Mitral valve prolapse: arrhythmic risk during pregnancy and postpartum.

BACKGROUND AND AIMS: Arrhythmic mitral valve prolapse (AMVP) is linked to life-threatening ventricular arrhythmias (VAs), and young women are considered at high risk. Cases of AMVP in women with malignant VA during pregnancy have emerged, but the arrhythmic risk during pregnancy is unknown. The authors aimed to describe features of women with high-risk AMVP who developed malignant VA during the perinatal period and to assess if pregnancy and the postpartum period were associated with a higher risk of malignant VA. METHODS: This retrospective international multi-centre case series included high-risk women with AMVP who experienced malignant VA and at least one pregnancy. Malignant VA included ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock from an implantable cardioverter defibrillator. The authors compared the incidence of malignant VA in non-pregnant periods and perinatal period; the latter defined as occurring during pregnancy and within 6 months after delivery. RESULTS: The authors included 18 women with AMVP from 11 centres. During 7.5 (interquartile range 5.8-16.6) years of follow-up, 37 malignant VAs occurred, of which 18 were pregnancy related occurring in 13 (72%) unique patients. Pregnancy and 6 months after delivery showed increased incidence rate of malignant VA compared to the non-pregnancy period (univariate incidence rate ratio 2.66, 95% confidence interval 1.23-5.76). CONCLUSIONS: The perinatal period could impose increased risk of malignant VA in women with high-risk AMVP. The data may provide general guidance for pre-conception counselling and for nuanced shared decision-making between patients and clinicians.

Lifetime exercise dose and ventricular arrhythmias in patients with mitral valve prolapse.

AIMS: Patients with mitral valve prolapse (MVP) have high risk of life-threatening ventricular arrhythmias (VAs). Data on the impact of exercise on arrhythmic risk in these patients are lacking. We explored whether lifetime exercise dose was associated with severe VA and with established risk factors in patients with MVP. Furthermore, we explored the circumstances at the VA event. METHODS AND RESULTS: In this retrospective cohort study, we included patients with MVP and assessed lifetime exercise dose as metabolic equivalents of task (MET) hours/week. Severe VA was defined as sustained ventricular tachycardia or fibrillation, aborted cardiac arrest, and appropriate shock by a primary preventive implantable cardioverter defibrillator. We included 136 MVP patients (48 years [interquartile range (IQR) 35-59], 61% female), and 17 (13%) had previous severe VA. The lifetime exercise dose did not differ in patients with and without severe VA (17 MET h/week [IQR 9-27] vs. 14 MET h/week [IQR 6-31], P = 0.34). Lifetime exercise dose > 9.6 MET h/week was a borderline significant marker for severe VA (OR 3.38, 95% CI 0.92-12.40, P = 0.07), while not when adjusted for age (OR 2.63, 95% CI 0.66-10.56, P = 0.17). Ventricular arrhythmia events occurred most frequently during wakeful rest (53%), followed by exercise (29%) and sleep (12%). CONCLUSION: We found no clear association between moderate lifetime exercise dose and severe VA in patients with MVP. We cannot exclude an upper threshold for safe levels of exercise. Further studies are needed to explore exercise and risk of severe VA.

The response to cardiac resynchronization therapy in LMNA cardiomyopathy.

AIMS: Cardiac implantable electronic device (CIED) therapy is fundamental to the management of LMNA cardiomyopathy due to the high frequency of atrioventricular block and ventricular tachyarrhythmias. We aimed to define the role of cardiac resynchronization therapy (CRT) in impacting heart failure in LMNA cardiomyopathy. METHODS AND RESULTS: From nine referral centres, LMNA cardiomyopathy patients who underwent CRT with available pre- and post-echocardiograms were identified retrospectively. Factors associated with CRT response were identified (defined as improvement in left ventricular ejection fraction [LVEF] ≥5% 6 months post-implant) and the associated impact on the primary outcome of death, implantation of a left ventricular assist device or cardiac transplantation was assessed. We identified 105 patients (mean age 51 ± 10 years) undergoing CRT, including 70 (67%) who underwent CRT as a CIED upgrade. The mean change in LVEF ∼6 months post-CRT was +4 ± 9%. A CRT response occurred in 40 (38%) patients and was associated with lower baseline LVEF or a high percentage of right ventricular pacing prior to CRT in patients with pre-existing CIED. In patients with a European Society of Cardiology class I guideline indication for CRT, response rates were 61%. A CRT response was evident at thresholds of LVEF ≤45% or percent pacing ≥50%. There was a 1.3 year estimated median difference in event-free survival in those who responded to CRT (p = 0.04). CONCLUSION: Systolic function improves in patients with LMNA cardiomyopathy who undergo CRT, especially with strong guideline indications for implantation. Post-CRT improvements in LVEF are associated with survival benefits in this population with otherwise limited options.

Progression of cardiac disease in patients with lamin A/C mutations.

AIMS: We aimed to study the progression of cardiac dysfunction in patients with lamin A/C mutations and explore markers of adverse cardiac outcome. METHODS AND RESULTS: We followed consecutive lamin A/C genotype-positive patients divided into tertiles according to age. Patients underwent repeated clinical examinations, electrocardiograms (ECGs), and echocardiograms. We followed left ventricular (LV) and right ventricular (RV) size and function, and the severity atrioventricular-valve regurgitations. Outcome was death, LVAD implant, or cardiac transplantation. We included 101 patients [age 44 (29-54) years, 39% probands, 50% female]. We analysed 576 echocardiograms and 258 ECGs during a follow-up of 4.9 (interquartile range 2.5-8.2) years. The PR-interval increased at young age from 204 ± 73 to 212 ± 69 ms (P < 0.001), LV ejection fraction (LVEF) declined from middle age from 50 ± 12% to 47 ± 13% (P < 0.001), while LV volumes remained unchanged. RV function and tricuspid regurgitation worsened from middle age with accelerating rates. Progression of RV dysfunction [odds ratio (OR) 1.3, 95% confidence interval (CI) (1.03-1.65), P = 0.03] and tricuspid regurgitation [OR 4.9, 95% CI (1.64-14.9), P = 0.004] were associated with outcome when adjusted for age, sex, comorbidities, LVEF, and New York Heart Association functional class. CONCLUSION: In patients with lamin A/C genotype, electrical disease started at young age. From middle age, LV function deteriorated progressively, while LV size remained unchanged. Worsening of RV function and tricuspid regurgitation accelerated in older age and were associated with outcome. Our systematic map on cardiac deterioration may help optimal monitoring and prognostication in lamin A/C disease.

Serelaxin a novel treatment for acute heart failure.

Acute heart failure (AHF) represents a major healthcare burden with a high risk of in-hospital and post-discharge mortality, which remained almost unchanged in the last few decades, underscoring the need of new treatments. Relaxin is a naturally occurring human peptide initially identified as a reproductive hormone and has been shown to play a key role in the maternal hemodynamic and renal adjustments that accommodate pregnancy. Recently, the new molecule serelaxin, a recombinant form of the naturally occurring hormone relaxin has been studied in patients hospitalized for AHF. In addition to vasodilation, serelaxin has anti-oxidative, anti-inflammatory and connective tissue regulating properties. In preclinical studies, it reduced both systemic and renal vascular resistance and, in the clinical trials Pre-RELAX-AHF and RELAX-AHF, it improved dyspnea and signs of congestion. In addition, serelaxin was associated with a reduction of 180-day mortality. The aim of this review is to summarize the pharmacological properties of serelaxin and the results of the preclinical and clinical studies.

Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure.

OBJECTIVE: Chronic heart failure (CHF) is characterized by several micronutrient deficits. Amino acid supplementation may have a positive effect on nutritional and metabolic status in patients with CHF. Levo-carnosine (ß-alanyl-L-histidine) is expressed at a high concentration in myocardium and muscle. Preliminary studies with L-carnosine in healthy individuals have suggested a potential role in improving exercise performance. To our knowledge, no study has been conducted in patients with heart failure. The aim of this study was to test the oral supplementation of L-carnosine and its effects on quality of life and exercise performance in patients with stable CHF. METHODS: Fifty patients with stable CHF and severe left-ventricular systolic dysfunction on optimal medical therapy were randomized 1:1 to receive oral orodispersible L-carnosine (500 mg OD) or standard treatment. Left-ventricular ejection fraction (LVEF) was measured by echocardiography. Cardiopulmonary stress test, 6-minute walking test (6 MWT) and quality-of-life (visual analog scale score and the EuroQOL five dimensions questionnaire [EQ-5D]) were performed at baseline and after 6 mo. RESULTS: Patients receiving orodispersible L-carnosine had an improvement in 6 MWT distance (P = 0.014) and in quality-of-life (VAS score) (P = 0.039) between baseline and follow-up. Compared with controls, diet supplementation with orodispersible L-carnosine was associated with an improvement in peakVO2 (P < 0.0001), VO2 at anaerobic threshold, peak exercise workload, 6 MWT and quality-of-life assessed by the EQ-5D test and the VAS score. CONCLUSION: This study suggests that L-carnosine, added to conventional therapy, has beneficial effects on exercise performance and quality of life in stable CHF. More data are necessary to evaluate its effects on left-ventricular ejection fraction and prognosis in CHF.

Amino acids and derivatives, a new treatment of chronic heart failure?

Amino acids play a key role in multiple cellular processes. Amino acids availability is reduced in patients with heart failure (HF) with deleterious consequences on cardiac and whole-body metabolism. Several metabolic abnormalities have been identified in the failing heart, and many of them lead to an increased need of amino acids. Recently, several clinical trials have been conducted to demonstrate the benefits of amino acids supplementation in patients with HF. Although they have shown an improvement of exercise tolerance and, in some cases, of left ventricular function, they have many limitations, namely small sample size, differences in patients' characteristics and nutritional supplementations, and lack of data regarding outcomes. Moreover recent data suggest that a multi-nutritional approach, including also antioxidants, vitamins, and metals, may be more effective. Larger trials are needed to ascertain safety, efficacy, and impact on prognosis of such an approach in HF.

[Efficacy of ACE-inhibitors in patients with recent myocardial infarction. Studies with zofenopril]. / Efficacia degli ACE-inibitori nei pazienti con recente infarto miocardico. Gli studi con zofenopril.

Several large-scale trials have demonstrated improved survival with the administration of ACE-inhibitors to patients with a recent myocardial infarction. Many ACE-inhibitors with different pharmacological properties have been shown to be safe and effective. More recently the data provided by the Survival of Myocardial Infarction Long-term Evaluation (SMILE) program indicate that zofenopril may favorably affect the prognosis of patients with a recent myocardial infarction and, according to the results of the SMILE-4 study, it may be superior to ramipril with respect to some variables (cardiovascular hospitalizations) when both these ACE-inhibitors are administered combined with acetylsalicylic acid.