Hearts, Volume 2, Issue 1 (March 2021) – 14 articles

Atrial fibrillation (AF) is the most common cardiac arrhythmia, largely associated to morbidity and mortality. Over the past decades, research in appearance and progression of this arrhythmia have turned into significant advances in its management. However, the incidence of AF continues to increase with the aging of the population and many important fundamental and translational underlaying mechanisms remain elusive. Here, we review recent advances in molecular and cellular basis for AF initiation, maintenance and progression. We first provide an overview of the basic molecular and electrophysiological mechanisms that lead and characterize AF. Next, we discuss the upstream regulatory factors conducting the underlying mechanisms which drive electrical and structural AF-associated remodeling, including genetic factors (risk variants associated to AF as transcriptional regulators and genetic changes associated to AF), neurohormonal regulation (i.e., cAMP) and oxidative stress imbalance (cGMP and mitochondrial dysfunction). Finally, we discuss the potential therapeutic implications of those findings, the knowledge gaps and consider future approaches to improve clinical management. Full article

Cardiac contractility modulation is an innovative therapy conceived for the treatment of heart failure. It is a device-based therapy, employing multiple electrodes to deliver relatively high-voltage (~7.5 V) biphasic signals to the endocardium of the right ventricular septum, in order to improve heart failure symptoms, exercise capacity and quality of life. Multiple clinical and mechanistic studies have been conducted to investigate the potential usefulness of this technology and, as of now, they suggest that it could have a place in therapy and meet a relevant medical need for a specific sub-category of underserved heart failure patients with reduced left ventricular ejection fraction. More studies are needed to further investigate its effect on outcomes such as mortality and rate of hospitalizations. Full article

The present study is an examination of sociodemographic and environmental correlates of hypertension and post-traumatic stress disorder (PTSD), with the goal of better understanding previously identified PTSD and hypertension associations. Data from 5877 adults up to age 54 were analyzed to examine racial and ethnic differences in hypertension, and relationships of socioeconomic status (SES; total family income), employment status, and marital status, and urbanicity (urban, suburban, or rural habitation) with hypertension and PTSD. Next, a total model was tested to determine which sociodemographic and environmental variables, and/or PTSD were significant independent correlates of hypertension. Higher rates of hypertension were evident among African Americans (13.8%), relative to Caucasian (7.7%) or Hispanic (6.7%) participants (p < 0.001). Low SES (family income under USD 19,000) and unemployment were associated with significantly greater likelihood (p < 0.001) of hypertension (9.8% vs. 7.6% for low SES; 14.3% vs. 8.3% for unemployment) and PTSD (16.6% vs. 8.7% for low SES; 21.3% vs. 9.6% for unemployment). Participants who were married versus those separated or divorced were significantly less likely (p < 0.001) to have hypertension (9.0% vs. 11.9%) or PTSD (10.8% vs. 18.3%). Urbanicity was not significantly associated with hypertension or PTSD. Unemployment and PTSD were the only significant independent factors associated with hypertension. Full article

In 1983, three of us reported in “Science” that umbilical-placental arteries and veins, obtained from normal pregnant women at term delivery, when exposed in vitro to low concentrations of Mg²⁺ went into vasospasm; the lower the Mg²⁺, the greater the contractile force developed. These blood vessels also demonstrated amplified contractile force development when challenged with circulating amines and peptides (e.g., norepinephrine, 5-HT, angiotensin II, etc.). We suggested that severe Mg deficiency during pregnancy could in part be responsible for spontaneous abortions, loss of fetuses, stillbirths, and developmental alterations in infants. Using short-term dietary Mg deficient animals, we have noted a great many molecular and biochemical alterations in ventricular, atrial and somatic vascular smooth muscle alterations including DNA methylation and histone changes leading us to speculate that Mg deficiency may represent a genotoxin promoting mutations and causing epigenetic changes. Over the last 35 years, we have new data on severely preeclamptic and gestational diabetic pregnant women that gives credence to our original hypothesis and demonstrates that recently- discovered developmental proteins, originally found 100 years ago in Drosophila fruit flies termed the “Notch pathway”, due to effects on its wings, appears to be important in development of the umbilical-placental blood vessels in pregnant women. Along with the developmental molecule, p53, these Notch proteins clearly alter the behavior of the umbilical-placental vessels. We believe these new findings probably help to explain many of the genetic-toxicity effects seen in women later in life who develop strokes and cardiovascular diseases. Notch alterations could also play an important role in babies born with cardiac defects. Full article

Implantable mechanical circulatory support (MCS) systems for ventricular assist device (VAD) therapy have emerged as an important strategy due to a shortage of donor organs for heart transplantation. A growing number of patients are receiving permanent assist devices, while fewer are undergoing heart transplantation (Htx). Continuous-flow (CF) pumps, as devices that can be permanently implanted, show promise for the treatment of both young and old patients with heart failure (HF). Further improvement of these devices will decrease adverse events, enable pulse modulation of continuous blood flow, and improve automatic remote monitoring. Ease of use for patients could also be improved. We herein report on the current state of the art regarding implantable CF pumps for use as MCS systems in the treatment of advanced refractory HF. Full article

Background: Obstructive sleep apnea (OSA) is one of the most common breathing disorders. There are uncertainties about its impact on the in-hospital outcomes of patients who suffer acute coronary syndromes. We studied the largest publicly available all-payer inpatient healthcare database in the United States (National Inpatient Sample) to determine the effects of obstructive sleep apnea on the in-hospital outcomes of patients admitted with non-ST elevation myocardial infarction (NSTEMI). Methods: All adult patients (age ≥ 18) admitted primarily for NSTEMI between September 2010 and September 2015 were identified in the National Inpatient Sample. They were then categorized into those with OSA and those without OSA. The main outcome was in-hospital mortality. Propensity scoring and logistic regression models were created to determine the outcomes. Results: There were 1,984,432 patients with NSTEMI (weighted estimates), 123,551 (6.23%) of who had diagnosed OSA while 1,860,881 (93.77%) did not. In-hospital mortality was significantly lower in the OSA group [2.61% vs. 3.53%, adjusted odd ratio (aOR) 0.73 and confidence interval (CI) (0.66–0.81)]. Patients with OSA were also less likely to require coronary artery bypass surgery: 13.85% and 12.77% (p-value 0.0003). The patients with OSA had higher mean hospital costs compared to the patients who did not have OSA: $17,326 vs. $16,984, adjusted mean ratio (aMR) 1.02; CI (1.01–1.02). Conclusion: In-hospital mortality was lower in NSTEMI patients with diagnosed OSA compared to patients without diagnosed OSA. This appears to contrast with the widely recognized adverse effects of OSA on the cardiovascular system. Full article

Cardiac development is a complex developmental process that is initiated soon after gastrulation, as two sets of precardiac mesodermal precursors are symmetrically located and subsequently fused at the embryonic midline forming the cardiac straight tube. Thereafter, the cardiac straight tube invariably bends to the right, configuring the first sign of morphological left–right asymmetry and soon thereafter the atrial and ventricular chambers are formed, expanded and progressively septated. As a consequence of all these morphogenetic processes, the fetal heart acquired a four-chambered structure having distinct inlet and outlet connections and a specialized conduction system capable of directing the electrical impulse within the fully formed heart. Over the last decades, our understanding of the morphogenetic, cellular, and molecular pathways involved in cardiac development has exponentially grown. Multiples aspects of the initial discoveries during heart formation has served as guiding tools to understand the etiology of cardiac congenital anomalies and adult cardiac pathology, as well as to enlighten novels approaches to heal the damaged heart. In this review we provide an overview of the complex cellular and molecular pathways driving heart morphogenesis and how those discoveries have provided new roads into the genetic, clinical and therapeutic management of the diseased hearts. Full article

Severe mitral valve regurgitation (MR) carries a significant burden both in prognosis and quality of life of patients, as well as on healthcare systems, with high rates of hospitalization for heart failure. While mitral valve surgery constitutes the first-line treatment option for primary MR in suitable patients, surgical treatment for secondary severe MR remains controversial, with a substantial lack of evidence on a survival benefit. In recent decades, percutaneous mitral valve repair has emerged as an alternative treatment for patients deemed not suitable for surgery. Among several devices under development or evaluation, the MitraClip system is the most widespread and is supported by the strongest evidence. While the role of MitraClip in patients with chronic primary MR who are not deemed suitable for surgery is well established, with consistent data showing improvement in both prognosis and quality of life, MitraClip treatment in secondary MR is a rapidly evolving field. Two recent randomized clinical trials generated apparently controversial results but actually provided an interesting pathophysiologic frame that could help discerning patients who will benefit from the procedure versus patients who will not. In this review, we will discuss current treatment options for mitral regurgitation, focusing on percutaneous mitral valve repair with the MitraClip system. Full article

Cancer patients receiving a potentially cardiotoxic oncologic therapy have an increased risk of cardiovascular adverse events (CVAEs), especially in presence of concomitant arterial hypertension (AH). Therefore, cancer patients should be evaluated before, during and after cardiotoxic treatments, to early identify new-onset or worsening AH or CVAEs. An expert panel of oncology networks from Piedmont and Aosta Valley (North-Western Italy) aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome and the risk–benefit ratio of diagnostic/therapeutic tools. We proposed an useful document for evaluating and managing AH related to cancer treatments. Patients should be divided into 4 cardiovascular (CV) risk groups before starting potentially cardiotoxic therapies: patients with low/moderate risk who should be entirely evaluated by oncologists and patients with high/very high risk who should be referred to a cardiologist or arterial hypertension specialist. According to the CV risk class, every patient should be followed up during cancer treatment to monitor any possible CV complications. Adequate control of AH related to antineoplastic treatments is crucial to prevent severe CVAEs. In the presence of high-profile risk or lack of response to anti-hypertensive therapy, the patients should be managed with a cardiovascular-oncology expert center. Full article

Advances in pediatric cancer therapies have dramatically improved the likelihood of survival. As survivors are aging, however, we are now understanding that treatment carries a significant risk of cardiovascular toxicity, which can develop immediately, or even many years after completing therapy. Anthracycline derivates are some of the most commonly used agents in pediatric oncology treatment protocols, which have a dose-dependent correlation with the development of cardiac toxicity. As we learn more about the mechanisms of toxicity, we are developing prevention strategies, including improvements in surveillance, to improve early diagnosis of heart disease. Current survivorship surveillance protocols often include screening echocardiograms to evaluate systolic function by measuring the ejection fraction or fractional shortening. However, these measurements alone are not enough to capture early myocardial changes. The use of additional imaging biomarkers, serum biomarkers, electrocardiograms, as well as cholesterol and blood pressure screening, are key to the early detection of cardiomyopathy and cardiovascular disease. Medical treatment strategies are the same as those used for heart failure from other causes, but earlier recognition and implementation can lead to improved long term outcomes. Full article

Background: Heart rate variability (HRV) is widely used in professional soccer players as a tool to assess individual response to training load. Different devices and methods are available for HRV assessment. The relationship between HRV and competitive soccer matches performance is not documented. Methods: We monitored HRV in professional soccer players throughout a game season. Measurements were performed with a portable lightweight device in weekly 5 min sessions from which we obtained the value of the square root of the mean squared differences of successive beat-to-beat intervals (rMSSD). Game parameters of run and velocity were collected. Results: Twenty-seven players were monitored with a total of 121 observations. The rMSSD significantly related with the total distance covered (p = 0.036) and with the distance covered running at >15 km/h (p = 0.039) during soccer games. Conclusions: HRV was associated with competition performance in professional soccer players. Full article

Over the years, pacemakers have evolved from a life-saving tool to prevent asystole to a device to treat heart rhythm disorders and heart failure, aiming at improving both cardiac function and clinical outcomes. Cardiac stimulation nowadays aims to correct the electrophysiologic roots of mechanical inefficiency in different structural heart diseases. This has led to awareness of the concealed risks of customary cardiac pacing that can inadvertently cause atrioventricular and inter-/intra-ventricular dyssynchrony, and has promoted the development of new pacing modalities and the use of stimulation sites different from the right atrial appendage and the right ventricular apex. The perspective of truly physiologic pacing is the leading concept of the continued research in the past 30 years, which has made cardiac stimulation procedure more sophisticated and challenging. In this article, we analyze the emerging evidence in favor of the available strategies to achieve an individualized physiologic setting in bradycardia pacing. Full article

Right heart catheterization remains necessary for the diagnosis of pulmonary hypertension and, therefore, for the prognostic evaluation of patients with chronic heart failure. The non-invaSive Assessment of Pulmonary vasculoPathy in Heart failure (SAPPHIRE) study was designed to assess the feasibility and prognostic relevance of a non-invasive evaluation of the pulmonary artery vasculature in patients with heart failure and pulmonary hypertension. Patients will undergo a right heart catheterization, cardiac resonance imaging, and a pulmonary function test in order to identify structural and functional parameters allowing the identification of combined pre- and postcapillary pulmonary hypertension, and correlate these findings with the hemodynamic data. Full article

A 68-year-old patient with triple vessel coronary artery disease was scheduled for elective coronary artery bypass grafting. Three days after the uneventful surgery, the patient went into cardiogenic shock, which was deemed to be caused by a dynamic left ventricular outflow tract obstruction and high-grade mitral regurgitation, which both had not been present before surgery. On an emergency basis, surgical transvalvular septal myectomy and mitral valve replacement were performed. After initial extra corporeal membrane oxygenation (ECMO) therapy and a prolonged (intensive care unit) ICU stay the patient finally recovered and is well one and a half years after surgery. Full article