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M-atrial natriuretic peptide (MANP) is a novel ANP (atrial natriuretic peptide) analog engineered to be an innovative particulate GC-A (guanylyl cyclase A) receptor activator. The rationale for its design was to develop a best-in-class GC-A activator with enhanced cGMP activating, natriuretic, aldosterone-suppressing, and blood pressure–lowering actions, compared with endogenous ANP, for the treatment of hypertension. Here, we report the first-in-human study on the safety, tolerability, neurohumoral, renal, and blood pressure–lowering properties of MANP in hypertension subjects. This was an open-label sequential single ascending dose design in which all subjects stopped all antihypertensive agents for 14 days before receiving a single subcutaneous injection of MANP. MANP was safe, well tolerated, activated cGMP, induced natriuresis, reduced aldosterone, and decreased blood pressure at or below the maximal tolerated dose. Thus, MANP has a favorable safety profile and produced expected pharmacological effects in human hypertension. Our results support further investigations of MANP as a potential future blood pressure–lowering, natriuretic and aldosterone-suppressing drug for hypertension especially resistant hypertension.

As a rare complication after lung transplant, cardiac constriction should not be missed. Physical exam, echocardiography, and catheterization are essential for diagnosis A 65-year-old man with previous coronary artery disease and idiopathic pulmonary fibrosis underwent bilateral lung transplant and subsequently presented for progressive dyspnea and volume overload. Cardiac imaging and cardiac catheterization confirmed constriction, and complete pericardiectomy was performed. The patient had rapid resolution of heart failure symptoms. Pericardial constriction is a rare complication following lung transplant, and we provide a review of the literature and discussion of potential contributing factors. (Level of Difficulty: Intermediate.), Graphical abstract, As a rare complication after lung transplant, cardiac constriction should not be missed. Physical exam, echocardiography, and catheterization are…

AIMS: To identify prevalence and predictors of undetected pre-clinical diastolic dysfunction (PDD) in a cohort of adult Hispanic patients with type 2 diabetes (T2D), and compare variations in epidemiology and echocardiographic characteristics between categorization based on the 2009 versus 2016 guidelines. METHODS: From 2013 to 2016, a cross-sectional cohort study of adults with T2D was performed. Patients without signs/symptoms of heart failure (HF) underwent 2D/Doppler echocardiographic screening, and were grouped into two subcohorts: 1) normal diastolic function, and 2) PDD, defined by the 2009 or 2016 ASE/EACVI criteria. RESULTS: Among 307 Hispanic subjects, by 2009 criteria, 193 (62.9%) had normal diastolic function, 113 (36.8%) diastolic dysfunction and 1 (0.3%) indeterminate. Those that had diastolic dysfunction (DD) were older (mean age 59.1±12.7 vs 52.2±12.2 years, p

Abstract: Coronavirus disease 2019 (COVID-19) first emerged in a group of patients who presented with severe pneumonia in Wuhan, China, in December 2019. A novel virus, now called SARSCoV- 2 (Severe Acute Respiratory Syndrome Coronavirus-2), was isolated from lower respiratory tract samples. The current outbreak of infection has spread to over 100 countries and killed more than 340,000 people as of 25th May, 2020. The predominant clinical manifestation of COVID-19 is a respiratory disease- ranging from mild flu-like symptoms to fulminant pneumonia and Acute Respiratory Distress Syndrome (ARDS). Patients with pre-existing cardiovascular risk factors are considered more susceptible to the virus, and these conditions are often worsened by the infection. Furthermore, COVID-19 infection has led to de novo cardiac complications, like acute myocardial injury and arrhythmias. In this review, we have focused on the cardiovascular manifestations of COVID-19 infection that have been reported in the literature so far. We have also outlined the effect of pre-existing cardiovascular disease as well as risk factors on the clinical course and outcomes of COVID-19 infection.

The management of postprocedure severe aortic periprosthetic regurgitation after transcatheter aortic valve replacement (TAVR) is unknown. While valve-in-valve TAVR has been associated with favorable outcomes for degenerative surgically implanted bioprosthetic valves, there are no evidence-based guidelines for immediate TAVR valve in TAVR valve for periprosthetic regurgitation. We present a patient who underwent a TAVR valve in TAVR valve implantation within 48 h of her first procedure and showed a good response.

Since the application of ultrasound technology to the field of cardiovascular diseases in the 1950s, echocardiography has evolved from M-mode to 2-dimensional (2D), Doppler, strain, and 3-dimensional (3D) imaging, providing noninvasive and accurate structural and hemodynamic information.

Objective To determine the risks of acute kidney injury development and long-term clinical outcomes of patients with hypertensive crisis. Patients and Methods This was a population study of Olmsted County residents with hypertensive crisis between January 1, 2000, and December 31, 2008, with follow-up until June 30, 2016. Results The results demonstrated that those with underlying chronic kidney disease upon admission for hypertensive crisis, defined as a systolic blood pressure above 180 mm Hg or diastolic blood pressure above 120 mm Hg, were more likely to develop acute kidney injury during hospitalization (odds ratio, 6.04; 95% CI, 1-26; P=.02). Hospitalization length of stay was increased when patients developed acute kidney injury during hypertensive crisis hospitalization (7.6±9 vs 3.4±4 days; P=.04). Furthermore, those who developed acute kidney injury had increased cardiac rehospitalization frequency over 10 years (87% vs 46%; P=.009). These results suggest that those with poor renal reserve are more likely to have further acute kidney damage in the setting of hypertensive crisis, likely due to decreased renal perfusion and neurohormonal dysregulation. Conclusion In patients hospitalized for hypertensive crisis, chronic renal insufficiency was a risk factor associated with acute kidney injury development during hospitalization. Those who developed acute kidney injury had longer hospitalizations with increased rehospitalization frequency. Future studies are warranted to further investigate whether the preservation of renal function will improve clinical outcomes in hospitalized patients with hypertensive crisis.

Background The cardiac intensive care unit ( CICU ) population is no longer composed of only patients with acute coronary syndromes, and includes those with acute heart failure and multiple comorbidities. We hypothesized that the GWTG ‐ HF (Get With The Guidelines–Heart Failure) risk score that predicts inpatient mortality in hospitalized patients with heart failure would predict mortality in CICU patients. Methods and Results We retrospectively analyzed CICU patients at a tertiary care hospital from 2007 to 2015. The GWTG ‐ HF risk score was calculated at CICU admission. As a secondary analysis, the EFFECT (Enhanced Feedback for Effective Cardiac Treatment) , OPTIMIZE‐HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure), and ADHERE (Acute Decompensated Heart Failure National Registry) risk scores were calculated. Kaplan–Meier survival analysis and the area under the receiver operating characteristic curve value were determined for inpatient and 1‐year mortality. The GWTG ‐ HF risk score was calculated in 9532 (95%) patients, with a median value of 40 (interquartile range, 35–47). Inpatient mortality occurred in 824 (8.6%) patients, and 2075 (21.8%) patients died by 1 year. Patients who died in hospital had a significantly higher mean GWTG ‐ HF score (47.7 versus 40.2; P GWTG ‐ HF risk score quartile ( P GWTG ‐ HF , EFFECT, OPTIMIZE‐HF, and ADHERE risk scores was assessed using area under the receiver operating characteristic curve values for hospital mortality, and were similar for all risk scores (0.72–0.74; P >0.05). The Hosmer–Lemeshow statistic suggested poor calibration for hospital mortality by the GWTG ‐ HF risk score ( P Conclusions The GWTG ‐ HF risk score and other heart failure prediction tools demonstrate good discrimination for inpatient and 1‐year mortality in a heterogeneous cohort of CICU patients. Our study emphasizes that prognostic variables overlap in cardiac patients, regardless of the admission diagnosis.

Introduction The prevalence and predictors of undetected pre-clinical diastolic dysfunction (PDD), Stage B heart failure, in the Hispanic population with type 2 diabetes (T2D) is not well defined. In 2016, the American Society of Echocardiography (ASE) recommended a revised diastolic dysfunction categorization guideline. Objectives To identify prevalence and predictors of PDD in Hispanic adults with T2D, and compare differences in clinical and echocardiographic characteristics utilizing 2009 versus 2016 ASE diastolic function guidelines. Methods A cross-sectional study of Hispanic adults with T2D from 2013 to 2016 was performed. Subjects without signs or symptoms of heart failure (HF) underwent 2D/Doppler echocardiography and grouped into two sub-cohorts: 1) normal diastolic function, and 2) PDD, defined by 2009 or 2016 ASE criteria. Univariable and multivariable logistic analysis were performed to identify characteristics associated with PDD. Results Among 307 subjects, by 2009 criteria, 63% and 37% had normal diastolic function and PDD, respectively. By 2016 criteria, 85%, 7%, and 8% had normal diastolic function, PDD, and indeterminate diastolic function, respectively. Those with PDD were older (mean age 59.1±12.7 vs 52.2±12.2 years, p Conclusions By utilizing 2016 versus 2009 diastolic function criteria to a Hispanic population with T2D, the prevalence of PDD decreased from 37% to 7%, consistent with the new guidelines being more specific and less sensitive for diagnosing PDD.

77-year-old man with a history of obesity, hypertension, dyslipidemia, hypothyroidism, and obstructive sleep apnea presented with a 2-year history of postprandial right upper quadrant and epigastric pain. He had not had a gastrointestinal work-up previously and had received only symptomatic treatments. His right upper quadrant discomfort was associated with eating. He presented after a recurrent acute episode of severe right upper quadrant pain that lasted “several hours,” which had improved but not completely resolved. On presentation, the patient’s vital signs were within normal limits. Physical examination revealed an obese man in noacutedistresswithminimalepigastrictenderness on palpation. His medications included aspirin, calcium-vitamin D, cyanocobalamin, furosemide, levothyroxine, lisinopril, metoprolol succinate, naproxen, niacin, fish oil, omeprazole, vitamin C, and vitamin E. Initial laboratory testing including a complete blood cell count, metabolic profile, and measurement of aminotransferase, bilirubin, and amylase levels yielded normal results.

Transesophageal echocardiography continues to have a central role in the diagnosis of infective endocarditis and its sequelae. Recent technological advances offer the option of 3-dimensional imaging in the evaluation of patients with infective endocarditis. We present an illustrative case and review the literature regarding the potential advantages and limitations of 3-dimensional transesophageal echocardiography in the diagnosis of complicated infective endocarditis. A 51-year-old man, an intravenous drug user who had undergone bioprosthetic aortic valve replacement 5 months earlier, presented with prosthetic valve endocarditis. Preoperative transesophageal echocardiography with 3D rendition revealed a large abscess involving the mitral aortic intervalvular fibrosa, together with a mycotic aneurysm that had ruptured into the left atrium, resulting in a left ventricle-to-left atrium fistula. Three-dimensional transesophageal echocardiography enabled superior preoperative anatomic delineation and surgical planning. We conclude that 3-dimensional transesophageal echocardiography can be a useful adjunct to traditional 2-dimensional transesophageal echocardiography as a tool in the diagnosis of infective endocarditis.

44-year-old man with a history of ulcerative colitis since age 20 years presented with acute-on-chronic epigastric abdominal pain associated with new-onset lowgrade fever, chills, and night sweats of 2- to 3-months’ duration. Despite multiple immunosuppressive regimens, including oral prednisone, azathioprine, sulfasalazine, and methotrexate, his ulcerative colitis symptoms had never been fully controlled. Approximately 18 months before the current presentation, infliximab had been prescribed. The patient could not recall if he had beenscreenedfortuberculosisatthattime.Despite

Objectives To determine the frequency and predictors of pericardial effusion following epicardial sheath removal. Background Pericardial effusion can occur following cardiac surgical or interventional procedures including percutaneous epicardial access (EpiAcc), which is increasingly used as part of electrophysiology ablation procedures. Methods A retrospective analysis of the Mayo Clinic comprehensive electronic medical record was performed from all patients who underwent planned EpiAcc as part of an electrophysiology ablation procedure between January 1, 2004 and June 30, 2013. Results Of 144 patients (mean age 51.3 ± 15.5 years, 68% male) who underwent planned EpiAcc as part of an electrophysiology ablation (95.8% pericardial access success rate), seven (4.9%) developed a postoperative pericardial effusion requiring repeat EpiAcc. Inferior access was utilized in 74 (51.4%) patients. Patients with pericardial effusion tended to be younger (41.1 years vs 51.8 years, P = 0.08) and were more likely to have undergone inferior approach access (85.7% vs 49.6%, P = 0.06) than those who did not develop postoperative pericardial effusion. Seventy-one percent of patients with postoperative pericardial effusion versus 32.1% of patients without postoperative pericardial effusion had a preprocedure ejection fraction ≥55% (P = 0.03). There were no procedural-related deaths, and no difference in mortality between groups. Conclusions Postoperative pericardial effusion requiring repeat access/drainage was relatively infrequent, occurring in 4.9% of patients shortly after epicardial procedures. While the majority occur early and therefore require close observation, some patients may present in a delayed manner.

Epicardial Access and Obesity Introduction Percutaneous epicardial access for ablative therapies is an increasingly common technique utilized for refractory ventricular arrhythmias. There are, however few known data on obesity and complication rates associated with this procedure. Methods and Results We retrospectively reviewed the charts of subjects undergoing epicardial access at Mayo Clinic between January 2004 and June 2013. Baseline clinical and echocardiographic data were collected for each subject, who was then classified into body mass index (BMI) categories as underweight, normal weight, overweight, and obese based on a BMI of

Subjects with diabetes mellitus (DM) have increased risk of heart failure (HF). Despite its efficacy in maintaining euglycemia, insulin has not been shown to reduce HF risk in DM. The cyclic guanosine 3',5'-monophosphate (cGMP) system plays an important role in preserving cardiorenal function. To

Annexin A1 (AnxA1) is a 37-kDa pro-resolving protein of the Annexin family of 13 proteins. It is expressed in the heart and kidney with anti-inflammatory properties, and is up regulated with tissue ischemia. Acute heart failure (AHF) is a state of tissue hypo-perfusion. The objective of the current

Preclinical Diastolic Dysfunction (PDD) has been broadly defined as subjects with left ventricular diastolic dysfunction, without the diagnosis of congestive heart failure (HF), and with normal systolic function. PDD is an entity which remains poorly understood, yet has definite clinical significance. Although few original studies have focused on PDD, it has been shown that PDD is prevalent, and that there is a clear progression from PDD to symptomatic heart failure including dyspnea, edema, and fatigue. In diabetic patients and patients with coronary artery disease or hypertension, it has been shown that patients with PDD have a significantly higher risk of progression to heart failure and death compared to patients without PDD. Because of these findings and the increasing prevalence of the heart failure epidemic, it is clear that an understanding of PDD is essential to decreasing patients’ morbidity and mortality. This review will focus on what is known concerning preclinical diastolic dysfunction, including definitions, staging, epidemiology, pathophysiology, and the natural history of the disease. In addition, given the paucity of trials focused on PDD treatment, studies targeting risk factors associated with the development of PDD and therapeutic trials for heart failure with preserved ejection fraction will be reviewed.

Cardiac conduction disturbances such as left bundle branch block (LBBB) and atrioventricular blocks (AVB) occur frequently following transcatheter aortic valve replacement (TAVR) and may be associated with adverse clinical events. There is a lack of consensus regarding permanent pacemaker implantation in the case of occurrence of TAVR-related bundle branch blocks or combination of AVB and bundle blocks. Furthermore, there are no guidelines regarding the use of the leadless pacemaker in this setting. We present a patient who underwent successful implantation of a leadless pacemaker for a new LBBB post-TAVR.

Background Modern advances in surgery and percutaneous interventions have resulted in new therapeutic possibilities for end-stage heart failure in congenital heart disease. We present a case of a patient with D-transposition of the great arteries undergoing multiple surgeries and percutaneous interventions for advanced heart failure. Description A 44-year-old man with D-transposition of the great arteries underwent a Blalock-Hanlon septectomy at age 9 days and a Mustard atrial switch procedure at age 3 years. He received an epicardial ventricular pacemaker at age 12 years for high grade atrioventricular (AV) block. He developed supraventricular tachycardia ten years ago, received electrophysiology ablation, and was found to have an inferior vena cava (IVC) baffle leak for which he underwent Amplatzer occluder device placement. Four years ago, he developed superior vena cava (SVC) and IVC baffle stenosis and underwent dilation and covered stent placements in the SVC and IVC baffles. His pacemaker was upgraded to a biventricular implantable cardioverter defibrillator (ICD) utilizing the epicardial ventricular lead and an endocardial lead through the covered stent in the SVC baffle for primary prevention of sudden cardiac death. Due to worsening heart failure despite inotropic support, the patient underwent systemic HeartWare ventricular assist device (VAD) implantation as a bridge to transplantation. Discussion The chest X-ray shows a HeartWare ventricular assist device attached to the systemic right ventricle. The biventricular ICD includes endocardial right-atrial lead, ICD lead in the non-systemic left-ventricle, and two epicardial ventricular leads. Multiple sternotomy wires, endotracheal tube and right internal jugular catheter are seen. The stented superior and inferior vena cava baffles and Amplatzer closure device for baffle leak project over the mediastinum. Conclusion Significant advances in surgery and percutaneous interventions allow for complex therapeutic options for patients with congenital heart disease and advanced heart failure.

Background Sudden cardiac death risk from stimulants clenbuterol and taurine for athletes is unknown. Description A 30-year-old body-builder who took clenbuterol and taurine for one week and was otherwise healthy without any cardiovascular disease was found unresponsive, requiring five external defibrillations for ventricular fibrillation (VF) to restore sinus rhythm. The left ventricular ejection fraction was 22% immediately after resuscitation and improved to 49% in 3 days. Coronary angiogram did not show any coronary artery disease and cardiac-magnetic-resonance was unremarkable. ECG showed no abnormal findings. Discussion Clenbuterol, a performance-enhancing drug, is a beta-2 agonist that increases fat metabolism and aerobic capacity and can cause hypertension and tachycardia. Taurine, found in energy drinks, can cause ventricular arrhythmias. Clenbuterol depletes taurine, so athletes take these in combination. While many people take sports supplements, few have sudden death. The VF is likely attributed to unknown underlying myocardial vulnerability and is precipitated by the combination of clenbuterol and taurine. Subcutaneous implantable cardioverter defibrillator (ICD) was placed in this patient for secondary prevention of sudden cardiac death. Conclusion Clenbuterol and taurine, used as performance-enhancing drugs in athletes, may trigger VF and heart failure in those with predisposing substrate.

This study determined whether there is development of tachyphylaxis to enhancement of cardiorenal response to acute volume loading (AVL) with B-type natriuretic peptide (BNP) after 12-week, twice-daily subcutaneous BNP administration in patients with preclinical diastolic dysfunction (PDD).PDD is characterized by normal systolic function and moderate or severe diastolic dysfunction but no symptoms of heart failure (HF). Impairment in cardiorenal endocrine response to stress by AVL exists in PDD and is corrected by acute administration of subcutaneous BNP.A double-blinded, placebo-controlled proof-of-concept study was conducted to compare 12 weeks of twice daily subcutaneous BNP, 10 μg/kg (n = 24), versus placebo (n = 12) in PDD. Subjects underwent 2 study visits, at baseline and after 12 weeks. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular AVL.Among those with PDD, there was a statistically significant improvement in diastolic function after 12 weeks of BNP, as measured by a decrease in the Doppler E/e' ratio (where E is early mitral inflow velocity and e' is mitral annulus early diastolic motion) (p = 0.004) and improvement of diastolic dysfunction grade (p = 0.008). After 12 weeks, there was statistically significantly greater sodium excretion, urine flow, and urinary cyclic guanosine monophosphate excretion to AVL (all p 0.001), as well as a trend toward greater glomerular filtration rate (p = 0.050) in the BNP group as compared to the placebo group.In subjects with PDD, chronic BNP administration resulted in sustained improvement in diastolic function without development of tachyphylaxis to the enhancement of cardiorenal response to volume expansion with BNP. (Human Brain Natriuretic Peptide [BNP] [or Nesiritide] to Help Heart, Kidney and Humoral Function; NCT00405548).

Natriuretic peptides (NPs) are a family of hormones that have significant cardiorenal properties. As an important component of blood pressure homeostasis in humans, NPs are potent vasodilatory hormones that mediate diuresis, natriuresis and cardiac remodeling (Levin et al., N Engl J Med 339(5):321–328, 1998). Neurohormonal signaling plays an essential role in cardiovascular disease. Whereas antagonism of the renin-angiotensin-aldosterone pathway, a mediator of pro-vascocontriction, leads to improved outcomes in heart failure, the potentiation of the NPs leads to vasodilation and improved cardiac remodeling. Therefore, NPs have been investigated both as a biomarker for cardiovascular disease as well as a potential treatment agent.

Background— The ROSE AHF trial (Renal Optimization Strategies Evaluation in Acute Heart Failure) found that when compared with placebo, neither low-dose dopamine (2 µg/kg per minute) nor low-dose nesiritide (0.005 μg/kg per minute without bolus) enhanced decongestion or preserved renal function in AHF patients with renal dysfunction. However, there may be differential responses to vasoactive agents in AHF patients with reduced versus preserved ejection fraction (EF). This post hoc analysis examined potential interaction between treatment effect and EF (EF ≤40% versus >40%) on the ROSE AHF end points. Methods and Results— ROSE AHF enrolled AHF patients (n=360; any EF) with renal dysfunction. The coprimary end points were cumulative urine volume and the change in serum cystatin-C in 72 hours. The effect of dopamine (interaction P =0.001) and nesiritide (interaction P =0.039) on urine volume varied by EF group. In heart failure with reduced EF, urine volume was higher with active treatment versus placebo, whereas in heart failure with preserved EF, urine volume was lower with active treatment. The effect of dopamine and nesiritide on weight change, sodium excretion, and incidence of AHF treatment failure also varied by EF group (interaction P Conclusions— In this post hoc analysis of ROSE AHF, the response to vasoactive therapies differed in patients with heart failure with reduced EF and heart failure with preserved EF. Investigations of AHF therapies should assess the potential for differential responses in AHF with preserved versus reduced EF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01132846.

Diastolic dysfunction encompasses both those who are asymptomatic and those who have heart failure symptoms. Preclinical diastolic dysfunction (PDD), defined as diastolic dysfunction with preserved ejection fraction (EF) without the presence of heart failure symptoms, is prevalent and may progress to heart failure with preserved EF (HFpEF). While the causative factors of HFpEF are multifactorial, targeting PDD and its associated comorbidities prior to development of symptoms can reduce development of heart failure. Diabetes, coronary artery disease, hypertension, and renal dysfunction are targets of treatment in those with diastolic dysfunction that may decrease the risk of heart failure development. This review will focus on PDD, its epidemiology, pathophysiology, comorbid conditions, and management that may prevent development of heart failure.

Dyspnea in the elderly can be due to a wide array of pathologies. We discuss a case of an elderly gentleman with an extensive cardiovascular history presenting with acute worsening of chronic dyspnea. Because of persistent respiratory distress unresponsive to standard therapy for congestive heart failure, chronotropic insufficiency, and pulmonary hypertension, further evaluation was undertaken which revealed that diaphragmatic weakness was the etiology of his respiratory failure. EMG and muscle biopsy confirmed the diagnosis of inclusion body myositis (IBM).

Cardiomyopathy (CM) has myriad causes, for which a systematic workup is essential. Here, we describe a rare case of restrictive cardiomyopathy from glycogen storage disease. 54 year old woman with history of unspecified connective tissue disease on hydroxychloroquine and breast cancer s/p