTRACT: Objectives To determine clinical and echocardiographic correlates of acute heart failure, cardiogenic shock and in-hospital mortality in a large cohort of tako-tsubo cardiomyopathy (TTC) patients. Background Despite good long-term prognosis, life-threatening complications due to hemodynamic instability can occur early in TTC patients. Methods The study population consisted of 227 patients (66.2 ± 12.2 years of age; females, 90.3%) enrolled in the Tako-tsubo Italian Network, undergoing transthoracic two-dimensional echocardiography on admission and at short-term follow-up (4.3 [4 to 6] weeks). Patients were divided into two groups according to the presence or absence of major adverse events, a composite of acute heart failure, cardiogenic shock, and in-hospital mortality. Results Major adverse events occurred in 59 patients (25.9%). The variables for elderly patients ≥75 years of age (42.4 vs. 23.8%; p = 0.011): left ventricular (LV) ejection fraction (35.1 ± 5.9 vs. 38.4 ± 4.6%, p < 0.001), wall motion score index (1.9 ± 0.2 vs. 1.7 ± 0.2, p < 0.001), E/e′ ratio (13.5 ± 4.3 vs. 9.9 ± 3.3 [where E/e′ is ratio of mitral E peak velocity and averaged e′ velocity], p < 0.001), LV outflow tract obstruction (23.7 vs. 8.9%, p = 0.006), pulmonary artery systolic pressure (47.4 ± 12.3 vs. 38.0 ± 9.2 mm Hg; p < 0.001), right ventricular involvement (28.8 vs. 9.5%; p < 0.001), and reversible moderate-to-severe mitral regurgitation (49.1 vs. 11.9%; p < 0.001), were significantly different between groups and were associated with adverse events. At multivariate analysis, LV ejection fraction (HR: 0.92; 95% CI: 0.89 to 0.95; p < 0.001), E/e′ ratio (HR: 1.13; 95% CI: 1.02 to 1.24; p = 0.011), reversible moderate to severe mitral regurgitation (HR: 3.25; 95% CI: 1.16 to 9.10; p = 0.025), and age ≥75 years (HR: 2.81; 95% CI: 1.05 to 7.52; p = 0.039) were independent correlates of major adverse events. Conclusions Echocardiographic parameters provide additional information compared to other variables routinely used in clinical practice to identify patients at higher risk of hemodynamic deterioration and poor in-hospital outcome, allowing prompt institution of appropriate pharmacological treatment and adequate mechanical support.
    JACC. Cardiovascular imaging 02/2014; 7(2). DOI:10.1016/j.jcmg.2013.09.020 · 7.19 Impact Factor
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    ABSTRACT: Background: In the medical literature, several cases of Tako-tsubo cardiomyopathy (TTC) with coronary artery disease (CAD) have been reported, and in clinical practice, several typical TTC cases show relevant stenoses of the coronary arteries spatially unrelated to the dysfunctional myocardium. Objective: This study aimed to evaluate the prevalence, clinical characteristics, and outcome of patients with TTC and relevant CAD in a large multicenter database. Methods: In 26 centers, 450 patients admitted with a diagnosis of TTC underwent coronary angiography within 48 h of hospital admission and were included prospectively in the Tako-tsubo Italian Network Registry. Results: Overall, 43 (9.6%) patients had at least one relevant (≥50%) coronary stenosis not supplying the dysfunctional myocardium, whereas 407 patients (90.4%) had irrelevant stenosis or angiographically normal coronary arteries. TTC patients with relevant CAD were more likely to be older in age, to have diabetes, a familial history of CAD, and acute functional mitral regurgitation compared with those without relevant CAD. At the 6-month follow-up, the incidence of death, TTC recurrence, and rehospitalization rates in patients with and without relevant CAD were similar. On multivariable Cox analysis, an independent predictor of death was the Charlson Comorbidity Index, whereas the presence of CAD did not influence the mid-term outcome significantly. Conclusion: The presence of CAD is a rather common finding in a large proportion of patients with TTC. Thus, when the stenotic artery does not supply the dysfunctional myocardium or when the extent of dysfunctional myocardium is wider than the territory of distribution supplied by a single stenotic coronary artery, the presence of angiographically relevant CAD should not be considered an exclusion criterion for TTC.
    Coronary Artery Disease 09/2013; 24(6):527-533. DOI:10.1097/MCA.0b013e3283645c4e · 1.50 Impact Factor
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    ABSTRACT: To describe the clinical characteristics and in-hospital outcomes of older adults with tako-tsubo cardiomyopathy (TTC). Partially retrospective, partially prospective observational study. Eleven Italian referral cardiac centers included in the Tako-tsubo Italian Network. One hundred ninety consecutive individuals with TTC (92.1% female, mean age 66) were divided into three groups according to age (<65, n = 78; 65-74, n = 61; ≥75, n = 51). Clinical findings and in-hospital outcomes were evaluated in each group. Participants aged 65 and older had a greater prevalence of hypertension (P = .001) and a lower glomerular filtration rate (P < .001), and those aged 65 to 74 had a greater prevalence of psychiatric disorders (P = .01), ST-segment elevation on admission (P = .01) and a cerebrovascular disease (P = .003) than those younger than 65. Despite similar left ventricular ejection fraction (LVEF) on admission (P = .26), the oldest group had a lower LVEF at discharge (P = .03). Inotropic agents were used more frequently in older adults (P = .03). In-hospital composite adverse events (all-cause death, acute heart failure, life-threatening arrhythmias, stroke, and cardiogenic shock; P = .03) and overall complications (P = .004) were more common in participants aged 75 and older. Overall in-hospital mortality was low (2.8%) but was more prevalent in participants aged 75 and older (6.3%). On multivariate analysis, age of 75 and older (hazard ratio (HR) = 2.45, 95% confidence interval (CI) = 1.28-5.82, P = .04) and LVEF on admission (HR = 0.874, 95% CI = 0.81-0.95, P < .001) were the only independent predictors of in-hospital adverse events. The clinical profile of participants aged 75 and older with TTC was different from that of those younger than 75 with TTC, and they had a higher in-hospital complication rate.
    Journal of the American Geriatrics Society 10/2011; 60(1):93-8. DOI:10.1111/j.1532-5415.2011.03730.x · 4.57 Impact Factor
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    ABSTRACT: The aim of this study was to assess the echocardiographic distribution of regional wall motion abnormalities (RWMA) in patients with tako-tsubo cardiomyopathy (TTC) compared with anterior ST-elevation myocardial infarction (ant-STEMI). Thirty-seven TTC and 37 ant-STEMI patients underwent standard echocardiographic examination at the time of hospital admission. RWMA and the involvement of the left ventricular territories supplied by each coronary artery according to the American Society of Echocardiography classification were reported. TTC patients showed a lower left ventricular ejection fraction (37.6 ± 5.1 vs. 40.9 ± 3.7%; P = 0.002) and a higher wall motion score index (WMSI; 1.98 ± 0.2 vs. 1.51 ± 0.14; P < 0.001) compared with ant-STEMI patients. No significant differences were observed between groups with regard to detection of RWMA in the territory supplied by the left anterior descending coronary artery (LAD) (37 vs. 37; P = 1). Conversely, in TTC patients, the territories supplied by the LAD/left circumflex coronary artery (LCX) (37 vs. 31; P = 0.011), LAD/right coronary artery (RCA) (34 vs. 13; P < 0.001), RCA (33 vs. 5; P < 0.001), and RCA/LCX (31 vs. 2; P < 0.001) were more frequently involved. A cut-off value of WMSI ≥1.75 (area under the curve 0.956) and for the number of territories with RWMA ≥4 (AUC = 0.928) predicted TTC with a sensitivity of 83 and 84% and a specificity of 100 and 97%, respectively. Echocardiography revealed a distinctive pattern of contractility in TTC patients, characterized by symmetrical RWMA extending equally into the territory of distribution of all coronary arteries.
    European Heart Journal – Cardiovascular Imaging 05/2011; 12(7):542-9. DOI:10.1093/ejechocard/jer059 · 2.65 Impact Factor
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    ABSTRACT: We report an unusual case of impending paradoxical embolization in a 69-year-old woman heterozygote carrier of factor V Leiden mutation. The patient presented to the emergency room with the clinical scenario of massive pulmonary embolism. Serial echocardiographic examinations revealed a large thrombus in the right atrium floating via a patent foramen ovale into the left atrium. Anticoagulation therapy was started. After 72 h, due to the unresolved thrombus, the patient underwent surgical treatment consisting of complete excision of the thrombus, closure of the foramen ovale, and pulmonary embolectomy. No in-hospital complications were noted. At 1-year follow-up, the patient is doing well on long-term anticoagulation treatment free of thromboembolic events.
    Journal of Cardiovascular Medicine 07/2010; 14(10). DOI:10.2459/JCM.0b013e32833893f9 · 1.51 Impact Factor
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    ABSTRACT: Acute cardiovascular events show definite temporal patterns of occurrence. Takotsubo cardiomyopathy (TTC) has been recently shown to exhibit a seasonal (summer) and circadian (morning) temporal distribution. The aim of this study, based on the database of a multicenter Italian network, was to investigate the possible existence of a weekly pattern of onset of TTC. The study included all cases of TTC admitted to the coronary care unit of 8 referral cardiac centers in Italy (five in Southern Italy and three in Northern Italy, respectively), belonging to the Takotsubo Italian Network (January 2002-December 2008). Day of admission was categorized into seven 1-day intervals according by week, and chronobiological analysis was performed by partial Fourier series. The database included 112 patients with TTC (92.9% females). The weekly distribution identified the highest number of cases on Monday and the lowest on Saturday. Chronobiologic analysis yielded a rhythmic pattern with a significant peak on Monday (P = .036). This study confirms a Monday preference for TTC occurrence on Monday, similar to that reported for acute myocardial infarction. Stress of starting weekly day life activities, could play a triggering role.
    The American journal of emergency medicine 07/2010; 28(6):715-9. DOI:10.1016/j.ajem.2009.04.023 · 1.27 Impact Factor
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    ABSTRACT: We describe a case of tako-tsubo cardiomyopathy in an elderly woman with a permanent pacemaker admitted to the ED with chest pain and dyspnea. Coronary angiography revealed normal coronary arteries. Typical left ventricular apical ballooning was demonstrated on contrast ventriculography. Left and right ventricular ballooning with pulmonary artery systolic hypertension was detected by transthoracic echocardiography. Velocity vector imaging and strain analysis showed a typical pattern of regional myocardial apical right ventricular contraction characterized by paradoxical positive longitudinal systolic strain. Biventricular involvement was associated with hemodynamic instability, signs of pulmonary vascular congestion, and bilateral basal pleural effusion. The patient's clinical condition gradually improved, and she was discharged after prolonged hospitalization. Predischarge echocardiography showed substantial recovery of left and right systolic function along with normalization of pulmonary artery systolic pressure. Right ventricular function should be carefully evaluated in patients with tako-tsubo cardiomyopathy, especially in the acute phase.
    Chest 04/2010; 137(4):973-5. DOI:10.1378/chest.09-0923 · 7.48 Impact Factor

  • Journal of the American Geriatrics Society 09/2009; 57(8):1509-11. DOI:10.1111/j.1532-5415.2009.02378.x · 4.57 Impact Factor
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    Journal of the American College of Cardiology 08/2009; 54(2):180-1. DOI:10.1016/j.jacc.2009.03.048 · 16.50 Impact Factor
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    ABSTRACT: We report a case of implantation of a second Amplatzer device in order to eliminate a residual postprocedural shunt after transcatheter patent foramen ovale closure. Echocardiographic and angiographic images are presented.
    Journal of Cardiovascular Medicine 06/2009; 10(9):736-7. DOI:10.2459/JCM.0b013e32832b4cb7 · 1.51 Impact Factor
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    ABSTRACT: Transthoracic Doppler echocardiography is a valuable tool to measure coronary flow reserve (CFR) and detect in-stent restenosis (ISR) after percutaneous coronary angioplasty in selected series of patients. To assess the usefulness of coronary flow reserve measured by echocardiography in detecting significant (> or =70%) ISR of the left anterior descending coronary artery in a large unselected population. Two hundred and twenty-three patients (age 61 +/- 10 years; 168 men) treated with left anterior descending stenting underwent CFR measurement by transthoracic Doppler echocardiography and venous adenosine infusion 24-72 h before control coronary angiography. Coronary-active drugs were continued, and patients with multiple risk factors and old anterior-apical myocardial infarction were included. Significant ISR occurred in 56 patients (25%). Patients with ISR had higher basal coronary flow velocity (27 +/- 10 cm/s vs. 24 +/- 7 cm/s; P < 0.002) and lower CFR (1.5 +/- 0.5 vs. 2.7 +/- 0.6; P < 0.0001) than those without ISR. A linear relation was found between ISR and CFR (r = -0.73; P < 0.0001) and remained significant after adjustment for blood pressure and heart rate (r = -0.74; P < 0.0001). A CFR less than two identified significant ISR (sensitivity 88%, specificity 88%, area under the curve = 0.943; P < 0.001). In a multivariate model of CFR prediction, myocardial infarction and heart rate were slightly contributory (ss = -0.19, P < 0.01; ss = -0.16, P < 0.03, respectively), whereas ISR had a large influence (ss = -0.66; P < 0.0001). The inverse correlation between ISR and CFR persisted in patients with myocardial infarction (r = -0.64; P < 0.0001) and in those treated with beta-blockers (r = -0. 71; P < 0.0001). Echocardiographic measurement of CFR detects significant left anterior descending ISR in unselected patients with multiple risk factors, old anterior-apical myocardial infarction, and taking beta-blockers.
    Journal of Cardiovascular Medicine 12/2008; 9(12):1254-9. DOI:10.2459/JCM.0b013e328312954e · 1.51 Impact Factor
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    ABSTRACT: Left cor triatriatum is a congenital heart disease characterized by an intra-atrial membrane determining obstruction and pressure gradient. We report an unusual case of cor triatriatum in a nonprofessional athlete presenting with effort dyspnoea. Although frequently diagnosed in the infant, it may also be a rare cause of effort dyspnoea in the adult.
    Journal of Cardiovascular Medicine 10/2008; 9(9):926-8. DOI:10.2459/JCM.0b013e3282fe6985 · 1.51 Impact Factor
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    ABSTRACT: Transient left ventricular ballooning also called tako-tsubo syndrome, is increasingly being recognized as cardiomyopathy mimicking the clinical scenario of an acute myocardial infarction. Generally, it is characterized by apical ballooning appearance of the left ventricle in the presence of normal coronary arteries on the angiogram. Recently, a variant form involving the midventricle with sparing of the apical and basal segments has been described. This syndrome is more prevalent in postmenopausal woman and usually preceded by extreme emotional and/or physical stress. We describe a case never reported before of transient left ventricular ballooning occurring during the early postpartum period after ergonovine injection rapidly evolving from a 'typical apical' ballooning into a 'midventricular' myocardial dysfunction.
    International journal of cardiology 09/2008; 138(2):e31-4. DOI:10.1016/j.ijcard.2008.06.041 · 4.04 Impact Factor
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    ABSTRACT: We report a case of transient tako-tsubo cardiomyopathy characterized by an unusual trigger in a woman victim of near-drowning syndrome. After 24 h, electrocardiogram changes and a typical echocardiographic pattern of apical ballooning with a mild increase of serum troponin level induced the suspicion of tako-tsubo cardiomyopathy despite the absence of chest pain. Left ventriculography confirmed the apical ballooning, and coronary angiography revealed normal coronary arteries. Electrocardiogram changes and apical contraction abnormalities were reversed within 1 month. In conclusion, we hypothesize that hypoxemia related to near-drowning syndrome could have induced transient myocardial dysfunction mediated by a sympathetic nerve activation.
    Journal of Cardiovascular Medicine 06/2008; 9(5):501-5. DOI:10.2459/JCM.0b013e3282f03aca · 1.51 Impact Factor
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    ABSTRACT: We report a case of a huge left atrial myxoma with an unusual clinical presentation characterized by acute pulmonary edema. The possible pathophysiologic mechanism has been discussed.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 02/2008; 21(8):978.e1-3. DOI:10.1016/j.echo.2007.10.016 · 4.06 Impact Factor
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    ABSTRACT: Penetrating aortic ulcer (PAU) is defined as an ulcerating atherosclerotic lesion that disrupts the aortic wall layers, penetrating the internal elastic lamina. The natural history of the disease and the preferred treatment are still debated. We report a case of painless PAU in a 78-year-old man detected by transesophageal echocardiography at the level of proximal descending aorta as an incidental finding. The patient underwent endovascular stent-graft placement without any complications at early and late follow-up.
    Journal of Cardiovascular Medicine 01/2008; 8(12):1049-51. DOI:10.2459/JCM.0b013e32801462c0 · 1.51 Impact Factor

Publication Stats

229 Citations
96.08 Total Impact Points


  • 2014
    • Civil Hospital, Conegliano
      Conegliano, Veneto, Italy
  • 2013-2014
    • Spedali Civili di Brescia
      Brescia, Lombardy, Italy
  • 2011
    • Università degli Studi di Salerno
      Fisciano, Campania, Italy