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Summary The authors examine several reports of the literature concerning thyrotoxic dilated cardiomyopathy. In particular, it is pointed out that this clinical manifestation of hyperthyroidism is rare in readily diagnosed and properly treated hyperthyroidism. Case reports are analyzed comparatively. A case deriving from the direct experience of the authors is also presented. Learning points: Dilated cardiomyopathy has been reported as the initial presentation of hyperthyroidism in only 6% of patients although Clinical picture of thyrotoxic dilated cardiomyopathy can degenerate into an overt cardiogenic shock sometimes requiring the use of devices for mechanical assistance to the circulation, or extracorporeal membrane oxygenation. For thyrotoxic dilated cardiomyopathy, evidence-based pharmacologic measures valid for heart failure should always be supplemented by the administration of specific thyroid therapies such as thionamides (methimazole, carbimazole or propylthiouracil), whose relatively long latency of action should be supported by the i.v. administration of small doses of beta-blocker. In cases of cardiogenic shock, the administration of beta-blocker should be carried out only after the restoration of satisfactory blood pressure levels- with the prudent use of synthetic catecholamines, if necessary.

The therapy or prevention of atrial fibrillation (AF) is defined as upstream therapy when conducted with the use of drugs, e.g., angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists, statins, and omega-3 fatty acids, not included in the classes of antiarrhythmic drugs recognized by the Vaughan Williams classification. In our review, we illustrate the rational bases of upstream AF therapy, which encompasses drugs having the property to reduce hemodynamic congestion and cardiac overload, as in the case of ACEIs or angiotensin receptor blockers, as well as drugs able to prevent atrial fibrosis or reduce oxidative stress, such as statins or omega-3 fatty acids, respectively. In this review, randomized controlled trials (RCTs) conducted with the abovementioned drugs are examined. Really, these RCTs have generated mixed results. In the context of the prevention and therapy of AF, our experience is then presented, relating to a patient with heart failure and reduced left ventricular ejection fraction, with a history of relapsing episodes of paroxysmal AF. In this patient, administration of sacubitril/valsartan at appropriate doses allowed recovery of the sinus rhythm. Therefore this case testifies how the upstream therapy of AF might have good results when conducted with sacubitril/valsartan. Thus, RCTs with adequate statistical power are warranted in order to confirm the preliminary encouraging result of our case report, and validate a useful role of sacubitril/valsartan as an upstream therapy of AF.

Background: Clinical efficacy of sacubitril/valsartan administered for the recommended indication of chronic heart failure (CHF) patients with New York Heart Association (NYHA) classes II-III appears to be higher than one would expect based on the drug-induced variations of the left ventricular ejection fraction (LVEF). More thorough investigations with the use of indicators of longitudinal systolic function have been therefore recommended to verify whether a part of the clinical improvement achieved with the use of sacubitril/valsartan could be supported by a reverse remodeling ensuing from changes other than a simple LVEF increase. Methods: In the present retrospective cohort study, which collected the pertinent data from two centers devoted to clinical management of outpatients with CHF and dating back to the years 2017 and 2018, we separated patients treated with sacubitril/valsartan from those treated with conventional medical therapy, including angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). For the rest, the therapies practiced in the two groups, patients under sacubitril/valsartan and controls, were almost identical, including similar doses of beta-blockers and mineralocorticoid receptor antagonists (MRAs) in the two cohorts, plus loop diuretics, with the latter administered at variable doses. The endpoints were the variations of LVEF and global left ventricular longitudinal strain (GLS) over a study period not shorter than 1 year. Results: One hundred thirty-two patients were collected within our retrospective cohort study, of whom 44 were treated with sacubitril/valsartan and 88 were subjected to conventional therapy. All patients were marked by heart failure with reduced (LVEF

Takotsubo syndrome (TTS) is an acute and mostly reversible cardiomyopathy that mimics an acute coronary syndrome with left ventricular (LV) systolic dysfunction without relevant obstructive coronary artery disease. Its prevalence is probably underestimated and reaches 1.2-2% in patients with acute coronary syndrome undergoing coronary catheterization. Although supraphysiological epinephrine levels have been associated with TTS, the detailed pathophysiology is incompletely understood. Chest pain is the most common clinical presentation; however, cardiac decompensation, cardiogenic shock, and sudden cardiac death due to ventricular fibrillation may also be the first clinical manifestations. Patients are mostly postmenopausal women, in whom the condition is commonly associated with emotional triggers; however, men have a higher prevalence of TTS being associated with physical triggers, which has a worse prognosis compared with TTS associated with emotional triggers. As a diagnosis of exclusion, TTS has no single definitive diagnostic test. According to the distribution of LV wall motion abnormalities, various morphological subtypes have been identified. The final diagnosis depends on cardiac imaging with left ventricular angiography during acute heart catheterization, as well as on echocardiography and cardiac magnetic resonance. Most patients recover completely, albeit several factors have been associated with worse prognosis. Management is based on observational data, while randomized multicenter studies are still lacking. This review provides a general overview of TTS and focuses on the hypothesized pathophysiology, and especially on current practices in diagnosis, prognosis, and treatment.

Amyloidosis is caused by extracellular deposition of insoluble abnormal fibrils constituted by misfolded proteins, which can modify tissue anatomy and hinder the function of multiple organs including the heart. Amyloidosis that can affect the heart includes mostly systemic amyloidosis (amyloid light chain, AL) and transthyretin amyloidosis (ATTR). The latter can be acquired in elderly patients (ATTRwt), or be inherited in younger individuals (ATTRm). The diagnosis is demanding given the high phenotypic heterogeneity of the disease. Therefore, "red flags," which are suggestive features giving support to diagnostic suspicion, are extremely valuable. However, the lack of broad awareness among clinicians represents a major obstacle for early diagnosis and treatment of ATTR. Furthermore, recent implementation of noninvasive diagnostic techniques has revisited the need for endomyocardial biopsy (EMB). In fact, unlike AL amyloidosis, which requires tissue confirmation and typing for diagnosis, ATTR can now be diagnosed noninvasively with the combination of bone scintigraphy and the absence of a monoclonal protein. Securing the correct diagnosis is pivotal for the newly available therapeutic options targeting both ATTRm and ATTRwt, and are directed to either stabilization of the abnormal protein or the reduction of the production of transthyretin. The purpose of this article is to review the contemporary aspects of diagnosis and management of transthyretin amyloidosis with cardiac involvement, summarizing also the recent therapeutic advances with tafamidis, patisiran, and inotersen.

Background: Secondary prevention of atrial fibrillation (AF) could be carried out by means of antiarrhythmic drugs; however this strategy has not received any endorsement because these drugs are burdened by a high risk of proarrhythmic events (flecainide, sotalol) or extracardiac effects (amiodarone). Methods: In our retrospective cohort study we have compared amiodarone 200 mg per day with the strategy implying the renunciation of any specific drug as well as with the approach using oral anticoagulant (rivaroxaban) or a combined approach including amiodarone plus rivaroxaban. Results: A total of 255 patients with a history of AF (paroxysmal, persistent or long-lasting persistent) successfully treated with achievement of sinus rhythm have been gathered. Amiodarone has been the most effective option for AF secondary prevention, with regard to the recurrences of AF as well as rehospitalizations: P (Kruskal-Wallis test) < 0.05 for both, over a median follow-up of 24 months. Conclusions: Patients kept free from any specific drug therapy have been shown to experience more numerous AF relapses and related rehospitalizations. On the contrary, the amiodarone use has been associated with a decreased risk of AF recurrences and hospital admissions. Thus, amiodarone might be an efficacious tool for realizing a successful long-term AF secondary prevention. Cardiol Res. 2019;10(4):223-229 doi: https://doi.org/10.14740/cr909

Background: Clinical management of patients with a history of atrial fibrillation (AF) focuses on the goal of preventing AF recurrences, or, if this is impossible due to the fact that the arrhythmia has by now become permanent, it is aimed at the control of the ventricular response. In patients with AF, an important topic is the comparative evaluation in the mid/long-term of clinical outcomes arising from the various therapeutic regimens, including pharmacological approaches as well as radiofrequency catheter ablation (abl). Methods: In the present cohort retrospective study, 175 cases of paroxysmal, persistent or long-lasting persistent AF have been grouped depending on therapeutic approach: abl-isolated or followed by chronic use of antiarrhythmics (74 cases), drug treatment for rate control strategy (60 cases), drug treatment for rhythm control strategy (41 cases). The effects respectively exerted by the three treatment modalities on the primary endpoint, namely a composite of death, disabling stroke, severe bleeding and cardiac arrest , have been compared through a median follow-up of 20 months (interquartile range = 18 - 24 months) using the Cox proportional-hazards regression analysis. Results: As documented by the Cox model, an increased risk of the primary composite endpoint was associated with the rhythm control strategy, as well as with the AF recurrences during the follow-up (for the former, hazard ratio (HR): 3.3159, 95% CI: 1.5415 to 7.1329, P = 0.0023; for the latter, HR: 1.0448, 95% CI: 1.0020 to 1.0895, P = 0.0410). Even hypertension was associated with an increased risk (HR: 1.1040; 95% CI: 1.0112 to 1.9662; P = 0.0477). On the contrary, a rate control strategy predicted a decreased risk of experiencing the primary endpoint (HR: 0.0711; 95% CI: 0.0135 to 0.3738; P = 0.0019) while abl did not exert a statistically significant effect on the same outcome. Conclusions: AF abl decreases the arrhythmic episodes but does not provide a statistically significant protection against the composite of death, disabling stroke, major bleeding and cardiac arrest after a 20-month follow-up. Moreover, in patients with a history of AF, rate control compared to rhythm control strategy provides better clinical outcomes over a mid-term follow-up. Cardiol Res. 2019;10(2):98-105 doi: https://doi.org/10.14740/cr829

The journal retracts the article “Platypnea-Orthodeoxia Syndrome: Multiple Pathophysiological Interpretations of a Clinical Picture Primarily Consisting of Orthostatic Dyspnea” by De Vecchis, R [...]

Case description A 64-year-old patient with chronic renal failure and persistent hyperkalaemia not corrected by dialysis, was prescribed sodium polystyrene sulfonate (SPS) at a low dose (30 g/day for 2 days a week during the long interdialytic interval). After 3 months of therapy, the patient developed intense abdominal pain with non-specific colitis identified with a colonoscopy. In addition, the biopsy specimens showed rhomboid SPS crystals in the intestinal mucosa. Fourteen months after discontinuing therapy, the patient again presented with colitis and persistent biopsy finding of SPS crystals. The patient died a few months later due to intestinal infarction. Discussion and conclusion SPS is a cation exchange resin used to treat hyperkalaemia resistant to dialysis, but may cause inflammation and ischaemia of the colon. In our patient, a short 3-month course of low-dose SPS therapy (without sorbitol, which is used to counter iatrogenic constipation caused by SPS) induced relapsing colitis, which was followed by massive intestinal infarction a few months later. In light of frequent reports of its enterotoxic effects, SPS should be replaced with the new potassium chelators (patiromer and sodium zirconium cyclosilicate). Learning points Sodium polystyrene sulfonate can cause life-threatening colitis.Alternatives medications should be used for the long-term reduction of potassium levels.

Anthracyclines are the cornerstone of treatment for many solid and hematological cancers such as breast cancer or lymphoma for the past 50 years. Nevertheless, in a non-negligible proportion of patients, they elicit dilated cardiomyopathy as a side effect, which causes in turn cardiac decompensation. Conversely, for some years, sacubitril/valsartan has been proposed as a new therapeutic paradigm for all varieties of heart failure with reduced left ventricular ejection fraction, due to its balanced enhancement of natriuretic peptides’ properties coupled with a blocking effect on the AT1 angiotensin receptors. In this article, two clinical cases are illustrated in which the therapeutic action of sacubitril/valsartan against anthracycline cardiomyopathy would seem to be demonstrated by the improvement of symptoms and echocardiographic parameters. Thus, further studies would be warranted for better evaluating the potential role of sacubitril/valsartan as a novel therapeutic tool against anthracycline cardiotoxicity.

The paper entitled "Health-related Quality of Life and Unscheduled Re-Hospitalizations After Coronary Revascularization: Significant Predictive Role of the MacNew Questionnaire" by Renato De Vecchis et al, which was published online on February 20, 2020, has been withdrawn by the Publisher due to self-plagiarism.

The paper entitled "Effects of a restricted water intake on various clinical and laboratory outcomes in patients with heart failure: a meta-analysis of randomized controlled trials" by Renato De Vecchis et al, which was published online on February 20, 2020, has been withdrawn by the Publisher due to self-plagiarism.

Background: The peak atrial longitudinal strain (PALS) is primarily an index of the reservoir function of atrial chambers. The conceptual basis exists to hypothesize that sacubitril/valsartan improves the expandability of atrial chambers in the reservoir phase of the atrial mechanical cycle, as a consequence of its effect of prolonging the half-life of natriuretic peptides. Therefore in this retrospective study we evaluated the repercussions of the administration of sacubitril/valsartan maintained for at least 12 months on the PALS. Methods: In our retrospective study a cohort of 40 patients treated with sacubitril/valsartan has been compared with a second cohort subjected to the conventional treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker. A general criterion to be satisfied was the presence of at least one episode of atrial fibrillation (AF) in the history of the enrolled patients. The study population was composed of New York Heart Association (NYHA) class II/III chronic heart failure (CHF) patients, due to the fact that the treating physicians of the patients whose clinical records were used as source of data, complied with the international guidelines that have so far validated sacubitril/valsartan exclusively for the CHF therapy. The aims were to verify whether the 1-year administration of sacubitril/valsartan is effective in improving the PALS, and also ascertain whether the drug is associated with a decreased risk of AF relapses over a mean retrospective observation period of 12 months. Results: Sacubitril/valsartan cohort was proven to benefit from a significant increase in average values of PALS (median: 26.5%; interquartile range (IQR): 22% - 30%), opposed to the much less pronounced increase in PALS found in the conventional therapy cohort (median: 22.5%; IQR: 18% - 25.5%). Additionally, the comparison made by means of one-way analysis of variance regarding the mean changes of PALS values, outlined clearly that the sacubitril/valsartan users had an increase in PALS after 1 year of therapy significantly greater (P < 0.001) compared to the patients taking the conventional drugs. Moreover, a risk significantly higher of AF recurrences (P = 0.001) was identified in the conventional therapy group compared to the sacubitril/valsartan group during a 12-month retrospective observation period. Conclusions: In the present retrospective cohort study a higher increase of PALS has been shown in the cohort treated with sacubitril/valsartan. Moreover, a reduced risk of AF recurrences has been shown in the sacubitril/valsartan users compared to the patients with CHF subjected to conventional treatment. J Clin Med Res. 2020;12(2):100-107 doi: https://doi.org/10.14740/jocmr4076

Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). We do not know to what extent the drug-induced QTc prolongation is able to predict malignant arrhythmias. Thus, we have retrospectively examined the clinical history of patients with diLQTc. The case record, concerning the period January 2008–December 2017, was collected from two hospitals. diLQTc was defined as drug-induced heart rate-corrected QT of ≥ 450 ms or ≥ 470 ms, respectively in male or female patients. The primary purpose was to verify whether in diLQTc patients the length of this electrocardiographic segment was associated with the risk of symptoms or events (TdP, ventricular fibrillation). Seventy-three validated cases of diLQTc were gathered. Among them, the QTc duration was not able to predict the occurrence of symptoms or events (odds ratio, 0.998; 95% CI, 0.984 to 1.013; p = 0.8821). Likewise, a diQTc lasting longer than 500 ms compared to diQTc comprised between 450 and 500 ms was not associated with an increased risk of arrhythmic events. In our diLQTc patients, QTc duration did not predict occurrence of symptoms, or arrhythmic events. Thus, other determinants should be postulated to clarify why sometimes diQTc prolongation propitiates ventricular malignant arrhythmias whereas in other cases this arrhythmogenic effect is lacking.

Background: Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). We don’t know to what extent the drug-induced QTc prolongation is able to predict malignant arrhythmias. Thus we have retrospectively examined the clinical history of patients with diLQTc. Methods: The case-record, concerning the period from January 2008 to December 2017, was collected from two hospitals. The diLQTc was defined as drug- induced heart rate-corrected QT of ≥ 450 ms or ≥ 470 ms, respectively in male or female patients. The primary purpose was to verify whether in diLQTc patients the length of this electrocardiographic segment was associated with the risk of symptoms or events (TdP, ventricular fibrillation). Results: A total of 73 validated cases of diLQTc were gathered. Among them, the QTc duration was not able to predict the occurrence of symptoms or events (odds ratio: 0.998; 95% CI: 0.984 to 1.013; P = 0.8821). Likewise, a diQTc lasting longer than 500 ms compared to diQTc comprised between 450 and 500 ms was not associated with an increased risk of arrhythmic events. Conclusions: In some probably genetically predisposed subjects, the occurrence of symptoms (dizziness, lipothymia, syncope ) and/or documented arrhythmic events (TdP), is related to intake of certain drugs (antiarrhythmics, antimicrobials such as quinolones and macrolides, etc.). Nevertheless, in our diLQTc patients, QTc duration didn’t predict occurrence of symptoms, or arrhythmic events. Thus, other determinants should be postulated to clarify why sometimes diQTc prolongation propitiates ventricular malignant arrhythmias whereas in other cases this arrhythmogenic effect is lacking. J Clin Med Res. 2018;10(7):593-600 doi: https://doi.org/10.14740/jocmr3470w

Background The risk of death in patients affected by ST-elevation segment myocardial infarction (STEMI) is well known, but more data are required to define the in-hospital mortality in special subsets. We sought to assess the prognostic value of indicators in patients with large anterior STEMI as a first acute coronary event, undergoing percutaneous coronary intervention (PCI) and intra-aortic balloon pump (IABP). Methods and results We evaluated 48 consecutive large anterior STEMI patients admitted as first acute coronary event, undergoing in acute phase both PCI and IABP. Patient demographics, clinical, noninvasive and invasive findings, together with in-hospital complications, were collected. Moreover, findings obtained after a 24-month follow-up were reported. The primary endpoint was in-hospital mortality, whereas the secondary endpoints were out of hospital mortality, rehospitalization for heart failure or reinfarction, and New York Heart Association (NYHA) class at least 2 at follow-up visit. The univariate analysis showed a significant association with symptom to balloon, left anterior descending coronary artery, myocardial blush grade, and wall motion score index. Results of the multivariable analysis revealed the strongest predictive power for in-hospital mortality of proximal left anterior descending coronary artery (odds ratio: 6.9; 95% confidence interval: 1.1-67.7) and of myocardial blush grade 0-1 (odds ratio: 5.5; 95% confidence interval: 1.0-38.8). In-hospital death occurred in 13 patients (27% of total cases), whereas, at follow-up, the mean of survival was 66.7 ± 7.0%. Conclusion The patients with large anterior STEMI as a first acute coronary event, undergoing PCI and IABP, had a very high in-hospital mortality, whereas the mortality rate over the follow-up period was lower. The involvement of a large territory at risk and the ineffective treatment in terms of myocardial reperfusion were the main predictors of in-hospital mortality.

The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results.To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF).The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care.Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group.The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events.The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups.In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes.clinicaltrials.gov Identifier: NCT01685840.

This review aims at summarizing essential aspects of epidemiology and pathophysiology of hyponatremia in chronic heart failure (CHF), to set the ground for a practical as well as evidence-based approach to treatment. As a guide through the discussion of the available evidence, a clinical case of hyponatremia associated with CHF is presented. For this case, the severe neurological signs at presentation justified an emergency treatment with hypertonic saline plus furosemide, as indicated. Subsequently, as the neurological emergency began to subside, the reversion of the trend toward hyponatremia overcorrection was realized by continuous infusion of hypotonic solutions, and administration of desmopressin, so as to prevent the very feared risk of an osmotic demyelination syndrome. This very disabling complication of the hyponatremia correction is then briefly outlined. Moreover, the possible advantages related to systematic correction of the hyponatremia that occurs in the course of CHF are mentioned. Additionally, the case of tolvaptan, a vasopressin receptor antagonist, is concisely presented in order to underline the different views that have led to different norms in Europe with respect to the USA or Japan as regards the use of this drug as a therapeutic resource against the hyponatremia.

Resumo Baixas doses de edoxabana e enoxaparina sódica foram objeto de uma comparação retrospectiva implementada com a técnica do escore de propensão a fim de mitigar os efeitos das diferenças nas características clínicas basais de duas coortes e minimizar o risco de viés. Posteriormente, usando um modelo de riscos proporcionais de Cox, avaliou-se a associação de cada tipo de terapia com o risco do composto de morte por todas as causas, acidente vascular cerebral/ataque isquêmico transitório, hospitalizações e ocorrência de sangramentos maiores. Para essa análise, um valor de p < 0,05 foi considerado estatisticamente significante. A terapia com enoxaparina e cirrose hepática como causadora de trombocitopenia estiveram associadas ao aumento do risco do endpoint composto (enoxaparina: hazard ratio (HR): 3,31; IC 95%: 1,54 a 7,13; p = 0,0023; cirrose hepática, HR: 1,04; 95% CI: 1,002 a 1,089; p = 0,0410). Por outro lado, a terapia com edoxabana mostrou-se significativamente associada à diminuição do risco do endpoint composto (HR: 0,071; 95% CI: 0,013 a 0,373; p = 0,0019). Com base nessa análise retrospectiva, o edoxaban em doses baixas seria uma ferramenta farmacológica segura e eficaz para a profilaxia de eventos cardioembólicos em pacientes com FA e trombocitopenia. Abstract Low-dose edoxaban and enoxaparin sodium have been the subject of a retrospective comparison implemented with the propensity score technique in order to mitigate the effects of the differences in the basal clinical features of two cohorts and minimize the risk of bias. Subsequently, using a Cox proportional-hazards model, the association of each type of therapy with the risk of the composite of all-cause death, stroke/transient ischemic attack, hospitalizations and major bleeding events was assessed. For this analysis, a p-value < 0.05 was considered statistically significant. Therapy with enoxaparin and liver cirrhosis as causing thrombocytopenia were associated with increased risk of the composite endpoint (enoxaparin: hazard ratio (HR): 3.31; 95% CI: 1.54 to 7.13; p = 0.0023; liver cirrhosis, HR: 1.04; 95% CI: 1.002 to 1.089; p = 0.0410). Conversely, edoxaban therapy was significantly associated with decreased risk of the composite endpoint (HR: 0.071; 95% CI: 0.013 to 0.373; p = 0.0019). Based on this retrospective analysis, edoxaban at low doses would appear as an effective and safe pharmacological tool for the prophylaxis of cardioembolic events in patients with AF and thrombocytopenia.

Background: Aldosterone receptor antagonists (ARAs) have been associated with improved clinical outcomes in patients with heart failure with reduced left ventricular ejection fraction (HFREF), but not in those with heart failure with preserved left ventricular ejection fraction (HFpEF). With the aim to study this topic more deeply, we carried out a meta-analysis of selective and non-selective ARAs in HFREF and HFpEF. Methods: We searched PubMed and Scopus databases. We decided to incorporate in the meta-analysis only randomized controlled trials (RCTs) of ARAs in patients with chronic heart failure (CHF) if they met the following criteria: experimental groups included patients with CHF treated with ARAs in addition to the conventional therapy; control groups included patients with CHF receiving conventional therapy without ARAs. Outcomes of interest were all-cause death, hospitalizations from cardiovascular cause, hyperkalemia, or gynecomastia. Results: We detected 15 studies representing 15,671 patients. ARAs were associated with a reduced odds of all-cause death (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.73 - 0.87) and hospitalizations from cardiovascular cause (OR: 0.73; 95% CI: 0.61 - 0.89). However, subgroup analysis showed that these advantages were limited to HFREF (all-cause death: OR: 0.77, 95% CI: 0.69 - 0.84; hospitalizations from cardiovascular cause: OR: 0.66, 95% CI: 0.51 - 0.85), but they did not affect the HFpEF group (all-cause death: OR: 0.91, 95% CI: 0.76 - 1.1; hospitalizations from cardiovascular cause: OR: 0.85, 95% CI: 0.7 - 1.09). ARAs increased the risk of hyperkalemia (OR: 2.17; 95% CI: 1.88 - 2.5). Non-selective ARAs, but not selective ARAs, increased the risk of gynecomastia (OR: 8.22, 95% CI: 4.9 - 13.81 vs. OR: 0.74, 95% CI: 0.43 - 1.27). Conclusions: ARAs reduced the risk of adverse cardiac events in HFREF but not HFpEF. In particular, ARA use in HFpEF patients is questionable, since in this CHF type, no significant improvement in all-cause death and cardiovascular hospitalizations was demonstrated with ARA treatment, in the face of the well-known risks of hyperkalemia and/or gynecomastia that chronic ARA therapy entails. Selective ARAs were equally effective as non-selective ARAs, without the risk of gynecomastia. J Clin Med Res. 2017;9(2):130-142 doi: https://doi.org/10.14740/jocmr2851w

BACKGROUND Clinical efficacy of sacubitril/valsartan administered for the recommended indication of patients with reduced (

Background Transcatheter ablation (Abl) of atrial fibrillation (AF) is regarded as the best therapeutic solution for severely symptomatic patients, in whom at least one antiarrhythmic drug has been tested. Methods In the present retrospective study, 175 cases of paroxysmal, persistent or long-lasting persistent AF have been gathered, and grouped depending on therapeutic approach: Abl, isolated or followed by chronic use of antiarrhythmics (N.=74), drug treatment for rate control strategy (N.=60), and drug treatment for rhythm control strategy (N.=41). The effects respectively exerted by the three treatment modalities on the primary endpoint, namely a composite of death, disabling stroke, severe bleeding and cardiac arrest, have been compared through a median follow-up of 20 months (interquartile range: 18-24 months) using the Cox proportional-hazards regression analysis. Further exposure variables were hypertension, the A-P diameter of the left atrium, the left ventricular ejection fraction and AF relapses. Results The rhythm control strategy and AF recurrences during the follow-up were associated with increased risk of the primary composite endpoint as documented by the Cox model (for the former, hazard ratio [HR]: 3.3159; 95% CI: 1.5415 to 7.1329; P=0.0023; for the latter, HR: 1.0448; 95% CI: 1.0020 to 1.0895; P=0.0410). Even hypertension was associated with an increased risk (HR: 1.1040; 95% CI: 1.0112 to 1.9662; P=0.0477). On the contrary, a rate control strategy predicted a decreased risk of experiencing the primary endpoint (HR: 0.0711; 95% CI: 0.0135 to 0.3738; P=0.0019) while Abl did not exert a statistically significant effect on the same outcome. Conclusions AF ablation is able to decrease the arrhythmic episodes but does not offer a statistically significant protection against the composite of death, disabling stroke, severe bleeding and cardiac arrest in the mid-term follow-up.

INTRODUCTION The efficacy and safety of sacubitril/valsartan used as an antihypertensive agent has not yet been completely assessed. Thus, to investigate them in elderly hypertensive patients, a meta-analysis has been performed. EVIDENCE ACQUISITION The meta-analysis incorporated only randomized controlled trials (RCTs) in which sacubitril/valsartan was compared with a reference drug. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events were taken as safety outcomes. EVIDENCE SYNTHESIS Five RCTs were included for a total of 1513 patients for analysis. In all studies, the comparator drug was an angiotensin receptor blocker (ARB) - valsartan in two cases and olmesartan in the remaining three cases. Compared with ARBs, there was a significant reduction in msSBP (weight mean difference [WMD] -5.41 mmHg, 95% CI: -7.0 to -3.8; P

Introduction The efficacy and safety profiles of the dronedarone were rather praised when the molecule was placed on the market (2009). However, there are today some safety concerns (in particular, risk of liver toxicity) that have led to limit the use of this drug to paroxysmal or persistent atrial fibrillation, and to exclude it from therapy protocols for ventricular tachyarrhythmias. The aim of the present study was to explore some efficacy and safety endpoints concerning dronedarone, by analyzing the evidence derived from quantitative evaluation (meta-analysis) of literature data. Evidence acquisition We comprised in the meta-analysis exclusively randomized controlled trials (RCTs) that reported relevant clinical outcomes with dronedarone. In addition, eligible RCTs had to have randomized 100 patients at least in order to have adequate statistical power, and they had to have clearly reported the outcomes of interest. Primary efficacy outcomes were a) all-cause mortality,b) major acute cardiovascular events and c) worsening heart failure. Secondary outcomes of interest were ventricular tachyarrhythmias, stroke and systemic embolism. We performed a number of sensitivity analyses to better ascertain the sources of heterogeneity. We also performed a number of subgroup analyses. Evidence synthesis At the end of the selection process, the studies regarded suitable for meta-analysis were seven. Dronedarone use was not associated with any significant advantage as regards all-cause mortality(pooled odds ratio =1.31; 95% CI: 0.78 to 2.18; P= 0.31) and major cardiovascular events (pooled odds ratio=1.45; 95% CI: 0.7 to 3.01; P=0.28), as well as regarding the endpoint" worsening heart failure" (pooled odds ratio =1.32; 95% CI: 0.87 to 2.01; P= 0.20). Moreover, using subgroup analyses, in patients with permanent AF, dronedarone use was associated with increased all-cause mortality compared to placebo(P=0.03),as well as with higher risk of major acute cardiovascular events (P=0.04) and episodes of worsening heart failure(P=0.02). In addition, when data from ATHENA study were excluded, dronedarone use was associated with increased all-cause mortality (post exclusion pooled odds ratio=1.77; 95% CI: 1.15 to 2.72; P=0.0089), increased risk of major cardiovascular events (post exclusion pooled odds ratio=2.16; 95% CI: 1.34 to 3.47; P= 0.0014) and increased risk of worsening heart failure(post exclusion pooled odds ratio= 1.618; 95% CI: 1.14 to 2.3; P=0.006). Conclusions In our meta-analysis, dronedarone did not provide any significant benefit with regard to all-cause mortality and major cardiovascular events, as well as regarding the risk of worsening heart failure. Sensitivity analyses then showed that the exclusion of a study, namely ATHENA study, caused a shift in the overall odds ratio, so as to convert the dronedarone use to the ominous role of predictor of higher mortality, worse cardiovascular morbidity and increased risk of worsening heart failure. Thus, dronedarone should be used with caution as second-line medication and exclusively for the secondary prevention of paroxysmal or persistent atrial fibrillation, in patients without signs or symptoms of cardiac decompensation, preferably for limited periods of time and under assiduous clinical and laboratory surveillance.

Recently, transcatheter ablation of atrial fibrillation (AF) has been validated by international societal guidelines as a technique suitable for both treatment and secondary prevention of paroxysmal, persistent or long-lasting persistent AF in highly symptomatic patients in whom at least one antiarrhythmic drug had been tested.

Background: For elderly patients suffering from arterial hypertension, a complete assessment of the efficacy and safety of sacubitril/valsartan used as an anti-hypertensive agent is not available yet. Therefore, we decided to perform a meta-analysis of randomized controlled trials (RCTs) to explore some endpoints concerning anti-hypertensive efficacy as well as safety of sacubitril/valsartan in elderly hypertensive patients. Methods: PubMed and Scopus have been extensively investigated with the help of some key words until June 15, 2018. The meta-analysis incorporated exclusively RCTs in which the anti-hypertensive efficacy and safety of sacubitril/valsartan were compared with those of a reference drug (comparator) that could be an angiotensin-converting enzyme inhibitor (ACEi), an angiotensin receptor blocker (ARB), a calcium channel blocker (CCB) or a beta-blocker. Continuous ambulatory blood pressure monitoring was required as an inclusion criterion in the studies to be included in the meta-analysis. The mean reductions in systolic blood pressure and diastolic blood pressure in the sitting position (msSBP and msDBP, respectively), as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events (AEs) were taken as safety outcomes. Results: Five RCTs were included with a total of 1,513 patients for analysis. In all studies, the comparator drug was an ARB (valsartan in two cases and olmesartan in the remaining three cases). Compared with ARBs, after 12 weeks there was a significant reduction in msSBP (weight mean difference (WMD) = - 5.41 mm Hg, 95% confidence interval (CI): -7.0 to -3.8; P < 0.01), msDBP (WMD = -1.22 mm Hg, 95% CI : -2.15 to -0.3; P < 0.01), maSBP (WMD = -4.58 mm Hg, 95% CI: -5.62 to -3.54; P < 0.01) and maDBP (WMD = -2.17 mm Hg, 95% CI: - 2.78 to -1.56; P < 0.01) in elderly hypertensive patients at 12 weeks. Conclusions: Sacubitril/valsartan may reduce arterial pressure more efficaciously than ARBs in elderly hypertensive patients. These results have to be confirmed by further RCTs with a good methodological quality, possibly with a greater sample size. Cardiol Res. 2019;10(1):24-33 doi: https://doi.org/10.14740/cr813

Background: B-type natriuretic peptide (BNP) is regarded as a reliable predictor of outcome in patients with acute decompensated heart failure (ADHF). However, according to some scholars, a single isolated measurement of serum BNP at the time of hospital admission would not be sufficient to provide reliable prognostic information. Methods: A retrospective study was carried out on patients hospitalized for ADHF, who had then undergone follow-up of at least 6 months, in order to see if there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Medical records had to be carefully examined to divide the case records into two groups, the former characterized by an increase in BNP during hospitalization, and the latter showing a decrease in BNP from the time of admission to the time of discharge. Results: Ultimately, 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge relative to admission, whereas 124 (70.06%) exhibited decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention (odds ratio: 3.72; P = 0.0001) and persistent orthopnea at discharge (odds ratio: 2.93; P = 0.0016). Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter (1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; P = 0.001 (one-way ANOVA)). In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the 6-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of 6-month all-cause mortality after adjustment for age, sodium at discharge, creatinine at discharge and New York Heart Association (NYHA) class at discharge (hazard ratio 34.49; 95% confidence intervals: 4.55 - 261.06; P = 0.001). Conclusions: Among patients with recent ADHF, increased BNP at the time of discharge from the hospital entailed a higher grade of congestion and higher 6-month mortality. J Clin Med Res. 2016;8(10):737-742 doi: http://dx.doi.org/10.14740/jocmr2691w

Background: In recent years, some observational studies suggested that pramipexole, a non-ergot dopamine agonist (DA) used for the treatment of Parkinson’s disease (PD), may increase the risk of heart failure (HF). However, the limitations inherent in observational studies made it difficult to determine whether the excess of incident HF was related to the drug or to other determinants. Thus, some concerns remained regarding the increased putative HF risk associated with non-ergot DAs as a class or individually. Methods: In our meta-analysis, primary endpoint was the risk of incident HF in patients with PD treated with non-ergot DAs compared to those treated with monotherapy with levodopa. Secondary outcome measures were all-cause mortality and cardiovascular events. For these purposes, only randomized controlled trials (RCTs) were considered, provided that they offered complete outcome data pertaining to the incident HF, all-cause mortality and risk of cardiovascular events. Systematic searches were performed in the databases of PubMed, Embase and ClinicalTrial.gov up to May 2015. The effect size was estimated using the pooled relative risk (RR) of non-ergot DAs versus placebo on incident HF as well as on all-cause mortality or cardiovascular events. Results: Six out of 27 RCTs reported at least one case of incident HF; therefore, we included them in the RR estimate, whereas 13 RCTs were included in the meta-analysis for mortality rates and 22 RCTs were included to evaluate cardiovascular events. Treatment with non-ergot DAs did not reveal an increase in the risk of incident HF as compared with the placebo group (pooled RR: 0.95; 95% CI: 0.30 - 2.90; P = 0.893). Similarly, patients treated with non-ergot DAs did not show any significant differences compared to controls with regard to all-cause mortality (pooled RR: 0.617; 95% CI: 0.330 - 1.153; P = 0.13) as well as with regard to cardiovascular events (pooled RR: 1.067; 95% CI: 0.663 - 1.717; P = 0.789). Conclusions: The use of non-ergot DAs in PD patients was not associated with an increased risk of incident HF, nor was it shown to increase the overall mortality or the risk of cardiovascular events compared to the PD patients taking monotherapy with levodopa alone. However, larger studies are warranted to confirm the cardiovascular safety of non-ergot DAs for PD management. J Clin Med Res. 2016;8(6):449-460 doi: http://dx.doi.org/10.14740/jocmr2541e

Background: In recent years, several systems have been implemented to achieve quick and non-invasive measurements of B-type natriuretic peptide (BNP). Among them, Alere TM Heart Check (AHC) BNP test represents the most recent advancement. It is a rapid point-of-care (POC) immunoassay, projected for measuring BNP directly from a capillary whole blood sample. This study aimed at comparing the analytical and clinical performances of this new POC to our reference method (Abbott Architect System). Methods: One hundred eleven patients with stable chronic heart failure (CHF) referring to one cardiac rehabilitation center were enrolled from December 2013 to May 2015. These patients were subjected to a simultaneous capillary (AHC) and plasma (Abbott) BNP measurements. Clinical and analytical performances of AHC were assessed and compared to the reference method. Results: Capillary BNP showed a good correlation with the reference method (r = 0.94, P < 0.0001), although the values diverged when BNP was higher than 1,500 pg/mL. Indeed, the AHC had a relatively poor precision and the coefficient of variability was 10.1% and 18% for low and high controls, respectively. However, both methods showed similar diagnostic performances in discriminating the patients with heart failure in New York Heart Association (NYHA) class I from those belonging to NYHA classes II-III, with values of area under the curve (AUC) of 0.983 and 0.984, respectively, and equivalent sensitivity, specificity, and positive and negative likelihood ratios. Conclusion: The AHC BNP test is a good POC able to provide reliable information about the hemodynamic status of CHF patients, especially of those belonging to NYHA classes I-III. Cardiol Res. 2016;7(2):51-58 doi: http://dx.doi.org/10.14740/cr468e

Knowledge of the right atrial pressure (RAP) values is critical to ascertain the existence of a state of hemodynamic congestion, irrespective of the possible presence of signs and symptoms of clinical congestion and cardiac overload that can be lacking in some conditions of concealed or clinically misleading cardiac decompensation. In addition, a more reliable estimate of RAP would make it possible to determine more accurately also the systolic pulmonary arterial pressure with the only echocardiographic methods. The authors briefly illustrate some of the criteria that have been implemented to obtain a non-invasive RAP estimate, some of which have been approved by current guidelines and others are still awaiting official endorsement from the Scientific Societies of Cardiology. There is a representation of the sometimes opposing views of researchers who have studied the problem, and the prospects for development of new diagnostic criteria are outlined, in particular those derived from the matched use of two- and three-dimensional echocardiographic parameters.

Background: The MacNew questionnaire is a neuro-behavioral tool which is easy and immediately usable. This self-reported questionnaire filled out by the patient allows the physician to achieve helpful information concerning the ways for optimizing the therapy and patient’s lifestyles. In this retrospective study, our aim was to assess whether relatively high scores found using the MacNew questionnaire in patients who had undergone percutaneous or surgical revascularization were associated with a decreased risk of unscheduled hospitalizations during the follow-up. Methods: A retrospective analysis concerning 210 patients was carried out. The clinical sheets of these patients were examined as regards the information provided in the specific questionnaires (MacNew Italian version) routinely administered during the hospitalization prescribed for recovering from recent interventions of coronary percutaneous or surgery revascularization. Every patient undergoing the psychological test with MacNew questionnaire was followed up for 3 years. Results: Using univariate analysis, a global score’s high value (i.e., above the median of the whole examined population) was shown to be associated with a significantly decreased risk of rehospitalization (HR (hazard ratio): 0.4312; 95% CI: 0.3463 - 0.5370; P < 0.0001). After adjustment for age, gender and myocardial infarction as initiating event, using a multivariate Cox proportional hazards regression model, the protection exerted by a high MacNew score against the risk of hospitalizations remained significant (HR: 0.0885; 95% CI: 0.0317 - 0.2472; P < 0.0001). Conclusions: A relatively elevated MacNew global score appears to be associated with a significantly decreased risk of unscheduled hospitalizations after coronary revascularization over a 3-year follow-up. J Clin Med Res. 2016;8(3):210-214 doi: http://dx.doi.org/10.14740/jocmr2447w

Stating a well-codified and widely accepted therapeutic conduct for patients with patent foramen ovale (PFO) and previous cryptogenic stroke is made difficult and somewhat controversial by several issues remained unresolved so far. In this short review, some aspects of the possible role played by the PFO in the pathogenesis of cryptogenic stroke are succinctly analyzed. First, some aspects of cardiovascular anatomy of the human fetus and the adult are outlined. Subsequently, the three randomized controlled trials (RCTs) that have been accomplished so far to compare the implant of a transeptal occluding device with a simple medical therapy in patients with PFO and history of cryptogenic stroke are briefly examined. These RCTs, when assessed using the "intention to treat" method, do not show a greater protective effect of therapy with transeptal device as regards the recurrences of stroke. Afterwards, there is a brief presentation of the findings of several meta-analyses that have been derived from the three above mentioned RCTs, whose results are strikingly discordant with each other. In fact, some of them come to the conclusion that the transcatheter closure of PFO does not offer significant advantages compared to antithrombotic therapy for the secondary prevention of cryptogenic stroke, while others based on subgroup analyses argue that the transcatheter closure of PFO with Amplatzer device, differently from the one performed using the STARFlex device, would be associated with significantly lower incidence of cerebrovascular events compared with medical therapy alone. Finally, the authors argue the need to adhere to the current scientific guidelines. They substantially deny an alleged superior efficacy of transcatheter PFO occlusion compared to medical therapy with antithrombotic agents (anticoagulants or antiplatelet agents), except for selected cases of patients with documented PFO and concomitant clinical-instrumental picture of deep venous thrombosis.

Background: Chronic atrial fibrillation (AF), coexisting with a history of recent coronary angioplasty with stent (PCI-S), represents an encoded indication for oral anticoagulation (OAC) with warfarin plus dual antiplatelet therapy (DAPT). Methods: Using a retrospective cohort study, we determined the respective impacts on cardiovascular outcomes of three different pharmacologic regimens, i.e., triple therapy (TT) with warfarin + clopidogrel and aspirin, dual therapy (DT) with warfarin + clopidogrel or aspirin, and DAPT with clopidogrel + aspirin. Outcomes of interest were all-cause mortality, ischemic cardiac events, ischemic cerebral events, and bleeding events. The inclusion criterion was the coexistence of an indication for OAC (e.g., chronic AF) with an indication for DAPT due to recent PCI-S. Results: Among the 98 patients enrolled, 48 (49%), 31 (31.6%), and 19 (19.4%) patients were prescribed TT, DT, and DAPT, respectively. Throughout a mean follow-up of 378 ± 15.7 days, there were no significant differences between the three regimens for all abovementioned outcomes. In particular, the total frequency of major bleeding was similar in the three groups: five cases (10.4%) in TT, one case (3.22%) in DT and no case in DAPT groups (Chi-square test, P = 0.1987). Conclusions: TT, DT and DAPT displayed similar efficacy and safety. Although the superiority of OAC vs. DAPT for stroke prevention in AF patients has been demonstrated by previous randomized trials, a smaller frequency of high thromboembolic risks’ features in DAPT group of the present study may have prevented the observation of a higher incidence of ischemic stroke in this group. J Clin Med Res. 2016;8(2):153-161 doi: http://dx.doi.org/10.14740/jocmr2443w

INTRODUCTION Recent evidence from relatively small randomized controlled trials would seem to support a useful role of ranolazine for the prevention and treatment of atrial fibrillation (AF). The present study is aimed at providing information about the possible beneficial anti-arrhythmic properties of ranolazine. In particular, the meta-analysis carried out in this study focuses on the application of ranolazine to prophylaxis and treatment of atrial fibrillation. EVIDENCE ACQUISITION Both methods randomized controlled trials (RCTs) and non-randomized observational studies concerning the effects of ranolazine on AF were included in the meta-analysis. In each of the considered studies, a comparison was made between a group of patients taking ranolazine and a second group treated instead with another antiarrhythmic therapy, or assigned to placebo. Efficacy outcomes were the risk of new-onset AF, the probability of conversion to sinus rhythm of patients with recent occurrence (≤48 h) of AF and the time to conversion to sinus rhythm. Safety endpoints were death, adverse events, QTc prolongation and hypotension. EVIDENCE SYNTHESIS Ten studies (8 RCTs and 2 nonrandomized observational studies) were gathered on the whole. Ranolazine was effective in preventing the occurrence of AF when compared to controls (RR=0.60; 95% CI: 0.43-0.83; P=0.002). Subgroup analysis showed a more pronounced preventive effect of ranolazine against AF in the postoperative setting of coronary artery bypass grafting (CABG) surgery (RR=0.39; 95% CI: 0.18-0.83; P=0.02) when compared to non-postoperative AF (RR=0.76; 95% CI: 0.63-0.92; P=0.04). Ranolazine enhanced the chances of successful cardioversion when added to intravenous amiodarone compared to amiodarone alone (RR 1.18; 95% CI: 1.05-1.33; P=0.004) and significantly decreased the time to cardioversion (SMD= -10.35 h; 95% CI: -18.13 hours to -2.57 hours; P