Myocarditis and inflammatory bowel diseases: A single-center experience and a systematic literature review.

BACKGROUND: Myocarditis and inflammatory bowel diseases (IBD) are rare conditions, but may coexist. Myocarditis in IBD may be infective, immune-mediated, or due to mesalamine toxicity. A gap of knowledge exists on the clinical features of patients that present myocarditis in association with IBD, especially for endomyocardial biopsy-proven cases. Our aims are: 1) to describe the clinical characteristics of patients with an associated diagnosis of myocarditis and IBD in a single-center hospital, 2) to perform a systematic review of the literature of analogous cases. METHODS: We retrospectively analyzed data of patients followed up at the outpatient Cardio-immunology and Gastroenterology Clinic of Padua University Hospital, to identify those with an associated diagnosis of myocarditis and IBD. In addition, a systematic review of the literature was conducted. We performed a qualitative analysis of the overall study population. RESULTS: The study included 104 patients (21 from our single center cohort, 83 from the literature review). Myocarditis in IBD more frequently affects young (median age 31 years) males (72%), predominantly with infarct-like presentation (58%), within an acute phase of the IBD (67%) and with an overall benign clinical course (87%). Nevertheless, a not negligible quote of patients may present giant cell myocarditis, deserve immunosuppression and have a chronic, or even fatal course. Histological evidence of mesalamine hypersensitivity is scarce and its incidence may be overestimated. CONCLUSIONS: Our study shows that myocarditis in association with IBD, if correctly managed, may have a spontaneous benign course, but predictors of worse prognosis must be promptly recognized.

Daratumumab plus bortezomib or daratumumab plus lenalidomide as salvage therapy for patients with myeloma: initial follow-up of an Italian multicentre retrospective clinical experience by 'Rete Ematologica Pugliese'.

We report herein a multicentre retrospective analysis of 192 consecutive patients with symptomatic refractory/relapsed multiple myeloma (RRMM) treated with daratumumab in combination with bortezomib or lenalidomide as salvage therapy at 9 haematological centres in Puglia. Choice of both regimens was based on previous treatment and/or physicians' preference. Considering the under-representation of older patients (very old patient ≥ 80 years) in clinical trials and the prognostic and predictive importance and value of frailty status, here, we further characterised the patient cohort by age. The overall response rate (ORR) was generally lower than what was previously reported in the CASTOR (ORR 72.6% vs 85%) and POLLUX (ORR 86.5% vs 93%) trials. The lower ORR in our analysis compared to the CASTOR and POLLUX trials could be related to a less selected population. Similarly, amongst very old patients, the ORR was encouraging: ORR to treatment with DVd (daratumumab + bortezomib + dexamethasone) was 66.7%, and ORR to treatment with DRd (daratumumab + lenalidomide + dexamethasone) was 92.3%. Median TTP (time to progression) was 10.8 months (1-year TTP: 44.7%; 2-year TTP: 25.3%) in the DVd group; median TTP was not reached in the DRd group (1-year TTP: 82.7%; 2-year TTP: 71.4%). Median OS (overall survival) was not reached either in the DRd group (1-year OS: 85.9%; 2-year OS: 73.7%) or the DVd group (1-year OS: 70.2%; 2-year OS: 58.9%).

Excimer laser technology in percutaneous coronary interventions: Cardiovascular laser society's position paper.

Excimer Laser Coronary Atherectomy (ELCA) is a well-established therapy that emerged for the treatment of peripheral vascular atherosclerosis in the late 1980s, at a time when catheters and materials were rudimentary and associated with the most serious complications. Refinements in catheter technology and the introduction of improved laser techniques have led to their effective use for the treatment of a wide spectrum of complex coronary lesions, such as thrombotic lesions, severe calcific lesions, non-crossable or non-expandable lesions, chronic occlusions, and stent under-expansion. The gradual introduction of high-energy strategies combined with the contrast infusion technique has enabled us to treat an increasing number of complex cases with a low rate of periprocedural complications. Currently, the use of the ELCA has also been demonstrated to be effective in acute coronary syndrome (ACS), especially in the context of large thrombotic lesions.

mRECIST criteria to assess recurrent thyroid carcinoma treatment response after radiofrequency ablation: a prospective study.

PURPOSE: Surgical removal is recommended for recurrent thyroid carcinomas (RTCs) unable to uptake radioiodine and/or not responsive to chemotherapy. However, repeated neck dissection is difficult for surgeons. Thus, radiofrequency ablation (RFA) was proposed for RTCs. The aim of this prospective study is to assess RTC treatment response after RFA, according to well-established criteria. METHODS: Sixteen lesions in 13 patients were treated by RFA. All patients refused/were excluded from repeated surgery or other conventional therapy. CT and US examinations were performed before RFA to evaluate lesion volume and vascularization. All RFA procedures were performed under US-guidance by an 18-gauge, electrode. Treatment response was evaluated by CT, according to RECIST 1.1 and to mRECIST guidelines; CT examinations were performed during follow-up (6-18 months); the volume of residual vital tumour tissue and the percentage of necrotic tissue were estimated by contrast enhanced CT. RESULTS: RFA was well tolerated by all patients; in two cases laryngeal nerve paralysis was observed. Mean pre-treatment volume was 4.18 ± 3.53 ml. Vital tumour tissue and percentage of necrosis at 6, 12 and 18 months were 0.18 ± 0.25, 0.11 ± 0.13, 0.29 ± 0.40 ml and 91.9 ± 11.1, 90.4 ± 13.3, 80.8 ± 23.1%. According to RECIST 1.1, target lesion response was classified as complete response (CR) in one case, partial response (PR) in 11/16, stable disease in 4/16 cases. According to mRECIST, 11/16 cases were classified as CR and the remaining 5 as PR. CONCLUSION: RFA is a safe procedure to treat the viable tumour tissue and to reduce the RTC volume; as to the criteria to assess treatment response, mRECIST appears to be more accurate.

Coronary microvascular dysfunction correlates with the new onset of cardiac allograft vasculopathy in heart transplant patients with normal coronary angiography.

Coronary microvascular dysfunction is emerging as a strong predictor of outcome in heart transplantation (HT). We assessed the validity of microvascular dysfunction, defined by means of a reduced coronary flow reserve (CFR), as a factor associated with new onset epicardial cardiac allograft vasculopathy (CAV) or death. We studied 105 patients at 4 ± 1 years post-HT with a normal coronary angiography (CA). New onset CAV was assessed by CA. CFR was assessed in the left anterior descending (LAD) coronary artery by transthoracic Doppler echocardiography and calculated as the ratio of hyperaemic to basal blood flow velocity. A CFR ≤ 2.5 was considered abnormal. Epicardial CAV onset or death was assessed during a follow-up of 10 years. New onset CAV was diagnosed in 30 patients (28.6%) (Group A), and the CA was normal in the remaining 75 patients (71.4%) (Group B). Group A had reduced CFR compared with group B (2.4 ± 0.6 vs. 3.2 ± 0.7, p < 0.0001). A CFR ≤ 2.5 was independently associated with a higher probability of new onset CAV (p < 0.0001) and a higher probability of death, regardless of CAV onset (p < 0.01). Microvascular dysfunction is independently associated with the onset of epicardial CAV, and associated with a higher risk of death, regardless of CAV onset.

"Real world" outcome of lenalidomide plus dexamethasone in the setting of recurrent and refractory multiple myeloma: extended follow-up of a retrospective multicenter study by the "rete ematologica pugliese".

This current retrospective multicenter analysis represents, to our knowledge, the first Italian study evaluating the efficacy and toxicity profile of "lenalidomide plus dexamethasone" as salvage therapy in patients with recurrent-refractory MM in the real life contest. Our study included patients who are usually excluded from clinical trials because of unfavorable baseline characteristics. Median OS was significantly longer in patients receiving "lenalidomide plus dexamethasone" for more than 12 months compared with those who had received "lenalidomide plus dexamethasone" for a shorter interval (P<0.0001). Median OS was not affected by best response achieved (P 0.4) and age (P 0.3). Quality of response did not correlate with number of previous lines of therapy (P 0.77) and age. Higher ORRs were recorded in the patients group with relapsed MM compared to those with refractory disease, but this difference was not statistically significant (P 0.38).

The SAPIEN 3 valve: lights and shadows.

Transcatheter aortic valve implantation (TAVI) has become an accepted alternative treatment option for high-risk or inoperable patients with symptomatic severe aortic stenosis. The future challenge for TAVI devices is to ensure results in terms of safety and efficacy that may justify an eligibility extension for this procedure to patients at intermediate and low risk for surgery. The ideal aortic valve prosthesis should be durable, with optimal hemodynamic performance and able to reduce the current major complications of TAVI procedure, in particular vascular complications (not infrequent with the transfemoral access route), paravalvular leaks, stroke and atrioventricular block requiring a permanent pacemaker. The SAPIEN 3™ (S3) (Edwards Lifesciences, Irvine, CA, USA) is the last Edwards family's transcatheter heart valves and incorporates a number of new and enhanced features intended to reduce the risk of vascular injury and paravalvular regurgitation, and to facilitate rapid and accurate positioning and implantation. The first data on S3 (SAPIEN3 trial) were presented at the EuroPCR 2014 and confirmed the advantage of the S3 compared with the previous Edwards valves (SAPIEN and SAPIEN XT) in terms of prevention of vascular complications and of moderate-severe paravalvular leaks, but showed an increase in the need of a permanent pacemaker post-TAVR. The S3 is certainly a promising evolution of transcatheter valves which may effectively reduce the risk of vascular complications and paravalvular leak. However, the S3 seems to be related to an increased risk of atrioventricular block, even if this complication could be due to the need to implant the valve in a higher position compared to previous models.

Impact of drug-eluting stent generation on patient- and stent-related adverse events of diabetic patients treated by percutaneous coronary intervention.

AIM: Aim of the present study was to assess stent- and patient-related outcomes of the first- vs. second-generation drug-eluting stents (DES) in diabetics, according to the insulin requirement status. METHODS: Data were obtained from a prospective, single-center registry of 816 consecutive patients with diabetes mellitus (23% insulin-requiring) who underwent percutaneous coronary intervention (PCI) between April 2003 and May 2012 with first- (N.=534) or second-generation DES (N.=282) at our Institution, with at least 12 months of follow-up. We assessed the occurrence of stent-related outcome, including cardiac death, target vessel-related myocardial infarction and target lesion revascularization, versus patient-related outcome, including any cause death, any myocardial infarction and any coronary revascularization. RESULTS: Patients treated with second-generation DES were older and had more complex lesions than patients treated with first-generation DES. Both among patients treated with first-generation DES and those treated with second generation DES, patient-related events were almost double than stent-related events. No interactions were observed between the DES generation type and insulin requirement status. CONCLUSION: In this observational study, first- and second-generation DES were equally safe and efficacious in diabetic patients undergoing PCI, regardless of insulin requirements. The greater number of patient-related than stent-related events in patients with complex clinical and lesion characteristics emphasizes that the optimization of secondary prevention is at least as important as the selection of which new generation DES to implant in a specific lesion.

Ventricular assist devices.

Despite major advances in the treatment of heart failure over the past two decades, improving the natural history of this condition, heart failure continues to be a major source of morbidity and mortality. Although availability of heart donor for transplantation has declined over the past several years, innovations in ventricular assist device (VAD) technology has provided an alternative therapeutic option for patients with advanced heart failure. Initiated as a mechanical option to "bridge" critically ill patients awaiting transplantation, VADs are being increasingly deployed as "destination" devices to provide long-term support. With technical advances resulting in improved mechanical reliability, reduced postoperative morbidity and greater likelihood of patient acceptance, there is interest in expanding the applicability of VAD beyond the current indication, as destination therapy for severely ill patients who are not candidates for transplant. This review examines the rational as well as the technical details of the different generation of VADs for mechanical cardiac support, implanted either surgical or percutaneously. These devices are at various stages of development and clinical investigation. One or more of these newer devices is likely to emerge as an important development in the treatment of patients with advanced heart failure.

Mid-term prognostic value of coronary artery disease in patients undergoing transcatheter aortic valve implantation: a meta-analysis of adjusted observational results.

AIMS: Coronary artery disease (CAD) negatively affects prognosis in patients undergoing surgical aortic valve replacement, being currently evaluated in the most common used risk score. Our meta-analysis aims to clarify the prognostic role of CAD on mid-term survival in patients undergoing TAVI. METHODS AND RESULTS: Studies reporting multivariate predictors of adverse outcomes in patients undergoing TAVI were systematically searched for and pooled, when appropriate, using a random-effect method. 960 citations were first screened and finally 7 studies (2472 patients) were included. Diagnosis of CAD was reported in 52%(42-65) of patients and 1169 Edwards SAPIEN and 1303 CoreValve prostheses were implanted. After a median follow up of 452 days (357-585) 24% of patients (19-33) died, and 23 (14-32) for cardiovascular death. At pooled analysis of multivariate approach, diagnosis of coronary artery disease did not increase risk of death (OR 1.0, 95% CI, confidence interval, 0.67-1.50 I(2) 0%). CONCLUSION: CAD does not affect mid-term TAVI outcome: this finding should be weighted to accurately evaluate risk and strategies for patients with severe aortic stenosis.

Computed tomography coronary angiography in the selection of outlier patients: a feasibility report.

PURPOSE: This study evaluated criteria, presence and distribution of outlier patients by means of computed tomography coronary angiography (CTCA) in a large institutional database. MATERIAL AND METHODS: From a population of 2,881 consecutive patients (1,842 men, mean age 62 ± 13 years) in sinus rhythm who underwent CTCA, we extracted data on patients with suspected coronary artery disease (CAD). We selected patient outliers in the fifth and sixth decades of life with the following criteria: ≥ 3 risk factors and absence of CAD, zero to one risk factors and ≥ 5 diseased coronary segments. Diabetes was excluded from risk factors because of the different impact on CAD. RESULTS: The patient population consisted of 2,432 individuals with suspected CAD (1,495 men, age 62 ± 13 years). The prevalence of obstructive CAD (≥ 50% lumen reduction at CTCA) was 36% (863/2,432). Patients with normal coronary arteries accounted for 34% of the total (837/2,432; 431 men, age 55 ± 14 years). Of these, 210 were in the fifth and 231 in the 6th decade (men 196, women 245); those with ≥ 3 risk factors accounted for 4.2% of the total (102/2,432; men 42, women 60). Patients with ≥ 5 diseased coronary segments accounted for 28% of the total (686/2,432; 510 men, age 68 ± 10 years). Of these, 115 were in the fifth and 270 in the sixth decade (men 309, women 76); those with zero to one risk factors accounted for 3.0% (73/2,432; men 66, women 7). CONCLUSIONS: CTCA is a reliable noninvasive diagnostic modality that can be used to identify outlier patients. This will enable dedicated trials aimed at characterising biomarkers and genomics of protective and nonprotective factors against CAD and its complications.

Coronary flow reserve by transthoracic echocardiography predicts epicardial intimal thickening in cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is the leading cause of morbidity and mortality in heart transplantation (HT). We sought to investigate the role of coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) in CAV diagnosis. CAV was defined as maximal intimal thickness (MIT) assessed by intravascular ultrasound (IVUS) > or =0.5 mm. CFR was assessed in the left anterior descending coronary artery in 22 HT recipients at 6 +/- 4 years post-HT. CAV was diagnosed in 10 patients (group A), 12 had normal coronaries (group B). The mean MIT was 0.7 +/- 0.1 mm (range 0.03-1.8). MIT was higher in group A (1.16 +/- 0.3 mm vs. 0.34 +/- 0.07 mm, p < 0.0001). CFR was 3.1 +/- 0.8 in all patients and lower in group A (2.5 +/- 0.6 vs. 3.7 +/- 0.3, p < 0.0001). CFR was inversely related with MIT (r =-0.774, p < 0.0001). A cut point of < or =2.9, identified as optimal by receiver operating characteristics analysis was 100% specific and 80% sensitive (PPV = 100%, NPV = 89%, Accuracy = 91%). CFR assessment by CE-TTE is a novel noninvasive diagnostic tool in the detection of CAV defined as MIT > or =0.5 mm. CFR by CE-TTE may reduce the need for routine IVUS in HT.

Aborted myocardial infarction: a clinical-magnetic resonance correlation.

This report illustrates a magnetic resonance image of aborted myocardial infarction after primary angioplasty. Myocardial oedema in the absence of late enhancement seems to be the magnetic resonance marker of the myocardium at risk of infarction that has been reperfused within 30 minutes and aborted in the clinic.

Ischemic cardiomyopathy: lack of clinical applicability of the WHO/ISFC classification of cardiomyopathies.

BACKGROUND: The classification of cardiomyopathies proposed by the WHO/ISFC Task Force defines ischemic cardiomyopathy as "a dilated cardiomyopathy with impaired contractile performance not explained by the extent of coronary disease or ischemic damage". The aim of this study was to verify the clinical applicability of the WHO/ISFC definition of ischemic cardiomyopathy. METHODS: Retrospective analysis of the clinical characteristics of patients with a left ventricular ejection fraction < 40%, in whom coronary angiography showed a) stenosis < or = 50% of a main coronary artery and/or b) stenosis > 50% of a distal portion of a main coronary artery or of a secondary branch. The patients with a clinical diagnosis of previous myocardial infarction were excluded. RESULTS: Fourteen patients with the angiographic characteristics listed above were identified. Twelve patients were males, mean age 59 years. They represented 3.8% of all the patients with left systolic ventricular dysfunction who underwent coronary angiography in the same period. The left ventricular end-diastolic volume was 170 +/- 45 ml/m2 and the ejection fraction was 27 +/- 6%. The cause of systolic left ventricular dysfunction was systemic arterial hypertension in 3 patients, diabetes mellitus in 2, a combination of these diseases in 4, chronic alcohol abuse in 1, a previous clinically silent myocardial infarction in 1, and idiopathic dilated cardiomyopathy in 3. CONCLUSIONS: In conclusion, in all our patients with severe left ventricular dysfunction which was not explained by the extent of coronary artery disease, at least one possible cause of impaired contractile performance could be identified. Thus the definition of ischemic cardiomyopathy according to the new WHO/ISFC classification of cardiomyopathies appears to be of scarce utility on clinical grounds and should be redefined and if necessary reclassified.

Serum IgG antibodies to human herpesvirus-6 (HHV-6) do not predict the progression of HIV disease to AIDS. Italian Seroconversion Study group.

OBJECTIVES: To evaluate if different levels of human herpesvirus 6 (HHV-6) antibodies can predict HIV disease progression. DESIGN: Longitudinal study of individuals with a documented date of HIV seroconversion. SETTING: Clinical centers located throughout Italy. PATIENTS: Individuals who serconverted for HIV between 1983 and 1995 in Italy. METHODS: Sera were tested for IgG antibodies to HHV-6 using a commercial enzyme immunoassay. A serum sample with an optical density (OD) > or =242 (i.e. the mean value of 10 negative controls +4x standard deviation) was considered as HHV-6 positive; the progression of HIV disease was evaluated estimating the relative hazards (RH) of AIDS (by Cox models) for individuals with higher levels vs. lower levels of HHV-6 antibodies or considering levels of antibodies based on 10% increase of the distribution (deciles). Rates of CD4 decline fitting linear regression were also estimated. RESULTS: A total of 381 persons were followed for a median time of 4 years (range: 0.15-9 years) following the date of collection of the serum sample. The median OD value of HHV-6 antibodies was 306, with an interquartile range of 241-440 and a range of 48-2330. A slight inverse correlation was found between HHV-6 antibody levels and age of the individual at the time of serum collection (Spearman rank correlation coefficient, -0.16; p = 0.0013). No association was found between HHV-6 and CD4 level or between HHV-6 and CD8 level at the date of serum collection. The unadjusted RH of progression to AIDS was 0.63 (95% CI: 0.42-0.96) for HHV-6 positive individuals vs. HHV-6 negative; when adjusting for possible confounders (CD4, age, pre-AIDS HIV-related pathologies at the date of sera collection, and previous anti-herpes treatment), the RH of AIDS increased to 0.80 (95% CI: 0.51-1.23). No particular association with HIV disease progression was found when using the deciles of the distribution of HHV-6 antibodies. The median CD4 cell loss was 5.0x10(6) cells/l per month among HHV-6 positive individuals and 5.7x10(6) cells/l per month among the others. CONCLUSIONS: The presence of high levels of HHV-6 antibodies does not seem to predict the clinical or immunologic progression of HIV disease.