Increasing Multiorgan Heart Transplantations From Donation After Circulatory Death Donors in the United States.

INTRODUCTION: Donation after circulatory death (DCD) donors are becoming an important source of organs for heart-transplantation (HT), but there are limited data regarding their use in multiorgan-HT. METHODS: Between January 2020 and June 2023, we identified 87 adult multiorgan-HTs performed using DCD-donors [77 heart-kidney, 6 heart-lung, 4 heart-liver] and 1494 multiorgan-HTs using donation after brain death (DBD) donors (1141 heart-kidney, 165 heart-lung, 188 heart-liver) in UNOS. For heart-kidney transplantations (the most common multiorgan-HT combination from DCD-donors), we also compared donor/recipient characteristics, and early outcomes, including 6-month mortality using Kaplan-Meier (KM) and Cox hazards-ratio (Cox-HR). RESULTS: Use of DCD-donors for multiorgan-HTs in the United States increased from 1% in January to June 2020 to 12% in January-June 2023 (p < 0.001); but there was a wide variation across UNOS regions and center volumes. Compared to recipients of DBD heart-kidney transplantations, recipients of DCD heart-kidney transplantations were less likely to be of UNOS Status 1/2 at transplant (35.06% vs. 69.59%) and had lower inotrope use (22.08% vs. 43.30%), lower IABP use (2.60% vs. 26.29%), but higher durable CF-LVAD use (19.48% vs. 12.97%), all p < 0.01. Compared to DBD-donors, DCD-donors used for heart-kidney transplantations were younger [28(22-34) vs. 32(25-39) years, p = 0.004]. Recipients of heart-kidney transplantations from DCD-donors and DBD-donors had similar 6-month survival using both KM analysis, and unadjusted and adjusted Cox-HR models, including in propensity matched cohorts. Rates of PGF and in-hospital outcomes were also similar. CONCLUSIONS: Use of DCD-donors for multiorgan-HTs has increased rapidly in the United States and early outcomes of DCD heart-kidney transplantations are promising.

Use of Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction After Cardiac Transplantation: Results of an A Priori Ventless Approach.

Primary graft dysfunction (PGD) after cardiac transplantation is a devastating complication with increasing frequency lately in the setting of donation after circulatory death (DCD). Severe PGD is commonly treated with extracorporeal membrane oxygenation (ECMO) using central or peripheral cannulation. We retrospectively reviewed the outcomes of PGD after cardiac transplantation requiring ECMO support at our center from 2015 to 2020, focused on our now preferential approach using peripheral cannulation without a priori venting. During the study period, 255 patients underwent heart transplantation at our center and 26 (10.2%) of them required ECMO for PGD. Of 24 patients cannulated peripherally 19 (79%) were alive at 30 days and 17 (71%) 1 year after transplant; two additional patients underwent central ECMO cannulation due to unfavorable size of femoral vessels and concern for limb ischemia. Successful decannulation with full graft function recovery occurred in 22 of 24 (92%) patients cannulated peripherally. Six of them had an indwelling intra-aortic balloon pump placed before the transplantation. None of the other 18 patients received a ventricular vent. In conclusion, the use of an a priori peripheral and ventless ECMO approach in patients with PGD after heart transplant is an effective strategy associated with high rates of graft recovery and survival.

Hypertension in Cancer Survivors.

PURPOSE OF REVIEW: With increasing survival after cancer treatment, there is a need for long-term management of risk factors and chronic medical conditions to realize the full benefit of improvement of outcomes. Hypertension is a major risk factor for cardiovascular disease and has a higher prevalence in cancer survivors compared to the general population. In this review article, we discuss the burden of hypertension in cancer survivors and how this impacts their long-term outcomes and risk of cancer recurrence. We then discuss the latest concepts regarding the pathophysiology of hypertension in cancer survivors in detail. There is a focus on inflammation and the role it plays in cancer and hypertension followed by a brief discussion on clonal hematopoiesis of indeterminate potential (CHIP) and associated hypertension. There is a brief review of various cancer therapies associated with development and worsening of hypertension control and the underlying mechanisms behind this. We conclude the review article by giving recommendations on blood pressure control in this unique patient population. RECENT FINDINGS: A lot of newer anti-cancer therapies have been implicated in the development or worsening of hypertension. We summarize the latest data, explore associations between these therapies and hypertension, and review the latest understanding of the underlying mechanisms driving this process. Hypertension is a major risk factor for cardiovascular disease in cancer survivors and must be recognized and treated promptly.

Epidemiology, Pathogenesis, and Diagnosis of Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is a widely underdiagnosed yet clinically significant form of granulomatous myocarditis associated with significant morbidity and mortality. Clinical presentation ranges from silent cardiac involvement detected on imaging to cardiomyopathy or sudden cardiac death. Diagnosis of CS remains challenging due to the lack of sensitivity and specificity of any single diagnostic method, underscoring the importance of elevated clinical suspicion and the use of multimodality imaging to guide diagnosis and treatment. In this review, we discuss the epidemiology, pathogenesis, clinical features, and diagnosis of this clinically evading and enigmatic disease.

Comparison of Surgical Embolectomy and Veno-arterial Extracorporeal Membrane Oxygenation for Massive Pulmonary Embolism.

Massive pulmonary embolism (MPE) is associated with a 20-50% mortality rate with guideline directed therapy. MPE treatment with surgical embolectomy (SE) or venoarterial extracorporeal membrane oxygenation (VA-ECMO) have shown promising results. In the context of a surgical management strategy for MPE, a comparison of outcomes associated with VA-ECMO or SE was performed. A retrospective review of a single institution cardiac surgery database was performed, identifying MPE treated with SE or VA-ECMO between 2005-2020. Primary outcome was in-hospital survival. 59 MPE [27 (46.8%) VA-ECMO vs 32 (54.2%) SE] were identified. All presented with elevated cardiac biomarkers, tachycardia (mean heart rate 113 ± 20 beats/minute), hypotension (mean systolic blood pressure 85 ± 22 mm Hg) and vasopressors requirement, without significant differences between cohorts. Preoperative CPR was performed in 37.3% (22/59), without a significant difference between cohorts. More VA-ECMO presented with questionable neurologic status (GCS ≤ 4) [9/27 (33.3%) vs 2/32 (6.2%), P = 0.008] and more VA-ECMO failed thrombolysis [8/27 (29.6) vs 2/32 (6.3), P = 0.014]. All presented with severe RV dysfunction, by discharge all had normalization of echocardiographic RV function. Overall mortality was 10.2%, with a trend toward higher mortality among VA-ECMO [14.9% (4/27) vs 6.3% (2/32) P = 0.14]. CPR was independently associated with death (OR 10.8, P = 0.02) whereas treatment modality was not (OR 0.24). In an extremely unstable MPE population VA-ECMO and SE were safely performed with low mortality while achieving RV recovery. Adverse outcomes were more closely associated with preoperative CPR than with treatment modality.

Hepatic Interactions in Atherosclerotic Heart Disease.

Atherosclerotic heart disease remains a major cause of morbidity and mortality worldwide. The past few decades have seen the emergence of chronic inflammation as a mediator of atherosclerosis. Although the heart and vascular system remain the organ systems most affected in the atherosclerotic process, chronic inflammation and ischemia trigger a systemic multi-organ response. The liver is a critical organ for systemic hemostasis and recent developments have established an important role of the liver in response to atherosclerosis and myocardial ischemia. In addition, the rapid emergence of systemic liver diseases has unraveled a pathophysiological link with heart disease with therapeutic implications. In this review, we explore the relationship between the liver and the heart in myocardial ischemia, describe epidemiological associations between various liver pathologies and coronary heart disease, and elucidate practical challenges in the clinical management of patients with concomitant coronary heart disease and hepatic abnormalities.

Prognostic Value of Peak Oxygen Uptake in Patients Supported With Left Ventricular Assist Devices (PRO-VAD).

OBJECTIVES: The purpose of this study was to examine whether peak oxygen uptake (pVO2) and other cardiopulmonary exercise test (CPET)-derived variables could predict intermediate-term mortality in stable continuous flow LVAD recipients. BACKGROUND: pVO2 is a cornerstone in the selection of patients for heart transplantation, but the prognostic power of pVO2 obtained in patients treated with a left ventricular assist device (LVAD) is unknown. METHODS: We collected data for pVO2 and outcomes in adult LVAD recipients in a retrospective, multicenter study and evaluated cutoff values for pVO2 including: 1) values above or below medians; 2) grouping patients in tertiles; and 3) pVO2 ≤14 ml/kg/min if the patient was not treated with beta-blockers (BB) or pVO2 ≤12 ml/kg/min if the patient was taking BB therapy. RESULTS: Nine centers contributed data from 450 patients. Patients were 53 ± 13 years of age; 78% were male; body mass index was 25 ± 5 kg/m2 with few comorbidities (stroke: 11%; diabetes: 18%; and peripheral artery disease: 4%). The cause of heart failure (HF) was most often nonischemic (66%). Devices included were the HeartMate II and 3 (Abbott); and Heartware ventricular assist devices Jarvik and Duraheart (Medtronic). The index CPET was performed at a median of 189 days (154-225 days) after LVAD implantation, and mean pVO2 was 14.1 ± 5 ml/kg/min (47% ± 14% of predicted value). Lower pVO2 values were strongly associated with poorer survival regardless of whether patients were analyzed for absolute pVO2 in ml/kg/min, pVO2 ≤12 BB/14 ml/kg/min, or as a percentage of predicted pVO2 values (P ≤ 0.001 for all). For patients with pVO2 >12 BB/14 and ventilation/carbon dioxide relationship (VE/VCO2) slope <35, the 1-year survival was 100%. CONCLUSIONS: Even after LVAD implantation, pVO2 has prognostic value, similar to HF patients not supported by mechanical circulatory support devices. (PROgnostic Value of Exercise Capacity Measured as Peak Oxygen Uptake [pVO2] in Recipients of Left Ventricular Assist Devices [PRO-VAD]; NCT04423562).

Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmia in Continuous-Flow Left Ventricular Assist Device.

Cardiac sympathetic denervation has been shown to reduce sustained ventricular arrhythmias and implantable cardioverter-defibrillator shocks by inhibiting sympathetic outflow to the heart. We describe the first case to our knowledge of cardiac sympathetic denervation in the left ventricular assist device population. (Level of Difficulty: Advanced.).

Statin Use and In-Hospital Mortality in Patients With Diabetes Mellitus and COVID-19.

Background Severe coronavirus disease 2019 (COVID-19) is characterized by a proinflammatory state with high mortality. Statins have anti-inflammatory effects and may attenuate the severity of COVID-19. Methods and Results An observational study of all consecutive adult patients with COVID-19 admitted to a single center located in Bronx, New York, was conducted from March 1, 2020, to May 2, 2020. Patients were grouped as those who did and those who did not receive a statin, and in-hospital mortality was compared by competing events regression. In addition, propensity score matching and inverse probability treatment weighting were used in survival models to examine the association between statin use and death during hospitalization. A total of 4252 patients were admitted with COVID-19. Diabetes mellitus modified the association between statin use and in-hospital mortality. Patients with diabetes mellitus on a statin (n=983) were older (69±11 versus 67±14 years; P<0.01), had lower inflammatory markers (C-reactive protein, 10.2; interquartile range, 4.5-18.4 versus 12.9; interquartile range, 5.9-21.4 mg/dL; P<0.01) and reduced cumulative in-hospital mortality (24% versus 39%; P<0.01) than those not on a statin (n=1283). No difference in hospital mortality was noted in patients without diabetes mellitus on or off statin (20% versus 21%; P=0.82). Propensity score matching (hazard ratio, 0.88; 95% CI, 0.83-0.94; P<0.01) and inverse probability treatment weighting (HR, 0.88; 95% CI, 0.84-0.92; P<0.01) showed a 12% lower risk of death during hospitalization for statin users than for nonusers. Conclusions Statin use was associated with reduced in-hospital mortality from COVID-19 in patients with diabetes mellitus. These findings, if validated, may further reemphasize administration of statins to patients with diabetes mellitus during the COVID-19 era.

Survival and Right Ventricular Function After Surgical Management of Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (PE) is associated with high morbidity and mortality because of right ventricular (RV) failure. There is evidence suggesting surgical therapy (surgical embolectomy or venoarterial extracorporeal membrane oxygenation [ECMO]) is safe and effective. OBJECTIVES: The aim of this study was to assess the safety and efficacy of surgical management of acute PE. METHODS: Surgical embolectomy and/or venoarterial ECMO were compared, between 2005 and 2019, for massive PE (MPE) versus high-risk submassive PE (SMPE). RV recovery was defined as improvements in central venous pressure, pulmonary artery systolic pressure, RV/left ventricular ratio, and RV fractional area change. RESULTS: One hundred thirty-six patients with PE (92 with SMPE and 44 with MPE) were identified. Patients with MPE more often presented with syncope (59.1% [26 of 44] vs. 25.0% [23 of 92]; p = 0.0003), Glasgow Coma Scale score ≤4 (22.7% [10 of 44] vs. 0% [0 of 92]), and failed thrombolysis (18.2% [8 of 44] vs. 4.3% [3 of 92]; p = 0.008). Pre-operative cardiopulmonary resuscitation occurred in 43.2% of patients with MPE (19 of 44). Most patients with SMPE were treated with embolectomy (98.9% [91 of 92]), while ECMO was used more in those with MPE (ECMO in 40.9% [18 of 44], embolectomy in 59.1% [26 of 44]). RV function improved as measured by central venous pressure (from 23.4 ± 4.9 to 10.5 ± 3.1 mm Hg), pulmonary artery systolic pressure (from 60.6 ± 14.2 to 33.8 ± 10.7 mm Hg), RV/left ventricular ratio (from 1.19 ± 0.33 to 0.87 ± 0.23; p < 0.005), and fractional area change (from 26.8 to 41.0; p < 0.005). Mortality was 4.4% (6 of 136; SMPE, 1.1% [1 of 92]; MPE, 11.6% [5 of 44]). Subgroup analysis showed morbidity and mortality were highly associated with pre-operative cardiopulmonary resuscitation. CONCLUSIONS: Surgical management of patients with MPE and high-risk SMPE is safe and highly effective at achieving RV recovery.

Hepatitis C-Positive Donors in Cardiac Transplantation: Problems and Opportunities.

PURPOSE OF REVIEW: With the growing need for donor hearts and longer transplant waiting lists, there is a growing interest in expanding the donor pool by reconsidering previously excluded donor candidates. There has been an increase in solid organ availability due to drug overdose deaths in the setting of the recent opioid epidemic. However, these donors often have transmissible infections such as hepatitis C. In this review, we discuss the challenges associated with heart transplantation from hepatitis C-infected donors as well as the recent advancements that are making the use of these organs possible. RECENT FINDINGS: With the introduction and widespread use of nucleic acid testing (NAT), the ability to distinguish viremic donors and those that have cleared the virus has become a reality. In addition, with the emergence of direct antiviral agents, there is an increase in data showing the short-term outcomes and success of hepatitis C treatment for recipients of viremic donor hearts. As techniques to distinguish donor hepatitis C infection status and successful treatments emerge, the percentage of accepted hepatitis C donor hearts is increasing. A number of studies showing success with hepatitis C organ transplants present a promising new avenue for organ procurement essential to meet the increasing demand for donor hearts.

Current pharmacotherapeutic strategies for cardiac arrhythmias in heart failure.

Introduction: Heart failure (HF) affects over 6 million Americans and is the most common cause of hospital readmissions in the United States. Cardiac arrhythmias are common comorbidities seen in patients with HF and are associated with an increase in morbidity and mortality. Pharmacotherapeutic agents along with device and ablation therapies are the mainstays of treatment for cardiac arrhythmias in HF.Areas covered: An extensive literature review of articles and clinical trials on PUBMED on the topic of pharmacotherapy for cardiac arrhythmias in heart failure was conducted. This review article summarizes the above literature to describe the prevalence of the various types of arrhythmias in HF, the recommended pharmacotherapies for the treatment of these arrhythmias in HF and the evidence that supports these recommendations.Expert opinion: Cardiac arrhythmias are common in HF and are the leading cause of death in this patient population. The management of cardiac arrhythmias in HF is challenging. Pharmacotherapy is the primary though increasingly adjunctive therapy for most cardiac arrhythmias. Further, antiarrhythmic drugs must be used with caution in this patient population due to their potential adverse effects.

Vulnerable Plaque: A Review of Current Concepts in Pathophysiology and Imaging.

Advances in our understanding of the natural history and biology of atherosclerotic vascular disease led to the concept of a vulnerable plaque (VP), which is predisposed toward more rapid progression and acute coronary events. With newer technologies, we now have at our disposal high-quality imaging studies, both invasive and noninvasive, which promise in identifying plaque characteristics that make it more vulnerable. Upcoming trials aim to evaluate the utility of imaging VP in predicting clinical events. We discuss the role of VP imaging in managing atherosclerotic vascular disease.

Newer hormonal pharmacotherapies for heart failure.

INTRODUCTION: Heart failure (HF) is characterized by maladaptive neurohormonal activation of the cardiovascular and renal systems resulting in circulatory inadequacy and frequent acute exacerbations. The increasing burden of HF prompted investigation of underlying pathophysiological mechanisms and the design of pharmacotherapeutics that would target these pathways. AREAS COVERED: A MEDLINE search for relevant original investigations and review articles of newer hormonal drugs for HF since the year 2005 till October 2017 provided us with necessary literature. Major trials and relevant clinical investigations were discussed. EXPERT COMMENTARY: A multitude of hormonal pathways central to HF were identified, including the natriuretic peptide system and neurohormones such as relaxin, arginine vasopressin, and endothelin. However, drugs targeting these novel pathways (aliskiren, tolvaptan, ularitide, serelaxin, bosentan, macitentan) failed to show mortality benefit. This emphasizes a tremendous unmet need in the pharmacotherapy for HF, especially for the subtypes of acute HF and HF with preserved ejection fraction. Sacubitril/valsartan demonstrated substantial mortality benefit in chronic systolic HF population and is endorsed by international HF guidelines. If proven to be efficacious in larger outcome trials, finerenone can be a valuable addition baseline HF therapy. More basic, translational, and phenotype specific clinical research is warranted to improve HF pharmacotherapy.

Pharmacological management of hypertension in the elderly and frail populations.

INTRODUCTION: Cardiovascular disease is a leading cause of mortality in the elderly. Hypertension is an important modifiable risk factor that contributes to cardiovascular morbidity and mortality. The prevalence of hypertension is known to increase with age, and hypertension has been associated with an increase in risk for cardiovascular disease in the elderly. There is a wealth of evidence that supports aggressive control of blood pressure to lower cardiovascular risk in the general population. However, there are limited data to guide management of hypertension in the elderly and frail patient subgroups. These subgroups are inadequately treated due to lack of clarity regarding blood pressure thresholds, treatment targets, comorbidities, frailty, drug interactions from polypharmacy, and high cost of care. Areas covered: We review the current evidence behind the definition, goals, and treatments for hypertension in the elderly and frail and outline a strategy that can be used to guide antihypertensive pharmacotherapy in this population. Expert commentary: Lower blood pressure to < 130/80 mm Hg in elderly patients if tolerated and promote use of combination therapy if the blood pressure is > 20/10 mm Hg over the goal blood pressure. Antihypertensive treatment regimens must be tailored to each individual based on their comorbidities, risk for adverse effects, and potential drug interactions ( Figure 1 ).

Sacubitril/valsartan in cardiovascular disease: evidence to date and place in therapy.

Cardiovascular (CV) disease is a major cause of morbidity and mortality in the developing and the developed world. Mortality from CV disease had plateaued in the recent years raising concerning alarms about the sustained efficacy of available preventive and treatment options. Heart failure (HF) is among the major contributors to the CV-related health care burden, a persisting concern despite the use of clinically proven guideline-directed therapies. A requirement for more efficient medical therapies coupled with recent advances in bio-innovation led to the creation of sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), which demonstrated substantial CV benefit when compared with the standard of care, enalapril, in patients with HF and reduced ejection fraction. Further investigations of this novel combination ARNI at the tissue level shed light into the anti-remodeling and cardioprotective effects of sacubitril/valsartan, while clinical studies in the phenotypes of HF with preserved ejection fraction, hypertension and subsets, coronary outcomes, postmyocardial infarction, and renal disease suggested that this combination could be beneficial across a wide spectrum of CV disease. Sacubitril/valsartan is a much-needed therapeutic advance in the avenue of CV disease.

Managing Hypertension in Patients Aged 75 Years and Older.

On the basis of the available data, we would diagnose a normal blood pressure in elderly persons including those 75 years of age and older if the blood pressure was below 120/80 mmHg. We would diagnose hypertension in elderly persons including those aged 75 years and older if the systolic blood pressure was 130 mmHg and higher or if the diastolic blood pressure was 80 mmHg and higher. We would treat these elderly patients with hypertension to a blood pressure goal of less than 130/80 mmHg if the blood pressure was obtained by automated blood pressure monitoring in a quiet room. We would consider treating high-risk persons aged 75 years and older to a blood pressure goal of less than 120/80 mmHg if they were carefully monitored for serious adverse events. If the blood pressure is more than 20/10 mmHg above the goal blood pressure, we would initiate antihypertensive drug therapy with two antihypertensive drugs. The initial drug of choice for the treatment of hypertension in adults aged 75 years and older should be based on co-morbidities, co-incidental indications, tolerability, and cost.