Diastolic Heart Failure Mechanisms and Assessment Revisited.

The syndrome of heart failure (HF) with preserved ejection fraction (HFpEF) makes up about half of the HF population. The HF mechanisms in these patients are varied and not fully understood. In addition, the term "diastolic HF" was switched to HFpEF because of difficulties in measuring the left ventricular (LV) diastolic performance. In the late stages, HFpEF carries a prognosis that is as bad as or worse than that of HFrEF. Hence, it is important to recognize LV diastolic impairment at an earlier stage so that the causal mechanisms, if any, can be treated to retard its progression. Despite the availability of numerous disease-modifying agents for HFrEF, there are hardly any available treatments for HFpEF. With our aging population, there will be an epidemic of HFpEF and hence this entity needs attention and respect. In this paper, we review the fundamental mechanisms of HFpEF, the physiology of LV filling and how LV diastolic function can be comprehensively measured. We also speculate how this may help with the early recognition of diastolic HF and its treatment.

Contemporary Management of the Failing Fontan.

Adult patients with congenital heart disease have now surpassed the pediatric population due to advances in surgery and improved survival. One such complex congenital heart disease seen in adult patients is the Fontan circulation. These patients have complex physiology and are at risk for several complications, including thrombosis of the Fontan pathway, pulmonary vascular disease, heart failure, atrial arrhythmias, atrioventricular valve regurgitation, and protein-losing enteropathy. This review discusses the commonly encountered phenotypes of Fontan circulatory failure and their contemporary management.

A case report of recurrent primary posterior mediastinal perivascular epithelioid cell tumour compressing the right inferior pulmonary vein, atria, and inferior vena cava.

Background: Perivascular epithelioid cell tumours (PEComas) are rare soft tissue neoplasms that commonly occur in the uterus, skin, and liver and less commonly in the retroperitoneum, colon, and mediastinum. Case summary: A 36-year-old male patient with a history of mediastinal PEComa status post resection, essential hypertension, and atrial fibrillation status post appendage ligation currently not on anticoagulation presented with a 1-week history of fevers, chills, productive cough, chest pain, dyspnoea on exertion, loss of appetite, and general weakness. Vital signs, physical exam, laboratory data, electrocardiogram, and chest radiograph were grossly unremarkable. A multimodality imaging approach utilizing transthoracic echocardiogram, transoesophageal echocardiogram (TEE), cardiac magnetic resonance imaging (cMRI), and computed tomography angiography of the chest, abdomen, and pelvis revealed a local 40 mm × 53 mm globular bilobed vascularized scar-free posterior mediastinal mass arising from the roof of the left and right atria and extending superiorly to the main pulmonary artery and inferiorly to the inferior vena cava. Based on the mass' size and proximity to vital structures and tumour recurrence, the case was presented during tumour board rounds, and the outcome was to surgically resect the mass and then have the patient follow up with medical oncology and radiation oncology for possible chemotherapy and radiation, respectively. Discussion: Perivascular epithelioid cell tumours are rare, and mediastinal PEComas are even rarer, warranting a multimodality imaging approach involving TEE and cMRI and a multidisciplinary approach involving anaesthesiologists, cardiologists, cardiothoracic surgeons, medical oncologists, pathologists, radiologists, and radiation oncologists.

Stem Cell-Derived Cardiomyocyte-Like Cells in Myocardial Regeneration.

Myocardial infarction results in the significant loss of cardiomyocytes (CMs) due to the ischemic injury following coronary occlusion leading to impaired contractility, fibrosis, and ultimately heart failure. Stem cell therapy emerged as a promising regenerative strategy to replenish the otherwise terminally differentiated CM to restore cardiac function. Multiple strategies have been applied to successfully differentiate diverse stem cell populations into CM-like phenotypes characterized by the expression status of signature biomarkers and observable spontaneous contractions. This article discusses the current understanding and applications of various stem cell phenotypes to drive the differentiation machinery toward CM-like lineage. Impact Statement Ischemic heart disease (IHD) extensively affects a large proportion of the population worldwide. Unfortunately, current treatments for IHD are insufficient to restore cardiac effectiveness and functionality. A growing field in regenerative cardiology explores the potential for stem cell therapy following cardiovascular ischemic episodes. The thorough understanding regarding the potential and shortcomings of translational approaches to drive versatile stem cells to cardiomyocyte lineage paves the way for multiple opportunities for next-generation cardiac management.

A case report of successful transaneurysmal repair of a giant isolated membranous ventricular septal aneurysm.

Background: Isolated membranous ventricular septal aneurysms are infrequent in clinical practice. Furthermore, current guidelines do not dictate how to diagnose or manage such lesions. Case summary: A 54-year-old male patient with a history of essential hypertension and tobacco use presented with chest pain associated with dyspnoea and nausea. Electrocardiogram was unrevealing. Physical exam was significant for a diastolic murmur heard best in the apex. Computed tomography angiography of the chest revealed an aneurysm measuring 5 cm in diameter along the ascending aorta. Transoesophageal echocardiography showed that the aneurysm originated from the membranous ventricular septum, coursed along the ascending aorta, and ended anteriorly to the surface of the right ventricle and ascending aorta. Cardiac magnetic resonance imaging confirmed these findings and demonstrated that the aneurysm comprised of two loculations. Given the size of the aneurysm and its proximal location to major cardiovascular structures, percutaneous repair was considered unsafe. Following a multidisciplinary meeting, the lesion was successfully resected via a transaneurysmal approach. Discussion: Isolated membranous ventricular septal aneurysms are best imaged via a combination of transoesophageal echocardiogram and cardiac magnetic resonance imaging and best managed via a multidisciplinary approach for optimal outcomes.

Importance of concomitant functional mitral regurgitation on survival in severe aortic stenosis patients undergoing aortic valve replacement.

BACKGROUND: Mitral regurgitation (MR) is commonly seen in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR). But the long-term implications of MR in AS are unknown. AIM: To investigate MR's impact on survival of patients undergoing surgical AVR for severe AS. METHODS: Of the 740 consecutive patients with severe AS evaluated between 1993 and 2003, 287 underwent AVR forming the study cohort. They were followed up to death or till the end of 2019. Chart reviews were performed for clinical, echocardiographic, and therapeutic data. MR was graded on a 1-4 scale. Mortality data was obtained from chart review and the Social Security Death Index. Survival was analyzed as a function of degree of MR. RESULTS: The mean age of the severe AS patients who had AVR (n = 287) was 72 ± 13 years, 46% women. Over up to 26 years of follow up, there were 201 (70%) deaths, giving deep insights into the determinants of survival of severe AS who had AVR. The 5, 10 and 20 years survival rates were 75%, 45% and 25% respectively. Presence of MR was associated with higher mortality in a graded fashion (P = 0.0003). MR was significantly associated with lower left ventricular (LV) ejection fraction and larger LV size. Impact of MR on mortality was partially mediated through lower LV ejection fraction and larger LV size. By Cox regression, MR, lower ejection fraction (EF) and larger LV end-systolic dimension were independent predictors of higher mortality (χ2 = 33.2). CONCLUSION: Presence of greater than 2+ MR in patients with severe AS is independently associated with reduced survival in surgically managed patients, an effect incremental to reduced EF and larger LV size. We suggest that aortic valve intervention should be considered in severe AS patients when > 2+ MR occurs irrespective of EF or symptoms.

Gender Effects on Left Ventricular Responses and Survival in Patients with Severe Aortic Regurgitation: Results from a Cohort of 756 Patients with up to 22 Years of Follow-Up.

OBJECTIVES: We sought to evaluate the effect of gender on biology, therapeutic decisions, and survival in patients with severe aortic regurgitation (AR). BACKGROUND: Gender affects adaptive response to the presence of valvular heart diseases and therapeutic decisions. The impact of these on survival in severe AR patients is not known. METHODS: This observational study was compiled from our echocardiographic database which was screened (1993-2007) for patients with severe AR. Detailed chart reviews were performed. Mortality data were obtained from the Social Security Death Index and analyzed as a function of gender. RESULTS: Of the 756 patients with severe AR, 308 (41%) were women. Over a follow-up of up to 22 years, there were 434 deaths. Women compared to men were older (64 ± 18 vs. 59 ± 17 years, p = 0.0002). Women also had smaller left ventricular (LV) end diastolic dimension (5.2 ± 1.1 vs. 6.0 ± 1.0 cm, p < 0.0001), higher EF (56% ± 17% vs. 52% ± 18%, p = 0.003), higher prevalence of diabetes mellitus (18% vs. 11%, p = 0.006), and higher prevalence of ≥2+ mitral regurgitation (52% vs. 40%, p = 0.0008) despite a smaller LV size. Women were also less likely to receive aortic valve replacement (AVR) (24% vs. 48%, p < 0.0001) compared to men and had a lower survival on univariate analysis (p = 0.001). However, after adjusting for group differences including AVR rates, gender was not an independent predictor of survival. However, the survival benefit associated with AVR was similar in both women and men. CONCLUSIONS: This study strongly suggests that female gender is associated with different biological responses to AR compared to men. There is also a lower AVR rate in women, but women derive similar survival benefit as men with AVR. Gender does not seem to affect survival in an independent fashion in patients with severe AR after adjusting for group differences and AVR rates.

Noninvasive Assessment With Transthoracic Echocardiography in End-Stage Heart Failure.

Heart failure is a common cardiac condition that carries a substantial risk of morbidity and mortality despite advances in management. Echocardiography plays a central role in its diagnosis, elucidation of mechanisms, and detailed hemodynamic analysis. In this E-Challenge, the authors review a few transthoracic echocardiographic findings that yield insights into the hemodynamics.

Mortality and Complications of COVID-19 Among Adult Congenital Heart Disease Patients: A Retrospective Cohort Study Using the National Inpatient Sample Database.

This study examines in-hospital mortality and complicated COVID-19 infection among adult congenital heart disease (ACHD) patients admitted with COVID-19, using the National Inpatient Sample (NIS). A total of 4219 COVID-19 patients with ACHD were included. We demonstrated that COVID-19 patients with ACHD were more likely to experience in-hospital mortality (OR 1.04, 95% CI 1.04-1.04, P < 0.01) and complicated COVID-19 infection (OR: 1.30, 95% CI: 1.11-1.53, P < 0.01). In our sub-group analysis, COVID-19 patients with tetralogy of Fallot (TOF) had higher mortality and COVID-19 patients with atrial septal defects (ASD) had a higher incidence of complicated infection when compared to COVID-19 patients with all other ACHDs. Risk factors for mortality among COVID-19 patients with ACHD include advanced age, lower income, unrepaired ACHD, malnutrition, and chronic liver disease. Accordingly, we recommend aggressive preventive care with vaccination and non-pharmacologic measures in order to improve survival for ACHD patients.

Left ventricular diastolic abnormalities in vegetarians compared with non-vegetarians.

Vegetarians have less hypertension, diabetes mellitus and obesity, hence possibly lower risk of congestive heart failure (HF). We studied associations between vegetarian diets and echocardiographic markers of stage B HF. In a cross-sectional study, dietary pattern was ascertained by a validated FFQ. Echocardiograms were interpreted using standardised criteria. Participants were free-living subjects in Southern California who were older Adventist Health Study-2 cohort members. After exclusions, 133 subjects aged >60 years were enrolled. Their mean age was 72·7 (sd 8·7) years, 48·1 % were female, 32 % were African American and 71 % were vegetarian. Non-vegetarians had higher body weight (80·3 (sd 15·17) kg v. 71·3 (sd 16·2), P < 0·005), body surface area (1·92 (sd 0·24) m2v. 1·81 (sd 0·22) m2, P = 0·01) and prevalence of hypertension (63 % v. 47 %, P = 0·10). Adjusting for age, sex, race and physical activity, it is found that vegetarians had greater echocardiographic mitral annular e' velocity (a measure of left ventricular (LV) relaxation) 7·44 v. 6·48 (non-vegetarian) cm/s (P = 0·011) and a yet greater contrast when vegans (7·66 cm/s, P = 0·011) were the group of interest. The ratio mid-to-late-diastolic mitral flow velocity (E/A) was also higher in vegans compared with non-vegetarians (1·02 and 0·84, respectively, P = 0·008). Mediation analyses suggested these associations may be partly related to higher blood pressures and BMI in the non-vegetarians. We conclude that vegetarians, especially vegans, appear to have better LV relaxation and fewer diastolic abnormalities than others. As dietary exposure is modifiable, one may speculate pending further investigation about the potential for reduction of stage B HF and later mortality.

Population Risk Factors for Severe Disease and Mortality in COVID-19 in the United States during the Pre-Vaccine Era: A Retrospective Cohort Study of National Inpatient Sample.

Background-Previous studies on coronavirus disease 2019 (COVID-19) were limited to specific geographical locations and small sample sizes. Therefore, we used the National Inpatient Sample (NIS) 2020 database to determine the risk factors for severe outcomes and mortality in COVID-19. Methods-We included adult patients with COVID-19. Univariate and multivariate logistic regression was performed to determine the predictors of severe outcomes and mortality in COVID-19. Results-1,608,980 (95% CI 1,570,803-1,647,156) hospitalizations with COVID-19 were included. Severe complications occurred in 78.3% of COVID-19 acute respiratory distress syndrome (ARDS) and 25% of COVID-19 pneumonia patients. The mortality rate for COVID-19 ARDS was 54% and for COVID-19 pneumonia was 16.6%. On multivariate analysis, age > 65 years, male sex, government insurance or no insurance, residence in low-income areas, non-white races, stroke, chronic kidney disease, heart failure, malnutrition, primary immunodeficiency, long-term steroid/immunomodulatory use, complicated diabetes mellitus, and liver disease were associated with COVID-19 related complications and mortality. Cardiac arrest, septic shock, and intubation had the highest odds of mortality. Conclusions-Socioeconomic disparities and medical comorbidities were significant determinants of mortality in the US in the pre-vaccine era. Therefore, aggressive vaccination of high-risk patients and healthcare policies to address socioeconomic disparities are necessary to reduce death rates in future pandemics.

Pathophysiology, Diagnosis, and Management of Coronary No-Reflow Phenomenon.

Coronary no-reflow phenomenon is a lethal mechanism of ongoing myocardial injury following successful revascularization of an infarct-related coronary artery. Incidence of this phenomenon is high following percutaneous intervention and is associated with adverse in-hospital and long-term outcomes. Several mechanisms such as ischemia-reperfusion injury and distal microthromboembolism in genetically susceptible patients and those with preexisting endothelial dysfunction have been implicated. However, the exact mechanism in humans is still poorly understood. Several investigative and treatment strategies within and outside the cardiac catheterization laboratory have been proposed, but they have not uniformly shown success in reducing mortality or in preventing adverse left ventricular remodeling resulting from this condition. The aim of this article is to provide a brief and concise review of the current understanding of the pathophysiology, clinical predictors, and investigations and management of coronary no-reflow phenomenon.

Synthetic Fibroblasts: Terra Incognita in Cardiac Regeneration.

Ischemic heart disease, a major risk factor for myocardial infarction (MI), occurs when the blood vessels supplying oxygen-rich blood to the heart become partially or fully occluded by lipid-rich plaques, resulting in myocardial cell death, remodeling, and scarring. In addition, MI occurs as result of lipid-rich plaque rupture, resulting in thrombosis and vessel occlusion. Cardiac fibroblasts (CFs) and CF-derived growth factors are crucial post-MI in myocardial remodeling. Information regarding the regenerative phenotypes of CFs is scarce; however, regenerative CFs are translationally relevant in myocardial regeneration following MI. The emerging technologies in regenerative cardiology offer cutting-edge translational opportunities, including synthetic cells. In this review, we critically reviewed the current knowledge and the ongoing research efforts on application of synthetic cells for improving cardiac regeneration post-MI. Impact statement Synthetic cells offer tremendous regenerative potential in otherwise deleterious cardiac remodeling postmyocardial infarction. Understanding the role of fibroblasts in cardiac healing and the therapeutic applications of synthetic cells would open a multitude of novel cardiac regenerative approaches. The novel concept of synthetic fibroblasts that emulate native cardiac fibroblasts can provide an effective solution in cardiac healing.

The impact of cognitive impairment in patients with acute coronary syndrome undergoing percutaneous revascularization: a systematic review and meta-analysis.

BACKGROUND: Cognitive impairment has been known to be associated with negative health impacts. Several studies recently demonstrated inconsistent outcomes among cognitive impaired patients with acute coronary syndrome (ACS). Our study aimed to determine the impact of cognitive impairment for patients with ACS. METHODS: Databases were searched through October 2020. Studies reporting revascularization rates, short- and long-term mortality among ACS patients with cognitive impairment were included. Effect estimates from the individual studies were extracted and combined using random effect and generic inverse variance method of DerSimonian and Laird. RESULTS: In total, 11 observational studies were included in the analysis consisting of 810 122 ACS patients, with 3.5% cognitive impairment patients. Our analysis suggested that cognitive impairment was associated with a lower rate of percutaneous coronary intervention (PCI) [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.42-0.96; I2 = 98.5%; P = 0.033]. Among patients undergoing PCI, cognitive impairment was statistically associated with increased 30-day mortality (OR, 1.34; 95% CI, 1.14-1.57; I2 = 83.1%; P < 0.001) and long-term mortality (OR, 1.80; 95% CI, 1.04-3.11; I2 = 36.3%; P = 0.034). CONCLUSION: Our study demonstrated that cognitive impairment was not only associated with lower rates of percutaneous revascularization but also with increased 30-day and long-term mortality.

Prognostic implications of echocardiographic measures of left and right atrial pressures on survival in patients with end stage renal disease.

BACKGROUND: Volume excess is common in patients with end stage renal disease (ESRD). We examined the prognostic value of clinical and echocardiographic measures of left (LA) and right atrial (RA) hypertension in this population. METHOD: We prospectively collected demographic, clinical, pharmacological, echocardiographic data on 575 consecutive ESRD patients on hemodialysis undergoing cardiac evaluation before renal transplantation in a dedicated cardiac clinic. Survival was analyzed as a function of clinical and echocardiographic measures of LA and (RA) hypertension. RESULT: Elevated LA pressure was seen in 48% of the patients based on E/e' velocity ratio of ≥ 15, and 28% had elevated RA pressure based on inferior vena caval size. Physical examination grossly underestimated the prevalence of both LA and RA hypertension. Atrial pressures were normal in 46% and both atrial pressures were elevated in 20% of the patients. Elevated LA pressure in the presence of normal RA pressure was found in 30%. Over a period of 20 ± 8 months, there were 43 deaths. There was a graded increase in mortality with increases in LA and bi-atrial hypertension (p = .009). The 2-year mortality rate was 6% in those with normal atrial pressures, 13% in those with isolated LA hypertension and 28% in those with bi-atrial hypertension. CONCLUSION: Mitral E/e' ratio and inferior vena caval size are vastly more sensitive than physical examination for recognition of elevated atrial pressures and are strong predictors of survival in ESRD patients. Limited echocardiographic examination may have a role in ESRD patients undergoing dialysis to help achieve euvolemic status.

Pathophysiology, Diagnosis, and Management of Coronary No-Reflow Phenomenon.

Coronary no-reflow phenomenon is a lethal mechanism of ongoing myocardial injury, following successful revascularization of an infarct-related coronary artery. Incidence of this phenomenon is high following percutaneous intervention, and is associated with adverse in-hospital and long-term outcomes. Several mechanisms such as ischemia-reperfusion injury and distal microthromboembolism in genetically susceptible patients and those with preexisting endothelial dysfunction have been implicated. However, the exact mechanism in humans is still poorly understood. Several investigative and treatment strategies within and outside the cardiac catheterization laboratory have been proposed, but have not uniformly shown success in reducing mortality or in preventing adverse left ventricular remodeling resulting from this condition. The aim of this article is to provide a brief and concise review of the current understanding of the pathophysiology, clinical predictors, and investigations and management of coronary no-reflow phenomenon.

Functional Assessment of Coronary Artery Lesions-Old and New Kids on the Block.

Angiography is inaccurate in assessing functional significance of coronary lesions, and often stenoses deemed severe on angiographic assessment do not restrict coronary blood flow at rest or with maximal dilatation. Angiography-guided revascularization has not shown improvement in hard clinical outcomes in stable ischemic heart disease (SIHD). Most current guidelines for SIHD recommend invasive functional assessment of lesions to guide revascularization if prior evidence of ischemia is not available. There has been several recent advances and development of novel methods in this arena. Various contemporary clinical trials have been undertaken for validation of these indices. Here we review the physiological basis, tools, techniques, and evidence base for various invasive (resting as well as hyperemic) and noninvasive methods for functional assessment of coronary lesions. Left main stenosis, bifurcation lesions, serial stenosis, and acute coronary syndrome each causes unique disequilibrium that may affect measurements and require special considerations for accurate functional assessment.

Management of ST Elevation Myocardial Infarction (STEMI) in Different Settings.

ST-segment elevation myocardial infarction (STEMI) is a life-threatening condition that requires emergent, complex, well-coordinated treatment. Although the primary goal of treatment is simple to describe-reperfusion as quickly as possible-the management process is complicated and is affected by multiple factors including location, patient, and practitioner characteristics. Hence, this narrative review will discuss the recommended management and treatment strategies of STEMI in the circumstances.