Manlio Cipriani

Value of transthoracic two-dimensional echocardiography in predicting viability in patients with healed Q-wave anterior wall myocardial infarction

The role of transthoracic echocardiography as a predictor of recovery after revascularization has not yet been established. Two-dimensional echocardiography was performed in 15 patients with a healed anterior wall myocardial infarction and severe, isolated stenosis of the left anterior descending coronary artery before, and 3 to 6 months after angiographically confirmed successful revascularization. The asynergic segments were classified into 2 groups according to 2 different echocardiographic patterns: those showing a normal acoustic reflectance with normal end-diastolic thickness (pattern A segments) and those showing an increase in acoustic reflectance and reduced end-diastolic thickness (pattern B segments). We hypothesized that pattern A segments were more likely to recover (viable myocardium) and that pattern B segments were consistent with irreversibility. A total of 240 segments in the 15 patients were evaluated before and after revascularization. Sixty-seven segments were asynergic; of these, 52 were judged to have pattern A and 15 pattern B. Of the 52 pattern A segments, 27 were hypokinetic and 25 akinetic. All of the pattern B segments were akinetic (n = 9) or dyskinetic (n = 6). Pattern A was predictive of postoperative recovery in 39 of 52 segments (75%) (p < 0.0001); pattern B was predictive of irreversibly damaged tissue in 13 of 15 segments (87%) (p < 0.0001). Thus, in patients with healed anterior wall myocardial infarction, resting transthoracic echocardiography is a simple and reliable predictor of the behavior of asynergic segments after revascularization.

Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis

Background: Previous reports have suggested that despite their dramatic presentation, patients with fulminant myocarditis (FM) might have better outcome than those with acute nonfulminant myocarditis (NFM). In this retrospective study, we report outcome and changes in left ventricular ejection fraction (LVEF) in a large cohort of patients with FM compared with patients with NFM. Methods: The study population consists of 187 consecutive patients admitted between May 2001 and November 2016 with a diagnosis of acute myocarditis (onset of symptoms <1 month) of whom 55 required inotropes and/or mechanical circulatory support (FM) and the remaining 132 were hemodynamically stable (NFM). We also performed a subanalysis in 130 adult patients with acute viral myocarditis and viral prodrome within 2 weeks from the onset, which includes 34 with FM and 96 with NFM. Patients with giant-cell myocarditis, eosinophilic myocarditis, or cardiac sarcoidosis and those <15 years of age were excluded from the subanalysis. Results: In the whole population (n=187), the rate of in-hospital death or heart transplantation was 25.5% versus 0% in FM versus NFM, respectively (P<0.0001). Long-term heart transplantation–free survival at 9 years was lower in FM than NFM (64.5% versus 100%, log-rank P<0.0001). Despite greater improvement in LVEF during hospitalization in FM versus NFM forms (median, 32% [interquartile range, 20%–40%] versus 3% [0%–10%], respectively; P<0.0001), the proportion of patients with LVEF <55% at last follow-up was higher in FM versus NFM (29% versus 9%; relative risk, 3.32; 95% confidence interval, 1.45–7.64, P=0.003). Similar results for survival and changes in LVEF in FM versus NFM were observed in the subgroup (n=130) with viral myocarditis. None of the patients with NFM and LVEF ≥55% at discharge had a significant decrease in LVEF at follow-up. Conclusions: Patients with FM have an increased mortality and need for heart transplantation compared with those with NFM. From a functional viewpoint, patients with FM have a more severely impaired LVEF at admission that, despite steep improvement during hospitalization, remains lower than that in patients with NFM at long-term follow-up. These findings also hold true when only the viral forms are considered and are different from previous studies showing better prognosis in FM.

Quantitative changes in late gadolinium enhancement at cardiac magnetic resonance in the early phase of acute myocarditis

BACKGROUND The presence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has diagnostic and prognostic value in patients with acute myocarditis (AM). Aim of our study was to quantify the changes in LGE extension (LGE%) early after AM and evaluate its relations with biventricular function and morphology. METHODS We investigated 76 consecutive patients with AM (acute onset of chest pain/heart failure/ventricular arrhythmias not explained by other causes, and raised troponin) that met CMR criteria based on myocardial oedema at T2-weighted images and LGE on post-contrast images at median time of 6days from onset of symptoms. We quantified LGE% at baseline and after 148days in 49 patients. RESULTS Median left ventricular (LV)-ejection fraction (EF) was 64% (interquartile range [Q1-Q3]: 56-67%), and LGE% 9.4% (Q1-Q3: 7.5-13.2%). LGE% was correlated with LV end-systolic volume index (LV-ESVi; r=+0.34; p=0.003). LGE% was inversely correlated with LV-EF (r=-0.31; p=0.009) and time to CMR scan (r=-0.25; p=0.028). In the 49 patients with a second CMR scan, despite no significant variations in LV-EF, a significant decrease of LGE% was observed (p<0.0001) with a relative reduction of 42% compared with baseline. Patients showing increased LV-ESVi at follow up had a lower decrease of LGE% (p=0.038). CONCLUSIONS In the acute phase of AM the LGE extension is a dynamic process that reflects impairment of LV function and is time dependent. LGE% appears one of the CMR parameters with the largest relative variations in the first months after AM.

Prognostic impact of late gadolinium enhancement in the risk stratification of heart transplant patients

Aims The aim of the present study was to assess the association of the presence and amount of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) with cardiovascular adverse events in patients with orthotopic heart transplantation (HTx). Methods and results We enrolled 48 patients (mean age, 54.7 ± 14.6 years; 37 men) at various stages after HTx. All patients underwent standard CMR at 1.5 T, to characterize both cardiac anatomy and LGE. Late gadolinium enhancement was detected in 26 patients (54%). All-cause and cardiovascular mortalities, and a composite of major adverse cardiovascular events (MACE) recurrence were evaluated during the follow-up period for a median of 5.16 years. Ten patients (21%) died and 26 (54%) were readmitted because of MACE. Multivariate Cox analysis identified as independent predictors of MACE a diagnosis of cardiac allograft vasculopathy (CAV) (HR 3.63; 1.5–8.7 95% CI; P = 0.0039), left ventricular end systolic volume index (HR 1.04; 95% CI 1.01–1.079; P = 0.008), LGE mass (HR 1.04; 1.01–1.06 95% CI; P = 0.0007), LGE % of left ventricular mass (HR 1.083; 1.03–1.13 95% CI; P = 0.0002). Independent predictors of all-cause death were CAV (HR 6.33; 95% CI 1.33–30.03; P = 0.0201), LGE mass (HR 1.04; 1.01–1.07 95% CI; P = 0.005), LGE % of left ventricular mass (HR 1.075; 1.02–1.13 95% CI; P = 0.007). Patients with CAV had a risk of MACE by 5 years of 67% (95% CI 0.309–0.851%); the addition of 7.9 LGE % to the risk model increased the predicted risk to 88% (95% CI 0.572–0.967%). Conclusions The current study demonstrated that the presence of CAV and the total amount of LGE have a significant independent association with MACE and mortality in HTx patients.

Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy

Mitral regurgitation (MR) is a common finding in patients with heart failure with debatable effects on prognosis. Reduction in MR is one of the mechanisms by which cardiac resynchronization therapy (CRT) exerts its beneficial effects. We investigated the prognostic impact of baseline MR and MR persistence after CRT on outcomes of treated patients.

Women with nonischemic cardiomyopathy have a favorable prognosis and a better left ventricular remodeling than men after cardiac resynchronization therapy

Aims Cardiac resynchronization therapy (CRT) is a well established therapy in heart failure patients who are on optimal medical therapy and have reduced left ventricular ejection fraction (LVEF) and wide QRS complexes. Although women and patients with nonischemic cardiomyopathy are under-represented in CRT trials and registries, there is evidence that these two groups of patients can benefit more from CRT. The aim of our analysis was to investigate the impact of female sex on mortality in a population that included a high percentage of patients (61%) with nonischemic cardiomyopathy. Methods We analyzed data on 507 consecutive patients (20% women) who received CRT at two Italian Heart Transplant centers and were followed up for a maximum of 48 months. Results After multivariate adjustment, women showed a trend toward better survival with regard to all-cause mortality [hazard ratio (HR) 0.32, confidence interval (CI) 0.10–1.04; P = 0.059]. However, this benefit was limited to nonischemic patients with regard to all-cause mortality (HR 0.20, CI 0.05–0.87, P = 0.032) and cardiovascular mortality (HR 0.14, CI 0.02–1.05, P = 0.056). Conclusion Female CRT recipients, at mid-term, have a favorable prognosis than male patients and this benefit appears to be more evident in nonischemic patients. Thus, we strongly believe that the apparent under-utilization of CRT in females is an anomaly that should be corrected.

A life-threatening presentation of eosinophilic granulomatosis with polyangiitis

: Necrotizing eosinophilic myocarditis (NEM) is a life-threatening condition that needs rapid diagnosis by endomyocardial biopsy and hemodynamic support usually by mechanical circulatory systems. We present the case of a 25-year-old Caucasian man who developed a refractory cardiogenic shock due to a NEM that was supported with a peripheral veno-arterial extracorporeal membrane oxygenation associated with intravenous steroids and recovered after 2 weeks. Further instrumental investigations lead to the final diagnosis of NEM as first presentation of eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), remarking the importance of identifying the systemic disorder that usually triggers the eosinophilic damage of the myocardium.

Clinical Presentation and Outcome in a Contemporary Cohort of Patients with Acute Myocarditis: The Multicenter Lombardy Registry

Background: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. Methods: A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. Results: At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). &bgr;-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation. Conclusions: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.

A prospective comparison of mid-term outcomes in patients treated with heart transplantation with advanced age donors versus left ventricular assist device implantation

OBJECTIVES In Europe, the age of heart donors is constantly increasing. Ageing of heart donors limits the probability of success of heart transplantation (HTx). The aim of this study is to compare the outcome of patients with advanced heart failure (HF) treated with a continuous-flow left ventricular assist device (CF-LVAD) with indication as bridge to transplantation (BTT) or bridge to candidacy (BTC) versus recipients of HTx with the donors age above 55 years (HTx with donors >55 years). METHODS we prospectively evaluated 301 consecutive patients with advanced HF treated with a CF-LVAD (n = 83) or HTx without prior bridging (n = 218) in our hospital from January 2006 to January 2015. We compared the outcome of CF-LVAD-BTT (n = 37) versus HTx with donors >55 years (n = 45) and the outcome of CF-LVAD-BTT plus BTC (n = 62) versus HTx with donors >55 years at the 1- and 2-year follow-up. Survival was evaluated according to the first operation. RESULTS The perioperative (30-day) mortality rate was 0% in the LVAD-BTT group vs 20% (n = 9) in the HTx group with donors >55 years (P = 0.003). Perioperative mortality occurred in 5% of the LVAD-BTT/BTC patients (n = 3) and in 20% of the HTx with donors >55 year group (P = 0.026). Kaplan-Meier curves estimated a 2-year survival rate of 94.6% in CF-LVAD-BTT vs 68.9% in HTx with donors >55 years [age- and sex-adjusted hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.08-0.81; P = 0.02 in favour of CF-LVAD]. Considering the post-HTx outcome, a trend in favour of CF-LVAD-BTT was also observed (age- and sex-adjusted HR 0.45; 95% CI 0.17-1.16; P = 0.09 in favour of CF-LVAD), whereas CF-LVAD-BTT/BTC showed a similar survival at 2 years compared with HTx with donors >55 years, both censoring the follow-up at the time of HTx and considering the post-HTx outcome. CONCLUSIONS Early and mid-term outcomes of patients treated with a CF-LVAD with BTT indication seem better than HTx with old donors. It must be emphasized that up to 19% of patients in the CF-LVAD/BTT group underwent transplantation in an urgent condition due to complications related to the LVAD. At the 2-year follow-up, CF-LVAD with BTT and BTC indications have similar outcome than HTx using old heart donors. These results must be confirmed in a larger and multicentre population and extending the follow-up.

Evoluzione delle indicazioni al trapianto cardiaco e all’impianto di dispositivi di assistenza ventricolare sinistra

Heart transplantation (HTx) is considered to be the gold standard treatment for advanced heart failure (HF) but it is available only for a minority of patients, due to paucity of donor hearts (278 HTx were performed in 2011 in Italy). Patients listed for HTx have a prolonged waiting time (that is about 2.3 years in the 2006-2010 time period in Italy) that is superior compared with patients who receive HTx (median time around 6 months), to underline the presence of an allocation system that prioritizes candidates in critical conditions. Patients listed for HTx have a poor quality of life and their annual mortality is around 8-10%. Another 10-15% of HTx candidates are removed from the waiting list each year because they are no longer suitable for transplantation. On the other hand, continuous-flow left ventricular assist devices (LVADs) have been demonstrated to improve survival and quality of life of patients with advanced/refractory HF. LVAD therapy can represent a valid alternative to HTx, and it is recommended for patients with advanced HF in the recent edition of the European Society of Cardiology guidelines on HF management. In the United States, a larger number of centers compared with European ones started to apply a strategy of LVAD implant for many patients who meet clinical criteria for listing for HTx. Data from our center concerning the last 6 years of LVAD implant (51 implants since 2006) reported a 75.5% survival rate at 1 year. In Italian series, as in our center, current HTx survival is only slightly superior (83% survival rate at 1 year), based on data from the Italian National Transplant Center. We report a proposal for updated listing criteria for HTx and indications for LVAD implant in patients with advanced acute and chronic HF. Criteria for identifying suitable patients for HTx and/or LVAD considering the shortage of donors are discussed.